Immunology Medicines – Drug Online https://edrug-online.com Medication Information Guide Sun, 04 Oct 2020 11:12:24 +0000 en-US hourly 1 https://wordpress.org/?v=5.8 IDACIO 40 mg / 0.8 ml solution for injection Uses, Dosage, Side Effects https://edrug-online.com/1489/idacio.html https://edrug-online.com/1489/idacio.html#respond Sun, 04 Oct 2020 11:12:11 +0000 https://edrug-online.com/?p=1489 IDACIO 40 mgIDACIO 40 mg / 0.8 ml solution for injection >> Generic drug of the Therapeutic class: Immunology Medicines Active ingredients: Adalimumab what is IDACIO medication used for and indication? Juvenile idiopathic arthritis Polyarticular juvenile idiopathic arthritis Idacio in combination with methotrexate is indicated for the treatment of progressive polyarticular juvenile idiopathic arthritis in patients from […]]]> IDACIO 40 mg

IDACIO 40 mg / 0.8 ml solution for injection >> Generic drug of the Therapeutic class: Immunology Medicines

Active ingredients: Adalimumab

what is IDACIO medication used for and indication?

Juvenile idiopathic arthritis

Polyarticular juvenile idiopathic arthritis

  • Idacio in combination with methotrexate is indicated for the treatment of progressive polyarticular juvenile idiopathic arthritis in patients from 2 years of age in case of insufficient response to one or more DMARDs.
  • Idacio can be administered as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is unsuitable (for efficacy in monotherapy see section Pharmacodynamic properties). Adalimumab has not been studied in patients less than 2 years of age.

Enthesitis-related arthritis

  • Idacio is indicated for the treatment of active arthritis associated with enthesitis in patients from 6 years of age with insufficient response or intolerance to conventional therapy.

Plaque psoriasis in children and adolescents

  • Idacio is indicated for the treatment of severe chronic plaque psoriasis in children from 4 years of age and adolescents with insufficient response to topical treatment and phototherapy or when these treatments are inappropriate.

Crohn’s disease in children and adolescents

  • Idacio is indicated for the treatment of moderate to severe active Crohn’s disease in children and adolescents from 6 years of age who have not responded to conventional treatment including first-line nutritional therapy and a corticosteroid and / or an immunomodulator, or in which these treatments are poorly tolerated or contraindicated.

Adolescent hidradenitis suppurativa (HS)

  • Idacio is indicated for the treatment of active, moderate to severe hidradenitis suppurativa (Verneuil’s disease) in adolescents from 12 years of age in case of insufficient response to conventional systemic treatment of HS . pharmacokinetics).

Uveitis in children and adolescents

  • Idacio is indicated for the treatment of chronic non-infectious anterior uveitis in children and adolescents from 2 years of age in case of insufficient response or intolerance to conventional treatment or for whom conventional treatment is inappropriate.

IDACIO  Dosage

The treatment Idacio should be initiated and supervised by a physician qualified specialist in the diagnosis and treatment of pathologies in which Idacio indicated. It is recommended that
ophthalmologists consult an appropriate specialist before initiating treatment with Idacio (see section 4.4). A special surveillance card will be given to patients treated with Idacio.

After proper training in the injection technique, patients can self-inject Idacio, if their doctor considers it possible, under the guise of appropriate medical supervision.

During treatment with Idacio, other concomitant treatments (such as corticosteroids and / or immunomodulators) should be optimized.

Dosage

Pediatric population

Juvenile idiopathic arthritis

Polyarticular juvenile idiopathic arthritis from 2 years old

  • The recommended dosage of Idacio for patients with polyarticular juvenile idiopathic arthritis from the age of 2 years depends on body weight (Table 1). Idacio is given every two weeks by injection under the skin.
  • The available data suggest that the clinical response is usually achieved within 12 weeks of treatment. Continuation of treatment should be carefully reconsidered in a patient who has not responded within this time frame.
  • There is no relevant use of adalimumab in patients under 2 years of age in this indication.
  • Other presentations of Idacio may be available depending on the therapeutic needs of each patient.

Enthesitis-related arthritis

  • The recommended dosage of Idacio for patients with enthesitis-related arthritis from the age of 6 years depends on body weight (Table 2). Idacio is given every two weeks as a subcutaneous injection.
  • Adalimumab has not been studied in patients less than 6 years of age with arthritis related to enthesitis.
  • Other presentations of Idacio may be available depending on the therapeutic needs of each patient.

Plaque psoriasis in children and adolescents

  • The recommended dosage of Idacio for patients with plaque psoriasis aged 4 to 17 years depends on body weight (Table 3). Idacio is administered as a subcutaneous injection.
  • The continuing treatment beyond 16 weeks should be carefully reconsidered in a patient not responding within this time.
  • If retreatment with Idacio is indicated, the recommendations mentioned above for dosage and duration of treatment should be followed.
  • The safety of adalimumab in children and adolescents with plaque psoriasis has been evaluated over a mean duration of 13 months.
  • There is no relevant use of adalimumab in children aged less than 4 years in this indication.
  • Other presentations of Idacio may be available depending on the therapeutic needs of each patient.

Adolescent hidradenitis suppurativa (from 12 years of age, weighing at least 30 kg)

  • There is no clinical trial conducted with adalimumab in adolescents with HS.
  • The dosage of adalimumab in these patients was determined frompharmacokinetic modeling and simulation.
  • The recommended dosage of Idacio is 80 mg at week 0 followed by 40 mg every two weeks from week 1 by subcutaneous injection.
  • In adolescents with insufficient response to Idacio 40 mg every two weeks, an increase in dosage to 40 mg every week or 80 mg every other week may be considered.
  • If necessary, antibiotics can be continued during treatment with Idacio. During treatment with Idacio, it is recommended that the patient cleanse his lesions daily with a topical antiseptic.
  • The continuing treatment beyond 12 weeks should be carefully reconsidered in patients showing no improvement during this period.
  • If treatment is interrupted, Idacio could be reintroduced if necessary.
  • The benefit and risk of continued long-term treatment should be assessed regularly (see data in adults under Pharmacodynamic properties).
  • There is no relevant use of adalimumab in children aged less than 12 years in this indication.
  • Other presentations of Idacio may be available depending on the therapeutic needs of each patient.

Crohn’s disease in children and adolescents

  • The recommended dosage of Idacio for patients with Crohn’s disease aged 6 to 17 years depends on body weight (Table 4). Idacio is administered as a subcutaneous injection.
  • The patients with an inadequate response to treatment is observed may benefit from increasing the dosage:
    • <40 kg: 20 mg every week
    • ≥ 40 kg: 40 mg every week or 80 mg every two weeks
  • Continuation of treatment should be carefully reconsidered in a patient who has not responded by week 12.
  • There is no relevant use of adalimumab in children aged less than 6 years in this indication.
  • Other presentations of Idacio may be available depending on the therapeutic needs of each patient.

Uveitis in children and adolescents

  • The recommended dosage of Idacio for children and adolescents with uveitis from the age of 2 years depends on body weight (Table 5). Idacio is administered as a subcutaneous injection.
  • In uveitis  in children and adolescents, no clinical trials have been conducted with adalimumab without concomitant treatment with methotrexate.
  • When initiating treatment with Idacio, a loading dose of 40 mg for patients <30 kg or 80 mg for patients ≥ 30 kg may be administered one week before the start of maintenance therapy. No clinical data are available from the use of a loading dose of adalimumab in children less than 6 years of age.
  • There is no relevant use of Idacio in children aged less than 2 years in this indication.
  • An annual reassessment of the benefits and risks associated with long-term continuous therapy is recommended.
  • Other presentations of Idacio may be available depending on the therapeutic needs of each patient.

Renal and / or hepatic impairment

  • Adalimumab has not been studied in these patient populations. It is not possible to recommend dosages.

Administration mode

  • Idacio is administered as a subcutaneous injection. Full instructions for use are provided in the package leaflet.
  • Other Idacio presentations are available.

IDACIO Contraindications

  • Hypersensitivity to the active substance or to any of the excipients listed in the Composition section.
  • Active tuberculosis or other severe infections such as sepsis and opportunistic infections .
  • Moderate to severe heart failure (NYHA classes III / IV) .

IDACIO Side Effects

Summary of the safety profile

  • Adalimumab has been studied in 9,506 patients in pivotal, controlled, open- label trials of 60 months and longer duration. These trials included patients with recent or old rheumatoid arthritis, juvenile idiopathic arthritis ( polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis) or patients with axial spondyloarthritis (ankylosing spondylitis and axial spondyloarthritis without radiographic evidence of AS ), psoriatic arthritis, Crohn’s disease, ulcerative colitis, psoriasis, hidradenitis suppurativa and uveitis. The Pivotal controlled studies included 6,089 patients who received adalimumab and 3,801 patients who received placebo or an active comparator during the controlled phase.
  • The percentage of patients who discontinued treatment due to adverse reactions during the double-blind, controlled phase of the pivotal studies was 5.9% in patients treated with adalimumab and 5.4% in patients in the group control.
  • The most commonly reported side effects are infections (such as nasopharyngitis, upper respiratory tract infections and sinusitis), injection site reactions (erythema, itching, bleeding, pain or swelling), headache and musculoskeletal pain.
  • Some serious side effects have been reported with adalimumab. The TNF antagonists, such as adalimumab affect the system immune and their use may affect the body’s defenses against infection and cancer.
  • Life-threatening and fatal infections (including sepsis, opportunistic infections and tuberculosis), hepatitis B reactivations and various cancers (including leukemia, lymphoma and hepatosplenic T-cell lymphoma) have also been reported with use of Idacio.
  • Of Severe hematological, neurological and autoimmune effects have also been reported. This includes rare cases of pancytopenia, bone marrow anemia, cases of central and peripheral demyelination, and cases of lupus, lupus-related events, and Stevens-Johnson syndrome.

Pediatric population

  • In general, the frequency and type of adverse events seen in children and adolescents were comparable to those seen in adult patients.

List of adverse reactions

  • The list of adverse reactions is based on clinical studies and post-marketing experience and is presented by class of organ systems (SOC) and by frequency in Table 6 below : very common (≥ 1/10); common (≥ 1/100, <1/10); uncommon (≥ 1 / 1,000, <1/100); rare (≥  1 / 10,000, <1 / 1,000) and not known (cannot be estimated from the available data). Within each frequency grouping , undesirable effects are presented in order of decreasing seriousness. The highest frequency observed in the various indications was included. The presence of an asterisk (*) in the “System organ class” column indicates that more information is available under the Contraindications sections ,Special warnings and precautions for use and Adverse effects .

Table 6 Adverse reactions

System organ class

Frequency

Side effects

Infections and infestations *

Very common

Infections
of the respiratory tract (including respiratory infection
bass and upper respiratory tract infection, pneumonia,
sinusitis, pharyngitis, rhino pharyngitis and pneumonia herpes)

Frequent

Systemic infections (including sepsis, candidiasis and influenza),

intestinal infections (including viral gastroenteritis),

infections
skin and soft tissue (including superficial périunguéal paronychia,
cellulitis, impetigo, necrotizing fasciitis and herpes zoster),

ear infections,

oral infections (including herpes, oral herpes and dental infections),

infections of the reproductive organs (including vulvovaginal yeast infection),

urinary tract infections (including pyelonephritis),

fungal infections,

joint infections

Rare

Neurological infections (including viral meningitis),

opportunistic infections and tuberculosis (including coccidioidomycosis,
histoplasmosis and Mycobacterium avium complex infections),
bacterial infections ,

eye infections, diverticulitis1)

Neoplasms benign, malignant and unspecified (incl cysts and polyps) *

Frequent

Skin cancer excluding melanoma (including basal cell carcinoma and squamous cell carcinoma),

benign tumor

Rare

Lymphoma **,

solid organ tumors (including breast, lung and thyroid cancer), melanoma **

Rare

Leukemia1)

Frequency not known

Hepatosplenic T1 lymphoma), Merkel cell carcinoma (cutaneous neuroendocrine carcinoma) 1)

Blood disorders

Very common

Leukopenia (including neutropenia and

 

System organ class

Frequency

Side effects

and the lymphatic system *

agranulocytosis), anemia

Frequent

Leukocytosis, thrombocytopenia

Rare

Idiopathic thrombocytopenic purpura

Rare

Pancytopenia

Immune system disorders *

Frequent

Hypersensitivity,

allergies (including seasonal allergy)

Rare

Sarcoidosis1), vasculitis

Rare

Anaphylaxis1)

Metabolism and nutrition disorders

Very common

Increased lipid level

Frequent

Hypokalaemia,

increased uric acid,

abnormal sodium level in the blood, hypocalcaemia,

hyperglycemia, hypophosphatemia, dehydration

Psychiatric disorders

Frequent

Mood disorders (including depression), anxiety,

insomnia

Nervous system disorders *

Very common

Headache

Frequent

Paresthesia (including hypoaesthesia), Migraine,

nerve root compression

Rare

Cerebrovascular accident1), Tremor,

neuropathy

Rare

Multiple sclerosis,

demyelinating conditions (e.g. optic neuritis, Guillain-Barré syndrome) 1)

Eye disorders

Frequent

Visual disturbances

 

System organ class

Frequency

Side effects

Conjunctivitis, Blepharitis, swelling of the eyes

Rare

Diplopia

Ear and labyrinth disorders

Frequent

Dizziness

Rare

Deafness, tinnitus

Cardiac disorders *

Frequent

Tachycardia

Rare

Myocardial infarction1), arrhythmias,

congestive heart failure

Rare

Cardiac arrest

Vascular disorders

Frequent

Hypertension, hot flashes. hematomas.

Rare

Aortic aneurysm, vascular occlusion, thrombophlebitis

Respiratory, thoracic and mediastinal disorders *

Frequent

Asthma, dyspnea, cough

Rare

Pulmonary embolism1) ,

interstitial lung disease,

chronic obstructive pulmonary disease, pneumonia,

pleural effusion1)

Rare

Pulmonary fibrosis1)

Gastrointestinal disorders

Very common

Abdominal pain, nausea and vomiting

Frequent

Gastrointestinal bleeding, dyspepsia,

gastroesophageal reflux disease, Gougerot-Sjögren syndrome

 

System organ class

Frequency

Side effects

Rare

Pancreatitis, dysphagia, facial edema

Rare

Intestinal perforation1)

Hepatobiliary disorders *

Very common

Elevation of liver enzymes

Rare

Cholecystitis and cholelithiasis, hepatic steatosis, hyperbilirubinemia

Rare

Hepatitis,

reactivation of hepatitis B1), autoimmune hepatitis1)

Frequency

indeterminate

Hepatic failure1)

Skin and subcutaneous tissue disorders

Very common

Rash (including exfoliative rash)

Frequent

Aggravation or onset of psoriasis (including palmoplantar pustular psoriasis) 1), urticaria,

bruising (including purpura), dermatitis (including eczema), onychoclasia,

hyperhidrosis, alopecia1), pruritus

Rare

Night sweats, scar

Rare

Erythema multiforme1), Stevens-Johnson syndrome1), angioedema1),

cutaneous vasculitis1), lichenoid skin reaction 1).

Frequency

indeterminate

Worsening of symptoms of dermatomyositis1)

Musculoskeletal and connective tissue disorders

Very common

Musculoskeletal pain

Frequent

Muscle spasms (including increased serum creatine phosphokinase)

Rare

Rhabdomyolysis,

systemic lupus erythematosus

Rare

Lupus-like syndrome1).

 

System organ class

Frequency

Side effects

Kidney and urinary tract disorders

Frequent

Renal failure, hematuria

Rare

Nocturia

Reproductive system and breast disorders

Rare

Erectile function disorders

General disorders and administration site conditions *

Very common

Injection site reaction (including erythema at the injection site)

Frequent

Chest pain, edema,

Fever1)

Rare

Inflammation

Investigations *

Frequent

Coagulation and bleeding disorders (including prolongation of activated partial thromboplastin time),

positivity to autoantibodies (including anti-double-stranded DNA antibodies),

increased blood lactate dehydrogenase level

Injury, poisoning and procedural complications

Frequent

Poor healing

* more information is available under the sections Contraindications , Special warnings and precautions for use and Undesirable effects .

** including open label extension studies.

1) including data from spontaneous reports Hidradenitis suppurativa (HS)

  • The safety profile in patients with HS treated with adalimumab weekly corresponds to the known safety profile of adalimumab.

Uveitis

  • The safety profile in patients with uveitis treated with adalimumab every other week is consistent with the safety profile known to adalimumab.

Description of selected adverse

reactions Injection site reactions

  • In the pivotal controlled trials in adults and children, 12.9% of patients treated with adalimumab experienced injection site reactions (erythema and / or pruritus , bleeding, pain or swelling) compared to 7.2% of patients receiving placebo or the active comparator. Injection site reactions generally did not require stopping the drug.

Infections

  • In the pivotal controlled trials in adults and children, the frequency of infections was 1.51 per patient-year in the adalimumab and 1.46 per patient-year in the placebo and control groups. The infections mainly consisted of nasopharyngitis, upper respiratory tract infections and sinusitis. Most patients continued with adalimumab after the infection cleared.
  • The incidence of serious infections was 0.04 per patient-year in the adalimumab group and 0.03 per patient-year in the placebo group and the control group.
  • In controlled and open-label studies with adalimumab in adults and in the pediatric population, serious infections (including fatal infections, which have rarely occurred) have been observed. reported including reports of tuberculosis (including miliary and extra-pulmonary sites) and invasive opportunistic infections (eg disseminated histoplasmosis or extrapulmonary histoplasmosis , blastomycosis, coccidioidomycosis, pneumocystosis, candidiasis, aspergillosis and listeriosis). Most cases of tuberculosis have occurred within the first eight months after starting treatment and may reflect reactivation of latent disease .

Malignant tumors and lymphoproliferative disorders

  • No case of cancer was observed in 249 pediatric patients representing an exposure of 655.6 patient-years during the studies with adalimumab in patients with juvenile idiopathic arthritis (polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis). In addition, no cases of cancer were observed in 192 pediatric patients representing an exposure of 498.1 patient-years in studies with adalimumab in pediatric Crohn ‘s disease.
  • No cases of cancer were observed in 77 pediatric patients corresponding to an exposure of 80 patient-years in a study with adalimumab in pediatric chronic plaque psoriasis . No cases of cancer were observed in 60 pediatric patients representing an exposure of 58.4 patient-years in a study with adalimumab in pediatric uveitis .
  • During the controlled periods of the pivotal clinical trials in adults with adalimumab lasting at least 12 weeks in patients with moderately to severely active rheumatoid arthritis, ankylosing spondylitis, axial spondyloarthritis without radiographic evidence of AS, psoriatic arthritis, psoriasis, hidradenitis suppurativa, Crohn’s disease, ulcerative colitis and uveitis, a rate (95% confidence interval) of cancers other than lymphomas or non-melanoma skin cancers, of 6 , 8 (4.4 – 10.5) per 1,000 patient-years among 5,291 patients treated with adalimumab, was observed versus a rate of 6.3 (3.4 – 11.8) per 1,000 patient-years among the 3,444 patients in the control group (the mean duration of treatment was 4.0 months for patients treated with adalimumab and 3.8 months for patients in the control group). The rate (95% confidence interval) of non melanoma skin cancer was 8.8 (6.0 – 13.0) per 1,000 patient-years for patients treated with adalimumab and 3.2 (1 , 3 – 7.6) per 1000 patient-years among patients in the control group. In these skin cancers, squamous cell carcinomas occurred at rates of 2.7 (1.4 – 5.4) per 1000 patient years in patients treated with adalimumab and 0.6 (0.1 – 4.5) per 1000 patient years in patients in the control group ( 95% confidence interval ). The rate (95% confidence interval) of lymphomas was 0.7 (0.2 – 2.7) per 1000 patient years in patients treated with adalimumab and 0.6 (0.1 – 4.5 ) per 1000 patient-years in patients in the control group.
  • By combining controlled portions of these tests and the tests Expansion open ended or current with a mean duration of around 3.3 years including 6427 patients and more than 26,439 patient- years of treatment, the observed rate of cancers, other than lymphomas and non-melanoma skin cancers is approximately 8.5 per 1,000 patient-years. The observed rate of non-melanoma skin cancer is approximately 9.6 per 1,000 patient-years and the observed rate of lymphomas is approximately 1.3 per 1,000 patient-years.
  • In post-marketing period from January 2003 to December 2010, primarily in patients with rheumatoid arthritis, the reported rate of cancer is approximately 2.7 per 1,000 patient-years of treatment. The reported rates for non-melanoma skin cancer and lymphoma are approximately 0.2 and 0.3 per 1000 patient-years of treatment, respectively .
  • At During post-marketing surveillance, rare cases of hepatosplenic T-cell lymphoma have been reported in patients treated with adalimumab.

Autoantibodies

The research repeated autoantibodies were performed on serum samples of patients from IV trials in arthritis rheumatoid. In these trials, initially negative antinuclear antibody titers were positive at week 24 in 11.9% of patients treated with adalimumab and 8.1% of patients on placebo and comparator. Two of the 3441 patients treated with adalimumab in all studies in rheumatoid arthritis and psoriatic arthritis showed clinical signs suggesting a new onset lupus-like syndrome . The condition of the patients improved after stopping treatment. No patient presented with lupus nephritis or central nervous symptoms.

Hepatobiliary events

  • In controlled phase III clinical trials in rheumatoid arthritis and psoriatic arthritis with a follow-up period of 4 to 104 weeks, elevations of ALT ≥ 3 x ULN occurred in 3.7% of patients treated with adalimumab and in 1.6% of patients in the control group.
  • In adalimumab phase III controlled clinical trials in patients with juvenile idiopathic polyarticular arthritis aged 4 to 17 years and patients with enthesitis-related arthritis aged 6 to 17 years, elevations of ALT ≥ 3 x ULN occurred in 6.1% of patients treated with adalimumab and in 1.3% of patients in the control group. Most of the elevations in ALT have occurred with concomitant use of methotrexate. No elevation of ALT ≥ 3 x ULN occurred in the phase III trial of adalimumab in patients with polyarticular juvenile idiopathic arthritis aged 2 to <4 years.
  • In phase III controlled clinical trials of adalimumab in patients with Crohn’s disease and ulcerative colitis with a control period of 4 to 52 weeks, elevations of ALT ≥ 3 x ULN occurred in 0.9% of patients treated with adalimumab and in 0.9% of patients in the control group.
  • In the phase III clinical trial of adalimumab in children and adolescents with Crohn’s disease which evaluated the efficacy and safety profile of two weight-based maintenance regimens following adjusted induction therapy by weight up to 52 weeks of treatment, elevations of ALT ≥ 3 x ULN are occurred in 2.6% of patients (5/192), of whom 4 were treated in combination with immunosuppressants at the start of the study.
  • In phase III controlled clinical trials in plaque psoriasis with a control period of 12 to 24 weeks, elevations of ALT ≥ 3 x ULN occurred in 1.8% of patients treated with adalimumab and in 1.8% % of patients in the control group.
  • It has not been observed ALT elevations ≥ 3 x ULN in the study phase III adalimumab in pediatric patients with plaque psoriasis .
  • In controlled clinical trials of adalimumab (starting doses of 160 mg at Week 0 and 80 mg at Week 2 followed by 40 mg every week from week 4), in patients with hidradenitis suppurativa with a control period of 12 to 16 weeks, elevations of ALT ≥ 3 x ULN occurred in 0.3% of patients treated with adalimumab and 0.6% of patients in the control group.
  • In controlled clinical trials of adalimumab (starting dose 80 mg at week 0 followed by 40 mg every two weeks from week 1) in adult patients with uveitis for up to 80 weeks , with a median duration of exposure of 166.5 days and 105.0 days, respectively, for patients treated with adalimumab and patients in the control group, elevations of ALT ≥ 3 x ULN occurred in 2.4% of patients treated with adalimumab and 2.4% of patients in the control group. In clinical trials across all indications, patients with elevated ALT were asymptomatic and in most cases the elevations were transient and reversible upon continued treatment. However, during post-marketing surveillance, hepatic insufficiency as well as less severe hepatic disorders , which may precede hepatic insufficiency, such as hepatitis including autoimmune hepatitis, have been reported. in patients receiving adalimumab.

Co-administration of azathioprine / 6-mercaptopurine

  • In studies in Crohn’s disease in adults, a higher incidence of severe tumors and infections was observed with the combination of adalimumab and azathioprine / 6-mercaptopurine compared to adalimumab used alone. Reporting of

suspected adverse reactions

  • The reporting of suspected adverse reactions after authorization of the medicinal product is important. It allows continuous monitoring of the benefit / risk ratio of the medicinal product. Healthcare professionals report any suspected adverse reactions via the national reporting system –see Annex V.

IDACIO Interactions

Adalimumab has been studied in patients with rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, and psoriatic arthritis taking adalimumab as monotherapy and in those taking methotrexate concomitantly. Antibody formation was lower when adalimumab was co-administered with methotrexate compared to its use as monotherapy. Administration of adalimumab without methotrexate resulted in increased antibody formation, increased clearance and reduced efficacy of adalimumab.

The combination of Idacio and anakinra is not recommended (see section Warnings and precautions for use “Simultaneous administration of biological DMARDs or anti-TNFs”).

The combination of Idacio and abatacept is not recommended (see section Warnings and precautions for use “Simultaneous administration of biological or anti-TNF DMARDs”).

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

Warnings and Precautions

Traceability

  • In order to improve the traceability of biological medicinal products, the name of the medicinal product  and the batch number of the administered product must be clearly recorded.

Infections

  • The patients receiving TNF-antagonists are more susceptible to serious infections. Impaired lung function can increase the risk of developing infections. Patients should therefore be closely monitored for infections (including tuberculosis) before, during and after treatment with Idacio. As the duration of elimination of adalimumab may be up to four months, monitoring should be continued throughout this period.
  • The treatment Idacio should not be initiated in patients with infections scalable, including chronic or localized infections until infections are not controlled. In patients who have been exposed to tuberculosis or who have traveled to areas at high risk of tuberculosis or endemic mycoses, for example histoplasmosis, coccidioidomycosis or blastomycosis, the risks and benefits of treatment with Idacio should be considered before initiation. treatment (see Other opportunistic infections).
  • The Patients who develop a new infection during treatment with Idacio must be monitored
    carefully and complete diagnostic workup should be practiced. If a serious new infection or sepsis develops, the administration of Idacio should be discontinued and appropriate antimicrobial or antifungal therapy should be started until the infection is controlled. The physician should exercise caution before using Idacio in patients with a history of recurrent infection or with underlying conditions that may predispose them to infections, including concomitant treatment with immunosuppressive drugs.

Serious infections

  • Of serious infections, including sepsis due to infectionsbacterial, mycobacterial, invasive fungal, parasitic, viral, or other opportunistic infections such as listeriosis, legionellosis and pneumocystis have been reported in patients treated with adalimumab.
  • The other serious infections seen in clinical trials include pneumonia, pyelonephritis, septic arthritis and septicemia. There have been reports of infections requiring hospitalization or with fatal outcome.

Tuberculosis

  • Of TB cases, including cases of TB reactivation and primary infection tuberculosis have been reported for patients receiving adalimumab. Cases of pulmonary and extra-pulmonary (i.e. disseminated) tuberculosis have been reported.
  • Before initiating treatment with Idacio, all patients should be tested for active or not active (“latent”) tuberculosis infection . This assessment should include a detailed medical evaluation in patients with a history of tuberculosis or possible previous exposure to patients with active tuberculosis and / or current or past immunosuppressive therapy. Appropriate screening tests (eg tuberculin skin test and chest x-ray) should be performed in all patients (according to local recommendations). It is advisable to note the performance and the results of these tests in the patient monitoring. Prescribers are reminded that the tuberculin skin test can give false negatives, especially in seriously ill or immunosuppressed patients.
  • If active tuberculosis is diagnosed, treatment with Idacio should not be initiated.
  • In all of the situations described below, the benefit / risk ratio of the treatment should be assessed very carefully.
  • In case of suspicion of latent tuberculosis, consulting a specialist, qualified in the treatment of tuberculosis should be considered.
  • In case of diagnosis of latent tuberculosis, prophylactic tuberculosis appropriate and in accordance with local recommendations must be implemented before the start of treatment with Idacio.
  • A TB prophylaxis should also be considered before introducing Idacio in patients with risk factors or multiple TB significant despite testing of negative tuberculosis and in patients with a history of latent or active tuberculosis in that the administration of an appropriate anti-tuberculosis treatment cannot be confirmed.
  • The case of reactivation of tuberculosis despite treatment prophylactic occurred in patients treated with adalimumab. Some patients who had been successfully treated for active tuberculosis developed the disease again during treatment with adalimumab.
  • The patients should be advised that they will need their doctor in case of occurrence of symptoms suggestive signs or infection tuberculosis (eg persistent cough, wasting / loss of weight, low grade fever, listlessness), during or after treatment Idacio.

Other opportunistic infections

  • Of opportunistic infections, including invasive fungal infections, have been observed in patients treated with adalimumab. These infections were not always detected in patients receiving TNF antagonists, resulting in delayed initiation of appropriate therapy, sometimes with fatal outcome.
  • In patients who present with signs and symptoms such as fever, malaise, weight loss, sweating, cough, dyspnea and / or pulmonary infiltrates or other serious systemic disease with or without concomitant shock , an invasive fungal infection should be suspected; in this case, the administration of Idacio should be stopped immediately.Diagnosis and initiation of empiric antifungal therapy in these patients should be made in consultation with a physician experienced in the management of patients with invasive fungal infections.

Reactivation of hepatitis B

  • A reactivation of hepatitis B occurred in patients who received a TNF antagonist including adalimumab and who were carriers chronic of this virus (that is to say antigen-positive area HBsAg positive) . Some cases have had a fatal outcome. Patients should be screened for HBV infection before initiating treatment with Idacio. For patients who test positive for hepatitis B, it is recommended to consult a doctor specializing in the treatment of hepatitis B.
  • In HBV carriers who require treatment with Idacio, watch carefully for signs and symptoms of active HBV infection throughout treatment and for several months after discontinuation. There are insufficient data available regarding the treatment of patients with HBV treated with antiviral drugs to prevent HBV reactivation and treated with a TNF antagonist. In patients who develop HBV reactivation, Idacio should be discontinued and effective antiviral therapy and appropriate additional therapy should be initiated.

Neurological events

  • The TNF blockers, including adalimumab, have been associated in rare circumstances the onset or exacerbation of symptoms clinical and / or radiographic evidence of demyelinating disease of the
    central nervous system including multiple sclerosis, Optic neuritis and peripheral demyelinating disease, including Guillain-Barré syndrome. Prescribers are advised with caution before treating patients with pre-existing or recently-occurring central or peripheral nervous system demyelinating disease with   ; Discontinuation of treatment should be considered if any of these disorders develop. The association between uveitis intermediate and demyelinating diseases of the central nervous system is known. Neurologic assessment should be performed in patients with non-infectious intermediate uveitis before initiating therapy with Idacio, and repeated regularly during therapy to check for pre-existing or active central nervous system demyelinating disease .

Allergic reactions

  • In clinical trials, serious allergic reactions associated with adalimumab were rarely reported and non-serious allergic reactions associated with adalimumab were uncommon. Cases of severe allergic reactions, including anaphylaxis, have been reported after administration of adalimumab.
  • If an anaphylactic or other serious allergic reaction occurs, the administration of Idacio should be stopped immediately and appropriate treatment initiated.

Immunosuppression

  • In a study of 64 patients with rheumatoid arthritis treated with adalimumab, there was no evidence
    of delayed-type hypersensitivity depression, decreased immunoglobulin levels or a change in the count of effector T and B lymphocytes, NK lymphocytes, monocytes / macrophages and neutrophilic granulocytes.

Malignant tumors and lymphoproliferative disorders

  • In the controlled part of clinical trials with anti-TNFs, more cases of cancer including lymphomas were observed in patients treated with an anti-TNF than in patients in thecontrol group . However, the incidence has been rare. During post-marketing surveillance, cases of leukemia have been reported in patients treated with anti-TNF. In addition, there is a background of increased risk of lymphoma and leukemia in patients with old, inflammatory and highly active rheumatoid arthritis , which complicates the estimation of risk. In the current state of knowledge, the possibility of a risk of developing lymphomas, leukemia or other malignant diseases in patients treated with anti-TNF cannot be excluded.
  • Of malignancies, some fatal, have been reported postmarketing in children, adolescents and
    young adults (up to age 22 years) treated with TNF antagonists (initiation of therapy before age 18), including adalimumab. About half of these cases were lymphomas. The other cases corresponded to other types of malignant tumors among which rare cancers generally associated with a context of immunosuppression. The risk of developing malignant tumors can not be excluded in children and adolescents treated with anti-TNF.
  • In the course of the post-marketing surveillance, rare cases of lymphoma  hepatosplenic T-cell lymphoma have been identified in patients treated with adalimumab. This rare form of T-cell lymphoma has a very aggressive course and is often fatal. Some of these hepatosplenic T-cell lymphomas seen with adalimumab
    have occurred in young adults having concomitant treatment with azathioprine or 6-mercaptopurine used in inflammatory bowel disease. The potential risk of combining azathioprine or 6-mercaptopurine with adalimumab should be carefully considered. A risk of developing  hepatosplenic T-cell lymphoma in patients treated with Idacio cannot be ruled out.
  • There are no studies in patients with a history of malignancies or in whom treatment with adalimumab is continued after the development of cancer. Therefore, increased caution should be observed when considering treatment of these patients with Idacio (see section 4.8).
  • All patients, especially those with a history of intense immunosuppressive therapy or with psoriasis and a
    history of puvatherapy, should be screened for skin cancer other than melanoma before and during treatment with Idacio. Cases of melanoma and Merkel cell carcinoma have also been reported in patients treated with anti-TNF inhibitors including adalimumab.
  • In a prospective clinical study evaluating the use of another anti-TNF agent , infliximab, in patients with
    moderate to severe chronic obstructive pulmonary disease (COPD), more cancers, especially of the lung, were reported. head and neck,
    among patients treated with infliximab compared to patients in the control group. All patients had a history of  heavy smoking. For this reason, care should be taken in the use of an anti-TNF in patients with COPD, and also in patients at risk for cancer due to heavy smoking.
  • Based on current data, it is not known whether treatment with adalimumab influences the risk of developing dysplasia or colon cancer. All patients with ulcerative colitis who are at high risk of dysplasia or colon cancer (for example, patients with old ulcerative colitis or primary sclerosing cholangitis) or who have a history of dysplasia or colon cancer should do regularly screened for dysplasia before treatment and throughout the course of their disease. This assessment should include colonoscopy and biopsies according to local recommendations.

Haematological reactions

  • From Rare reports of pancytopenia including aplastic anemia have been reported with TNF antagonists. Adverse effects of the blood system including medically significant cytopenias (eg , thrombocytopenia, leukopenia) have been observed with adalimumab. It should be recommended for all patients seek immediate medical advice if they have signs or symptoms suggestive of blood disorders (eg, persistent fever, bruising, bleeding, pallor) while Idacio.
  • Discontinuation of treatment with Idacio should be considered for patients in whom significant blood abnormalities are confirmed.

Vaccinations

  • Similar antibody responses to the standard 23-valence pneumococcal vaccine and to the trivalent influenza vaccine were observed in a study in 226 adults with rheumatoid  arthritis treated with adalimumab or placebo. There are no data available on the secondary transmission of infection from live vaccines in patients receiving adalimumab.
  • In children and adolescents, it is recommended, if possible, that all immunizations be up to date according to current immunization recommendations before initiating treatment with adalimumab.
  • The adalimumab in patients may receive multiple vaccines simultaneously, except in respect of livevaccines. Administration of live vaccines (eg, BCG vaccine) to infants who have been exposed to adalimumab in utero is not recommended for 5 months after the mother’s last injection of adalimumab during pregnancy.

Congestive heart failure

  • In a clinical trial with another TNF antagonist, worsening congestive heart failure and increased mortality from congestive heart failure were observed . Of cases of congestive heart failure worsening also been reported in patients receiving adalimumab. Idacio should be used with caution in patients with mild heart failure (NYHA classes I / II). Idacio is contraindicated in moderate to severe heart failure (see section Contraindications). Treatment with Idacio should be stopped in patients with new or worsening symptoms. congestive heart failure.

Autoimmune processes

  • The treatment Idacio may cause antibody formation autoimmune. The impact of long-term treatment with adalimumab on the development of autoimmune diseases is unknown. If a patient develops symptoms of a lupus-like syndrome following treatment with Idacio and exhibits a positive anti- double-stranded DNA reaction , treatment with Idacio should not be continued.

Simultaneous administration of biological DMARDs or anti-TNF

  • Some serious infections were seen in clinical studies in the concurrent use of anakinra and another TNF antagonist, etanercept, with no added clinical benefit compared to etanercept alone. Due to the nature of the side effects seen with treatment with etanercept and anakinra, similar side effects may also result from the combination of anakinra and other TNF blockers. Therefore, the combination of adalimumab and anakinra is not recommended (see section Interactions with other medicinal products and other forms of interactions).
  • Concomitant administration of adalimumab with other biologic DMARDs (eg anakinra and abatacept) or with other TNF blockers is not recommended due to the possible increased risk of infections, including serious infections, and other potential pharmacological interactions (see section Interactions with other medicinal products and other forms of interactions).

Surgery

  • There is limited experience with safety during surgical procedures in patients treated with adalimumab. The long half-life of adalimumab should be taken into account if surgery is planned. A patient treated with Idacio requiring surgery should be carefully monitored for infections and appropriate action should be taken. There is limited experience with the safety of adalimumab in patients operated on for arthroplasty.

Hail Occlusion

  • In Crohn’s disease, treatment failure may indicate the presence of fixed fibrous strictures that may require surgical treatment. The available data suggest that adalimumab does not worsen or cause strictures.

Older subjects

  • The frequency of serious infections in subjects treated with adalimumab over 65 years of age (3.7%) is higher than in patients under 65 years of age (1.5%). Some cases have had a fatal outcome. A special attention regarding the risk of infection should be given when treating elderly patients.

Pediatric population

  • See Vaccinations above.

Excipients with known effect

  • This medicine contains less than 1 mmol (23 mg) sodium per 0.8 ml dose , that is to say essentially ‘sodium-free’.

PREGNANCY & BREAST-FEEDING & FERTILITY

Women of childbearing age

  • The women of childbearing age should consider the use of a method of effective contraception during treatment with Idacio and continue for at least five months after the last administration of Idacio.

Pregnancy

  • A large number (approximately 2,100) of pregnancies exposed to adalimumab for which data were collected prospectively, resulting in a live birth with a known term outcome , including more than 1,500 pregnancies exposed to adalimumab during the first trimester, does not reveal any increase in the rate of malformations in the newborn.
  • In a prospective cohort study, 257 women with rheumatoid arthritis (RA) or Crohn’s disease (CD) treated
    with adalimumab at least during the first trimester and 120 women with untreated RA or CD by adalimumab were included. The prevalence at birth of major congenital anomalies was the primary endpoint. The rate of pregnancies resulting in at least one living newborn with a major congenital defect was 6/69 (8.7%) in women treated with adalimumab with RA and 5/74 (6.8 %) in untreated women with RA (unadjusted OR 1.31, 95% CI  0.38-4.52), and 16/152 (10.5%) in women treated with adalimumab with CD and 3/32 (9.4%) in untreated women with CD (Unadjusted OR 1.14, 95% CI 0.31-4.16). The adjusted OR (considering baseline differences) was 1.10 ( 95% CI 0.45-2.73) for RA and CD combined. No notable difference was reported between women treated with adalimumab and women not treated with adalimumab for secondary endpoints of spontaneous abortion, minor birth defects, preterm delivery, height. at birth and serious or opportunistic infections , and stillbirth or malignancy. Interpretation of the data may be affected due to methodological limitations of the study, including the small sample size and the non-randomized study design.
  • In a developmental toxicity study performed in monkeys, there were no signs of possible maternal toxicity, embryotoxicity or teratogenic potential.
  • Preclinical data on the postnatal toxicity of adalimumab are not available (see section Preclinical safety data).
  • Due to its inhibition of TNF- α , adalimumab administered during pregnancy could affect normal immune responses in the newborn. Adalimumab should be used during pregnancy only if needed.
  • In women treated with adalimumab during pregnancy, adalimumab can cross the placenta and pass into the blood of their child. As a result, these children may have an increased risk of infections. The administration of live vaccines (eg, BCG vaccine ) to children who have been exposed to adalimumab in utero is not recommended for 5 months after the mother’s last injection during pregnancy.

Feeding with milk

  • Limited data from the published literature indicate that adalimumab is excreted in breast milk at very low concentrations, with adalimumab being present in breast milk at concentrations equivalent to 0.1% -1% of maternal serum levels. .
  • When administered orally, immunoglobulin G proteins undergo intestinal proteolysis and exhibit low bioavailability.
  • No effects on breastfed newborns / infants are expected. As a result, Idacio can be used during breastfeeding.

Fertility

Preclinical data on the effects of adalimumab on fertility are not available.

What happens if I overdose from IDACIO?

No dose related toxicity was observed in clinical trials. The highest dose evaluated consisted of repeated doses of 10 mg / kg IV, which is approximately 15 times the recommended dose.

What is  Forms and Composition ?

Appearance and shape

  • Solution for injection (for injection).
  • Clear, colorless solution.
  •  Idacio 40 mg / 0.8 mL, solution for injection for pediatric use in a single use vial 0.8 mL of solution in a vial (type I glass) with a rubber stopper (synthetic rubber) sealed with an aluminum crimp.
  • Each pack contains 1 vial, 1 sterile injection syringe, 1 sterile needle, 1 vial adapter and 2 alcohol swabs.

Other shapes

  • IDACIO 40 mg, solution for injection in pre-filled syringe, box of 2 pre-filled syringes (+ alcohol swabs) of 0.80 mL
  • IDACIO 40 mg, solution for injection in pre-filled pen, box of 2 pre-filled pens (+ alcohol swabs) of 0.80 mL

Composition

Active ingredient Solution injectable SC
Adalimumab 40 mg *

* per unit dose

  • Active ingredients: Adalimumab
  • Excipients: Monosodium phosphate dihydrate , Disodium disodium phosphate dihydrate , Mannitol , Sodium chloride , Citric acid monohydrate , Sodium citrate , Polysorbate 80 , Sodium hydroxide (for pH adjustment) , Water for injections , Original substrates: Hamster protein No excipient with known effect is not present in the composition of this drug

NOT’s

Edrug-online contains comprehensive and detailed information about drugs available in the medical field, and is divided into four sections:

general information:

  • Includes a general description of the drug, its use, brand names, FAQs, and relevant news and articles

Additional information:

  • General explanation about dealing with the medicine: how to take the medicine, the doses and times of it, the start and duration of its effectiveness, the recommended diet during the period of taking the medicine, the method of storage and storage, recommendations in cases for forgetting the dose and instructions to stop taking the drug and take additional doses.

Special warnings:

  • For pregnant and breastfeeding women, the elderly, boys and drivers, and use before surgery.

Side effects:

  • It treats possible side effects and drug interactions that require attention and its effect on continuous use.
  • The information contained in this medicine is based on medical literature, but it is not a substitute for consulting a doctor.
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amgevita Uses, Dosage, Side Effects, Precautions & Warnings https://edrug-online.com/1474/amgevita.html https://edrug-online.com/1474/amgevita.html#respond Fri, 02 Oct 2020 12:12:29 +0000 https://edrug-online.com/?p=1474 what is amgevita  medication used for and indication Generic drug of the Therapeutic class: Immunology Medicines Active ingredients: Adalimumab what is amgevita  medication used for and indication? Rheumatoid arthritis AMGEVITA in combination with methotrexate is indicated for: the treatment of moderately to severely active rheumatoid arthritis in adults when the response to DMARDs, including methotrexate, is inadequate. the treatment of severe, active and […]]]> what is amgevita  medication used for and indication

 Generic drug of the Therapeutic class: Immunology Medicines

Active ingredients: Adalimumab

what is amgevita  medication used for and indication?

Rheumatoid arthritis

AMGEVITA in combination with methotrexate is indicated for:

  • the treatment of moderately to severely active rheumatoid arthritis in adults when the response to DMARDs, including methotrexate, is inadequate.
  • the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate.
  • AMGEVITA can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate.
  • AMGEVITA slows the progression of structural damage to the joints measured by radiography and improves functional capacity when administered in combination with methotrexate.

Juvenile idiopathic arthritis

Polyarticular juvenile idiopathic arthritis

  • AMGEVITA in combination with methotrexate is indicated for the treatment of progressive polyarticular juvenile idiopathic arthritis in patients from 2 years of age in case of insufficient response to one or more DMARDs. AMGEVITA can be administered as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is unsuitable (for efficacy as monotherapy, see section Pharmacodynamic properties). Adalimumab has not been studied in patients less than 2 years of age.

Enthesitis-related arthritis

AMGEVITA is indicated for the treatment of active arthritis associated with enthesitis in patients from 6 years of age with insufficient response or intolerance to conventional therapy (see section 5.1).

Axial spondyloarthritis

Ankylosing spondylitis (AS)

  • AMGEVITA is indicated for the treatment of severe and active ankylosing spondylitis in adults who have had an inadequate response to conventional therapy.

Axial spondyloarthritis without radiographic evidence of AS

  • AMGEVITA is indicated for the treatment of severe axial spondyloarthritis without radiographic evidence of AS, but with objective evidence of inflammation on MRI and / or elevated CRP in adults who have had an inadequate response or intolerance to anti -nonsteroidal inflammatory drugs.

Psoriatic arthritis

  • AMGEVITA is indicated for the treatment of active and progressive psoriatic arthritis in adults when the response to previous disease-modifying therapy has been inadequate. AMGEVITA slows the progression of peripheral joint structural damage as measured by radiography, in patients with symmetrical polyarticular forms of the disease (see section 5.1) and improves functional capacity.

Psoriasis

  • AMGEVITA is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who require systemic therapy.

Plaque psoriasis in children and adolescents

  • AMGEVITA is indicated for the treatment of severe chronic plaque psoriasis in children from 4 years of age and adolescents with insufficient response to topical treatment and light therapy or when these treatments are inappropriate.

Hidradenitis suppurativa (HS)

  • AMGEVITA is indicated for the treatment of active, moderate to severe hidradenitis suppurativa (Verneuil’s disease) in adults and adolescents from 12 years of age in case of insufficient response to conventional systemic therapy for HS (see section Properties). Pharmacodynamics and Pharmacokinetic Properties).

Crohn’s disease

  • AMGEVITA is indicated for the treatment of moderate to severe active Crohn’s disease in adult patients who have not responded despite appropriate and well-managed treatment with a corticosteroid and / or immunosuppressant; or in which these treatments are contraindicated or poorly tolerated.

Crohn’s disease in children and adolescents

  • AMGEVITA is indicated for the treatment of moderate to severe active Crohn’s disease in children and adolescents from 6 years of age who have not responded to conventional therapy including first-line nutritional therapy and a corticosteroid and / or an immunomodulator, or in which these treatments are poorly tolerated or contraindicated.

Ulcerative colitis

  • AMGEVITA is indicated for the treatment of active, moderate to severe ulcerative colitis in adult patients who have had an inadequate response to conventional therapy, including corticosteroids and 6-mercaptopurine (6-MP) or azathioprine (AZA), or in whom these treatments are contraindicated or poorly tolerated.

Uveitis

  • AMGEVITA is indicated for the treatment of non-infectious, intermediate, posterior uveitis and panuveitis in adult patients who have had an insufficient response to corticosteroid therapy, in patients requiring corticosteroid sparing, or in whom corticosteroid therapy is inappropriate.

Uveitis in children and adolescents

  • AMGEVITA is indicated for the treatment of chronic non-infectious anterior uveitis in children and adolescents from 2 years of age with insufficient response or intolerance to conventional treatment or for whom conventional treatment is inappropriate.

amgevita  Dosage

The
treatment AMGEVITA should be initiated and supervised by a physician
qualified specialist in the diagnosis and treatment of
pathologies in which AMGEVITA indicated. It is recommended that
ophthalmologists consult an appropriate specialist before
initiating treatment with AMGEVITA (see section 4.4). A special surveillance card will be given to patients treated with AMGEVITA.

After
proper training in the injection technique, patients can
self-inject AMGEVITA, if their doctor considers it possible, under the
guise of appropriate medical supervision.

While taking
AMGEVITA, other concomitant therapies (such
as corticosteroids and / or immunomodulators) should be optimized.

amgevita Dosage
amgevita Dosage

Dosage

Rheumatoid arthritis

  • In
    adult patients with rheumatoid arthritis, the
    recommended dose of AMGEVITA is a single dose of 40 mg adalimumab
    administered every two weeks, subcutaneously. Administration of methotrexate should be continued during treatment with AMGEVITA.
  • The
    glucocorticoids, salicylates, nonsteroidal anti-inflammatory
    drugs or analgesics may be continued during
    treatment with AMGEVITA. As regards the combination with other
    anti-rheumatic drugs other than methotrexate (see
    sections Warnings and precautions for use and Pharmacodynamic properties).
  • As
    monotherapy, some patients with decreased
    response to AMGEVITA 40 mg every other week may
    benefit from an increase in dosage to adalimumab 40 mg
    every week or 80 mg every other week. .
  • The
    available data for adalimumab suggest that
    clinical response is usually achieved within 12 weeks of treatment. The
    Continued therapy should be reconsidered in patients who have
    not responded within this time.

Interruption of treatment

  • It
    may be necessary to stop treatment, eg before
    surgery or in patients with severe infection.
  • The
    re-introduction of AMGEVITA after a period of 70 days or more should
    lead to clinical response of the same magnitude and a profile
    similar to that observed tolerance before treatment interruption.

Ankylosing spondylitis, axial spondyloarthritis without radiographic evidence of AS, and psoriatic arthritis

  • The
    recommended dosage of AMGEVITA for patients with
    ankylosing spondylitis, axial spondyloarthritis without
    radiographic evidence of AS and for patients with
    psoriatic arthritis is 40 mg adalimumab as a single dose every two
    weeks, by injection.

subcutaneous.

  • The
    available data suggest that the clinical response is
    usually achieved within 12 weeks of treatment. Continuation of
    treatment should be reconsidered in a patient who has not responded
    within these time limits.

Psoriasis

  • The
    recommended dose of AMGEVITA to start treatment in
    adults is 80 mg subcutaneously. The dosage will continue
    one week later with 40 mg subcutaneously every other week.
  • The
    continuing treatment beyond 16 weeks should be carefully
    reconsidered in a patient not responding within this time.
  • Beyond
    16 weeks, in case of insufficient response to AMGEVITA 40 mg every
    other week, patients may benefit from an increase
    in dosage to 40 mg every week or 80 mg every other
    week. The benefits and risks of continuous treatment of 40 mg
    weekly or 80 mg every two weeks should be
    carefully reconsidered in a patient with
    insufficient response after increasing the dose (see section 5.1).
    If sufficient response is obtained with 40 mg every week or
    80 mg every two weeks, the dosage may then be reduced
    to 40 mg every 2 weeks.

Hidradenitis suppurativa

  • The
    recommended dosage regimen of AMGEVITA in adult
    patients with hidradenitis suppurativa (HS) is an initial dose of 160
    mg on Day 1 (given as 4 injections of 40 mg in one
    day or 2 injections of 40 mg mg per day for two
    consecutive days ), followed by a dose of 80 mg two weeks after on Day 15
    (given as 2 injections of 40 mg over one day). Two
    weeks later (Day 29), continue with a dose of 40 mg every
    week or 80 mg every two weeks (given as
    two 40 mg injections per day). If necessary, antibiotics
    can be continued during treatment with AMGEVITA. During
    during treatment with AMGEVITA, it is recommended that the patient cleanse
    his lesions daily with a topical antiseptic.
  • The
    continuing treatment beyond 12 weeks should be carefully
    reconsidered in patients showing no improvement during
    this period.
  • If
    treatment is interrupted, AMGEVITA 40 mg every week or 80
    mg every other week may be reintroduced (see section 5.1).
  • The benefit and risk of continued long-term treatment should be assessed regularly.

Crohn’s disease

  • In
    adult patients with moderate to
    severe active Crohn’s disease , the recommended induction regimen of AMGEVITA is
    80 mg at week 0, followed by 40 mg at week 2. If it is
    necessary to obtain faster response to treatment, schedule
    160 mg at week 0 (given as 4 injections of 40 mg
    per day or 2 injections of 40 mg per day for two
    consecutive days ), 80 mg at week 2 (given in the form of two
    injections of 40 mg per day), can be used knowing that the risk
    of adverse events is then higher during this
    induction phase .
  • Following
    induction therapy, the recommended dose is 40
    mg administered every two weeks by subcutaneous injection. If
    a patient has stopped treatment with AMGEVITA and the signs and
    symptoms of disease return, AMGEVITA may be
    re-administered. Experience with re-administration of treatment
    beyond 8 weeks after the previous dose is limited.
  • During
    maintenance treatment, corticosteroids may be
    gradually reduced in accordance with
    clinical practice recommendations .
  • Some
    patients in whom a decreased response to treatment with
    AMGEVITA 40 mg every other week is observed may benefit
    from an increase in the dose to AMGEVITA 40 mg every
    week or 80 mg every other week.
  • Some
    patients who have not responded to treatment at week 4 may
    continue maintenance therapy until week 12.
    Continuation of treatment should be carefully reconsidered in a
    patient who has not responded within this time.

Ulcerative colitis

  • In
    adult patients with moderate to
    severe ulcerative colitis , the recommended induction regimen of AMGEVITA is
    160 mg at week 0 (given as 4 injections of 40 mg
    per day or 2 injections of 40 mg per day. day for two
    consecutive days ) and 80 mg at week 2 (given as two
    40 mg injections per day). After induction therapy, the
    recommended dose is 40 mg every two weeks, by
    subcutaneous injection.
  • During
    maintenance treatment, corticosteroids may be
    gradually reduced in accordance with
    clinical practice recommendations .
  • Some
    patients in whom a decreased response to treatment with
    AMGEVITA 40 mg every two weeks is observed may
    benefit from an increase in the dose to AMGEVITA 40 mg every
    week or 80 mg every two weeks.
  • The
    clinical response is usually achieved within 2 to 8 weeks of
    treatment. Treatment with AMGEVITA should not be continued in
    patients who have not responded within this time frame .

Uveitis

  • In
    adult patients with uveitis, the recommended dose
    of AMGEVITA is an initial dose of 80 mg followed by a dose of 40 mg
    every two weeks starting one week after
    the first dose. There
    is limited experience with initiating treatment with adalimumab monotherapy. The
    treatment can be started AMGEVITA in combination with
    corticosteroids and / or other immunomodulatory therapies not
    organic. The combined corticosteroid dose may be gradually
    reduced in accordance with clinical practice, starting two weeks
    after initiation of treatment with AMGEVITA.
  • An
    annual reassessment of the benefits and risks associated
    with long-term continuous therapy is recommended (see section 5.1).

Special populations

Older subjects

  • No dosage adjustment is necessary.

Renal and / or hepatic impairment

  • Adalimumab has not been studied in these patient populations. It is not possible to recommend dosages.

Pediatric population

Juvenile idiopathic arthritis

Polyarticular juvenile idiopathic arthritis from 2 years old

  • The
    recommended dosage of AMGEVITA for patients with
    polyarticular juvenile idiopathic arthritis from the age of 2 years depends
    on body weight (Table 1). AMGEVITA is administered every two
    weeks as a subcutaneous injection.

Table 1. Amgevita dosage in patients with polyarticular juvenile idiopathic arthritis

  • The
    clinical response is usually achieved within 12 weeks of
    treatment. Continuation of treatment should be carefully
    reconsidered in a patient who has not responded within this time frame.
  • There is no relevant use of adalimumab in patients under 2 years of age in this indication.

Enthesitis-related arthritis

  • The
    recommended dosage of AMGEVITA for patients with
    enthesitis-related arthritis from the age of 6 years depends on body weight
    (Table 2). AMGEVITA is administered every two weeks
    as a subcutaneous injection.

Table 2. Dosage of AMGEVITA in Patients with Enthesitis-Related Arthritis

  • Adalimumab has not been studied in patients less than 6 years of age with arthritis related to enthesitis.

Plaque psoriasis in children and adolescents

  • The
    recommended dosage of AMGEVITA for patients with
    plaque psoriasis aged 4 to 17 years depends on body weight
    (Table 3). AMGEVITA is administered by subcutaneous injection.

Table 3. Amgevita dosage in children and adolescents with plaque psoriasis

  • The
    continuing treatment beyond 16 weeks should be carefully
    reconsidered in a patient not responding within this time.
  • If
    retreatment with AMGEVITA is indicated, the above recommendations
    for dosage and duration of treatment should be followed.
  • The
    safety of adalimumab in children and adolescents with
    plaque psoriasis has been evaluated over a mean duration of 13 months.
  • There is no relevant use of AMGEVITA in children aged less than 4 years in this indication.

Adolescent hidradenitis suppurativa (from 12 years of age, weighing at least 30 kg)

  • There
    is no clinical trial conducted with adalimumab in
    adolescents with HS. The dosage of AMGEVITA in these patients
    was determined from pharmacokinetic modeling and
    simulation.
  • The
    recommended dose of AMGEVITA is 80 mg at week 0 followed by
    40 mg every two weeks from week 1 by subcutaneous injection.
  • In
    adolescents with insufficient response to AMGEVITA 40 mg every
    two weeks, an increase in the dosage to 40 mg every
    week or 80 mg every other week may be considered.
  • If
    necessary, antibiotics can be continued during
    treatment with AMGEVITA. During treatment with AMGEVITA, it is
    recommended that the patient cleanse his lesions daily with a
    topical antiseptic.
  • The
    continuing treatment beyond 12 weeks should be carefully
    reconsidered in patients showing no improvement during
    this period.
  • If treatment is interrupted, AMGEVITA could be reintroduced if necessary.
  • The
    benefit and risk of continued long-term treatment should
    be assessed regularly (see data in
    adults under Pharmacodynamic properties).
  • There is no relevant use of AMGEVITA in children aged less than 12 years in this indication.

Crohn’s disease in children and adolescents

  • The
    recommended dosage of AMGEVITA for patients with
    Crohn’s disease aged 6 to 17 years depends on body weight (Table
    4). AMGEVITA is administered by subcutaneous injection.

Table 4. Dosage of AMGEVITA in Children and Adolescents with Crohn’s Disease

  • 40 mg in week 0 and 20 mg in week 2
  • 80 mg in week 0 and 40 mg in week 2
  • 80 mg in week 0 and 40 mg in week 2
  • 160 mg in week 0 and 80 mg in week 2

The
patients with an inadequate response to treatment is observed
may benefit from increasing the dosage:

  • <40 kg: 20 mg every week
  • ≥ 40 kg: 40 mg every week or 80 mg every two weeks
  • Continuation of treatment should be carefully reconsidered in a patient who has not responded by week 12.
    • There is no relevant use of adalimumab in children aged less than 6 years in this indication.

Uveitis in children and adolescents

  • The
    recommended dose of AMGEVITA for children and adolescents
    with uveitis from the age of 2 years depends on body weight
    (Table 5). AMGEVITA is administered by subcutaneous injection.
  • In
    uveitis in children and adolescents, no clinical trials have been
    conducted with AMGEVITA without concomitant treatment with methotrexate.
  • Table 5. Dosage of AMGEVITA in Children and Adolescents with Uveitis
  • When initiating treatment with AMGEVITA, a loading dose of 40 mg for patients <
    30 kg or 80 mg for patients ≥ 30 kg may be administered one
    week before the start of maintenance therapy. No
    clinical data are available from the use of a loading dose of
    AMGEVITA in children less than 6 years of age .
  • There is no relevant use of AMGEVITA in children aged less than 2 years in this indication.
  • An
    annual reassessment of the benefits and risks associated
    with long-term continuous therapy is recommended.

Pediatric ulcerative colitis

  • The
    safety and efficacy of adalimumab in children 4 to 17 years of age
    have not been established. No data is available. There is no relevant
    use of adalimumab in children aged less than
    4 years in this indication.

Psoriatic arthritis and axial spondyloarthritis including ankylosing spondylitis

  • There
    is no relevant use of adalimumab in the population
    pediatric in indications, ankylosing spondylitis and
    psoriatic arthritis.

Administration mode

  • AMGEVITA is administered by subcutaneous injection. Full instructions for use are provided in the package leaflet.

Contraindications

  • Hypersensitivity adalimumab
  • Hamster protein hypersensitivity
  • Active tuberculosis
  • Severe infection
  • Stage III or IV heart failure
  • Pregnancy
  • Lack of effective female contraception

Hypersensitivity to the active substance or to any of the excipients listed in the Composition section.

Active tuberculosis or other severe infections such as sepsis and opportunistic infections.

Moderate to severe heart failure (NYHA classes III / IV) .

amgevita  Side Effects

  • Adalimumab has been studied in 9,506 patients in pivotal,
    open- label, controlled trials of 60 months and longer duration. These trials included
    patients with recent or old rheumatoid arthritis,
    juvenile idiopathic arthritis (polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis) or patients with axial spondyloarthritis (ankylosing spondylitis and
    axial spondyloarthritis without radiographic evidence of AS ),
    psoriatic arthritis, Crohn’s disease, ulcerative
    colitis, psoriasis and hidradenitis suppurativa and uveitis. The
    pivotal controlled studies involved 6,089 patients who received
    adalimumab and 3,801 patients who received placebo or an
    active comparator during the controlled phase.
  • The
    percentage of patients who discontinued treatment due
    to adverse reactions during the double-blind, controlled phase
    of the pivotal studies was 5.9% in patients treated with
    adalimumab and 5.4% in patients of the control group.
  • The
    most frequently reported side effects are infections
    (such as nasopharyngitis, upper
    respiratory tract infections and sinusitis),
    injection site reactions (erythema, itching, bleeding, pain or
    swelling), headache and musculoskeletal pain.
  • Some
    serious side effects have been reported with adalimumab. The
    TNF antagonists, such qu’AMGEVITA affect the immune system
    and their use may affect the defenses of the
    body against infections and cancer.
  • Life-
    threatening and fatal
    infections (including sepsis, opportunistic infections and tuberculosis),
    hepatitis B reactivations and various cancers (including leukemia, lymphoma and
    hepatosplenic T-cell lymphoma) have also been reported
    with use of adalimumab.
  • Severe
    haematological, neurological and autoimmune effects have
    also been reported. This includes rare cases of pancytopenia,
    bone marrow anemia , cases of central and peripheral demyelination, and
    cases of lupus, lupus-related events, and
    Stevens-Johnson syndrome .

Pediatric population

In
general, the frequency and type of adverse events seen
in children and adolescents were comparable to those seen in
adult patients.

List of side effects

  • The
    list of undesirable effects is based on clinical studies and
    post-marketing experience and is presented by
    system organ and frequency in Table 6 below: very
    common (≥ 1/10); common (≥ 1/100 to <1/10); uncommon (≥
    1 / 1,000 to <1/100); rare (≥ 1 / 10,000 to <1 / 1,000) and
    not known (cannot be estimated from the
    available data ).
  • Within each frequency grouping,
    undesirable effects are presented in order of decreasing seriousness. The
    highest frequency observed in the various indications was
    included.
  • The presence of an asterisk (*) in the column “Class of
    organ systems ”indicates that more information is
    available under the sections Contraindications, Warnings and precautions for use and Undesirable effects.

Table 6. Adverse reactions

* Further information is available under the sections Contraindications, Warnings and precautions for use and Adverse reactions.

** including open label extension studies.

1) including data from spontaneous notifications

Hidradenitis suppurativa (HS)

  • The
    safety profile in patients with HS treated with
    weekly adalimumab is consistent with the
    known safety profile of adalimumab.

Uveitis

  • The
    safety profile in patients with uveitis treated with
    adalimumab every two weeks is consistent with the
    known safety profile of adalimumab.

Description of selected adverse reactions

Injection site reactions

  • In
    pivotal controlled trials in adults and children, 12.9% of
    patients treated with adalimumab experienced
    injection site reactions (erythema and / or pruritus, bleeding, pain or swelling)
    versus 7 , 2% of patients receiving placebo or active comparator.
    Injection site reactions generally did not require
    stopping the drug.

Infections

  • In the pivotal controlled trials in adults and children, the frequency of infections was 1.51
    per patient-year in the adalimumab group and 1.46 per
    patient-year in the placebo group and the control group. . The
    infections mainly consisted of nasopharyngitis,
    upper respiratory tract infections and sinusitis. Most
    patients continued with adalimumab after the infection cleared.
  • The incidence
    of serious infections was 0.04 per patient-year in the
    adalimumab group and 0.03 per patient-year in the placebo group and the
    control group.
  • In
    open-label, controlled studies with adalimumab in
    adults and in the pediatric population, serious infections (
    including fatal infections, which have rarely occurred)
    have been reported including reports of tuberculosis. (including
    miliary and extrapulmonary localizations) and
    invasive opportunistic infections (eg disseminated
    histoplasmosis or extrapulmonary histoplasmosis, blastomycosis, coccidioidomycosis,
    pneumocystosis, candidiasis, aspergillosis and listeriosis). Most
    cases of tuberculosis have occurred within the first eight months after
    starting treatment and may reflect reactivation of
    latent disease.

Malignant tumors and lymphoproliferative disorders

  • No
    cases of cancer were observed in 249 pediatric patients
    representing an exposure of 655.6 patient-years in studies of
    adalimumab in patients with juvenile
    idiopathic arthritis (polyarticular juvenile idiopathic
    arthritis and arthritis related to enthesitis). In addition, no cases of cancer were
    observed in 192 pediatric patients representing an exposure of
    498.1 patient-years in studies with adalimumab in
    pediatric Crohn’s disease. No cases of cancer were observed in 77
    pediatric patients corresponding to an exposure of 80
    patient-years in a study with adalimumab in psoriasis in
    chronic pediatric plaques. No cases of cancer were observed in
    60 pediatric patients representing an exposure of 58.4
    patient-years in a study with adalimumab in
    pediatric uveitis .
  • During
    the controlled periods of pivotal adult clinical trials with
    adalimumab lasting at least 12 weeks in patients
    with moderately to severely active rheumatoid arthritis,
    ankylosing spondylitis, axial spondyloarthritis without
    radiographic evidence of AS , psoriatic arthritis, psoriasis,
    hidradenitis suppurativa, Crohn’s disease, ulcerative
    colitis and uveitis, a rate (95% confidence interval) of
    cancers other than lymphomas or non-melanoma skin cancers,
    6.8 (4.4 – 10.5) per 1,000 patient-years among the 5,291 patients
    treated with adalimumab, was observed versus a rate of 6.3
    (3.4 – 11.8) per 1000 patient-years among the 3444 patients in
    the control group (the mean duration of treatment was 4.0 months for
    patients treated with adalimumab and 3.8 months for patients
    in the control group). The rate (95% confidence interval) of
    non-melanoma skin cancer was 8.8 (6.0 – 13.0) per 1000
    patient-years for patients treated with adalimumab and 3.2
    (1.3 – 7.6) per 1000 patient years among patients in the
    control group . In these skin cancers, squamous
    cell carcinomas occurred at rates of 2.7 (1.4 – 5.4) per 1000
    patient years in patients treated with adalimumab and 0.6 (0 , 1 –
    4.5) per 1000 patient-years in patients in the control group
    (95% confidence interval). The rate (95% confidence interval)
    of lymphoma was 0.7 (0.2 – 2.7) per 1000 patient years in
    patients treated with adalimumab and 0.6 (0.1 – 4, 5) per 1000 patient-years in patients in the control group.
  • By
    combining the controlled periods of these trials
    with the completed or ongoing open-label extension trials of adalimumab with an
    average duration of approximately 3.3 years including 6,427 patients and more than 26,439
    patient-years of treatment, the The observed rate of cancers, other than
    lymphomas and non-melanoma skin cancers is approximately 8.5 per
    1,000 patient-years. The observed rate of non-
    melanoma skin cancer is approximately 9.6 per 1,000 patient-years and the
    observed rate of lymphomas is approximately 1.3 per 1,000 patient-years.
  • In
    post-marketing from January 2003 to December 2010, primarily in
    patients with rheumatoid arthritis, the reported rate of
    cancer is approximately 2.7 per 1,000 patient-years of
    treatment. The reported rates for
    non-melanoma skin cancer and lymphoma are approximately 0.2 and 0.3
    per 1000 patient-years of treatment, respectively (see section 4.4).
  • In
    post-marketing surveillance, rare cases of
    hepatosplenic T-cell lymphoma have been reported in patients
    treated with adalimumab.

Autoantibodies

  • Repeated
    autoantibody tests were performed on
    serum samples from patients in the IV trials in rheumatoid
    arthritis. In these trials,
    initially negative antinuclear antibody titers were positive at week 24 in 11.9% of
    patients treated with adalimumab and 8.1% of patients on placebo and
    comparator. Two of the 3,441 patients treated with adalimumab in
    all rheumatoid arthritis and
    psoriatic arthritis studies exhibited clinical signs suggestive of a
    new onset lupus-like syndrome . The condition of the patients
    improved after stopping treatment. No patient presented
    lupus nephritis or central nervous symptoms.

Hepato-biliary events

  • In
    phase III controlled clinical trials of adalimumab in
    rheumatoid arthritis and psoriatic arthritis with a
    control period of 4 to 104 weeks, elevations of ALT ≥ 3 x N occurred in 3.7% of patients treated with adalimumab and in 1.6% of patients in the control group.
  • In
    phase III controlled clinical trials of adalimumab in
    patients with juvenile idiopathic polyarticular arthritis aged
    4 to 17 years and patients with enthesitis-related arthritis
    aged 6 to 17 years, elevations of ALT ≥ 3 x N occurred in
    6.1% of patients treated with adalimumab and in 1.3% of patients
    in the control group. Most of the elevations in ALT have occurred
    with concomitant use of methotrexate. No
    elevation of ALT ≥ 3 x N occurred in the phase
    III trial of adalimumab in patients with
    polyarticular juvenile idiopathic arthritis aged 2 to <4 years.
  • In
    phase III controlled clinical trials of adalimumab in
    patients with Crohn’s disease and ulcerative colitis
    with a control period of 4 to 52 weeks, elevations of ALT
    ≥ 3 x N occurred in 0.9% of patients treated with adalimumab
    and in 0.9% of patients in the control group.
  • In
    the phase III clinical trial of adalimumab in children and
    adolescents with Crohn’s disease that evaluated the efficacy and
    safety profile of two
    weight-based maintenance regimens following adjusted induction therapy by weight
    up to 52 weeks of treatment, elevations of ALT ≥ 3 x N
    occurred in 2.6% of patients (5/192), of whom 4 were
    treated in combination with immunosuppressants at the start of the study .
  • In
    phase III controlled clinical trials of adalimumab in
    plaque psoriasis with a control period of 12 to 24 weeks,
    elevations of ALT ≥ 3 x N occurred in 1.8% of patients
    treated with adalimumab and in 1.8% of patients in the control group.
  • It
    has not been observed ALT elevations ≥ 3 x N in the study
    phase III adalimumab in pediatric patients with
    plaque psoriasis.
  • In
    controlled clinical trials of adalimumab (starting doses of 160 mg
    at Week 0 and 80 mg at Week 2 followed by 40 mg each week
    from week 4), in patients with
    HS with a period of control from 12 to 16 weeks,
    elevations of ALT ≥ 3 x N occurred in 0.3% of patients
    treated with adalimumab and 0.6% of patients in the control group.
  • In
    controlled clinical trials of adalimumab (starting dose 80 mg at
    week 0 followed by 40 mg every two weeks from
    week 1) in adult patients with uveitis for
    up to 80 weeks , with a median duration of exposure of
    166.5 days and 105.0 days for patients treated with
    adalimumab and patients in the control group, respectively, elevations of ALT
    ≥ 3 x N occurred in 2.4% of patients treated with adalimumab
    and 2.4% of patients in the control group.
  • In
    clinical trials across all indications, patients with
    elevated ALT were asymptomatic and in most cases the
    elevations were transient and reversible upon continued
    treatment. However, during post-marketing surveillance,
    hepatic insufficiency as well as less
    severe hepatic disorders , which may precede hepatic insufficiency, such as
    hepatitis including autoimmune hepatitis, have been reported in
    patients receiving l.adalimumab.

Concomitant administration of azathioprine / 6-mercaptopurine

  • In
    studies in Crohn’s disease in adults, a
    higher incidence of tumors and serious infections was observed with
    the combination of adalimumab and azathioprine / 6-mercaptopurine
    compared to adalimumab used alone.

Reporting of suspected adverse reactions

  • The
    declaration of suspected adverse reactions after authorization of the
    drug is important. It allows continuous monitoring of the
    benefit / risk ratio of the medicinal product. Healthcare professionals
    report any suspected adverse reactions via the national reporting system – see Annex V.

amgevita  Interactions

  • Adalimumab has been studied in patients with rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, and psoriatic arthritis taking adalimumab as monotherapy and in those taking methotrexate concomitantly. Antibody formation was lower when adalimumab was co-administered with methotrexate compared to its use as monotherapy. Administration of adalimumab without methotrexate resulted in increased antibody formation, increased clearance and reduced efficacy of adalimumab .
  • The combination of AMGEVITA and anakinra is not recommended (see section Warnings and precautions for use “Simultaneous administration of biological DMARDs and anti-TNFa”).
  • The combination of AMGEVITA and abatacept is not recommended (see section Warnings and precautions for use “Simultaneous administration of biological DMARDs and anti-TNFa”).
  • In the absence of a compatibility study, this medicinal product must not be mixed with other medicinal products.

Drive and use machines

Amgevita may have a minor effect on the ability to drive and use machines. Dizziness and visual disturbances may occur after administration of Amgevita ( see Undesirable effects ).

Warnings and Precautions

Traceability

  • In order
    to improve the traceability of biological medicinal products, the name
    of the medicinal product (see section 1) and the batch number of the
    administered product must be clearly recorded.

Infections

  • The
    patients receiving TNF-antagonists are more susceptible to
    serious infections. Impaired lung function can increase the
    risk of developing infections. Patients should therefore be
    carefully monitored for infections (including
    tuberculosis) before, during and after treatment with AMGEVITA. As the
    duration of elimination of adalimumab may be up to four months,
    monitoring should be continued throughout this period.
  • The
    treatment AMGEVITA should not be initiated in patients with
    active infections, including chronic infections or
    localized, are not controlled. In patients who have been exposed
    to tuberculosis or who have traveled to areas at high risk for
    tuberculosis or endemic mycoses, for example histoplasmosis,
    coccidioidomycosis or blastomycosis, the risks and benefits of
    treatment with AMGEVITA should be considered before
    initiation. treatment (see Opportunistic infections).
  • The
    Patients who develop a new infection during
    treatment with AMGEVITA must be monitored
    carefully and complete diagnostic workup should be practiced.
  • If
    a serious new infection or sepsis
    develops, administration of AMGEVITA should be discontinued and
    appropriate antimicrobial or antifungal therapy should be started until
    the infection is controlled.
  • Caution should be exercised by the physician before using AMGEVITA in patients with a
    history of recurrent infection or with
    underlying conditions which may predispose them to infections, including
    concomitant treatment with immunosuppressive drugs.

Serious infections

  • Of
    serious infections, including sepsis due to infections
    bacterial, mycobacterial, invasive fungal, parasitic,
    viral, or other opportunistic infections such as listeriosis,
    legionellosis and pneumocystis have been reported in patients
    treated with adalimumab.
  • The
    other serious infections seen in clinical trials include
    pneumonia, pyelonephritis, septic arthritis and septicemia. There have been reports
    of infections requiring hospitalization or with fatal outcome.

Tuberculosis

  • Of
    TB cases, including cases of TB reactivation
    and primary infection tuberculosis have been reported for patients
    receiving adalimumab. Cases of pulmonary and
    extra-pulmonary (i.e. disseminated) tuberculosis have been reported.
  • Before
    initiating treatment with AMGEVITA, all patients should
    be tested for active or non-active (“
    latent”) tuberculosis infection . This assessment should include a detailed medical evaluation
    in patients with a history of tuberculosis or
    possible previous exposure to patients with active tuberculosis and / or
    current or past immunosuppressive therapy. Appropriate
    screening tests (eg tuberculin skin test and
    chest x-ray) should be performed in all patients
    (according to local recommendations). It is advisable to note
    the performance and the results of these tests in the
    patient monitoring. Prescribers are reminded that
    the tuberculin skin test can give false negatives, especially in
    seriously ill or immunosuppressed patients.
  • If active tuberculosis is diagnosed, treatment with AMGEVITA should not be initiated.
  • In
    all the situations described below,
    the benefit / risk ratio of the treatment should be assessed very carefully.
  • In
    case of suspicion of latent tuberculosis, consulting a
    specialist, qualified in the treatment of tuberculosis
    should be considered.
  • In
    case of diagnosis of latent tuberculosis, prophylactic
    tuberculosis appropriate and in accordance with local recommendations
    must be implemented before the start of treatment with AMGEVITA.
  • A
    TB prophylaxis should also be considered before
    introducing AMGEVITA in patients with factors
    multiple risk or tuberculosis despite a significant test
    screening for tuberculosis negative and in patients with
    a history of latent or active tuberculosis in that the administration
    of an appropriate anti-tuberculosis treatment cannot be confirmed.
  • The
    case of reactivation of tuberculosis despite treatment
    prophylactic occurred in patients treated with
    adalimumab. Some patients who had been successfully treated
    for active tuberculosis developed the disease again during
    treatment with adalimumab.
  • The
    patients should be advised that they will need their doctor
    in case of occurrence of symptoms suggestive signs or infection
    tuberculosis (eg persistent cough, wasting / loss of
    weight, low grade fever, listlessness), during or after treatment AMGEVITA.

Other opportunistic infections

  • Of
    opportunistic infections, including invasive fungal infections,
    have been observed in patients treated with adalimumab. These
    infections were not always detected in patients receiving
    TNF antagonists, resulting in delayed initiation of
    appropriate therapy, sometimes with fatal outcome.
  • In
    patients who present with signs and symptoms such as fever,
    malaise, weight loss, sweating, cough, dyspnea and / or
    pulmonary infiltrates or other serious systemic disease with or without
    concomitant shock , an invasive fungal infection should be suspected; in
    this case, the administration
    of AMGEVITA should be stopped immediately . Diagnosis and
    initiation of empiric antifungal therapy in these patients should be made in
    consultation with a physician experienced in the management of
    patients with invasive fungal infections.

Reactivation of hepatitis B

  • A
    reactivation of hepatitis B occurred in patients who received
    a TNF antagonist including adalimumab and who were carriers
    chronic of this virus (that is to say surface antigen positive – Ag
    positive HBs) . Some cases have had a fatal outcome. Patients
    should be screened for HBV infection before
    initiating treatment with AMGEVITA. For patients who
    test positive for hepatitis B, it is
    recommended to consult a doctor specializing in the treatment of
    hepatitis B.
  • In
    HBV carriers who require treatment with AMGEVITA,
    careful monitoring of signs and symptoms of active
    HBV infection should be observed throughout treatment and for several months after
    discontinuation. There are insufficient data available regarding
    the treatment of patients with HBV treated with antiviral drugs to
    prevent HBV reactivation and treated with a TNF antagonist.
    In patients who develop HBV reactivation, AMGEVITA
    should be discontinued and effective antiviral therapy and
    appropriate additional therapy should be initiated.

Neurological events

  • The
    TNF blockers, including adalimumab, have been associated in rare
    circumstances the onset or exacerbation of symptoms
    clinical and / or radiographic evidence of demyelinating disease of the
    central nervous system including multiple sclerosis,
    Optic neuritis and peripheral demyelinating disease, including
    Guillain-Barré syndrome.
  • Prescribers are advised with caution before treating patients with pre-existing or recently-occurring
    central or peripheral nervous system demyelinating disease with AMGEVITA ; Discontinuation of
    treatment with AMGEVITA should be considered in the event of any
    of these troubles. The association between intermediate uveitis and
    demyelinating diseases of the central nervous system is known.
  • Aneurological assessment should be performed in patients with
    non-infectious intermediate uveitis before initiating
    treatment with AMGEVITA, and repeated regularly during
    treatment to look for any system demyelinating disease of
    preexisting or progressive CNS.

Allergic reactions

  • In
    clinical trials, serious allergic reactions associated
    with adalimumab were rarely reported and
    non-serious allergic reactions associated with adalimumab were uncommon. Cases of
    severe allergic reactions, including anaphylactic reactions
    have been reported after administration of adalimumab. If
    an anaphylactic or other
    severe allergic reaction occurs, administration of AMGEVITA should be
    stopped immediately and appropriate treatment initiated.

Dry natural rubber

  • The
    needle cap of the pre-filled pen contains
    dry natural rubber (a derivative of latex), which may cause
    allergic reactions .

Immunosuppression

In
a study of 64 patients with rheumatoid
arthritis treated with adalimumab, there was no evidence
of delayed-type hypersensitivity depression,
decreased immunoglobulin levels. or a change in the
count of effector T and B lymphocytes, NK lymphocytes,
monocytes / macrophages and neutrophilic granulocytes.

Malignant tumors and lymphoproliferative disorders

  • In
    the controlled part of the adalimumab clinical trials with anti-TNF drugs,
    more cases of cancer including lymphomas were observed in
    patients treated with an anti-TNF agent than in patients in the
    control group . However, the incidence has been rare. During
    post-marketing surveillance, cases of leukemia have been reported in
    patients treated with anti-TNF. In addition, there is a background of
    increased risk of lymphoma and leukemia in patients with
    old, inflammatory and highly
    active rheumatoid arthritis , which complicates the estimation of risk. In the current state of
    knowledge, the possibility of a risk of developing lymphomas,
    leukemia or other malignant diseases in patients treated
    with anti-TNF cannot be excluded.
  • Of
    malignancies, some fatal, have been reported
    postmarketing in children, adolescents and
    young adults (up to age 22 years) treated with TNF antagonists
    (initiation of therapy before age 18), including
    adalimumab. About half of these cases were lymphomas. The
    other cases corresponded to other types of malignant tumors among
    which rare cancers generally associated with a context
    of immunosuppression. The risk of developing malignant tumors can
    not be excluded in children and adolescents treated with anti-TNF.
  • In the
    course of the post-marketing surveillance, rare cases of lymphoma
    hepatosplenic T-cell lymphoma have been identified in patients
    treated with adalimumab. This rare form of T-cell lymphoma
    has a very aggressive course and is often fatal. Some of these
    hepatosplenic T-cell lymphomas seen with adalimumab
    have occurred in young adults who were concomitantly treated
    with azathioprine or 6-mercaptopurine used in
    inflammatory bowel disease. The potential risk of combining
    azathioprine or 6-mercaptopurine with AMGEVITA should be
    carefully considered. A risk of developing
    hepatosplenic T-cell lymphoma in patients treated with
    AMGEVITA cannot be excluded.
  • There
    are no studies in patients with a history of
    malignancies or in whom treatment with adalimumab is continued
    after the development of cancer. Therefore, additional caution
    should be observed when considering treatment of these patients
    with AMGEVITA.
  • All
    patients, especially those with a history of
    intense immunosuppressive therapy or with psoriasis and a
    history of puvatherapy, should be screened for
    non-melanoma skin cancer before and during treatment with
    AMGEVITA. Cases of melanoma and Merkel cell carcinoma have
    also been reported in patients treated with anti-TNF inhibitors
    including adalimumab.
  • In
    a prospective clinical study evaluating the use of another
    anti-TNF agent , infliximab, in patients with
    moderate to severe chronic obstructive pulmonary disease (COPD),
    more cancers, especially of the lung, were reported. head and neck,
    among patients treated with infliximab compared to patients
    in the control group. All patients had a history of
    heavy smoking. For this reason, care should be
    taken in the use of an anti-TNF in patients with COPD,
    and also in patients at risk for cancer due to
    heavy smoking .
  • Based
    on current data, it is not known whether treatment with
    adalimumab influences the risk of developing dysplasia or
    colon cancer. All patients with ulcerative colitis
    who are at high risk of dysplasia or colon cancer (for
    example, patients with old ulcerative colitis or
    primary sclerosing cholangitis) or who have a history of
    dysplasia or colon cancer should do
    regularly screened for dysplasia before treatment and
    throughout the course of their disease. This assessment should include
    colonoscopy and biopsies according to local recommendations.

Haematological reactions

From
Rare reports of pancytopenia including aplastic anemia have been
reported with TNF antagonists. Adverse effects of the blood system
including medically significant cytopenias (eg
, thrombocytopenia, leukopenia) have been observed with adalimumab. It
should be recommended for all patients seek immediate
medical advice if they have signs or symptoms suggestive of
blood disorders (eg, persistent fever, bruising,
bleeding, pallor) while AMGEVITA. Discontinuation of treatment with AMGEVITA
should be considered for patients in whom
significant blood abnormalities are confirmed.

Vaccinations

  • Similar
    antibody responses to the
    standard 23-valence pneumococcal vaccine and to the trivalent influenza vaccine were
    observed in a study in 226 adults with rheumatoid
    arthritis treated with adalimumab or placebo. There are no
    data available on the secondary transmission of infection from
    live vaccines in patients receiving adalimumab.
  • In
    children and adolescents, it is recommended, if possible, that
    all immunizations be up to date according to current
    immunization guidelines before initiating treatment with AMGEVITA.
  • The
    patients AMGEVITA may receive multiple vaccines
    simultaneously, except in respect of live vaccines.
    Administration of live vaccines (eg, BCG vaccine) to
    infants who have been exposed to AMGEVITA in utero is not
    recommended for 5 months after the last injection of AMGEVITA
    in the mother during pregnancy.

Congestive heart failure

In
a clinical trial with another TNF antagonist,
worsening congestive heart failure and
increased mortality from congestive heart failure were observed . Of
cases of congestive heart failure worsening have also been
reported in patients receiving adalimumab. AMGEVITA should be
used with caution in patients with
mild heart failure (NYHA classes I / II). AMGEVITA is contraindicated in
moderate to severe heart failure (see section 4.3). Treatment with AMGEVITA should be stopped in patients who experience new symptoms or worsening of their symptoms of congestive heart failure.

Autoimmune processes

  • The
    treatment AMGEVITA may cause antibody formation
    autoimmune. The impact of long-term treatment with AMGEVITA on the
    development of autoimmune diseases is unknown. If a patient
    develops lupus-like symptoms following
    treatment with AMGEVITA and exhibits a positive anti-
    double-stranded DNA reaction , treatment with AMGEVITA should not be continued.

Simultaneous administration of biological DMARDs or anti-TNF

  • Some
    serious infections were seen in clinical studies in
    the concurrent use of anakinra and another TNF antagonist,
    etanercept, with no added clinical benefit compared to
    etanercept alone. Due to the nature of the side effects
    seen with treatment with etanercept and anakinra,
    similar side effects may also result from the combination
    of anakinra and other TNF blockers. Therefore the combination
    of AMGEVITA and anakinra is not recommended (see section Interactions with other medicinal products and other forms of interactions).
  • Co- administration of AMGEVITA with other biologic DMARDs
    (e.g. anakinra and abatacept) or with other TNF blockers is not
    recommended due to the possible increased risk
    of infections, including serious infections, and other
    potential pharmacological interactions (see section Interactions with other medicinal products and other forms of interactions).

Surgery

  • There is limited experience
    with safety during surgical procedures in
    patients treated with adalimumab. The long half-life of
    adalimumab should be taken into account if surgery
    is planned. A patient treated with AMGEVITA requiring
    surgery should be carefully monitored for
    infections and appropriate actions should be taken.
    There
    is limited experience with the safety of adalimumab in patients undergoing arthroplasty.

Hail Occlusion

In
Crohn’s disease, treatment failure may indicate the presence of
fixed fibrous strictures that may require surgical treatment.
The available data suggest that adalimumab does not worsen or
cause strictures.

Older subjects

The
frequency of serious infections in subjects treated with
adalimumab over 65 years of age (3.7%) is higher than in
patients under 65 years of age (1.5%). Some cases have had a fatal outcome. Particular attention should be paid to the risk of infection when treating the elderly.

Pediatric population

  • See Vaccinations above.

Excipients with known effect

  • This
    medicine contains less than 1 mmol sodium (23 mg) per 0.8
    mL dose , that is to say essentially ‘sodium free’.

PREGNANCY & BREAST-FEEDING & FERTILITY

Women of childbearing age

  • Women of childbearing potential should consider using effective contraception during treatment with Amgevita and continue to use it for at least five months after the last administration of Amgevita.

Pregnancy

  • A large number (approximately 2,100) of pregnancies exposed to adalimumab for which data were collected prospectively, resulting in a live birth with a known course to term, including more than 1,500 pregnancies exposed to adalimumab in the first trimester , does not reveal any increase in the rate of malformations in newborns.
  • In a prospective cohort study, 257 women with rheumatoid arthritis (RA) or Crohn’s disease (CD) treated with adalimumab at least during the first trimester and 120 women with untreated RA or CD by adalimumab were included. The prevalence at birth of major congenital anomalies was the primary endpoint. The rate of pregnancies resulting in at least one living newborn with a major birth defect was 6/69 (8.7%) in women treated with adalimumab with RA and 5/74 (6.8 %) in untreated women with RA (unadjusted OR: 1.31, 95% CI: 0.38-4.52), and 16/152 (10.5%) in women treated with ‘adalimumab with CD and 3/32 (9, 4%) in untreated women with CD (unadjusted OR: 1.14, 95% CI: 0.31-4.16). The adjusted OR (considering baseline differences) was 1.10 (95% CI: 0.45-2.73) for RA and CD combined. No notable difference was reported between women treated with adalimumab and women not treated with adalimumab for secondary endpoints of spontaneous abortion, minor congenital anomalies, preterm delivery, height. at birth and serious or opportunistic infections, and stillbirth or malignancy. Interpretation of the data may be affected due to methodological limitations of the study, including the small sample size and the non-randomized study design. 31-4,16). The adjusted OR (considering baseline differences) was 1.10 (95% CI: 0.45-2.73) for RA and CD combined. No notable difference was reported between women treated with adalimumab and women not treated with adalimumab for secondary endpoints of spontaneous abortion, minor congenital anomalies, preterm delivery, height. at birth and serious or opportunistic infections, and stillbirth or malignancy. Interpretation of the data may be affected due to methodological limitations of the study, including the small sample size and the non-randomized study design. 31-4,16). The adjusted OR (considering baseline differences) was 1.10 (95% CI: 0.45-2.73) for RA and CD combined. No notable difference was reported between women treated with adalimumab and women not treated with adalimumab for secondary endpoints of spontaneous abortion, minor congenital anomalies, preterm delivery, height. at birth and serious or opportunistic infections, and stillbirth or malignancy. Interpretation of the data may be affected due to methodological limitations of the study, including the small sample size and the non-randomized study design. No notable difference was reported between women treated with adalimumab and women not treated with adalimumab for secondary endpoints of spontaneous abortion, minor congenital anomalies, preterm delivery, height. at birth and serious or opportunistic infections, and stillbirth or malignancy. Interpretation of the data may be affected due to methodological limitations of the study, including the small sample size and the non-randomized study design. No notable difference was reported between women treated with adalimumab and women not treated with adalimumab for secondary endpoints of spontaneous abortion, minor congenital anomalies, preterm delivery, height. at birth and serious or opportunistic infections, and stillbirth or malignancy. Interpretation of the data may be affected due to methodological limitations of the study, including the small sample size and the non-randomized study design. birth size and serious or opportunistic infections, and stillbirth or malignancy. Interpretation of the data may be affected due to methodological limitations of the study, including the small sample size and the non-randomized study design. birth size and serious or opportunistic infections, and stillbirth or malignancy. Interpretation of the data may be affected due to methodological limitations of the study, including the small sample size and the non-randomized study design.
  • In a developmental toxicity study performed in monkeys, there were no signs of possible maternal toxicity, embryotoxicity or teratogenic potential. There are no preclinical data on the postnatal toxicity of adalimumab ( see Preclinical Safety ).
  • Due to its inhibitory effect on TNFα, adalimumab administered during pregnancy may affect the normal immune responses of the newborn. Amgevita should be used during pregnancy only if needed.
  • In women treated with adalimumab during pregnancy, adalimumab can cross the placenta and pass into the blood of their child. As a result, these children may have an increased risk of infections. The administration of live vaccines (eg BCG vaccine) to children who have been exposed to adalimumab in utero is not recommended for 5 months after the mother’s last injection during pregnancy.

Feeding with milk

  • Limited data from the published literature indicate that adalimumab is excreted in human milk at very low concentrations, with adalimumab being present in human milk at concentrations equivalent to 0.1% -1% of maternal serum levels. .
  • When administered orally, immunoglobulin G proteins undergo intestinal proteolysis and exhibit low bioavailability. No effects on breastfed newborns / infants are expected. Therefore, Amgevita can be used during breast-feeding.

Fertility

  • Preclinical data on the effects of adalimumab on fertility are not available.

What happens if I overdose from amgevita  ?

  • No dose related toxicity was observed in clinical trials. The highest dose evaluated consisted of repeated doses of 10 mg / kg IV, which is approximately 15 times the recommended dose.

What is  Forms and Composition ?

SHAPES and PRESENTATIONS

20 mg solution for injection (SC injection) (clear, colorless to slightly yellow) : 

  • 0.4 mL pre-filled single-dose syringe, with needle and needle protective cap, pack of 1.

Solution for injection (SC injection) (clear, colorless to slightly yellow) 40 mg: 

  • 0.8 mL single-dose pre-filled syringe, with needle and needle shield, packs of 1, 2 and 6 (3 x 2). 0.8 mL pre-filled single-dose pen*(SureClick), with protectiveneedlecap**, packs of 1, 2 and 6 (3 x 2).
    *  The pen is a disposable, portable, single-use mechanical injection device.
  • **  The needle cap of the pre-filled pen contains dry natural rubber (a derivative of latex) ( see Warnings and Precautions for use ).
COMPOSITION
  p ser 0.4 mL p ser or pen 0.8 mL
Adalimumab * 20 mg 40 mg
  • Excipients: glacial acetic acid, sucrose, polysorbate 80, sodium hydroxide (to adjust pH), water for injections.
  • Each mL contains 50 mg of adalimumab.
  • *  Adalimumab is a recombinant human monoclonal antibody produced in Chinese hamster ovary cells.

NOT’s

Edrug-online contains comprehensive and detailed information about drugs available in the medical field, and is divided into four sections:

general information:

  • Includes a general description of the drug, its use, brand names, FAQs, and relevant news and articles

Additional information:

  • General explanation about dealing with the medicine: how to take the medicine, the doses and times of it, the start and duration of its effectiveness, the recommended diet during the period of taking the medicine, the method of storage and storage, recommendations in cases for forgetting the dose and instructions to stop taking the drug and take additional doses.

Special warnings:

  • For pregnant and breastfeeding women, the elderly, boys and drivers, and use before surgery.

Side effects:

  • It treats possible side effects and drug interactions that require attention and its effect on continuous use.
  • The information contained in this medicine is based on medical literature, but it is not a substitute for consulting a doctor.
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hyrimoz injections Uses, Dosage, Side Effects, Precautions & Warnings https://edrug-online.com/1483/hyrimoz.html https://edrug-online.com/1483/hyrimoz.html#respond Sat, 19 Sep 2020 09:34:58 +0000 https://edrug-online.com/?p=1483 hyrimoz adalimumabhyrimoz (adalimumab) injections >>>  Generic drug of the Therapeutic class: Immunology Medicines Active ingredients: Adalimumab what is HYRIMOZ  medication used for and indication? Rheumatoid arthritis Hyrimoz in combination with methotrexate is indicated for: the treatment of moderately to severely active rheumatoid arthritis in adults when the response to DMARDs, including methotrexate, is inadequate. the treatment […]]]> hyrimoz adalimumab

hyrimoz (adalimumab) injections >>>  Generic drug of the Therapeutic class: Immunology Medicines

Active ingredients: Adalimumab

what is HYRIMOZ  medication used for and indication?

Rheumatoid arthritis

Hyrimoz in combination with methotrexate is indicated for:

  • the treatment of moderately to severely active rheumatoid arthritis in adults when the response to DMARDs, including methotrexate, is inadequate.
  • the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate.
  • Hyrimoz can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate.
  • Adalimumab has been shown to slow the progression of structural damage to joints measured by radiography and to improve functional capacity when given in combination with methotrexate.

Juvenile idiopathic arthritis

Polyarticular juvenile idiopathic arthritis

  • Hyrimoz in combination with methotrexate is indicated for the treatment of progressive polyarticular juvenile idiopathic arthritis in patients from 2 years of age in case of insufficient response to one or more DMARDs. Hyrimoz can be administered as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is unsuitable (for efficacy as monotherapy, see section Pharmacodynamic properties).
  • Adalimumab has not been studied in patients less than 2 years of age.

Enthesitis-related arthritis

  • Hyrimoz is indicated for the treatment of active arthritis associated with enthesitis in patients from 6 years of age with insufficient response or intolerance to conventional therapy.

Axial spondyloarthritis

Ankylosing spondylitis (AS)

  • Hyrimoz is indicated for the treatment of severe and active ankylosing spondylitis in adults who have had an inadequate response to conventional therapy.

Axial spondyloarthritis without radiographic evidence of AS

  • Hyrimoz is indicated for the treatment of severe axial spondyloarthritis without radiographic evidence of AS, but with objective evidence of inflammation on MRI and / or elevated CRP in adults who have had an inadequate response or intolerance to anti -nonsteroidal inflammatory drugs.

Psoriatic arthritis

  • Hyrimoz is indicated for the treatment of active and progressive psoriatic arthritis in adults when the response to previous disease-modifying therapy has been inadequate.
  • Adalimumab has been shown to slow the progression of peripheral joint structural damage as measured by radiography in patients with symmetrical polyarticular forms of the disease (see section 5.1) and to improve functional capacity.

Psoriasis

Hyrimoz is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who require systemic therapy.

  • Plaque psoriasis in children and adolescents
  • Hyrimoz is indicated for the treatment of severe chronic plaque psoriasis in children from 4 years of age and in adolescents with insufficient response to topical treatment and light therapy or when these treatments are inappropriate.

Hidradenitis suppurativa (HS)

  • Hyrimoz is indicated for the treatment of active, moderate to severe hidradenitis suppurativa (Verneuil’s disease) in adults and adolescents from 12 years of age in case of insufficient response to conventional systemic treatment of HS (see section Properties). Pharmacodynamics and Pharmacokinetic Properties).

Crohn’s disease

  • Hyrimoz is indicated for the treatment of moderate to severe active Crohn’s disease in adult patients who have not responded despite appropriate and well-managed treatment with a corticosteroid and / or immunosuppressant; or in whom this treatment is contraindicated or poorly tolerated.

Crohn’s disease in children and adolescents

  • Hyrimoz is indicated for the treatment of moderate to severe active Crohn’s disease in children and adolescents from 6 years of age who have failed to respond to conventional therapy comprising first-line nutritional therapy and a corticosteroid and / or an immunomodulator, or in which these treatments are poorly tolerated or contraindicated.

Ulcerative colitis

  • Hyrimoz is indicated for the treatment of active, moderate to severe ulcerative colitis in adult patients who have had an inadequate response to conventional therapy, including corticosteroids and 6-mercaptopurine (6-MP) or azathioprine (AZA), or in whom this treatment is contraindicated or poorly tolerated.

Uveitis

  • Hyrimoz is indicated for the treatment of non-infectious, intermediate, posterior uveitis and panuveitis in adult patients who have had an insufficient response to corticosteroid therapy, in patients requiring corticosteroid sparing, or in whom corticosteroid therapy is inappropriate.

Uveitis in children and adolescents

  • Hyrimoz is indicated for the treatment of chronic non-infectious anterior uveitis in children and adolescents from 2 years of age with insufficient response or intolerance to conventional treatment or for whom conventional treatment is inappropriate.

hyrimoz dosage

The treatment Hyrimoz should be initiated and supervised by a physician qualified specialist in the diagnosis and treatment of pathologies in which Hyrimoz indicated. It is recommended that ophthalmologists consult an appropriate specialist before initiating treatment with Hyrimoz . Patients treated with Hyrimoz will be given a Patient Alert Card.

After proper training in the injection technique, patients can self-inject Hyrimoz, if their doctor considers it possible, under the guise of appropriate medical supervision.

During treatment with Hyrimoz, other concomitant treatments (such as corticosteroids and / or immunomodulators) should be optimized.

hyrimoz dose

Rheumatoid arthritis

  • In adult patients with rheumatoid arthritis, the recommended dose of Hyrimoz is a single dose of 40 mg adalimumab given every two weeks, subcutaneously.
  • The administration of methotrexate should be continued during treatment with Hyrimoz.
  • The glucocorticoids, salicylates, nonsteroidal anti-inflammatory drugs or analgesics may be continued during treatment with Hyrimoz. Regarding the combination with other anti-rheumatic drugs other than methotrexate, see sections Warnings and precautions for use and Pharmacodynamic properties.
  • As monotherapy, some patients with decreased response to Hyrimoz 40 mg every other week may benefit from an increase in dosage to 40 mg adalimumab every week or 80 mg every other week. .
  • The available data suggest that the clinical response is usually achieved within 12 weeks of treatment. Continuation of treatment should be reconsidered in a patient who has not responded within these time limits.
  • Hyrimoz is only available in a 40 mg pre-filled syringe and 40 mg pre-filled pen . Therefore, Hyrimoz cannot be administered to patients requiring a dose lower than the full dose of 40 mg.

Interruption of treatment

  • It may be necessary to stop treatment, eg before surgery or in patients with severe infection.
  • The available data suggest that re-introduction of adalimumab after stopping 70 days or more results in a clinical response of the same magnitude and a similar safety profile to that observed before stopping treatment.

Ankylosing spondylitis, axial spondyloarthritis without radiographic evidence of AS, and psoriatic arthritis

  • The recommended dosage of Hyrimoz for patients with ankylosing spondylitis, axial spondyloarthritis without radiographic evidence of AS and for patients with psoriatic arthritis is 40 mg adalimumab as a single dose every two weeks, by subcutaneous injection. .
  • The available data suggest that the clinical response is usually achieved within 12 weeks of treatment. Continuation of treatment should be reconsidered in a patient who has not responded within these time limits.

Psoriasis

  • The recommended dose of Hyrimoz to start treatment in adults is 80 mg subcutaneously. The dosage will continue one week later with 40 mg subcutaneously every other week.
  • The continuing treatment beyond 16 weeks should be carefully reconsidered in a patient not responding within this time.
  • Beyond 16 weeks, in case of insufficient response to Hyrimoz 40 mg every two weeks, patients may benefit from an increase in dosage to 40 mg every week or 80 mg every two weeks. The benefits and risks of continued treatment with 40 mg weekly or 80 mg every other week should be carefully reconsidered in a patient with insufficient response after increasing the dose (see section 5.1). If sufficient response is obtained with 40 mg every week or 80 mg every other week, the dosage may then be reduced to 40 mg every 2 weeks.
  • Hyrimoz is only available in a 40 mg pre-filled syringe and 40 mg pre-filled pen . Therefore, Hyrimoz cannot be administered to patients requiring a dose lower than the full dose of 40 mg.

Hidradenitis suppurativa

  • The recommended dosage regimen of Hyrimoz in adult patients with hidradenitis suppurativa (HS) is an initial dose of 160 mg on Day 1 (given as 4 injections of 40 mg in one day or 2 injections of 40 mg mg per day for two consecutive days ), followed by an 80 mg dose two weeks later on Day 15 (given as two 40 mg injections in one day). Two weeks later (Day 29), continue with a dose of 40 mg every week or 80 mg every two weeks (given as two 40 mg injections per day). If necessary, antibiotics can be continued during treatment with Hyrimoz. During treatment with Hyrimoz, the patient is recommended to cleanse his lesions daily with a topical antiseptic .
  • The continuing treatment beyond 12 weeks should be carefully reconsidered in patients showing no improvement during this period.
  • If treatment is interrupted, Hyrimoz 40 mg every week or 80 mg every other week may be reintroduced.
  • The benefit and risk of continued long-term treatment should be assessed regularly .
  • Hyrimoz is only available in a 40 mg pre-filled syringe and 40 mg pre-filled pen . Therefore, Hyrimoz cannot be administered to patients requiring a dose lower than the full dose of 40 mg.

Crohn’s disease

  • In adult patients with moderate to severe active Crohn’s disease , the recommended induction regimen of Hyrimoz is 80 mg at week 0, followed by 40 mg at week 2. If it is necessary to obtain faster response to treatment, schedule 160 mg at week 0 (given as 4 injections of 40 mg per day or 2 injections of 40 mg per day for two consecutive days ), 80 mg at week 2 (given in the form of two injections of 40 mg per day), can be used knowing that the risk of adverse events is then higher during this induction phase .
  • Following induction therapy, the recommended dose is 40 mg administered every two weeks by subcutaneous injection. If a patient has stopped treatment with Hyrimoz and signs and symptoms of the disease return, Hyrimoz may be re-administered. Experience with re-administration of treatment beyond 8 weeks after the previous dose is limited.
  • During maintenance treatment, corticosteroids may be gradually reduced in accordance with clinical practice recommendations .
  • Some patients in whom a decreased response to treatment with Hyrimoz 40 mg every two weeks is observed may benefit from an increase in the dosage to Hyrimoz 40 mg every week or 80 mg every two weeks.
  • Some patients who have not responded to treatment at week 4 may continue maintenance therapy until week 12. Continuation of treatment should be carefully reconsidered in a patient who has not responded within this time.
  • Hyrimoz is only available in a 40 mg pre-filled syringe and 40 mg pre-filled pen . Therefore, Hyrimoz cannot be administered to patients requiring a dose lower than the full dose of 40 mg.

Ulcerative colitis

  • In adult patients with moderate to severe ulcerative colitis , the recommended induction regimen of Hyrimoz is 160 mg at week 0 (given as 4 injections of 40 mg per day or 2 injections of 40 mg per day for two consecutive days ) and 80 mg at week 2 (given as two 40 mg injections per day). After induction therapy, the recommended dose is 40 mg administered every two weeks by subcutaneous injection.
  • During maintenance treatment, corticosteroids may be gradually reduced in accordance with clinical practice recommendations .
  • Some patients in whom a decreased response to treatment with Hyrimoz 40 mg every two weeks is observed may benefit from an increase in the dosage to Hyrimoz 40 mg every week or 80 mg every two weeks.
  • The available data suggest thatthe clinical response is usually achieved within 2 to 8 weeks of treatment. Treatment with Hyrimoz should not be continued in patients who have not responded within this time frame .
  • Hyrimoz is only available in a 40 mg pre-filled syringe and 40 mg pre-filled pen . Therefore, Hyrimoz cannot be administered to patients requiring a dose lower than the full dose of 40 mg.

Uveitis

  • In adult patients with uveitis, the recommended dose of Hyrimoz is an initial dose of 80 mg followed by a dose of 40 mg every two weeks starting one week after the first dose. There is limited experience with initiating treatment with adalimumab as monotherapy. Treatment with Hyrimoz can be started in combination with corticosteroid therapy and / or with other non-biological immunomodulatory treatments. The combined corticosteroid dose may be gradually reduced in accordance with clinical practice, starting two weeks after initiation of treatment with Hyrimoz.
  • An annual reassessment of the benefits and risks associated with long-term continuous therapy is recommended .
  • Hyrimoz is only available in a 40 mg pre-filled syringe and 40 mg pre-filled pen . Therefore, Hyrimoz cannot be administered to patients requiring a dose lower than the full dose of 40 mg.

Special populations

Older subjects

  • No dosage adjustment is necessary.
  • Renal and / or hepatic impairment
  • Adalimumab has not been studied in these patient populations. It is not possible to recommend dosages.

Pediatric population

  • Hyrimoz is only available in a 40 mg pre-filled syringe / pre-filled pen. Therefore, Hyrimoz cannot be administered to pediatric patients requiring a dose lower than the full dose of 40 mg. If another dose is required, other formulations of adalimumab offering such a possibility should be used.

Juvenile idiopathic arthritis

Polyarticular juvenile idiopathic arthritis from 2 years old

  • The recommended dosage of Hyrimoz for patients with polyarticular juvenile idiopathic arthritis from the age of 2 years depends on body weight (Table 1). Hyrimoz is given every two weeks as a subcutaneous injection.
  • The available data suggest that the clinical response is usually achieved within 12 weeks of treatment. Continuation of treatment should be carefully reconsidered in a patient who has not responded within this time frame.
  • There is no relevant use of adalimumab in patients under 2 years of age in this indication.
  • Hyrimoz is only available in a 40 mg pre-filled syringe and 40 mg pre-filled pen . Therefore, Hyrimoz cannot be administered to patients requiring a dose lower than the full dose of 40 mg.

Enthesitis-related arthritis

  • The recommended dosage of Hyrimoz for patients with enthesitis-related arthritis from the age of 6 years depends on body weight (Table 2). Hyrimoz is given every two weeks as a subcutaneous injection.
  • Adalimumab has not been studied in patients less than 6 years of age with arthritis related to enthesitis.
  • Hyrimoz is only available in a 40 mg pre-filled syringe and 40 mg pre-filled pen . Therefore, Hyrimoz cannot be administered to patients requiring a dose lower than the full dose of 40 mg.

Plaque psoriasis in children and adolescents

  • The recommended dosage of Hyrimoz for patients with plaque psoriasis aged 4 to 17 years depends on body weight (Table 3). Hyrimoz is administered as a subcutaneous injection.
  • The continuing treatment beyond 16 weeks should be carefully reconsidered in a patient not responding within this time.
  • If retreatment with adalimumab is indicated, the above recommendations for dosage and duration of treatment should be followed.
  • The safety of adalimumab in children and adolescents with plaque psoriasis has been evaluated over a mean duration of 13 months.
  • There is no relevant use of adalimumab in children aged less than 4 years in this indication.
  • Hyrimoz is only available in a 40 mg pre-filled syringe and 40 mg pre-filled pen . Therefore, Hyrimoz cannot be administered to patients requiring a dose lower than the full dose of 40 mg.

Adolescent hidradenitis suppurativa (from 12 years of age, weighing at least 30 kg)

  • There is no clinical trial conducted with adalimumab in adolescents with HS. The dosage of adalimumab in these patients was determined from pharmacokinetic modeling and simulation .
  • The recommended dose of Hyrimoz is 80 mg at week 0 followed by 40 mg every two weeks from week 1 by subcutaneous injection.
  • In adolescents with an insufficient response to Hyrimoz 40 mg every two weeks, an increase in dosage to 40 mg every week or 80 mg every other week may be considered.
  • If necessary, antibiotics can be continued during treatment with Hyrimoz. During treatment with Hyrimoz, the patient is recommended to cleanse his lesions daily with a topical antiseptic.
  • The continuing treatment beyond 12 weeks should be carefully reconsidered in patients showing no improvement during this period.
  • If treatment is interrupted, Hyrimoz could be reintroduced if necessary.
  • The benefit and risk of continued long-term treatment should be assessed regularly (see data in adults under Pharmacodynamic properties).
  • There is no relevant use of adalimumab in children aged less than 12 years in this indication.
  • Hyrimoz is only available in a 40 mg pre-filled syringe and 40 mg pre-filled pen . Therefore, Hyrimoz cannot be administered to patients requiring a dose lower than the full dose of 40
    mg.

Crohn’s disease in children and adolescents

  • The recommended dosage of Hyrimoz for patients with Crohn’s disease aged 6 to 17 years depends on body weight (Table 4). Hyrimoz is administered as a subcutaneous injection.
    • 40 mg in week 0 and 20 mg in week 2
    • 80 mg in week 0 and 40 mg in week 2
    • 80 mg in week 0 and 40 mg in week 2
    • 160 mg in week 0 and 80 mg in week 2

* Note: Hyrimoz is currently available in a 40 mg pre-filled syringe and 40 mg pre-filled pen.

The patients with an inadequate response to treatment is observed may benefit from increasing the dosage:

≥ 40 kg: 40 mg every week or 80 mg every two weeks

  • Continuation of treatment should be carefully reconsidered in a patient who has not responded by week 12.
  • There is no relevant use of adalimumab in children aged less than 6 years in this indication.
  • Hyrimoz is only available in a 40 mg pre-filled syringe and 40 mg pre-filled pen . Therefore, Hyrimoz cannot be administered to patients requiring a dose lower than the full dose of 40 mg.

Uveitis in children and adolescents

  • The recommended dosage of Hyrimoz for children and adolescents with uveitis from the age of 2 years depends on body weight (Table 5). Hyrimoz is administered as a subcutaneous injection.
  • In uveitis in children and adolescents, no experience is available on treatment with adalimumab without concomitant treatment with methotrexate.

When initiating treatment with Hyrimoz, a loading dose of 40 mg for patients

  • <30 kg or 80 mg for patients ≥ 30 kg can be administered one week before the start of maintenance treatment. No clinical data are available from the use of a loading dose of adalimumab in children less than 6 years of age.
  • There is no relevant use of Hyrimoz in children aged less than 2 years in this indication.
  • An annual reassessment of the benefits and risks associated with long-term continuous therapy is recommended.
  • Hyrimoz is only available in a 40 mg pre-filled syringe and 40 mg pre-filled pen . Therefore, Hyrimoz cannot be administered to patients requiring a dose lower than the full dose of 40 mg.

Pediatric ulcerative colitis

  • The safety and efficacy of adalimumab in children 4 to 17 years old have not been established. No data is available.
  • There is no relevant use of adalimumab in children aged less than 4 years in this indication.

Psoriatic arthritis and axial spondyloarthritis including ankylosing spondylitis

  • There is no relevant use of Humira in population pediatric indications in ankylosing spondylitis and psoriatic arthritis.

Administration mode

  • Hyrimoz is administered as a subcutaneous injection.
  • The complete instructions are provided in the manual.
  • Other strengths and presentations of adalimumab are available.

HYRIMOZ  Contraindications

  • Hypersensitivity adalimumab
  • Hamster protein hypersensitivity
  • Active tuberculosis
  • Severe infection
  • Stage III or IV heart failure
  • Pregnancy
  • Lack of effective female contraception

Hypersensitivity to the active substance or to any of the excipients listed in the Composition section.

Active tuberculosis or other severe infections such as sepsis and opportunistic infections.

Moderate to severe heart failure (NYHA classes III / IV).

hyrimoz injection side effects

Summary of the safety profile

  • Adalimumab has been studied in 9,506 patients in pivotal, open- label, controlled trials of 60 months and longer duration. These trials included patients with recent or old rheumatoid arthritis, juvenile idiopathic arthritis ( polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis) or patients with axial spondyloarthritis (ankylosing spondylitis and axial spondyloarthritis without radiographic evidence of AS ), psoriatic arthritis, Crohn’s disease, ulcerative colitis, psoriasis, hidradenitis suppurativa and uveitis. The pivotal controlled studies involved 6,089 patients who received adalimumab and 3,801 patients who received placebo or an active comparator during the controlled phase.
  • The percentage of patients who discontinued treatment due to adverse reactions during the double-blind, controlled phase of the pivotal studies was 5.9% in patients treated with adalimumab and 5.4% in patients in the group control.
  • The most frequently reported side effects are infections (such as nasopharyngitis, upper respiratory tract infections and sinusitis), injection site reactions (erythema, itching, bleeding, pain or swelling), headache and musculoskeletal pain.
  • Some serious side effects have been reported with adalimumab. The TNF antagonists, such as adalimumab affect the system immune and their use may affect the body’s defenses against infection and cancer.
  • Life- threatening and fatal infections (including sepsis, opportunistic infections and tuberculosis), hepatitis B reactivations and various cancers (including leukemia, lymphoma and hepatosplenic T-cell lymphoma) have also been reported with use of adalimumab.
  • Severe haematological, neurological and autoimmune effects have also been reported. This includes rare cases of pancytopenia, bone marrow anemia, cases of central and peripheral demyelination, and cases of lupus, lupus-related events, and Stevens-Johnson syndrome.

Pediatric population

  • In general, the frequency and type of adverse events seen in children and adolescents were comparable to those seen in adult patients.

List of side effects

  • The list of adverse reactions is based on clinical studies and post-marketing experience and is presented by system organ class (SOC) and frequency in Table 6 below : very common (≥ 1/10) ; common (≥ 1/100, <1/10); uncommon (≥ 1 / 1,000, <1/100); rare (≥ 1 / 10,000, <1 / 1,000) and not known (cannot be estimated from the available data ). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
  • The highest frequency observed in the various indications was included. The presence of an asterisk (*) in the column ” System organ class” indicates that more information is available under the sections Contraindications, Warnings and precautions for use and Adverse reactions.

Table 6 Adverse reactions

System organ class Frequency Side effects
Infections and infestations * Very common Infections
of the respiratory tract (including respiratory infection
bass and upper respiratory tract infection, pneumonia,
sinusitis, pharyngitis, rhino pharyngitis and pneumonia herpes).
Frequent Systemic infections (including sepsis, candidiasis and influenza).

Intestinal infections (including viral gastroenteritis).

Skin and soft tissue infections

(including superficial periungual whitlow, cellulitis, impetigo, necrotizing fasciitis and shingles). Ear infections.

Oral infections (including herpes, oral herpes and dental infections).

Infections of the reproductive organs (including vulvovaginal yeast infection).

Urinary tract infections (including pyelonephritis).

Fungal infections. Joint infections.

Rare Neurological infections (including meningitis
System class

organs

Frequency Side effects
viral).

Opportunistic infections and tuberculosis

(including coccidioidomycosis, histoplasmosis, and Mycobacterium avium complex infections).

Bacterial infections. Eye infections.

Diverticulitis 1) .

Benign tumors,

malignant and unspecified (incl cysts and polyps) *

Frequent Skin cancer excluding melanoma

(including basal cell carcinoma and squamous cell carcinoma). Benign tumor.

Rare Lymphoma **.

Tumors of solid organs (including breast, lung and thyroid cancer).

Melanoma**.

Rare Leukemia 1) .
Frequency

indeterminate

Hepatosplenic T-cell lymphoma 1) .

Merkel cell carcinoma (cutaneous neuroendocrine carcinoma) 1)

Ailments

hematology and lymphatic system *

Very common Leukopenia (including neutropenia and

agranulocytosis). Anemia.

Frequent Leukocytosis. Thrombocytopenia.
Rare Idiopathic thrombocytopenic purpura.
Rare Pancytopenia.
System disorders

immune*

Frequent Hypersensitivity.

Allergies (including seasonal allergy).

Rare Sarcoidosis 1) .

Vasculitis.

Rare Anaphylaxis 1) .
Metabolism disorders

and nutrition

Very common Increased lipid level.
Frequent Hypokalaemia.

Increased uric acid.

Abnormal sodium level in the blood. Hypocalcemia.

Hyperglycemia. Hypophosphatemia. Dehydration.

Psychiatric disorders Frequent Mood disorders (including depression).

Anxiety.

System class

organs

Frequency Side effects
Insomnia.
Nervous system disorders * Very common Headache.
Frequent Paresthesia (including hypoaesthesia). Migraine.

Compression of nerve roots.

Rare Cerebrovascular accident 1) .

Tremors. Neuropathy.

Rare Multiple sclerosis.

Demyelinating disorders (eg optic neuritis, Guillain-Barré syndrome) 1) .

Eye disorders Frequent Visual defects.

Conjunctivitis. Blepharitis.

Swelling of the eyes.

Rare Diplopia.
Ear disorders and

labyrinth

Frequent Dizziness.
Rare Deafness.

Tinnitus.

Cardiac disorders * Frequent Tachycardia.
Rare Myocardial infarction 1) .

Arrhythmias.

Congestive heart failure.

Rare Cardiac arrest.
Vascular disorders Frequent Hypertension.

Hot flashes. Hematomas.

Rare Aneurysm of the aorta.

Vascular occlusion. Thrombophlebitis.

Respiratory disorders,

thoracic and mediastinal *

Frequent Asthma.

Dyspnea.

Cough.

Rare Pulmonary embolism 1) .

Interstitial lung disease.

Chronic obstructive pulmonary disease. Pneumopathy.

Pleural effusion 1) .

System class

organs

Frequency Side effects
Rare Pulmonary fibrosis 1) .
Gastrointestinal disorders Very common Abdominal pain. Nausea and vomiting.
Frequent Gastrointestinal bleeding.

Dyspepsia.

Gastroesophageal reflux. Gougerot-Sjögren syndrome.

Rare Pancreatitis. Dysphagia. Facial edema.
Rare Intestinal perforation 1) .
Ailments

hepatobiliary *

Very common Elevated liver enzymes.
Rare Cholecystitis and gallstones.

Fatty liver. Hyperbilirubinemia.

Rare Hepatitis.

Reactivation of hepatitis B 1) . Autoimmune hepatitis 1) .

Frequency not known Hepatic failure 1) .
Skin disorders and

subcutaneous tissue

Very common Rash (including exfoliative rash).
Frequent Worsening or onset of psoriasis

(including palmoplantar pustular psoriasis) 1) .

Urticaria.

Bruises (including purpura). Dermatitis (including eczema).

Onychoclasia. Hyperhidrosis. Alopecia 1) .

Pruritus.

Rare Night sweats. Scar.
Rare Erythema multiforme 1) .

Stevens-Johnson syndrome 1) . Angioedema 1) .

Cutaneous vasculitis 1) . Skin lichenoid reaction 1) .

Frequency not known Worsening of symptoms of dermatomyositis 1)
System class

organs

Frequency Side effects
Musculoskeletal and connective tissue disorders Very common Musculoskeletal pain.
Frequent Muscle contractures (including increased serum creatine phosphokinase).
Rare Rhabdomyolysis.

Systemic lupus erythematosus.

Rare Lupus-like syndrome 1) .
Kidney and

urinary tract

Frequent Renal failure.

Haematuria.

Rare Nocturia.
Disorders of the organs of

reproduction and breast

Rare Erectile function disorders.
General disorders and administration site conditions * Very common Reaction at the injection site (including erythema at the injection site).
Frequent Chest pain.

Edema.

Fever 1) .

Rare Inflammation.
Investigations * Frequent Coagulation disorders and disorders

haemorrhagic (including prolongation of activated partial thromboplastin time).

Positivity to autoantibodies (including anti-double-stranded DNA antibodies).

Increase in blood lactate dehydrogenase level.

Injury, poisoning and complications related to

procedures

Frequent Delayed healing.

* Further information is available under the sections Contraindications, Warnings and precautions for use and Adverse reactions.

** including open label extension studies.

1) including data from spontaneous notifications

Hidradenitis suppurativa (HS)

  • The safety profile in patients with HS treated with adalimumab weekly is consistent with the known safety profile of adalimumab.

Uveitis

  • The safety profile in patients with uveitis treated with adalimumab every two weeks is consistent with the known safety profile of adalimumab.

Description of selected adverse reactions

Injection site reactions

In pivotal controlled trials in adults and children, 12.9% of patients treated with adalimumab experienced injection site reactions (erythema and / or pruritus, bleeding, pain or swelling) versus 7.2 % of patients receiving placebo or active comparator. Injection site reactions generally did not require stopping the drug.

Infections

  • In the pivotal controlled trials in adults and children, the frequency of infections was 1.51 per patient-year in the adalimumab group and 1.46 per patient-year in the placebo group and the control group. . The infections mainly consisted of nasopharyngitis, upper respiratory tract infections and sinusitis. Most patients continued with adalimumab after the infection cleared.
  • The incidence of serious infections was 0.04 per patient-year in the adalimumab group and 0.03 per patient-year in the placebo group and the control group.
  • In open-label, controlled studies with adalimumab in adults and in the pediatric population, serious infections ( including fatal infections, which have rarely occurred) have been reported including reports of tuberculosis (including miliary and extra-pulmonary localizations) and invasive opportunistic infections (eg disseminated histoplasmosis or extrapulmonary histoplasmosis, blastomycosis, coccidioidomycosis, pneumocystosis, candidiasis, aspergillosis and listeriosis). Most cases of tuberculosis have occurred within the first eight months afte starting treatment and may reflect reactivation of latent disease.

Malignant tumors and lymphoproliferative disorders

No cases of cancer were observed in 249 pediatric patients representing exposure of 655.6 patient-years in studies with adalimumab in patients with juvenile idiopathic arthritis (juvenile arthritis idiopathic polyarticular arthritis and enthesitis-related). In addition, no cases of cancer were observed in 192 pediatric patients

representing exposure

  • of 498.1 patient-years in studies with adalimumab in pediatric Crohn’s disease. No cases of cancer were observed in 77 pediatric patients corresponding to an exposure of 80 patient-years in a study with adalimumab in pediatric chronic plaque psoriasis . No cases of cancer were observed in 60 pediatric patients representing an exposure of 58.4 patient-years in a study with adalimumab in pediatric uveitis .
  • During the controlled periods of pivotal adult clinical trials with adalimumab lasting at least 12 weeks in patients with moderately to severely active rheumatoid arthritis, ankylosing spondylitis, axial spondyloarthritis without radiographic evidence of AS , psoriatic arthritis, psoriasis, hidradenitis suppurativa, Crohn’s disease, ulcerative colitis and uveitis, a rate (95% confidence interval) of cancers other than lymphomas or non-melanoma skin cancers, of 6.8 (4.4 to 10.5) was observed for 1000 patient years among the 5 291 patients treated with adalimumab versus a rate of 6.3 (3.4 – 11.8) per 1,000 patient-years among the 3,444 patients in the control group (the mean duration of treatment was 4.0 months for patients treated with adalimumab and 3.8 months for patients in the control group) . The rate (95% confidence interval) of non-melanoma skin cancer was 8.8 (6.0 – 13.0) per 1,000 patient-years for patients treated with adalimumab and 3.2 (1 , 3 – 7.6) per 1000 patient-years among patients in the control group . In these skin cancers, squamous cell carcinomas occurred at rates of 2.7 (1.4 – 5.4) per 1000 patient years in patients treated with adalimumab and 0.6 (0.1 – 4.5) per 1,000 patient-years in patients in the control group ( 95% confidence interval ). The rate (95% confidence interval) of lymphomas was 0.7 (0.2 – 2.7) per 1,000 patient years in patients treated with adalimumab and 0.6 (0.1 – 4.5 ) per 1000 patient-years in patients in the control group.
  • By combining controlled portions of these tests and the tests Expansion open ended or current with a mean duration of around 3.3 years including 6427 patients and more than 26,439 patient- years of treatment, the observed rate of cancers, other than lymphomas and non-melanoma skin cancers is approximately 8.5 per 1,000 patient-years. The observed rate of non-melanoma skin cancer is approximately 9.6 per 1,000 patient-years and the observed rate of lymphomas is approximately 1.3 per 1,000 patient-years.
  • In post-marketing period from January 2003 to December 2010, primarily in patients with rheumatoid arthritis, the reported rate of cancer is approximately 2.7 per 1,000 patient-years of treatment. The reported rates for non-melanoma skin cancer and lymphoma are approximately 0.2 and 0.3 per 1000 patient-years of treatment, respectively.
  • In post-marketing surveillance, rare cases of hepatosplenic T-cell lymphoma have been reported in patients treated with adalimumab .

Autoantibodies

  • Repeated autoantibody tests were performed on serum samples from patients in the IV trials in rheumatoid arthritis. In these trials, initially negative antinuclear antibody titers were positive at week 24 in 11.9% of patients treated with adalimumab and 8.1% of patients on placebo and comparator. Two of the 3,441 patients treated with adalimumab in all rheumatoid arthritis and psoriatic arthritis studies presented clinical signs suggestive of a new onset lupus-like syndrome . The condition of the patients improved after stopping treatment. No patient presented lupus nephritis or central nervous symptoms.

Hepatobiliary events

  • In phase III controlled clinical trials of adalimumab in rheumatoid arthritis and psoriatic arthritis with a control period of 4 to 104 weeks, elevations of ALT ≥ 3 x ULN occurred in 3.7% of patients treated by adalimumab and in 1.6% of patients in the control group.
  • In phase III controlled clinical trials of adalimumab in patients with polyarticular juvenile idiopathic arthritis aged 4 to 17 years and patients with enthesitis-related arthritis aged 6 to 17 years, elevations of ALT ≥ 3 x ULN occurred in 6.1% of patients treated with adalimumab and in 1.3% of patients in the control group. Most of the elevations in ALT have occurred with concomitant use of methotrexate. No elevation of ALT ≥ 3 x ULN occurred in the phase III trial of adalimumab in patients with polyarticular juvenile idiopathic arthritis aged 2 to <4 years.
  • In phase III controlled clinical trials of adalimumab in
    patients with Crohn’s disease and ulcerative colitis
    with a control period of 4 to 52 weeks, elevations of ALT
    ≥ 3 x ULN occurred in 0.9 % of patients treated with adalimumab
    and in 0.9% of patients in the control group.
  • In the Phase III clinical trial of adalimumab in children and
    adolescents with Crohn’s disease which evaluated the efficacy and
    safety profile of two weight-based maintenance regimens following induction therapy weight-adjusted
    up to 52 weeks of treatment, elevations of ALT ≥ 3 x ULN
    occurred in 2.6% of patients (5/192), of whom 4 were
    treated in combination with immunosuppressants at the start of treatment. study.
  • In phase III controlled clinical trials of adalimumab in plaque psoriasis with a control period of 12 to 24 weeks, elevations of ALT ≥ 3 x ULN occurred in 1.8% of patients
    treated with adalimumab and in 1.8% of patients in the control group.
  • It has not been observed ALT elevations ≥ 3 x ULN in the study
    phase III adalimumab in pediatric patients with
    plaque psoriasis.
  • In controlled clinical trials of adalimumab (starting doses of 160 mg at week 0 and 80 mg at week 2 followed by 40 mg each week from week 4), in patients with HS with severe 12-16 week control period , elevations of ALT ≥ 3 x ULN occurred in 0.3% of patients treated with adalimumab and 0.6% of patients in the control group .
  • In controlled clinical trials of adalimumab (starting dose 80 mg at week 0 followed by 40 mg every two weeks from week 1) in adult patients with uveitis for up to 80 mg weeks, with a median duration of exposure of 166.5 days and 105.0 days for patients treated with adalimumab and patients in the control group, respectively, elevations of ALT ≥ 3 x ULN occurred in 2.4% of patients. patients treated with adalimumab and 2.4% of patients in the control group.
  • In clinical trials across all indications, patients with elevated ALT were asymptomatic and in most cases the
    elevations were transient and reversible upon continued treatment. However, during post-marketing surveillance, hepatic insufficiency as well as less severe hepatic disorders , which may precede hepatic insufficiency, such as hepatitis including autoimmune hepatitis, have been reported in patients receiving l. ‘adalimumab.

Concomitant administration of azathioprine / 6-mercaptopurine

  • In studies in Crohn’s disease in adults, a higher incidence of tumors and serious infections was observed with
    the combination of adalimumab and azathioprine / 6-mercaptopurine compared to adalimumab used alone.

HYRIMOZ  Interactions

  • Adalimumab has been studied in patients with rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, and psoriatic arthritis taking adalimumab as monotherapy and in those taking
    methotrexate concomitantly. Antibody formation was lower when adalimumab was co-administered with methotrexate compared to its use as monotherapy.
  • Administration of adalimumab without methotrexate resulted in increased antibody formation, increased clearance and reduced efficacy of adalimumab.
  • The combination of adalimumab and anakinra is not recommended (see section Warnings and precautions for use “Simultaneous administration of biological DMARDs and anti-TNFs”).
  • The combination of adalimumab and abatacept is not recommended (see section Warnings and precautions for use “Simultaneous administration of biological DMARDs and anti-TNF drugs”).
  • In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

Drive and use machines

Hyrimoz may have minor influence on the ability to drive and use machines. Dizziness and visual disturbances may occur after administration of Hyrimoz ( see Undesirable effects ).

Warnings and Precautions

In order to improve the traceability of biological medicinal products, the name of the medicinal product and the batch number of the administered product must be clearly recorded.

Infections

The patients receiving TNF-antagonists are more susceptible to serious infections. Impaired lung function can increase the risk of developing infections. Patients should therefore be monitored closely for infections (including tuberculosis) before, during and after treatment with Hyrimoz. As the duration of elimination of adalimumab may be up to four months, monitoring should be continued throughout this period.

  • The treatment Hyrimoz should not be initiated in patients with active infections, including chronic infections or localized, are not controlled. In patients who have been exposed to tuberculosis or who have traveled to areas at high risk for tuberculosis or endemic mycoses, for example histoplasmosis, coccidioidomycosis or blastomycosis, the risks and benefits of treatment with Hyrimoz should be considered before initiation. treatment (see Other opportunistic infections).
  • The Patients who develop a new infection during treatment with Hyrimoz must be monitored carefully and complete diagnostic workup should be practiced. If a serious new infection or sepsis occurs, administration of Hyrimoz should be discontinued and appropriate antimicrobial or antifungal therapy should be started until the infection is controlled. Caution should be exercised by the physician before using Hyrimoz in patients with a history of recurrent infection or with underlying conditions that may predispose them to infections, including concomitant treatment with immunosuppressive drugs.

Serious infections

  • Of serious infections, including sepsis due to infections bacterial, mycobacterial, invasive fungal, parasitic, viral, or other opportunistic infections such as listeriosis, legionellosis and pneumocystis have been reported in patients treated with adalimumab.
  • The other serious infections seen in clinical trials include pneumonia, pyelonephritis, septic arthritis and septicemia. There have been reports of infections requiring hospitalization or with fatal outcome.

Tuberculosis

Of TB cases, including cases of TB reactivation and primary infection tuberculosis have been reported for patients receiving adalimumab. Cases of pulmonary and extra-pulmonary (i.e. disseminated) tuberculosis have been reported.

Before initiating treatment with Hyrimoz, all patients should be screened for active and inactive (“latent”) tuberculosis infection . This assessment should include a detailed medical evaluation in patients with a history of tuberculosis or possible previous exposure to patients with active tuberculosis and / or current or past immunosuppressive therapy. Appropriate screening tests (eg tuberculin skin test and chest x-ray) should be performed in all patients (according to local recommendations). It is advisable to record the performance and results of these tests in the patient monitoring card. Prescribers are reminded that
the tuberculin skin test can give false negatives, especially in seriously ill or immunosuppressed patients.

  • If active tuberculosis is diagnosed, treatment with Hyrimoz should not be initiated .
  • In all of the situations described below, the benefit / risk ratio of the treatment should be assessed very carefully.
  • In case of suspicion of latent tuberculosis, consulting a specialist, qualified in the treatment of tuberculosis should be considered.
  • In case of diagnosis of latent tuberculosis, prophylactic tuberculosis appropriate and in accordance with local recommendations must be implemented before the start of treatment with Hyrimoz.
  • A TB prophylaxis should also be considered before introducing Hyrimoz in patients with risk factors or multiple TB significant despite testing of negative tuberculosis and in patients with a history of latent or active tuberculosis in that the administration of an appropriate anti-tuberculosis treatment cannot be confirmed.
  • The case of reactivation of tuberculosis despite treatment prophylactic occurred in patients treated with adalimumab. Some patients who had been successfully treated for active tuberculosis developed the disease again during treatment with adalimumab.
  • The patients should be advised that they will need their doctor in case of occurrence of symptoms suggestive signs or infection tuberculosis (eg persistent cough, wasting / loss of weight, low grade fever, listlessness), during or after treatment Hyrimoz.

Other opportunistic infections

  • Of opportunistic infections, including invasive fungal infections, have been observed in patients treated with adalimumab. These infections were not always detected in patients receiving TNF antagonists, resulting in delayed initiation of appropriate therapy, sometimes with fatal outcome.
  • In patients who present with signs and symptoms such as fever, malaise, weight loss, sweating, cough, dyspnea and / or pulmonary infiltrates or other serious systemic disease with or without concomitant shock , an invasive fungal infection should be suspected; in this case, the administration of Hyrimoz should be stopped immediately. Diagnosis and initiation of empiric antifungal therapy in these patients should be made in consultation with a physician experienced in the management of patients with invasive fungal infections.

Reactivation of hepatitis B

  • A reactivation of hepatitis B occurred in patients who received a TNF antagonist including adalimumab and who were carriers chronic of this virus (that is to say surface antigen positive – Ag positive HBs) . Some cases have had a fatal outcome. Patients should be screened for HBV infection before initiating treatment with Hyrimoz. For patients who test positive for hepatitis B, it is recommended to consult a doctor specializing in the treatment of hepatitis B.
  • In HBV carriers who require treatment with Hyrimoz, careful monitoring of signs and symptoms of active
    HBV infection should be observed throughout treatment and for several months after discontinuation. There are insufficient data available on the treatment of patients with HBV treated with antiviral and
    TNF antagonist to prevent HBV reactivation. In patients who develop HBV reactivation, Hyrimoz should be discontinued and effective antiviral therapy as well as appropriate additional therapy should be initiated.

Neurological events

  • The TNF blockers, including adalimumab, have been associated in rare circumstances the onset or exacerbation of symptoms clinical and / or radiographic evidence of demyelinating disease of the central nervous system including multiple sclerosis, Optic neuritis and peripheral demyelinating disease, including Guillain-Barré syndrome. Prescribers are advised with caution before treating patients with pre-existing or recently-occurring central or peripheral nervous system demyelinating disease with Hyrimoz ; Discontinuation of treatment should be considered if any of these disorders develop. The association between uveitis intermediate and demyelinating diseases of the central nervous system is known. Neurologic assessment should be performed in patients with non-infectious intermediate uveitis before initiating therapy with Hyrimoz, and repeated regularly during therapy to check for pre-existing or active central nervous system demyelinating disease .

Allergic reactions

  • In clinical trials, serious allergic reactions associated with adalimumab were rarely reported and non-serious allergic reactions associated with adalimumab were uncommon. Cases of severe allergic reactions, including anaphylactic reactions have been reported after administration of adalimumab. If  an anaphylactic reaction or other severe allergic reaction occurs, administration of Hyrimoz should be stopped immediately and appropriate treatment initiated.

Immunosuppression

  • In  a study of 64 patients with rheumatoid arthritis treated with adalimumab, there was no evidence of delayed-type hypersensitivity depression, decreased immunoglobulin levels or a change in the count of effector T and B lymphocytes, NK lymphocytes, monocytes / macrophages and neutrophil granulocytes.

Malignant tumors and lymphoproliferative disorders

  • In the controlled part of clinical trials with anti-TNFs, more cases of cancer including lymphomas were observed in patients treated with an anti-TNF than in patients in the control group . However, the incidence has been rare. During post-marketing surveillance, cases of leukemia have been reported in patients treated with anti-TNF. In addition, there is a background of increased risk of lymphoma and leukemia in patients with old, inflammatory and highly active rheumatoid arthritis , which complicates the estimation of risk. In the current state of knowledge, the possibility of a risk of developing lymphomas,
    leukemia or other malignant diseases in patients treated with anti-TNF cannot be excluded.
  • Of malignancies, some fatal, have been reported postmarketing in children, adolescents and young adults (up to age 22 years) treated with TNF antagonists (initiation of therapy before age 18), including
    adalimumab. About half of these cases were lymphomas. The other cases corresponded to other types of malignant tumors among which rare cancers generally associated with a context of immunosuppression. The risk of developing malignant tumors can not be excluded in children and adolescents treated with anti-TNF.
  • In the course of the post-marketing surveillance, rare cases of lymphoma hepatosplenic T-cell lymphoma have been identified in patients treated with adalimumab. This rare form of T-cell lymphoma has a very aggressive course and is often fatal. Some of these hepatosplenic T-cell lymphomas seen with adalimumab have occurred in young adults who were concomitantly treated with azathioprine or 6-mercaptopurine used in inflammatory bowel disease. The potential risk of combining azathioprine or 6 mercaptopurine with Hyrimoz should be carefully considered. A risk of developing Hepatosplenic T-cell lymphoma in patients treated with Hyrimoz cannot be excluded.
  • There are no studies in patients with a history of malignancies or in whom treatment with adalimumab is continued after the development of cancer. Therefore, increased caution should be observed when considering treatment of these patients with Hyrimoz .
  • All patients, especially those with a history of intense immunosuppressive therapy or with psoriasis and a history of puvatherapy, should be examined for skin cancer other than melanoma before and during treatment with Hyrimoz. Cases of melanoma and Merkel cell carcinoma have also been reported in patients treated with anti-TNF inhibitors  including adalimumab.
  • In a prospective clinical study evaluating the use of another anti-TNF agent , infliximab, in patients with moderate to severe chronic obstructive pulmonary disease (COPD), more cancers, especially of the lung,  were reported. head and neck, among patients treated with infliximab compared to patients in the control group. All patients had a history of heavy smoking. For this reason, care should be taken in the use of an anti-TNF in patients with COPD, and also in patients at risk for cancer due to heavy smoking .
  • Based on current data, it is not known whether treatment with adalimumab influences the risk of developing dysplasia or colon cancer. All patients with ulcerative colitis who are at high risk of dysplasia or colon cancer (for example, patients with old ulcerative colitis or primary sclerosing cholangitis) or who have a history of dysplasia or colon cancer should do regularly screened for dysplasia before treatment and throughout the course of their disease. This assessment should include colonoscopy and biopsies according to local recommendations.

Haematological reactions

  • From Rare reports of pancytopenia including aplastic anemia have beenreported with TNF antagonists. Adverse effects of the blood system including medically significant cytopenias (eg , thrombocytopenia, leukopenia) have been observed with adalimumab. Itshould be recommended for all patients seek immediate medical advice if they have signs or symptoms suggestive of blood disorders (eg, persistent fever, bruising, bleeding, pallor) while Hyrimoz. Discontinuation of treatment with Hyrimoz
    should be considered for patients in whom significant blood abnormalities are confirmed.

Vaccinations

  • Similar antibody responses to the standard 23-valence pneumococcal vaccine and to the trivalent influenza vaccine were observed in a study in 226 adults with rheumatoid arthritis treated with adalimumab or placebo. There are no data available on the secondary transmission of infection from live vaccines in patients receiving adalimumab.
  • In children and adolescents, it is recommended, if possible, that all immunizations be up to date according to current immunization recommendations before initiating treatment with Hyrimoz.
  • The patients Hyrimoz may receive concurrent vaccinations, except in respect of live vaccines. Administration of live vaccines (eg, BCG vaccine) to infants who have been exposed to adalimumab in utero is not recommended for 5 months after the mother’s last injection of adalimumab during pregnancy.

Congestive heart failure

  • In a clinical trial with another TNF antagonist, worsening congestive heart failure and increased mortality from congestive heart failure were observed . Of cases of congestive heart failure worsening were also reported in adalimumab patients. Hyrimoz should be used with caution in patients with mild heart failure (NYHA classes I / II). Hyrimoz is contraindicated in moderate to severe heart failure..Treatment with Hyrimoz should be stopped in patients with new or worsening symptoms. congestive heart failure.

Autoimmune processes

  • The treatment Hyrimoz may cause antibody formation autoimmune. The impact of long-term treatment with adalimumab on the development of autoimmune diseases is unknown. If a patient develops symptoms of a lupus-like syndrome following treatment with Hyrimoz and exhibits a positive anti- double-stranded DNA reaction , treatment with Hyrimoz should not be continued.

Simultaneous administration of biological DMARDs or anti-TNF

  • Some serious infections were seen in clinical studies in the concurrent use of anakinra and another TNF antagonist, etanercept, with no added clinical benefit compared to etanercept alone. Due to the nature of the side effects seen with treatment with etanercept and anakinra, similar side effects may also result from the combination of anakinra and other TNF blockers. Therefore, the combination of adalimumab and anakinra is not recommended (see section Interactions with other medicinal products and other forms of interactions).
  • Concomitant administration of adalimumab with other biologic DMARDs (eg anakinra and abatacept) or with other TNF blockers is not recommended due to the possible increased risk of infections, including serious infections, and other potential pharmacological interactions (see section Interactions with other medicinal products and other forms of interactions).

Surgery

  • There is limited experience with safety during surgical procedures in patients treated with adalimumab. The long half-life of adalimumab should be taken into account if surgery is planned. A patient treated with Hyrimoz requiring surgery should be carefully monitored for infections and appropriate actions should be taken.
  • There is limited experience with the safety of adalimumab in patients operated on for arthroplasty.

Hail Occlusion

  • In Crohn’s disease, treatment failure may indicate the presence of fixed fibrous strictures that may require surgical treatment.
  • The available data suggest that adalimumab does not worsen or cause strictures.

Older subjects

  • The frequency of serious infections in subjects treated with adalimumab over 65 years of age (3.7%) is higher than in patients under 65 years of age (1.5%). Some cases have had a fatal outcome. A special attention regarding the risk of infection should be given when treating elderly patients.

Pediatric population

  • See Vaccinations above.

Sodium content

  • This medicine contains less than 1 mmol (23 mg) sodium per 0.8 ml dose , that is to say essentially ‘sodium-free’.

PREGNANCY & BREAST-FEEDING & FERTILITY

Women of childbearing age

  • Women of childbearing potential should consider using effective contraception during treatment with Hyrimoz and continue for at least five months after the last administration of Hyrimoz.

Pregnancy

  • A large number (approximately 2,100) of pregnancies exposed to adalimumab for which data were collected prospectively, resulting in a live birth with a known term outcome, including more than 1,500 pregnancies exposed to adalimumab during the first trimester, does not reveal any increase in the rate of malformations in the newborn.
  • In a prospective cohort study, 257 women with rheumatoid arthritis (RA) or Crohn’s disease (CD) treated with adalimumab at least during the first trimester and 120 women with untreated RA or CD by adalimumab were included. The prevalence at birth of major congenital anomalies was the primary endpoint. The rate of pregnancies resulting in at least one living newborn with a major birth defect was 6/69 (8.7%) in women treated with adalimumab with RA and 5/74 (6.8 %) in untreated women with RA (unadjusted OR 1.31, 95% CI 0.38-4.52), and 16/152 (10.5%) in women treated with adalimumab with CD and 3/32 (9, 4%) in untreated women with CD (unadjusted OR 1.14, 95% CI 0.31-4.16). The adjusted OR (considering baseline differences) was 1.10 (95% CI 0.45-2.73) for RA and CD combined. No notable difference was reported between women treated with adalimumab and women not treated with adalimumab for secondary endpoints of spontaneous abortion, minor congenital anomalies, preterm delivery, height. at birth and serious or opportunistic infections, and stillbirth or malignancy. Interpretation of the data may be affected due to methodological limitations of the study, including the small sample size and the non-randomized study design. Adjusted OR (considering baseline differences) was 1.10 (95% CI 0.45-2.73) for RA and CD combined. No notable difference was reported between women treated with adalimumab and women not treated with adalimumab for secondary endpoints of spontaneous abortion, minor congenital anomalies, preterm delivery, height. at birth and serious or opportunistic infections, and stillbirth or malignancy. Interpretation of the data may be affected due to methodological limitations of the study, including the small sample size and the non-randomized study design. Adjusted OR (considering baseline differences) was 1.10 (95% CI 0.45-2.73) for RA and CD combined. No notable difference was reported between women treated with adalimumab and women not treated with adalimumab for secondary endpoints of spontaneous abortion, minor congenital anomalies, preterm delivery, height. at birth and serious or opportunistic infections, and stillbirth or malignancy. Interpretation of the data may be affected due to methodological limitations of the study, including the small sample size and the non-randomized study design. has been reported between women treated with adalimumab and women not treated with adalimumab for secondary endpoints of spontaneous abortion, minor congenital anomalies, preterm delivery, size at birth and severe or opportunistic infections, and stillbirth or malignancy. Interpretation of the data may be affected due to methodological limitations of the study, including the small sample size and the non-randomized study design. has been reported between women treated with adalimumab and women not treated with adalimumab for secondary endpoints of spontaneous abortion, minor congenital anomalies, preterm delivery, size at birth and severe or opportunistic infections, and stillbirth or malignancy. Interpretation of the data may be affected due to methodological limitations of the study, including the small sample size and the non-randomized study design. and stillbirth or malignancy. Interpretation of the data may be affected due to methodological limitations of the study, including the small sample size and the non-randomized study design. and stillbirth or malignancy. Interpretation of the data may be affected due to methodological limitations of the study, including the small sample size and the non-randomized study design.
  • In a developmental toxicity study performed in monkeys, there were no signs of possible maternal toxicity, embryotoxicity or teratogenic potential. There are no preclinical data on the postnatal toxicity of adalimumab ( see Preclinical Safety ).
  • Due to its inhibitory effect on TNFα, adalimumab administered during pregnancy may affect the normal immune responses of the newborn. Adalimumab should be used during pregnancy only if needed.
  • In women treated with adalimumab during pregnancy, adalimumab can cross the placenta and pass into the blood of their child. As a result, these children may have an increased risk of infections. Giving live vaccines (for example, BCG vaccine) to children who have been exposed to adalimumab

in utero is not recommended for 5 months after the mother’s last injection during pregnancy.

Feeding with milk 

  • Limited data from the published literature indicate that adalimumab is excreted in breast milk at very low concentrations, with adalimumab being present in breast milk at concentrations equivalent to 0.1% -1% of maternal serum levels. . When administered orally, immunoglobulin G proteins undergo intestinal proteolysis and exhibit low bioavailability.
  • No effects on breastfed newborns / infants are expected. Therefore, Hyrimoz can be used during breast-feeding.

Fertility

  • Preclinical data on the effects of adalimumab on fertility are not available.

What happens if I overdose from HYRIMOZ  ?

What is  Forms and Composition ?

SHAPES and PRESENTATIONS
  • Solution for injection (SC injection) (clear to slightly opalescent, colorless to slightly yellowish) 40 mg: 
    0.8 ml single-dose pre-filled syringe, single use, with rubber stopper, needle with automatic needle shield with collar, cap rubber needle and plunger, box of 2, in a blister pack.
  • SensoReady 0.8 mL single-dose pre-filled pen, disposable, triangular in shape, with transparent viewing window and label, containing single-use pre-filled syringe, with needle, rubber inner needle cap and rubber stopper, box of 2.
COMPOSITION
  p syringe or pen
Adalimumab * 40 mg
  • *  Adalimumab is a recombinant human monoclonal antibody produced in Chinese hamster ovary cells.
  • Excipients: adipic acid, citric acid monohydrate, sodium chloride, mannitol, polysorbate 80, hydrochloric acid (for pH adjustment), sodium hydroxide (for pH adjustment), water for injections.

NOT’s

Edrug-online contains comprehensive and detailed information about drugs available in the medical field, and is divided into four sections:

general information:

  • Includes a general description of the drug, its use, brand names, FAQs, and relevant news and articles

Additional information:

  • General explanation about dealing with the medicine: how to take the medicine, the doses and times of it, the start and duration of its effectiveness, the recommended diet during the period of taking the medicine, the method of storage and storage, recommendations in cases for forgetting the dose and instructions to stop taking the drug and take additional doses.

Special warnings:

  • For pregnant and breastfeeding women, the elderly, boys and drivers, and use before surgery.

Side effects:

  • It treats possible side effects and drug interactions that require attention and its effect on continuous use.
  • The information contained in this medicine is based on medical literature, but it is not a substitute for consulting a doctor.
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imraldi 40 mg Injection reviews | Uses, Dosage, Side Effects & Precautions https://edrug-online.com/1492/imraldi.html https://edrug-online.com/1492/imraldi.html#respond Sat, 29 Aug 2020 12:23:59 +0000 https://edrug-online.com/?p=1492 What is Imraldiimraldi 40 mg Injection reviews >> Generic drug of the Therapeutic class: Immunology Medicines Active ingredients: Adalimumab what is IMRALDI ? Pharmaceutical form: Solution for injection Route of administration: Sc ATC code: L04AB04 Pharmacotherapeutic group: Adalimumab Prescribing and dispensing conditions: Medicinal product subject to medical prescription (List I). Medicines on list I (red box on […]]]> What is Imraldi

imraldi 40 mg Injection reviews >> Generic drug of the Therapeutic class: Immunology Medicines

Active ingredients: Adalimumab

what is IMRALDI ?

  • Pharmaceutical form: Solution for injection
  • Route of administration: Sc
  • ATC code: L04AB04
  • Pharmacotherapeutic group: Adalimumab
  • Prescribing and dispensing conditions: Medicinal product subject to medical prescription (List I).
  • Medicines on list I (red box on the box) can only be dispensed for the duration of treatment mentioned on the prescription. 
  • Initial hospital prescription. Prescription and renewal reserved for specialists in rheumatology, pediatrics, internal medicine, gastroenterology and hepatology, dermatology or ophthalmology. Exceptional drug. 
  • Reimbursement according to the indication (OJ of 17/10/2018): The only therapeutic indications giving rise to the right to additional reimbursement by health insurance are, for the specialty referred to below: In adults: – treatment of severe chronic plaque psoriasis in adults, defined by: – ​​failure (insufficient response, contraindication or intolerance) to at least two treatments among non-biological systemic treatments and phototherapy; – and an extended form and / or a significant psychosocial impact; – in combination with methotrexate, treatment of moderately to severely active rheumatoid arthritis in adults when the response to DMARDs, including methotrexate, is inadequate; IMRALDI can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate.
  •  IMRALDI slows the progression of structural joint damage measured by radiography and improves functional abilities when it is given in combination with methotrexate.
  • treatment of severe and active ankylosing spondylitis in adults who have had an inadequate response to conventional treatment; – treatment of severe axial spondyloarthritis without radiographic signs of AS, but with objective signs of inflammation on MRI and / or a high level of CRP in adults who have had an inadequate response or intolerance to nonsteroidal anti-inflammatory drugs ; – treatment of active, moderate to severe Crohn’s disease in adult patients who have not responded despite an appropriate and well-conducted treatment with a corticosteroid and / or an immunosuppressant, or in whom this treatment is contraindicated or poorly tolerated; – treatment of active and progressive psoriatic arthritis in adults when the response to previous disease-modifying treatment has been inadequate; IMRALDI slows the progression of peripheral joint structural damage, as measured by radiography, in patients with symmetrical polyarticular forms of the disease and improves functional ability. – treatment of active, moderate to severe ulcerative colitis in adult patients who have not responded adequately to conventional treatment, including corticosteroids and azathioprine or 6-mercaptopurine, or in whom this treatment is poorly tolerated or contraindicated. In children: – treatment of severe chronic plaque psoriasis in children from 4 years of age and adolescents defined by: – failure (insufficient response, contraindication or intolerance) to at least two treatments among non-biological systemic treatments and phototherapy; – and an extended form and / or a significant psychosocial impact; – treatment of active, severe Crohn’s disease in children and adolescents from 6 years of age who have not responded to conventional treatment including a corticosteroid, an immunomodulator and first-line nutritional treatment, or in which these treatments are poorly tolerated or contraindicated; – In combination with methotrexate, treatment of progressive polyarticular juvenile idiopathic arthritis in children and adolescents from 2 years of age in the event of an insufficient response to one or more DMARDs. IMRALDI can be administered as monotherapy in cases of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate.
  • ADALIMUMAB has not been studied in children under 2 years of age.
  • Specialty Identifier Code (CIS): 61192750
  • Actual benefit (SMR): Important, Important, Moderate
  • Laboratory holder AMM: Samsung bioepis nl bv ( 08/24/2017 )
  • Operating laboratory: Biogen france

This medicine does not belong to any generic group.

Sources:

  • Summary of Product Characteristics (SPC) of French and European marketing authorizations (AMM)
  • Drug interactions booklet from the National Agency for the Safety of Medicines and Health Products (ANSM)
  • ANSM generic directory
  • Reference documents of the Haute Autorité de Santé (HAS): transparency sheets, good use sheets, SAM documents (Decision Support System by Medicines)
  • Prices and reimbursements from the Economic Committee for Health Products (CEPS)
  • Information from laboratories holding Marketing Authorization (see above in the “Other information” tab of this page)
  • Information wholesalers distributors
  • Health insurance (CNAMTS): guide to long-term assignments (ALD)
  • Technical Agency for Information on Hospitalization (ATIH): CIM10 classification
  • World Health Organization (WHO): ATC classification
  • European Pharmacopoeia: Standard Terms and EPhMRA Classification
  • Ministry of Health: doping substances

what is IMRALDI medication used for and indication?

Rheumatoid arthritis

Imraldi in combination with methotrexate is indicated for:

 

  • the treatment of moderately to severely active rheumatoid arthritis in adults when the response to DMARDs, including methotrexate, is inadequate.
  • the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate.
  • Imraldi can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate.
  • It has been demonstrated that adalimumab slows the progression of damage structural joint measured radiographically and improves function, when given in combination with methotrexate.

Juvenile idiopathic arthritis

Polyarticular juvenile idiopathic arthritis

  • Imraldi in combination with methotrexate is indicated for the treatment of progressive polyarticular juvenile idiopathic arthritis in patients from 2 years of age in case of insufficient response to one or more DMARDs. Imraldi can be administered as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is unsuitable (for efficacy as monotherapy, see section Pharmacodynamic properties). Adalimumab has not been studied in patients less than 2 years of age.

Enthesitis-related arthritis

  • Imraldi is indicated for the treatment of active arthritis associated with enthesitis in patients from 6 years of age with insufficient response or intolerance to conventional therapy (see section 5.1).

Axial spondyloarthritis

Ankylosing spondylitis (AS)

  • Imraldi is indicated for the treatment of severe and active ankylosing spondylitis in adults who have had an inadequate response to conventional therapy .

Axial spondyloarthritis without radiographic evidence of AS 

  • Imraldi is indicated for the treatment of severe axial spondyloarthritis without radiographic evidence of AS, but with objective evidence of inflammation on MRI and / or elevated CRP in adults who have had an inadequate response or intolerance to anti -nonsteroidal inflammatory drugs.

Psoriatic arthritis

  • Imraldi is indicated for the treatment of active and progressive psoriatic arthritis in adults when the response to previous disease-modifying therapy has been inadequate.
  • It has been demonstrated that adalimumab slows the progression of damage peripheral joint as measured by X-ray in patients with polyarticular forms symmetrical disease (see section Pharmacodynamic properties) and improves functional capacity.

Psoriasis

  • Imraldi is indicated for the treatment of chronic, moderate to severe plaque psoriasis in adult patients who require systemic therapy.

Plaque psoriasis in children and adolescents

  • Imraldi is indicated for the treatment of severe chronic plaque psoriasis in children from 4 years of age and in adolescents with insufficient response to topical treatment and light therapy or when these treatments are inappropriate.

Hidradenitis suppurativa (HS)

  • Imraldi is indicated for the treatment of active, moderate to severe hidradenitis suppurativa ( Verneuil’s disease ) in adults and adolescents from 12 years of age in the event of an insufficient response to conventional systemic therapy for HS (see section Properties). Pharmacodynamics and Pharmacokinetic Properties).

Crohn’s disease

Imraldi is indicated for the treatment of moderate tosevere active Crohn’s disease in adult patients who have  not responded despite appropriate and well-administered treatment with a corticosteroid and / or immunosuppressant; or in whom this treatment is contraindicated or poorly tolerated.

Crohn’s disease in children and adolescents

  • Imraldi is indicated for the treatment of moderate to severe active Crohn’s disease in children and adolescents from 6 years of age who have failed to respond to conventional therapy including first-line nutritional therapy and a corticosteroid and / or an immunomodulator, or in which these treatments are poorly tolerated or  contraindicated.

Ulcerative colitis

  • Imraldi is indicated for the treatment of active, moderate to severe ulcerative colitis in adult patients who have had an inadequate response to conventional therapy, including corticosteroids and 6-mercaptopurine (6-MP) or azathioprine (AZA), or in whom this treatment is contraindicated or poorly tolerated.

Uveitis

  • Imraldi is indicated for the treatment of non-infectious, intermediate, posterior uveitis and panuveitis in adult patients who have had an insufficient response to corticosteroid therapy, in patients requiring corticosteroid sparing, or in whom corticosteroid therapy is inappropriate.

Uveitis in children and adolescents

  • Imraldi is indicated for the treatment of chronic non- infectious anterior uveitis in children and adolescents from 2 years of age with insufficient response or intolerance to conventional treatment or for whom conventional treatment is inappropriate.

IMRALDI  Dosage

  • The treatment Imraldi should be initiated and supervised by a physician qualified specialist in the diagnosis and treatment of pathologies in which Imraldi indicated.
  • It is recommended that ophthalmologists consult an appropriate specialist before initiating treatment with Imraldi.
  • Patients treated with Imraldi will receive a Patient Alert Card.
  • After  proper training in the injection technique, patients can self-inject Imraldi, if their doctor considers it possible, under the guise of appropriate medical supervision.
  • During treatment with Imraldi, other concomitant treatments (such as corticosteroids and / or immunomodulators) should be optimized.

Dosage

Rheumatoid arthritis

  • In adult patients with rheumatoid arthritis, the recommended dose of Imraldi is a single dose of 40 mg adalimumab given every two weeks, subcutaneously. The administration of methotrexate should be continued during treatment with Imraldi.
  • The glucocorticoids, salicylates, nonsteroidal anti-inflammatory drugs or analgesics may be continued during treatment with Imraldi. Regarding the combination with anti-rheumatic drugs other than methotrexate, see sections Warnings and precautions for use and Pharmacodynamic properties.
  • As monotherapy, some patients who experience a decrease in their response to Imraldi 40 mg every other week may benefit from an increase in the dosage to adalimumab 40 mg every week or 80 mg every other week.
  • Available data suggest that clinical response is usually achieved within 12 weeks of treatment. Continuation of treatment should be reconsidered in a patient who has not responded within these time limits.

Interruption of treatment

  • It may be necessary to stop treatment, eg before surgery or in patients with severe infection.
  • The available data suggest that re-introduction of adalimumab after stopping 70 days or more results in a clinical response of the same magnitude and a similar safety profile to that observed before stopping.

Ankylosing spondylitis, axial spondyloarthritis without radiographic evidence of AS, and psoriatic arthritis

  • The recommended dose of Imraldi for patients with ankylosing spondylitis, axial spondyloarthritis without radiographic evidence of AS, and for patients withpsoriatic arthritis is 40 mg adalimumab as a single dose  every two weeks, by subcutaneous injection. .
  • Available data suggest that clinical response is usually achieved within 12 weeks of treatment. Continuation of treatment should be reconsidered in a patient who has not responded within these time limits.

Psoriasis

  • The recommended dose of Imraldi to start treatment in adults is 80 mg subcutaneously. The dosage will continue one week later with 40 mg subcutaneously every other week. 
  • The continuing treatment beyond 16 weeks should be carefully reconsidered in a patient not responding within this time.
  • Beyond 16 weeks, in case of insufficient response to Imraldi 40 mg every two weeks, patients may benefit from an increase in the administration dose to 40 mg every week or 80 mg every two weeks. The benefits and risks of continuous treatment of 40 mg every week or 80 mg every other week should be carefully reconsidered in a patient with insufficient response after increasing the dosage. 
  • If sufficient response is obtained with 40 mg every week or 80 mg every two weeks, the dosage may then be reduced to 40 mg every 2 weeks.

Hidradenitis suppurativa

  • The recommended dosage regimen of Imraldi in adult patients with hidradenitis suppurativa (HS) is an initial dose of 160 mg on day 1 (given as 4 injections of 40 mg in one day or 2 injections of 40 mg mg per day for two consecutive days ), followed by an 80 mg dose two weeks later, on day 15 (given as two 40 mg injections over one day).
  • Two weeks later (day 29), continue with a dose of 40 mg every week or 80 mg every two weeks (given as two 40 mg injections per day). If necessary, antibiotics can be continued during treatment with Imraldi. During treatment with Imraldi, it is recommended that the patient cleanse his lesions daily with a topical antiseptic.
  • The continuing treatment beyond 12 weeks should be carefully reconsidered in patients showing no improvement during this period.
  • If treatment is interrupted, Imraldi 40 mg every week or 80 mg every other week may be reintroduced .
  • The benefit and risk of continued long-term treatment should be assessed regularly.

Crohn’s disease

  • In adult patients with moderate to severe active Crohn’s disease , the recommended induction regimen of Imraldi is 80 mg at week 0, followed by 40 mg at week 2. If needed. achieve a faster response to treatment, schedule 160 mg at week 0 (given as 4 injections of 40 mg per day or 2 injections of 40 mg per day for two
    injections of 40 mg per day), can be used knowing that the risk of adverse events is then higher during this
    induction phase .
  • Following induction therapy, the recommended dose is 40 mg administered every two weeks by subcutaneous injection. If a patient has stopped treatment with Imraldi and the signs and symptoms of the disease return, Imraldi may be re-administered. Experience with re-administration of treatment beyond 8 weeks after the previous dose is limited.
  • During maintenance treatment, corticosteroids may be gradually reduced in accordance with clinical practice recommendations .
  • Some patients in whom a decreased response to treatment with Imraldi 40 mg every two weeks is observed may benefit from an increase in the dose to Imraldi 40 mg every week or 80 mg every other week.
  • Some patients who have not responded to treatment at week 4 may continue maintenance therapy until week 12. Continuation of treatment should be carefully reconsidered in a patient who has not responded within this time.

Ulcerative colitis

  • In adult patients with moderate to severe ulcerative colitis , the recommended induction regimen of Imraldi is 160 mg at week 0 (given as 4 injections of 40 mg per day or 2 injections of 40 mg per day. day for two consecutive days ) and 80 mg at week 2 (given as two 40 mg injections per day). After induction therapy, the recommended dose is 40 mg administered every two weeks by subcutaneous injection.
  • During maintenance treatment, corticosteroids may be gradually reduced in accordance with clinical practice recommendations .
  • Some patients in whom a decreased response to treatment with Imraldi 40 mg every two weeks is observed may benefit from an increase in the dose to Imraldi 40 mg every week or 80 mg every other week.
  • The available data suggest that the clinical response is usually achieved within 2 to 8 weeks of treatment. Treatment with Imraldi should not be continued in patients who have not responded within this time frame .

Uveitis

  • In adult patients with uveitis, the recommended dose of Imraldi is an initial dose of 80 mg followed by a dose of 40 mg every two weeks starting one week after the administration of the first dose. There
    is limited experience with initiating treatment with Imraldi as monotherapy. Treatment with Imraldi can be started in combination with corticosteroid therapy and / or with other non-biological immunomodulatory treatments.
  • The combined corticosteroid dose may be gradually reduced in accordance with clinical practice, starting two weeks after initiation of treatment with Imraldi.
  • An annual reassessment of the benefits and risks associated with long-term continuous therapy is recommended .

Special populations

Older subjects

  • No dosage adjustment is necessary.

Renal and / or hepatic impairment

  • Adalimumab has not been studied in these patient populations. It is not possible to recommend dosages.

Pediatric population

Juvenile idiopathic arthritis

Polyarticular juvenile idiopathic arthritis from 2 years old

  • The recommended dose of Imraldi for patients with polyarticular juvenile idiopathic arthritis from the age of 2 years depends on body weight (Table 1). Imraldi is given every two weeks as a subcutaneous injection.

Table 1. Dosage of Imraldi in patients with polyarticular juvenile idiopathic arthritis

Patient weight Dosing regimen

  • 10 kg to <30 kg 20 mg every 2 weeks
  • ≥ 30 kg 40 mg every 2 weeks

The clinical response is usually achieved within 12 weeks of treatment. Continuation of treatment should be carefully reconsidered in a patient who has not responded within this time frame.

There is no relevant use of adalimumab in patients under 2 years of age in this indication.

Enthesitis-related arthritis

  • The recommended dose of Imraldi for patients with enthesitis-related arthritis from the age of 6 years depends on body weight (Table 2). Imraldi is administered every two weeks as a subcutaneous injection.

Table 2. Dosage of Imraldi in patients with enthesitis-related arthritis

Patient weight Dosing regimen

  • 15 kg to <30 kg 20 mg every 2 weeks
  • ≥ 30 kg 40 mg every 2 weeks
  • Adalimumab has not been studied in patients less than 6 years of age with arthritis related to enthesitis.

Plaque psoriasis in children and adolescents

  • The recommended dose of Imraldi for patients with plaque psoriasis aged 4 to 17 years depends on body weight (Table 3). Imraldi is administered as a subcutaneous injection.

Table 3. Dosage of Imraldi in Children and Adolescents with Plaque Psoriasis Patient Weight Dosing Regimen

  • 15 kg to <30 kg Initial dose of 20 mg then 20 mg every two weeks starting one week after the initial dose.
  • ≥ 30 kg Initial dose of 40 mg then 40 mg every two weeks starting one week after administration of the initial dose.

The continuing treatment beyond 16 weeks should be carefully reconsidered in a patient not responding within this time.

If retreatment with Imraldi is indicated, the above recommendations for dosage and duration of treatment should be followed.

The safety of adalimumab in children and adolescents with plaque psoriasis has been evaluated over a mean duration of 13 months.

There is no relevant use of adalimumab in children aged less than 4 years in this indication.

Adolescent hidradenitis suppurativa (from 12 years of age, weighing at least 30 kg)

  • There is no clinical trial conducted with adalimumab in adolescents with HS. The dosage of adalimumab in these patients was determined from pharmacokinetic modeling and simulation .
  • The recommended dose of Imraldi is 80 mg at week 0 followed by 40 mg every two weeks from week 1 by subcutaneous injectio.
  • In adolescents with an insufficient response to Imraldi 40 mg every two weeks, an increase in dosage to 40 mg every week or 80 mg both may be considered.
  • If necessary, antibiotics can be continued during treatment with Imraldi. During treatment with Imraldi, the patient is recommended to cleanse their lesions daily with a topical antiseptic.
  • The continuing treatment beyond 12 weeks should be carefully reconsidered in patients showing no improvement during this period.
  • If treatment is interrupted, Imraldi could be reintroduced if necessary.
  • The benefit and risk of continued long-term treatment should be assessed regularly (see data in adults under Pharmacodynamic properties).
  • There is no relevant use of adalimumab in children aged less than 12 years in this indication.

Crohn’s disease in children and adolescents

  • The recommended dose of Imraldi for patients with Crohn’s disease aged 6 to 17 years depends on body weight (Table 4). Imraldi is administered as a subcutaneous injection.

Table 4. Dosage of Imraldi in children and adolescents with Crohn’s disease

Patient weight Induction dose Maintenance dose from week 4
<40 kg If a faster response to treatment is required, bearing
in mind that the risk of adverse events associated with a
higher induction dose may be greater, the following dosage
may be used:
20 mg every 2 weeks
≥ 40 kg If a faster response to treatment is required, bearing
in mind that the risk of adverse events associated with a
higher induction dose may be greater, the following dosage
may be used:
40 mg every 2 weeks
  • 40 mg in week 0 and 20 mg in week 2
  • 80 mg in week 0 and 40 mg in week 2
  • 80 mg in week 0 and 40 mg in week 2
  • 160 mg in week 0 and 80 mg in week 2

Patients in whom an insufficient response to treatment is observed may benefit from an increase in the dosage:

  • <40 kg: 20 mg every week
  • ≥ 40 kg: 40 mg every week or 80 mg every two weeks

Continuation of treatment should be carefully reconsidered in a patient who has not responded by week 12.

There is no relevant use of adalimumab in children aged less than 6 years in this indication.

Pediatric ulcerative colitis

  • The safety and efficacy of adalimumab in children 4 to 17 years old have not yet been established. No data is available. There is no relevant use of Imraldi in children aged less than 4 years in this indication.

Psoriatic arthritis and axial spondyloarthritis including ankylosing spondylitis

  • There is no relevant use of adalimumab in the population pediatric indications in ankylosing spondylitis and psoriatic arthritis.

Pediatric uveitis

  • The recommended dose of Imraldi for children and adolescents with uveitis from the age of 2 years depends on body weight (Table 5). Imraldi is administered as a subcutaneous injection.
  • In uveitis in children and adolescents, no clinical trials have been conducted with adalimumab without concomitant treatment with methotrexate.

Table 5. Dosage of Imraldi in Children and Adolescents with Uveitis Patient Weight Dosing Regimen

  • <30 kg 20 mg every two weeks in combination with methotrexate
  • ≥ 30 kg 40 mg every two weeks in combination with methotrexate

When initiating treatment with Imraldi, a loading dose of 40 mg for patients <30 kg or 80 mg for patients ≥ 30 kg may be administered one week before the start of maintenance therapy . No clinical data are available from the use of a loading dose of adalimumab in children less than 6 years of age.

There is no relevant use of adalimumab in children under 2 years of age in this indication.

An annual reassessment of the benefits and risks associated with long-term continuous therapy is recommended .

Administration mode

  • Imraldi is administered as a subcutaneous injection. Full instructions for use are provided in the package leaflet.
  • A 40 mg pre-filled syringe and pre-filled pen are also available for patients to administer a full 40 mg dose .

IMRALDI Contraindications

  • Hypersensitivity to the active substance or to any of the excipients listed in the Composition section.
  • Active tuberculosis or other severe infections such as sepsis and opportunistic infections .
  • Moderate to severe heart failure (NYHA classes III / IV) .

What are the side effects of Imraldi?

Summary of the safety profile

  • Adalimumab
    has been studied in 9,506 patients in pivotal,
    open- label, controlled trials of 60 months and longer duration. These trials included
    patients with recent or old rheumatoid arthritis,
    juvenile idiopathic arthritis (
    polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis) or patients
    with axial spondyloarthritis (ankylosing spondylitis and
    axial spondyloarthritis without radiographic evidence of AS ),
    psoriatic arthritis, Crohn’s disease, ulcerative
    colitis, psoriasis, hidradenitis suppurativa and uveitis. The
    pivotal controlled studies involved 6,089 patients who received
    adalimumab and 3,801 patients who received placebo or an
    active comparator during the controlled phase.
  • The
    percentage of patients who discontinued treatment due
    to adverse reactions during the double-blind, controlled phase
    of the pivotal studies was 5.9% in patients treated with
    adalimumab and 5.4% in patients of the control group.
  • The
    most frequently reported side effects are infections
    (such as nasopharyngitis, upper
    respiratory tract infections and sinusitis),
    injection site reactions (erythema, itching, bleeding, pain or
    swelling), headache and musculoskeletal pain.
  • Some
    serious side effects have been reported with adalimumab. The
    TNF antagonists, such as adalimumab affect the system
    immune and their use may affect the
    body’s defenses against infection and cancer.
  • Life-
    threatening and fatal
    infections (including sepsis, opportunistic infections and tuberculosis),
    hepatitis B reactivations and various cancers (including leukemia, lymphoma and
    hepatosplenic T-cell lymphoma) have also been reported
    with use of adalimumab.
  • Severe
    haematological, neurological and autoimmune effects have been
    reported. This includes rare cases of pancytopenia,
    bone marrow anemia , cases of central and peripheral demyelination, and
    cases of lupus, lupus-related events, and
    Stevens-Johnson syndrome .

Pediatric population

  • In
    general, the frequency and type of adverse events seen
    in children and adolescents were comparable to those seen in
    adult patients.

List of side effects

The
list of undesirable effects is based on clinical studies and
post-marketing experience and is presented by
system organ and frequency in Table 6 below: very
common (  1/10); common (  1/100, <1/10); uncommon (  1 / 1,000, <1/100); rare ( 
1 / 10,000, <1 / 1,000) and not known (cannot be estimated
from the available data). Within each frequency
grouping, undesirable effects are presented in order of decreasing
seriousness. The highest frequency observed in the various
indications was included. The presence of an asterisk (*) in the
“System organ class” column indicates that more
information is available under the sections Contraindications, Warnings and precautions for use and Undesirable effects.

Table 6 Adverse reactions

System organ class Frequency Side effects
Infections and infestations * Very common Infections
of the respiratory tract (including respiratory infection
bass and upper respiratory tract infection, pneumonia,
sinusitis, pharyngitis, nasopharyngitis and pneumonia herpes).
Frequent Systemic infections (including sepsis, candidiasis and influenza).
Intestinal infections (including viral gastroenteritis). Skin and
soft tissue infections (including superficial periungual whitlow, cellulitis,
impetigo, necrotizing fasciitis and shingles). Ear infections.
Oral infections (including herpes, oral herpes and
dental infections ). Infections of the reproductive organs (including
vulvovaginal yeast infection ).
Urinary tract infections (including pyelonephritis).
Fungal infections.
Joint infections.
Rare Neurological infections (including viral meningitis). Opportunistic infections and
tuberculosis (including coccidioidomycosis, histoplasmosis and
Mycobacterium avium complex infections ). Bacterial infections.
Eye infections . Diverticulitis1).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) * Frequent Skin cancer excluding melanoma (including basal cell carcinoma and squamous cell carcinoma).
System organ class Frequency Side effects
Benign tumor.
Rare Lymphoma **. Tumors of solid organs (including breast, lung and thyroid cancer). Melanoma**.
Rare Leukemia1)
Frequency not known T1 lymphocyte hepatosplenic lymphoma). Merkel cell carcinoma (cutaneous neuroendocrine carcinoma) 1)
Blood and lymphatic system disorders * Very common Leukopenia (including neutropenia and agranulocytosis). Anemia.
Frequent Leukocytosis. Thrombocytopenia.
Rare Idiopathic thrombocytopenic purpura.
Rare Pancytopenia.
Immune system disorders * Frequent Hypersensitivity. Allergies (including seasonal allergy).
Rare Sarcoidosis1). Vasculitis.
Rare Anaphylaxis1).
Metabolism and nutrition disorders Very common Increased lipid level.
Frequent Hypokalaemia.
Increased uric acid. Abnormal sodium level in the blood.
Hypocalcemia. Hyperglycemia. Hypophosphatemia. Dehydration.
Psychiatric disorders Frequent Mood disorders (including depression). Anxiety. Insomnia.
Nervous system disorders * Very common Headache.
Frequent Paresthesia (including hypoaesthesia). Migraine. Compression of nerve roots.
Rare Stroke1). Tremors. Neuropathy.
Rare Multiple sclerosis. Demyelinating disorders (eg optic neuritis, Guillain-Barré syndrome) 1).
Eye disorders Frequent Visual disturbances. Conjunctivitis. Blepharitis. Swelling of the eyes.
Rare Diplopia.
Ear and labyrinth disorders Frequent Dizziness.
Rare Deafness. Tinnitus.
Cardiac disorders * Frequent Tachycardia.
Rare Myocardial infarction1). Arrhythmias.
System organ class Frequency Side effects
Congestive heart failure.
Rare Cardiac arrest.
Vascular disorders Frequent Hypertension. Hot flashes. Hematomas.
Rare Aortic aneurysm. Vascular occlusion. Thrombophlebitis.
Respiratory, thoracic and mediastinal disorders * Frequent Asthma. Dyspnea. Cough.
Rare Pulmonary embolism1) Interstitial lung disease. Chronic obstructive pulmonary disease. Pneumopathy. Pleural effusion1).
Rare Pulmonary fibrosis1) .
Gastrointestinal disorders Very common Abdominal pain. Nausea and vomiting.
Frequent Gastrointestinal bleeding. Dyspepsia. Gastroesophageal reflux. Gougerot-Sjögren syndrome.
Rare Pancreatitis. Dysphagia. Facial edema.
Rare Intestinal perforation1).
Hepatobiliary disorders * Very common Elevation of liver enzymes.
Rare Cholecystitis and gallstones. Fatty liver. Hyperbilirubinemia.
Rare Hepatitis. Reactivation of hepatitis B1). Autoimmune hepatitis1).
Frequency not known Hepatic failure1)
Skin and subcutaneous tissue disorders Very common Rash (including exfoliative rash).
Frequent Worsening
or onset of psoriasis (including
palmoplantar pustular psoriasis ) 1). Urticaria. Bruises (including purpura). Dermatitis
(including eczema). Onychoclasia. Hyperhidrosis. Alopecia 1). Pruritus.
Rare Night sweats. Scar.
Rare Erythema multiforme1). Stevens-Johnson syndrome1). Angioedema1) Cutaneous vasculitis1)
System organ class Frequency Side effects
Skin lichenoid reaction 1).
Frequency not known Worsening of symptoms of dermatomyositis1)
Musculoskeletal and connective tissue disorders Very common Musculoskeletal pain.
Frequent Muscle spasms (including increased serum creatine phosphokinase).
Rare Rhabdomyolysis. Systemic lupus erythematosus.
Rare Lupus-like syndrome1).
Kidney and urinary tract disorders Frequent Renal failure. Haematuria.
Rare Nocturia.
Reproductive system and breast disorders Rare Erectile function disorders.
General disorders and administration site conditions * Very common Reaction at the injection site (including erythema at the injection site).
Frequent Chest pain. Edema. Fever1).
Rare Inflammation.
Investigations * Frequent Disorders
of coagulation and bleeding disorders (including a lengthening of
activated partial thromboplastin time). Positivity to autoantibodies (including
anti-double-stranded DNA antibodies). Increase in blood
lactate dehydrogenase level.
Injury, poisoning and procedural complications Frequent Poor healing.

* Further information is available under the sections Contraindications, Warnings and precautions for use and Adverse reactions.

** including open label extension studies.

1) including data from spontaneous notifications

Hidradenitis suppurativa (HS)

  • The
    safety profile in patients with HS treated with
    weekly adalimumab is consistent with the
    known safety profile of adalimumab.

Uveitis

  • The
    safety profile in patients with uveitis treated with
    adalimumab every two weeks is consistent with the
    known safety profile of adalimumab.

Description of selected adverse reactions

Injection site reactions

In
pivotal controlled trials in adults and children, 12.9% of
patients treated with adalimumab experienced
injection site reactions (erythema and / or pruritus, bleeding, pain or swelling)
versus 7 , 2% of patients receiving placebo or active comparator.
Injection site reactions generally did not require
stopping the drug.

Infections

  • In
    the pivotal controlled trials in adults and children, the
    frequency of infections was 1.51 per patient-year in the
    adalimumab group and 1.46 per patient-year in the placebo group and the
    control group. . The infections mainly consisted of
    nasopharyngitis, upper respiratory tract infections and
    sinusitis. Most patients continued with adalimumab after
    the infection cleared.
  • The incidence
    of serious infections was 0.04 per patient-year in the
    adalimumab group and 0.03 per patient-year in the placebo group and the
    control group.
  • In
    controlled and open-label studies with adalimumab in
    adults and in the pediatric population, serious infections (
    including fatal infections, which have rarely occurred)
    have been reported including reports of tuberculosis. (including
    miliary and extrapulmonary localizations) and
    invasive opportunistic infections (eg disseminated
    histoplasmosis or extrapulmonary histoplasmosis, blastomycosis, coccidioidomycosis,
    pneumocystosis, candidiasis, aspergillosis and listeriosis). Most
    cases of tuberculosis have occurred within the first eight months after
    starting treatment and may reflect reactivation of
    latent disease.

Malignant tumors and lymphoproliferative disorders

  • No
    cases of cancer were observed in 249 pediatric patients
    representing an exposure of 655.6 patient-years in studies of
    adalimumab in patients with juvenile
    idiopathic arthritis (polyarticular juvenile idiopathic
    arthritis and arthritis related to enthesitis). In addition, no cases of cancer were
    observed in 192 pediatric patients representing an exposure of
    498.1 patient years in studies with adalimumab in
    pediatric Crohn’s disease. No cases of cancer were observed in 77
    pediatric patients corresponding to an exposure of 80
    patient-years in a study with adalimumab in psoriasis in
    chronic pediatric plaques. No cases of cancer were observed in
    60 pediatric patients representing an exposure of 58.4
    patient-years in a study with adalimumab in
    pediatric uveitis .
  • During
    the controlled periods of pivotal adult clinical trials with
    adalimumab lasting at least 12 weeks in patients
    with moderately to severely active rheumatoid arthritis,
    ankylosing spondylitis, axial spondyloarthritis without
    radiographic evidence of AS , psoriatic arthritis, psoriasis,
    Crohn’s disease, ulcerative colitis and uveitis, a rate
    (95% confidence interval) of cancers other than lymphoma or
    non-melanoma skin cancer, of 6.8 ( 4.4 – 10.5) per 1,000
    patient-years among the 5,291 patients treated with adalimumab, was
    observed versus a rate of 6.3 (3.4 – 11.8) per 1,000
    patient-years among the 3,444 patients in the control group (the
    mean duration of treatment was 4.0 months for patients treated with
    adalimumab and 3.8 months for patients in the control group). The
    rate (95% confidence interval) of
    non-melanoma skin cancer was 8.8 (6.0 – 13.0) per 1000 patient-years for
    patients treated with adalimumab and 3. 2 (1.3 – 7.6) per 1000
    patient years among patients in the control group. In these
    skin cancers , squamous cell carcinomas occurred at rates
    of 2.7 (1.4 – 5.4) per 1,000 patient years in patients treated
    with adalimumab and 0.6 (0 , 1 – 4.5) per 1,000 patient years in
    patients in the control group (95% confidence interval). The rate
    (95% confidence interval) of lymphoma was 0.7 (0.2 – 2.7)
    per 1000 patient years in patients treated with adalimumab and
    0.6 (0.1 – 4, 5) per 1000 patient-years in patients in the control group.
  • By
    combining controlled portions of these tests and the tests
    Expansion open ended or current with a mean duration
    of around 3.3 years including 6427 patients and more than 26,439 patient-
    years of treatment, the observed rate of cancers, other than lymphomas
    and non-melanoma skin cancers is approximately 8.5 per 1,000
    patient-years. The observed rate of non-melanoma skin cancer
    is approximately 9.6 per 1,000 patient-years and the
    observed rate of lymphoma is approximately 1.3 per 1,000 patient-years.
  • In
    post-marketing from January 2003 to December 2010, primarily in
    patients with rheumatoid arthritis, the reported rate of
    cancer is approximately 2.7 per 1,000 patient-years of
    treatment. The rates reported for
    non-melanoma skin cancer and lymphoma are approximately 0.2 and 0.3
    per 1000 patient-years of treatment, respectively (see section 4.4).
  • In
    post-marketing surveillance, rare cases of
    hepatosplenic T-cell lymphoma have been reported in patients
    treated with adalimumab.

Autoantibodies

  • Repeated
    autoantibody tests were performed on
    serum samples from patients in the IV trials in rheumatoid
    arthritis. In these trials,
    initially negative antinuclear antibody titers were positive at week 24 in 11.9% of
    patients treated with adalimumab and 8.1% of patients on placebo and
    comparator. Two of the 3441 patients treated with adalimumab in
    all rheumatoid arthritis and
    psoriatic arthritis studies presented clinical signs suggestive of a
    new onset lupus-like syndrome . The condition of the patients
    improved after stopping treatment. No patient presented
    lupus nephritis or central nervous symptoms.

Hepato-biliary events

  • In
    phase III controlled clinical trials of adalimumab in
    rheumatoid arthritis and psoriatic arthritis with a
    control period of 4 to 104 weeks, elevations of ALT ≥ 3 × N occurred in 3.7% of patients treated. with adalimumab and in 1.6% of patients in the control group.
  • In
    phase III controlled clinical trials of adalimumab in
    patients with polyarticular juvenile idiopathic arthritis aged
    4 to 17 years and patients with enthesitis-related arthritis
    aged 6 to 17 years, elevations of ALT ≥ 3 × N occurred in
    6.1% of patients treated with adalimumab and in 1.3% of patients
    in the control group. Most of the elevations in ALT have occurred
    with concomitant use of methotrexate. No
    elevation of ALT ≥ 3 × N occurred in the phase
    III trial of adalimumab in patients with
    polyarticular juvenile idiopathic arthritis aged 2 to <4 years.
  • In
    phase III controlled clinical trials of adalimumab in
    patients with Crohn’s disease and ulcerative colitis
    with a control period of 4 to 52 weeks, ALT elevations
    ≥ 3 × N occurred in 0.9 % of patients treated with adalimumab and in 0.9% of patients in the control group.
  • In
    the phase III clinical trial of adalimumab in children and
    adolescents with Crohn’s disease which evaluated the efficacy
    and safety profile of two
    weight-based maintenance regimens following treatment with weight-adjusted induction
    up to 52 weeks of treatment, elevations of ALT ≥ 3 × N
    occurred in 2.6% of patients (5/192), of whom 4
    were treated in combination with immunosuppressants at the start of
    the treatment. ‘study.
  • In
    phase III controlled clinical trials of adalimumab in
    plaque psoriasis with a control period of 12 to 24 weeks,
    elevations of ALT ≥ 3 × N occurred in 1.8% of patients
    treated with adalimumab and in 1.8% of patients in the control group.
  • Elevations of ALT ≥ 3 × N were not observed in the phase III study of adalimumab in pediatric patients with plaque psoriasis .
  • In
    controlled clinical trials of adalimumab (starting doses of 160
    mg at week 0 and 80 mg at week 2 followed by 40 mg each
    week from week 4), in patients with
    HS with severe 12-16
    week control period , elevations of ALT ≥ 3 × N occurred in 0.3% of patients treated with adalimumab and 0.6% of patients in the control group.
  • In
    controlled clinical trials of adalimumab (starting dose 80 mg
    at week 0 followed by 40 mg every two weeks from
    week 1) in adult patients with uveitis for
    up to 80 mg weeks, with a median duration of exposure of
    166.5 days and 105.0 days respectively for patients treated with
    adalimumab and patients in the control group, elevations of ALT
    ≥ 3 × N occurred in 2.4 % of patients treated with adalimumab
    and 2.4% of patients in the control group.
  • In
    clinical trials across all indications, patients with
    elevated ALT were asymptomatic and in most cases the
    elevations were transient and reversible upon continued
    treatment. However, during post-marketing surveillance,
    hepatic insufficiency as well as less
    severe hepatic disorders , which may precede hepatic insufficiency, such as
    hepatitis including autoimmune hepatitis, have been reported in
    patients receiving Hepatitis. ‘adalimumab.

Concomitant administration of azathioprine / 6-mercaptopurine

  • In
    studies in Crohn’s disease in adults, a
    higher incidence of tumors and serious infections was observed with
    the combination of adalimumab and azathioprine / 6-mercaptopurine
    compared to adalimumab used alone.

IMRALDI Interactions

  • Adalimumab has been studied in patients with rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, and psoriatic arthritis taking adalimumab as monotherapy and in those taking methotrexate concomitantly. Antibody formation was lower when adalimumab was co-administered with methotrexate compared to its use as monotherapy. Administration of adalimumab without methotrexate resulted in increased antibody formation, increased clearance and reduced efficacy of adalimumab.
  • The combination of Imraldi and anakinra is not recommended (see section Warnings and precautions for use “Simultaneous administration of biological DMARDs and anti-TNF drugs”).
  • The combination of Imraldi and abatacept is not recommended (see section Warnings and precautions for use “Simultaneous administration of biological DMARDs and anti-TNF drugs”).
  • In the absence of a compatibility study, this medicinal product must not be mixed with other medicinal products.

Drive and use machines

Warnings and Precautions

Traceability

  • In order
    to improve the traceability of biological medicinal products, the name and
    batch number of the administered product should be clearly recorded.

Infections

  • The
    patients receiving TNF-antagonists are more susceptible to
    serious infections. Impaired lung function can increase the
    risk of developing infections. Patients should therefore be
    closely monitored for infections (including
    tuberculosis) before, during and after treatment with Imraldi. As the
    duration of elimination of adalimumab may be up to four months,
    monitoring should be continued throughout this period.
  • The
    treatment Imraldi should not be initiated in patients with
    active infections, including chronic infections or
    localized, are not controlled. In patients who have been exposed
    to tuberculosis or who have traveled to areas at high risk for
    tuberculosis or endemic mycoses, for example histoplasmosis,
    coccidioidomycosis or blastomycosis, the risks and benefits of
    treatment with Imraldi should be considered before
    initiation. treatment (see Opportunistic infections).
  • The
    Patients who develop a new infection during
    treatment with Imraldi must be monitored
    carefully and complete diagnostic workup should be practiced. If
    a serious new infection or sepsis
    develops , the administration of Imraldi should be discontinued and
    appropriate antimicrobial or antifungal therapy should be started until
    the infection is controlled. The physician should exercise
    caution before using Imraldi in patients with a
    history of recurrent infection or with
    underlying conditions that may predispose them to infections, including
    concomitant treatment with immunosuppressive drugs.

Serious infections

  • Of
    serious infections, including sepsis due to infections
    bacterial, mycobacterial, invasive fungal, parasitic,
    viral, or other opportunistic infections such as listeriosis,
    legionellosis and pneumocystis have been reported in patients
    treated with adalimumab.
  • The
    other serious infections seen in clinical trials include
    pneumonia, pyelonephritis, septic arthritis and septicemia. There have been reports of infections requiring hospitalization or with fatal outcome.

Tuberculosis

  • Of
    TB cases, including cases of TB reactivation
    and primary infection tuberculosis have been reported for patients
    receiving adalimumab. Cases of pulmonary and
    extra-pulmonary (i.e. disseminated) tuberculosis have been reported.
  • Before
    starting treatment with Imraldi, all patients should
    be tested for active or non-active (“
    latent”) tuberculosis infection . This assessment should include a detailed medical evaluation
    in patients with a history of tuberculosis or
    possible previous exposure to patients with active tuberculosis and / or
    current or past immunosuppressive therapy. Appropriate
    screening tests (eg tuberculin skin test and
    chest x-ray) should be performed in all patients
    (according to local recommendations). It is advisable to note
    the performance and the results of these tests in the
    patient monitoring. Prescribers are reminded that
    the tuberculin skin test can give false negatives, especially in
    seriously ill or immunosuppressed patients.
  • If active tuberculosis is diagnosed, treatment with Imraldi should not be initiated (see section 4.3).
  • In
    all of the situations described below,
    the benefit / risk ratio of the treatment should be assessed very carefully.
  • In
    case of suspicion of latent tuberculosis, consulting a
    specialist, qualified in the treatment of tuberculosis
    should be considered.
  • In
    case of diagnosis of latent tuberculosis, prophylactic
    tuberculosis appropriate and in accordance with local recommendations
    must be implemented before the start of treatment with Imraldi.
  • A
    TB prophylaxis should also be considered before
    introducing Imraldi in patients with risk factors
    or multiple TB significant despite testing
    of negative tuberculosis and in patients with a history of
    latent or active tuberculosis in that the administration of an
    appropriate anti-tuberculosis treatment cannot be confirmed.
  • The
    case of reactivation of tuberculosis despite treatment
    prophylactic occurred in patients treated with
    adalimumab. Some patients who had been successfully treated
    for active tuberculosis developed the disease again during
    treatment with adalimumab.
  • The
    patients should be advised that they will need their doctor
    in case of occurrence of symptoms suggestive signs or infection
    tuberculosis (eg persistent cough, wasting / loss of
    weight, low grade fever, listlessness), during or after treatment Imraldi.

Other opportunistic infections

  • Of
    opportunistic infections, including invasive fungal infections,
    have been observed in patients treated with adalimumab. These
    infections were not always detected in patients receiving
    TNF antagonists, resulting in delayed initiation of
    appropriate therapy, sometimes with fatal outcome.
  • In
    patients who present with signs and symptoms such as fever,
    malaise, weight loss, sweating, cough, dyspnea and / or
    pulmonary infiltrates or other serious systemic disease with or without
    concomitant shock , an invasive fungal infection should be suspected; in
    this case, the administration of Imraldi should be stopped immediately.
    Diagnosis and initiation of
    empiric antifungal therapy in these patients should be made in consultation with a
    physician experienced in the management of patients with
    invasive fungal infections.

Reactivation of hepatitis B

  • A
    reactivation of hepatitis B occurred in patients who received
    a TNF antagonist including adalimumab and who were carriers
    chronic of this virus (that is to say surface antigen positive – Ag
    positive HBs) . Some cases have had a fatal outcome. Patients
    should be screened for HBV infection before
    initiating treatment with Imraldi. For patients who
    test positive for hepatitis B, it is
    recommended to consult a doctor specializing in the treatment of
    hepatitis B.
  • In
    carriers of HBV who require treatment with Imraldi,
    careful monitoring of signs and symptoms of active
    HBV infection should be observed throughout treatment and for several months after
    discontinuation. There are insufficient data available regarding
    the treatment of patients with HBV treated with antiviral drugs to
    prevent HBV reactivation and treated with a TNF antagonist.
    In patients who develop HBV reactivation, Imraldi should
    be discontinued and effective antiviral therapy as well as
    appropriate complementary therapy initiated.

Neurological events

  • The
    TNF blockers, including adalimumab, have been associated in rare
    circumstances the onset or exacerbation of symptoms
    clinical and / or radiographic evidence of demyelinating disease of the
    central nervous system including multiple sclerosis,
    Optic neuritis and peripheral demyelinating disease, including
    Guillain-Barré syndrome. Prescribers are advised with caution before
    treating with Imraldi patients with
    pre-existing
    or recently-occurring central or peripheral nervous system demyelinating disease ; Stopping treatment with Imraldi should be
    considered if any of these conditions develop .
  • The association
    between intermediate uveitis and demyelinating diseases of the
    central nervous system is known. Neurologic assessment should be
    performed in patients with non-
    infectious intermediate uveitis before initiating treatment with Imraldi, and repeated
    regularly during treatment to check for any pre-existing or progressive central nervous system demyelinating disease.

Allergic reactions

  • In
    clinical trials, serious allergic reactions associated
    with adalimumab were rarely reported and
    non-serious allergic reactions associated with adalimumab were uncommon. Cases of
    severe allergic reactions, including anaphylactic reactions
    have been reported after administration of adalimumab. If
    an anaphylactic reaction or other
    serious allergic reaction occurs, the administration of Imraldi should be
    stopped immediately and appropriate treatment initiated.

Immunosuppression

  • In
    a study of 64 patients with rheumatoid
    arthritis treated with adalimumab, there was no evidence
    of delayed-type hypersensitivity depression,
    decreased immunoglobulin levels. or a change in the
    count of effector T and B lymphocytes, NK lymphocytes,
    monocytes / macrophages and neutrophilic granulocytes.

Malignant tumors and lymphoproliferative disorders

  • In
    the controlled part of clinical trials with anti-TNFs,
    more cases of cancer including lymphomas were observed in
    patients treated with an anti-TNF than in patients in the
    control group . However, the incidence has been rare. During
    post-marketing surveillance, cases of leukemia have been reported in
    patients treated with anti-TNF. In addition, there is a background of
    increased risk of lymphoma and leukemia in patients with
    old, inflammatory and highly
    active rheumatoid arthritis , which complicates the estimation of risk. In the current state of
    knowledge, the possibility of a risk of developing lymphomas,
    leukemia or other malignant diseases in patients treated
    with anti-TNF cannot be excluded.
  • Of
    malignancies, some fatal, have been reported
    postmarketing in children, adolescents and
    young adults (up to age 22 years) treated with TNF antagonists
    (initiation of therapy before age 18), including
    adalimumab. About half of these cases were lymphomas. The
    other cases corresponded to other types of malignant tumors among
    which rare cancers generally associated with a context
    of immunosuppression. The risk of developing malignant tumors can
    not be excluded in children and adolescents treated with anti-TNF.
  • In the
    course of the post-marketing surveillance, rare cases of lymphoma
    hepatosplenic T-cell lymphoma have been identified in patients
    treated with adalimumab. This rare form of T-cell lymphoma
    has a very aggressive course and is often fatal. Some of these
    hepatosplenic T-cell lymphomas seen with adalimumab
    have occurred in young adults who were concomitantly treated
    with azathioprine or 6-mercaptopurine used in
    inflammatory bowel disease. The potential risk of combining
    azathioprine or 6 mercaptopurine with adalimumab should be
    carefully considered. A risk of developing
    hepatosplenic T-cell lymphoma in patients treated with
    Imraldi cannot be excluded .
  • There
    are no studies in patients with a history of
    malignancies or in whom treatment with adalimumab is continued
    after the development of cancer. Therefore, increased caution
    should be observed when considering treatment of these patients
    with adalimumab.
  • All
    patients, especially those with a history of
    intense immunosuppressive therapy or with psoriasis and with a
    history of puvatherapy, should be examined for
    skin cancer other than melanoma before and during treatment with
    Imraldi. Cases of melanoma and Merkel cell carcinoma have
    also been reported in patients treated with anti-TNF inhibitors
    including adalimumab.
  • In
    a prospective clinical study evaluating the use of another
    anti-TNF agent , infliximab, in patients with
    moderate to severe chronic obstructive pulmonary disease (COPD),
    more cancers, especially of the lung, were reported. head and neck,
    among patients treated with infliximab compared to patients
    in the control group. All patients had a history of
    heavy smoking. For this reason, care should be
    taken in the use of an anti-TNF in patients with
    COPD, and also in patients at risk for cancer due to
    heavy smoking.
  • Based
    on current data, it is not known whether treatment with
    adalimumab influences the risk of developing dysplasia or
    colon cancer. All patients with ulcerative colitis
    who are at high risk of dysplasia or colon cancer (for
    example, patients with old ulcerative colitis or
    primary sclerosing cholangitis) or who have a history of
    dysplasia or colon cancer should do
    regularly screened for dysplasia before treatment and
    throughout the course of their disease. This assessment should include
    colonoscopy and biopsies according to local recommendations.

Haematological reactions

  • From
    Rare reports of pancytopenia including aplastic anemia have been
    reported with TNF antagonists. Adverse blood system effects
    including medically significant cytopenias (eg
    , thrombocytopenia, leukopenia) have been observed with adalimumab. It
    should be recommended for all patients seek immediate
    medical advice if they have signs or symptoms suggestive of
    blood disorders (eg. Persistent fever, bruising,
    bleeding, pallor) while Imraldi. Discontinuation of treatment with Imraldi
    should be considered for patients in whom
    significant blood abnormalities are confirmed.

Vaccinations

  • Similar
    antibody responses to the
    standard 23-valence pneumococcal vaccine and to the trivalent influenza vaccine were
    observed in a study in 226 adults with rheumatoid
    arthritis treated with adalimumab or placebo. There are no
    data available on the secondary transmission of infection from
    live vaccines in patients receiving adalimumab.
  • In
    children and adolescents, it is recommended, if possible, that
    all vaccinations be up to date according to current
    vaccination recommendations before initiating treatment with
    adalimumab.
  • The
    adalimumab in patients may receive multiple vaccines
    simultaneously, except in respect of live vaccines.
    Administration of live vaccines (eg, BCG vaccine) to
    infants who have been exposed to adalimumab in utero is not
    recommended for 5 months after
    the mother’s last injection of adalimumab during pregnancy.

Congestive heart failure

  • In
    a clinical trial with another TNF antagonist,
    worsening congestive heart failure and
    increased mortality from congestive heart failure were observed . Of
    cases of congestive heart failure worsening were also
    reported in adalimumab patients. Imraldi should be used
    with caution in patients with
    mild heart failure (NYHA classes I / II). Imraldi is contraindicated in
    moderate to severe heart failure (see section 4.3).
    Treatment with Imraldi should be stopped in patients who experience
    new or worsening symptoms.
    congestive heart failure.

Autoimmune processes

  • The
    treatment Imraldi may cause antibody formation
    autoimmune. The impact of long-term treatment with adalimumab on
    the development of autoimmune diseases is unknown. If a patient
    develops lupus-like symptoms following
    treatment with Imraldi and exhibits a positive anti-
    double-stranded DNA reaction , treatment with Imraldi should not be continued.

Simultaneous administration of biological DMARDs or anti-TNF

  • Some
    serious infections were seen in clinical studies in
    the concurrent use of anakinra and another TNF antagonist,
    etanercept, with no added clinical benefit compared to
    etanercept alone. Due to the nature of the side effects
    seen with treatment with etanercept and anakinra,
    similar side effects may also result from the combination
    of anakinra and other TNF blockers. Therefore the combination
    of adalimumab and anakinra is not recommended (see section Interactions with other medicinal products and other forms of interactions).
  •  Concomitant administration of adalimumab with other biologic
    DMARDs (eg anakinra and abatacept) or with other TNF blockers is not
    recommended due to the possible increased risk
    of infections, including serious infections, and other
    potential pharmacological interactions (see section Interactions with other medicinal products and other forms of interactions).

Surgery

  • There is limited experience
    with safety during surgical procedures in
    patients treated with adalimumab. The long half-life of
    adalimumab should be taken into account if surgery
    is planned. A patient treated with Imraldi requiring
    surgery should be carefully monitored for
    infections and appropriate actions should be taken.
    There is limited experience with the safety of adalimumab in patients operated on for arthroplasty.

Hail Occlusion

  • In
    Crohn’s disease, treatment failure may indicate the presence of
    fixed fibrous strictures that may require surgical treatment.
    The available data suggest that adalimumab does not worsen or
    cause strictures.

Older subjects

  • The
    frequency of serious infections in subjects treated with
    adalimumab over 65 years of age (3.7%) is higher than in
    patients under 65 years of age (1.5%). Some cases have had a
    fatal outcome . Particular attention
    should be paid to the risk of infection when treating the elderly.

Pediatric population

  • See Vaccinations above.

Excipients with known effect

  • This medicine
    contains 20 mg sorbitol per pre-filled syringe / pre-filled pen. The
    patients with rare hereditary fructose intolerance
    should not take this medicine.
  • In
    addition, this medicine contains less than 1 mmol sodium (23 mg) per
    0.8 ml dose , which means that it is practically “sodium-free”.

PREGNANCY & BREAST-FEEDING & FERTILITY

Women of childbearing age

  • Women of childbearing potential should consider using an effective method of contraception during treatment with Imraldi and continue it for at least five months after the last administration of Imraldi.

Pregnancy

  • A large number (approximately 2,100) of pregnancies exposed to adalimumab for which data were collected prospectively, resulting in a live birth with a known term outcome, including more than 1,500 pregnancies exposed to adalimumab during the first trimester, does not reveal any increase in the rate of malformations in the newborn.
  • In a prospective cohort study, 257 women with rheumatoid arthritis (RA) or Crohn’s disease (CD) treated with adalimumab at least during the first trimester and 120 women with untreated RA or CD by adalimumab were included. The prevalence at birth of major congenital anomalies was the primary endpoint. The rate of pregnancies resulting in at least one living newborn with a major birth defect was 6/69 (8.7%) in women treated with adalimumab with RA and 5/74 (6.8 %) in untreated women with RA (unadjusted OR 1.31, 95% CI 0.38-4.52), and 16/152 (10.5%) in women treated with adalimumab with CD and 3/32 (9, 4%) in untreated women with CD (unadjusted OR 1.14, 95% CI 0.31-4.16). The adjusted OR (considering baseline differences) was 1.10 (95% CI 0.45-2.73) for RA and CD combined. No notable difference was reported between women treated with adalimumab and women not treated with adalimumab for secondary endpoints of spontaneous abortion, minor congenital anomalies, preterm delivery, height. at birth and serious or opportunistic infections, and stillbirth or malignancy. Interpretation of the data may be affected due to methodological limitations of the study, including the small sample size and the non-randomized study design. Adjusted OR (considering baseline differences) was 1.10 (95% CI 0.45-2.73) for RA and CD combined. No notable difference was reported between women treated with adalimumab and women not treated with adalimumab for secondary endpoints of spontaneous abortion, minor congenital anomalies, preterm delivery, height. at birth and serious or opportunistic infections, and stillbirth or malignancy. Interpretation of the data may be affected due to methodological limitations of the study, including the small sample size and the non-randomized study design. Adjusted OR (considering baseline differences) was 1.10 (95% CI 0.45-2.73) for RA and CD combined. No notable difference was reported between women treated with adalimumab and women not treated with adalimumab for secondary endpoints of spontaneous abortion, minor congenital anomalies, preterm delivery, height. at birth and serious or opportunistic infections, and stillbirth or malignancy. Interpretation of the data may be affected due to methodological limitations of the study, including the small sample size and the non-randomized study design. has been reported between women treated with adalimumab and women not treated with adalimumab for secondary endpoints of spontaneous abortion, minor congenital anomalies, preterm delivery, size at birth and severe or opportunistic infections, and stillbirth or malignancy. Interpretation of the data may be affected due to methodological limitations of the study, including the small sample size and the non-randomized study design. has been reported between women treated with adalimumab and women not treated with adalimumab for secondary endpoints of spontaneous abortion, minor congenital anomalies, preterm delivery, size at birth and severe or opportunistic infections, and stillbirth or malignancy. Interpretation of the data may be affected due to methodological limitations of the study, including the small sample size and the non-randomized study design. and stillbirth or malignancy. Interpretation of the data may be affected due to methodological limitations of the study, including the small sample size and the non-randomized study design. and stillbirth or malignancy. Interpretation of the data may be affected due to methodological limitations of the study, including the small sample size and the non-randomized study design.
  • In a developmental toxicity study performed in monkeys, there were no signs of possible maternal toxicity, embryotoxicity or teratogenic potential. There are no preclinical data on the postnatal toxicity of adalimumabsee Preclinical Safety ).
  • Due to its inhibitory effect on TNFα, adalimumab administered during pregnancy may affect the normal immune responses of the newborn. Adalimumab should be used during pregnancy only if needed.
  • In women treated with adalimumab during pregnancy, adalimumab can cross the placenta and pass into the blood of their child. As a result, these children may have an increased risk of infections. The administration of live vaccines (eg BCG vaccine) to children who have been exposed to adalimumab in utero is not recommended for 5 months after the mother’s last injection during pregnancy.

Feeding with milk

  • Limited data from the published literature indicate that adalimumab is excreted in human milk at very low concentrations, with adalimumab being present in human milk at concentrations equivalent to 0.1% – 1% of maternal serum levels. . When administered orally, immunoglobulin G proteins undergo intestinal proteolysis and exhibit low bioavailability. No effects on breastfed newborns / infants are expected. Therefore, adalimumab can be used during breast-feeding.

Fertility

  • Preclinical data on the effects of adalimumab on fertility are not available.

What happens if I overdose from IMRALDI?

What is  Forms and Composition ?

SHAPES and PRESENTATIONS
  • 40 mg solution for injection (SC) (clear, colorless): 0.8 ml single-dose pre-filled syringe, single use, with needle, rigid needle shield, rubber plunger (bromobutyl), plunger rod, syringe with safety guard and collar for patient use, packs of 1 and 2, with 2 alcohol swabs.
  • 0.8 ml single-dose pre-filled pen, single use, containing one pre-filled syringe, with needle, rigid needle shield and rubber plunger (bromobutyl), packs of 1 and 2, with 2 alcohol swabs.
COMPOSITION
  p ser or pen
Adalimumab * 40 mg
  • *  Adalimumab is a recombinant human monoclonal antibody produced in Chinese hamster ovary cells.
  • Excipients: sodium citrate, citric acid monohydrate, histidine, histidine hydrochloride monohydrate, sorbitol, polysorbate 20, water for injections.
  • Excipients with known effect: sorbitol (20.0 mg).

NOT’s

Edrug-online contains comprehensive and detailed information about drugs available in the medical field, and is divided into four sections:

general information:

  • Includes a general description of the drug, its use, brand names, FAQs, and relevant news and articles

Additional information:

  • General explanation about dealing with the medicine: how to take the medicine, the doses and times of it, the start and duration of its effectiveness, the recommended diet during the period of taking the medicine, the method of storage and storage, recommendations in cases for forgetting the dose and instructions to stop taking the drug and take additional doses.

Special warnings:

  • For pregnant and breastfeeding women, the elderly, boys and drivers, and use before surgery.

Side effects:

  • It treats possible side effects and drug interactions that require attention and its effect on continuous use.
  • The information contained in this medicine is based on medical literature, but it is not a substitute for consulting a doctor.
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HULIO 40 mg Injection Uses, Dosage, Side Effects, Precautions & Warnings https://edrug-online.com/1479/hulio-injection.html https://edrug-online.com/1479/hulio-injection.html#respond Fri, 28 Aug 2020 11:15:27 +0000 https://edrug-online.com/?p=1479 what is HULIO  medication used for and indicationAdalimumab]]> what is HULIO  medication used for and indication

Generic drug of the Therapeutic class: Immunology Medicines

Active ingredients: Adalimumab

what is HULIO  medication used for and indication?

Rheumatoid arthritis

Hulio in combination with methotrexate is indicated for:

  • the treatment of moderately to severely active rheumatoid arthritis in adults when the response to DMARDs, including methotrexate, is inadequate.
  • the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate.
  • Hulio can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is unsuitable.
  • Hulio has been shown to slow the progression of structural damage to joints measured by radiography and improve functional ability when given in combination with methotrexate.

Juvenile idiopathic arthritis

Polyarticular juvenile idiopathic arthritis

  • Hulio in combination with methotrexate is indicated for the treatment of progressive polyarticular juvenile idiopathic arthritis in patients from 2 years of age with insufficient response to one or more DMARDs.
  • Hulio can be administered as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is unsuitable (for efficacy in monotherapy, see section Pharmacodynamic properties). Adalimumab has not been studied in patients less than 2 years of age.

Enthesitis-related arthritis

  • Hulio is indicated for the treatment of active arthritis associated with enthesitis in patients from 6 years of age with insufficient response or intolerance to conventional therapy .

Axial spondylitis

Ankylosing spondylitis (AS)

  • Hulio is indicated for the treatment of severe and active ankylosing spondylitis in adults who have had an inadequate response to conventional therapy.

Axial spondyloarthritis without radiographic evidence of AS

  • Hulio is indicated for the treatment of severe axial spondyloarthritis without radiographic evidence of AS, but with objective evidence of inflammation on MRI and / or elevated CRP in adults who have had an inadequate response or intolerance to anti -nonsteroidal inflammatory drugs.

Psoriatic arthritis

  • Hulio is indicated for the treatment of active and progressive psoriatic arthritis in adults when the response to previous disease-modifying therapy (DMARD) has been inadequate. Hulio has been shown to slow the progression of peripheral joint structural damage as measured by radiography, in patients with symmetrical polyarticular forms of the disease (see section 5.1) and improve functional ability.

Psoriasis

  • Hulio is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who require systemic therapy.

Plaque psoriasis in children and adolescents

  • Hulio is indicated for the treatment of severe chronic plaque psoriasis in children from 4 years of age and adolescents with insufficient response to topical therapy and light therapy or when these treatments are inappropriate.

Hidradenitis suppurativa (HS)

  • Hulio is indicated for the treatment of active, moderate to severe hidradenitis suppurativa (Verneuil’s disease) in adults and adolescents from 12 years of age in case of insufficient response to conventional systemic treatment of hidradenitis suppurativa (see sections Pharmacodynamic properties and Pharmacokinetic properties).

Crohn’s disease

  • Hulio is indicated for the treatment of moderate to severe active Crohn’s disease in adult patients who have not responded despite appropriate and well-managed treatment with a corticosteroid and / or immunosuppressant; or in whom this treatment is contraindicated or poorly tolerated.

Crohn’s disease in children and adolescents

  • Hulio is indicated for the treatment of moderate to severe active Crohn’s disease in children and adolescents from 6 years of age who have failed to respond to conventional therapy including first-line nutritional therapy and a corticosteroid and / or an immunomodulator, or in which these treatments are poorly tolerated or contraindicated.

Ulcerative colitis

  • Hulio is indicated for the treatment of active, moderate to severe ulcerative colitis in adult patients who have had an inadequate response to conventional therapy, including corticosteroids and 6-mercaptopurine (6-MP) or azathioprine (AZA), or in whom this treatment is contraindicated or poorly tolerated.

Uveitis

  • Hulio is indicated for the treatment of non-infectious, intermediate, posterior uveitis and panuveitis in adult patients who have had an insufficient response to corticosteroid therapy, in patients requiring corticosteroid sparing, or in whom corticosteroid therapy is inappropriate.

Uveitis in children and adolescents

  • Hulio is indicated for the treatment of chronic non-infectious anterior uveitis in children and adolescents from 2 years of age with insufficient response or intolerance to conventional treatment or for whom conventional treatment is inappropriate.

HULIO  Dosage

Treatment with Hulio should
be started and supervised by a specialist physician qualified in
the diagnosis and treatment of conditions for which
Hulio is indicated.

It is recommended that ophthalmologists consult
an appropriate specialist before initiating treatment with Hulio.

A surveillance card will be given to patients treated with Hulio.

After proper training
in the injection technique, patients can self-inject Hulio,
if their doctor considers it possible, and provided
appropriate medical supervision.

During treatment with
Hulio, other concomitant treatments (such as corticosteroids
and / or immunomodulators) should be optimized.

Dosage

Rheumatoid arthritis

  • In adult patients
    with rheumatoid arthritis, the recommended dose of Hulio
    is a single dose of 40 mg adalimumab given every two
    weeks, subcutaneously. Administration of methotrexate should
    be continued during treatment with Hulio.
  • Glucocorticoids,
    salicylates, nonsteroidal anti-inflammatory drugs or pain
    relievers may be continued while taking Hulio. As
    regards the combination with other anti-rheumatic drugs
    other than methotrexate (see sections Warnings and precautions for use and Pharmacodynamic properties).
  • As monotherapy, some
    patients who experience a decrease in their response to Hulio
    40 mg every other week may benefit from an increase
    in the dosage to 40 mg adalimumab every week or 80 mg
    every other week. .
  • Available data suggest that clinical response is usually achieved within 12 weeks of treatment.
  • Continuation of treatment should be reconsidered in a patient who has not responded within these time limits.
  • Other presentations of Hulio may be available depending on the therapeutic needs of each patient.

Interruption of treatment

  • Treatment may need to be interrupted, for example before
    surgery or in case of severe infection.
  • The available data
    suggest that re-introduction of adalimumab after stopping 70
    days or more results in a clinical response of the same magnitude and a
    safety profile similar to that observed before stopping
    treatment.

Ankylosing spondylitis, axial spondylitis without radiographic evidence of AS, and psoriatic arthritis

  • The recommended dose
    of Hulio for patients with ankylosing spondylitis,
    axial spondylitis without radiographic evidence of AS, and for
    patients with psoriatic arthritis is 40 mg adalimumab
    as a single dose every two weeks, by subcutaneous injection. .
  • Available data suggest that clinical response is usually achieved within 12 weeks of treatment.
    Continuation of treatment should be reconsidered in a patient
    who has not responded within these time limits.

Psoriasis

  • The recommended dose
    of Hulio to start treatment in adults is 80 mg
    subcutaneously. The dosage will continue one week later with 40 mg
    subcutaneously every other week.
  • Continuation of treatment
    beyond 16 weeks should be carefully reconsidered in a
    patient who has not responded within this time.
  • Beyond 16 weeks, in
    case of insufficient response to Hulio 40 mg every other week,
    patients may benefit from an increase in dosage to 40 mg
    every week or 80 mg every other week. The benefits and
    risks of continuous treatment of 40 mg weekly or 80
    mg every other week should be carefully reconsidered
    in a patient with insufficient response after increasing
    the dosage.
  • In
    case of sufficient response obtained with 40 mg weekly or 80
    mg every two weeks, the dosage may then be reduced to
    40 mg every 2 weeks.
  • Other presentations of Hulio may be available depending on the therapeutic needs of each patient.

Hidradenitis suppurativa

  • The
    recommended dosage regimen of Hulio in adult patients with hidradenitis
    suppurativa (HS) is an initial dose of 160 mg on day 1 (given
    as 4 injections of 40 mg over one day or 2 injections of
    40 mg mg per day for two consecutive days), followed by an 80
    mg dose two weeks later, on day 15 (given as two
    40 mg injections over one day).
  • Two weeks later (Day 29),
    continue with a dose of 40 mg every week or 80 mg
    every two weeks (given as two
    40 mg injections per day).
  • If necessary, antibiotics can be
    continued during treatment with Hulio. During treatment with
    Hulio, it is recommended that the patient cleanse his
    lesions daily with a topical antiseptic.
  • Continuation of treatment
    beyond 12 weeks should be carefully reconsidered in
    patients who do not show improvement during this period.
  • If treatment is
    interrupted, Hulio 40 mg every week or 80 mg every other
    week may be reintroduced .
  • The benefit and risk of continued long-term treatment should be assessed regularly.
  • Other presentations of Hulio may be available depending on the therapeutic needs of each patient.

Crohn’s disease

  • In adult patients
    with moderate to severe active Crohn’s disease, the
    recommended induction regimen of Hulio is 80 mg at week 0,
    followed by 40 mg at week 2.
  • If needed. get a
    faster response to treatment, schedule 160 mg at week 0
    (given as 4 injections of 40 mg per day or 2
    injections per day for two consecutive days), 80 mg at week
    2 (given as of two injections of 40 mg per day), can
    be used knowing that the risk of adverse events is then
    higher during this induction phase.
  • After
    induction therapy , the recommended dose is 40 mg administered every
    two weeks by subcutaneous injection. If a patient has stopped
    treatment with Hulio, and if signs and symptoms of disease
    return, Hulio may be re-administered. Experience with re-
    administration of treatment beyond 8 weeks after the
    previous dose is limited.
  • During
    maintenance treatment , corticosteroids may be gradually reduced in
    accordance with clinical practice recommendations.
  • Some patients in
    whom a decreased response to treatment with Hulio 40 mg every
    two weeks is observed may benefit from an increase in
    the dose to Hulio 40 mg every week or 80 mg every
    two weeks.
  • Some patients who have
    not responded to treatment at week 4 may continue
    maintenance therapy until week 12. Continuation of
    treatment should be carefully reconsidered in a patient
    who has not responded within this time.
  • Other presentations of Hulio may be available depending on the therapeutic needs of each patient.

Ulcerative colitis

  • In adult patients
    with moderate to severe ulcerative colitis, the
    recommended induction regimen of Hulio is 160 mg at week 0
    (given as 4 injections of 40 mg per day or 2
    injections of 40 mg per day. day for two consecutive days) and 80
    mg at week 2 (given as two 40 mg injections
    per day). After induction therapy, the recommended dose is
    40 mg administered every two weeks by subcutaneous injection.
  • During
    maintenance treatment , corticosteroids may be gradually reduced in
    accordance with clinical practice recommendations.
  • Some patients in
    whom a decreased response to treatment with Hulio 40 mg every
    two weeks is observed may benefit from an increase in
    the dose to Hulio 40 mg every week or 80 mg every
    two weeks.
  • Available data
    suggest that clinical response is usually achieved within
    2 to 8 weeks of treatment. Treatment with Hulio should not be
    continued in patients who have not responded within this time frame .
  • Other presentations of Hulio may be available depending on the therapeutic needs of each patient.

Uveitis

  • In adult
    patients with uveitis, the recommended dose of Hulio is an
    initial dose of 80 mg followed by a dose of 40 mg every two weeks
    starting one week after the first dose.
  • There
    is limited experience with initiating treatment with adalimumab monotherapy. Treatment with Hulio can be started in combination with corticosteroid therapy and / or with other
    non-biological immunomodulatory treatments .
  • The combined corticosteroid dose may
    be gradually reduced in accordance with clinical practice,
    starting two weeks after initiation of treatment with Hulio.
  • An annual reassessment
    of the benefits and risks associated with long-
    term continuous therapy is recommended (see section 5.1).
  • Other presentations of Hulio may be available depending on the therapeutic needs of each patient.

Special populations

Older subjects

  • No dosage adjustment is necessary.

Renal and / or hepatic impairment

  • Adalimumab has not been studied in these patient populations. It is not possible to recommend dosages.

Pediatric population

Juvenile idiopathic arthritis

Polyarticular juvenile idiopathic arthritis from 2 years old

  • The recommended dosage of Hulio for patients with polyarticular juvenile idiopathic arthritis from the age of 2 years depends on body weight
    (Table 1).
  • Hulio is given every two weeks as a subcutaneous injection.

Table 1: Dosage of Hulio in Patients with Polyarticular Juvenile Idiopathic Arthritis

  • Available data suggest that clinical response is usually achieved within 12 weeks of treatment.
  • Continuation of treatment should be carefully reconsidered in a patient who has not responded within this time frame.
  • There is no relevant use of adalimumab in patients under 2 years of age in this indication.
  • Other presentations of Hulio may be available depending on the therapeutic needs of each patient.

Enthesitis-related arthritis

  • The recommended dosage of Hulio for patients with enthesitis-related arthritis from the age of 6 years depends on body weight (Table 2).
  • Hulio is given every two weeks as a subcutaneous injection.

Table 2: Dosage of Hulio in Patients with Enthesitis-Related Arthritis

  • Adalimumab has not been studied in patients less than 6 years of age with arthritis related to enthesitis.
  • Other presentations of Hulio may be available depending on the therapeutic needs of each patient.

Plaque psoriasis in children and adolescents

  • The recommended dosage of Hulio for patients with plaque psoriasis aged 4 to
    17 years depends on body weight (Table 3).
  • Hulio is administered as a subcutaneous injection.

Table 3: Dosage of Hulio in Children and Adolescents with Plaque Psoriasis

  • Continuation of treatment beyond 16 weeks should be carefully reconsidered in a
    patient who has not responded within this time.
  • If retreatment with Hulio is indicated, the recommendations mentioned above for
    dosage and duration of treatment should be followed.
  • The safety of adalimumab in children and adolescents with plaque psoriasis has been
    evaluated over a mean duration of 13 months.
  • There is no relevant use of adalimumab in children aged less than 4 years in this indication.
  • Other presentations of Hulio may be available depending on the therapeutic needs of each patient.

Adolescent hidradenitis suppurativa (from 12 years of age, weighing at least 30 kg)

  • There is no clinical trial conducted with adalimumab in adolescents with
    hidradenitis suppurativa. The dosage of adalimumab in these patients was determined from pharmacokinetic modeling and simulation.
  • The recommended dose of Hulio is 80 mg at week 0 followed by 40 mg every two
    weeks from week 1 by subcutaneous injection.
  • In adolescents with insufficient response to Hulio 40 mg every two weeks, an increase in the dosage to 40 mg every week or 80 mg every two weeks may be considered.
  • If necessary, antibiotics can be continued during treatment with Hulio.
  • During treatment with Hulio, it is recommended that the patient
    cleanse his lesions daily with a topical antiseptic.
  • Continuation of treatment beyond 12 weeks should be carefully reconsidered in patients who do not show improvement during this period.
  • If treatment is interrupted, Hulio can be reintroduced if necessary.
  • The benefit and risk of continued long-term treatment should be assessed regularly (see data in adults under Pharmacodynamic properties).
  • There is no relevant use of adalimumab in children under 12 years of age in this indication.
  • Other presentations of Hulio may be available depending on the therapeutic needs of each patient.

Crohn’s disease in children and adolescents

  • The recommended dosage of Hulio for patients with Crohn’s disease aged 6 to 17 years depends on body weight (Table 4).
  •  Hulio is administered as a subcutaneous injection.

Table 4: Dosage of Hulio in Children and Adolescents with Crohn’s Disease

  • Patients in whom an insufficient response to treatment is observed may benefit from an increase in the dosage:
    • <40 kg: 20 mg per week
    • ≥ 40 kg: 40 mg per week or 80 mg every two weeks.
  • Continuation of treatment should be carefully reconsidered in a patient who has not responded by week 12.
  • There is no relevant use of adalimumab in children aged less than 6 years for this indication.
  • Other presentations of Hulio may be available depending on the therapeutic needs of each patient.

Uveitis in children and adolescents

  • The recommended dosage of Hulio for children and adolescents with uveitis fromthe age of 2 years depends on body weight (Table 5).
  • Hulio is administered as a subcutaneous injection.
  • In uveitis in children and adolescents, no clinical trials have been conducted with Hulio without concomitant treatment with methotrexate.

Table 5: Hulio Dosage for Pediatric Patients with Uveitis

  • When initiating treatment with Hulio, a loading dose of 40 mg for patients <30 kg or 80 mg for patients ≥ 30 kg may be administered one week before the start of maintenance therapy.
  • No clinical data are available from the use of a loading dose of Hulio in children under 6 years of age.
  • There is no relevant use of adalimumab in children under 2 years of age in this indication.
  • An annual reassessment of the benefits and risks associated with long-term continuous therapy is recommended.
  • Other presentations of Hulio may be available depending on the therapeutic needs of each patient.

Pediatric ulcerative colitis

  • The safety and efficacy of adalimumab in children aged 4 to 17 years have not yet been established.
  • No data is available.
  • There is no relevant use of adalimumab in children aged less than 4 years in this indication.

Psoriatic arthritis and axial spondylitis including ankylosing spondylitis

  • There is no relevant use of adalimumab in the pediatric population in the indications, ankylosing spondylitis and psoriatic arthritis.

Administration mode

  • Hulio is administered as a subcutaneous injection. Full instructions for use are provided in the package leaflet.
  • A 40 mg vial for children and adolescents is available for patients requiring a dose lower than the full 40 mg dose.

Contraindications

  • Hypersensitivity to the active substance or to any of the excipients listed in the Composition section.
  • Active tuberculosis or other severe infections such as sepsis and opportunistic infections.
  • Moderate to severe heart failure (NYHA classes III / IV).

HULIO  Side Effects

Summary of the safety profile

  • Adalimumab has been studied in 9,506 patients in pivotal, open- label, controlled trials of 60 months and longer duration. These trials included patients with recent or old rheumatoid arthritis, juvenile idiopathic arthritis ( polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis) or patients with axial spondylitis (ankylosing spondylitis and axial spondylitis without radiographic evidence of AS ), psoriatic arthritis, Crohn’s disease, ulcerative colitis, psoriasis, hidradenitis suppurativa and uveitis.
  • The pivotal controlled studies involved 6,089 patients who received adalimumab and 3,801 patients who received placebo or an active comparator during the controlled phase.
  • The percentage of patients who discontinued treatment due to adverse reactions during the double-blind, controlled phase of the pivotal studies was 5.9% in patients treated with adalimumab and 5.4% in patients of the control group.
  • The most frequently reported side effects are infections (such as nasopharyngitis, upper respiratory tract infections and sinusitis), injection site reactions (erythema, itching, bleeding, pain or swelling), headache and musculoskeletal pain.
  • Some serious side effects have been reported with adalimumab.
  • The TNF antagonists, such as adalimumab affect the system immune and their use may affect the body’s defenses against infection and cancer.
  • Life-threatening and fatal infections (including sepsis, opportunistic infections and tuberculosis), hepatitis B reactivations and various cancers (including, leukemia, lymphoma and hepatosplenic T-cell lymphoma) have also been reported with use of adalimumab.
  • Severe haematological, neurological and autoimmune effects have also been reported. This includes rare cases of pancytopenia, bone marrow anemia, cases of central and peripheral demyelination, and cases of lupus, lupus-related events, and Stevens-Johnson syndrome.

Pediatric population

  • In general, the frequency and type of adverse events seen in children and adolescents were comparable to those seen in adult patients.

List of side effects

  • The list of adverse reactions is based on clinical studies and post-marketing experience and is presented by system organ class (SOC) and frequency in Table 6 below : very common (≥ 1/10) ; common (≥ 1/100, <1/10); uncommon (≥ 1 / 1,000, <1/100); rare (≥ 1 / 10,000, <1 / 1,000) and not known (cannot be estimated from the available data ). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
  • The highest frequency observed in the various indications was included.
  • The presence of an asterisk (*) in the column “Class of organ systems ”indicates that more information is available under the sections Contraindications, Warnings and precautions for use and Undesirable effects.

Table 6: Adverse reactions

  • * Further information is available under the sections Contraindications, Warnings and precautions for use and Adverse reactions.
  • ** including open label extension studies.

1) including data from spontaneous notifications

Hidradenitis suppurativa

The safety profile in patients with hidradenitis suppurativa treated with adalimumab weekly is consistent with the known safety profile of adalimumab.

Uveitis

  • The safety profile in patients with uveitis treated with adalimumab every two weeks is consistent with the known safety profile of adalimumab.

Description of selected adverse reactions

Injection site reactions

  • In pivotal controlled trials in adults and children, 12.9% of patients treated with adalimumab experienced injection site reactions (erythema and / or pruritus, bleeding, pain, or swelling) versus 7 , 2% of patients receiving placebo or active comparator.
  • Injection site reactions generally did not require stopping the drug.

Infections

  • In the pivotal controlled trials in adults and children, the frequency of infections was 1.51 per patient-year in the adalimumab group and 1.46 per patient-year in the placebo group. and the control group.
  • The infections mainly consisted of nasopharyngitis, upper respiratory tract infections and sinusitis.
  • Most patients continued with adalimumab after the infection cleared.=
  • The incidence of serious infections was 0.04 per patient-year in the adalimumab-treated group , and 0.03 per patient-year in the placebo and control groups.
  • In open-label, controlled studies with adalimumab in adults and in the pediatric population, serious infections (including fatal infections, which have rarely occurred) have been reported including reports of tuberculosis (including miliary and extra-pulmonary localizations) and invasive opportunistic infections (eg disseminated histoplasmosis or extrapulmonary histoplasmosis, blastomycosis, coccidioidomycosis, pneumocystosis, candidiasis, aspergillosis and listeriosis). Most cases of tuberculosis have occurred within the first eight months after starting treatment and may reflect reactivation of latent disease.

Malignant tumors and lymphoproliferative disorders

  • No cases of cancer were observed in 249 pediatric patients representing an exposure of 655.6 patient-years in studies with adalimumab in patients with juvenile idiopathic arthritis (polyarticular juvenile idiopathic arthritis and arthritis related to enthesitis). In addition, no cases of cancer were observed in 192 pediatric patients representing an exposure of 498.1 patient-years in studies with adalimumab in Crohn’s disease in children and adolescents. No cases of cancer were observed in 77 pediatric patients corresponding to an exposure of 80 patient-years in a study with adalimumab in psoriasis chronic pediatric plaques. No cases of cancer were observed in 60 pediatric patients representing an exposure of 58.4 patient-years in a study with adalimumab in pediatric uveitis .
  • During the controlled periods of the pivotal clinical trials in adults withadalimumab of at least 12 weeks duration in patients with moderately to severely active rheumatoid arthritis, ankylosing spondylitis, axial spondylitis without radiographic evidence of AS , psoriatic arthritis, psoriasis, hidradenitis suppurativa, Crohn’s disease, ulcerative colitis and uveitis, a rate (95% confidence interval) of cancers other than lymphomas or non-melanoma skin cancers, of 6.8 (4.4 – 10.5) per 1000 patient-years among the 5291 patients treated with adalimumab, was observed compared to a rate 6.3 (3.4 – 11.8) per 1,000 patient-years among the 3,444 patients in the control group (the mean duration of treatment was 4.0 months for patients treated with adalimumab and 3 , 8 months for patients in the control group). The rate (95% confidence interval) of non-melanoma skin cancer was 8.8 (6.0 – 13.0) per 1000 patient-years for patients treated with adalimumab and 3.2 (1.3 – 7.6) per 1000 patient-years among patients in the control group .
  • In these skin cancers, squamous cell carcinomas occurred at
    rates (95% confidence interval) of 2.7 (1.4 – 5.4) per 1,000
    patient years in patients treated with adalimumab and 0.6 (0.1 –
    4.5) per 1000 patient years in patients in the control group. The
    rate (95% confidence interval) of lymphomas was 0.7 (0.2 –
    2.7) per 1000 patient years in patients treated with
    adalimumab and 0.6 (0.1 – 4 , 5) per 1000 patient-years in
    patients in the control group.
  • By combining controlled portions of these tests and the tests
    Expansion open ended or current with a mean duration
    of around 3.3 years including 6427 patients and more than 26,439 patient-
    years of treatment, the observed rate of cancers, other than lymphomas
    and non-melanoma skin cancers is approximately 8.5 per 1,000
    patient-years. The observed rate of non-melanoma skin cancer
    is approximately 9.6 per 1,000 patient-years and the
    observed rate of lymphomas is approximately 1.3 per 1,000 patient-years.
  • In post-marketing period from January 2003 to December 2010, primarily in
    patients with rheumatoid arthritis, the reported rate of
    cancer is approximately 2.7 per 1,000 patient-years of
    treatment. The reported rates for
    non-melanoma skin cancer and lymphoma are approximately 0.2 and 0.3
    per 1000 patient-years of treatment, respectively (see section 4.4).
  • Inpost-marketing surveillance, rare cases of hepatosplenic T-cell lymphoma have been reported in patients treated with adalimumab.

Autoantibodies

  • Repeated autoantibody tests were performed on serum samples from patients in the IV trials in rheumatoid
    arthritis.
  • In these trials, initially negative antinuclear antibody titers were positive at week 24 in 11.9% of
    patients treated with adalimumab and 8.1% of patients on placebo and comparator.
  • Two of the 3,441 patients treated with adalimumab in all rheumatoid arthritis and psoriatic arthritis studies exhibited clinical signs suggestive of a new onset lupus-like syndrome . The condition of the patients
    improved after stopping treatment.
  • No patient presented lupus nephritis or central nervous symptoms.

Hepatobiliary events

  • In phase III controlled clinical trials of adalimumab in rheumatoid arthritis and psoriatic arthritis with a control period of 4 to 104 weeks, elevations of ALT ≥ 3 × ULN occurred in 3.7% of patients treated with adalimumab and in 1.6% of patients in the control group.
  • In phase III controlled clinical trials of adalimumab in patients with polyarticular juvenile idiopathic arthritis aged 4 to 17 years and patients with enthesitis-related arthritis aged 6 to 17 years, elevations of ALT ≥ 3 × ULN occurred in 6.1% of patients treated with adalimumab and in 1.3% of patients in the control group.
  • Most of the elevations in ALT have occurred with concomitant use of methotrexate.
  • No elevation of ALT ≥ 3 × ULN occurred in the phase III trial of adalimumab in patients with polyarticular juvenile idiopathic arthritis aged 2 to less than 4 years.
  • In phase III controlled clinical trials of adalimumab in patients with Crohn’s disease and ulcerative
    colitis with a control period of 4 to 52 weeks, elevations of ALT ≥ 3 × ULN occurred in 0 , 9% of patients treated with adalimumab and in 0.9% of patients in the control group.
  • In the Phase III clinical trial of adalimumab in children and adolescents with Crohn’s disease that evaluated
    the efficacy and safety profile of two weight-based maintenance regimens following treatment of ‘ weight- adjusted induction up to 52 weeks of treatment, elevations of ALT ≥ 3 × ULN occurred in 2.6% of patients (5/192), of whom 4 were treated in combination with immunosuppressants at the start of
    study.
  • In phase III controlled clinical trials of adalimumab in plaque psoriasis with a control period of 12 to 24 weeks, elevations of ALT ≥ 3 × ULN occurred in 1.8% of patients treated with l adalimumab and in 1.8% of patients in the control group .
  • It has not been observed ALT elevations ≥ 3 x ULN in the study Phase III on adalimumab in pediatric patients with plaque psoriasis.
  • In controlled clinical trials of adalimumab (starting doses 160 mg at week 0 and 80 mg at week 2, followed by 40 mg weekly from week 4), in patients with HS With a control period of 12 to 16 weeks, elevations of ALT ≥ 3 × ULN occurred in 0.3% of patients treated with adalimumab and 0.6% of patients in the control group .
  • In controlled clinical trials of adalimumab (starting dose 80 mg at week 0 followed by 40 mg every other week from week 1) in adult patients with uveitis for up to 80 weeks, with a median duration of exposure of 166.5 days and 105.0 days respectively for patients treated with adalimumab and patients in the control group, elevations of ALT ≥ 3 × ULN occurred in 2, 4% of patients treated with adalimumab and 2.4% of patients in the control group.

 

  • In clinical trials across all indications, patients with elevated ALT were asymptomatic and in most cases the
    elevations were transient and reversible upon continued treatment. However, during post-marketing surveillance, hepatic insufficiency as well as less severe hepatic disorders , which may precede hepatic insufficiency, such as hepatitis including autoimmune hepatitis, have been reported in patients receiving Hepatitis. ‘adalimumab.

Concomitant administration of azathioprine / 6-mercaptopurine

  • In studies in Crohn’s disease in adults, a higher incidence of tumors and serious infections was observed with the combination of adalimumab and azathioprine / 6-mercaptopurine compared to adalimumab used alone.

HULIO  Interactions

  • Adalimumab has been studied in patients with rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, and psoriatic arthritis taking adalimumab as monotherapy and in those taking methotrexate concomitantly. Antibody formation was lower when adalimumab was co-administered with methotrexate compared to its use as monotherapy.
  • Administration of adalimumab without methotrexate resulted in increased antibody formation, increased clearance and reduced efficacy of adalimumab.
  • The combination of Hulio and anakinra is not recommended (see section Warnings and precautions for use “Simultaneous administration of biological DMARDs and anti-TNF drugs”).
  • The combination of Hulio and abatacept is not recommended (see section Warnings and precautions for use “Simultaneous administration of biological DMARDs and anti-TNF drugs”)
  • In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

Drive and use machines

Warnings and Precautions

PREGNANCY & BREAST-FEEDING & FERTILITY

Women of childbearing age

  • Women of childbearing potential should consider using effective contraception to prevent pregnancy and continue for at least five months after the last administration of Hulio.

Pregnancy

  • A large number (approximately 2,100) of pregnancies exposed to adalimumab for which data were collected prospectively, resulting in a live birth with a known term outcome, including more than 1,500 pregnancies exposed to adalimumab during the first trimester, does not reveal any increase in the rate of malformations in the newborn.
  • In a prospective cohort study, 257 women with rheumatoid arthritis (RA) or Crohn’s disease (CD) treated with adalimumab at least during the first trimester and 120 women with untreated RA or CD by adalimumab were included. The prevalence at birth of major congenital anomalies was the primary endpoint. The rate of pregnancies resulting in at least one living newborn with a major birth defect was 6/69 (8.7%) in women treated with adalimumab with RA and 5/74 (6.8 %) in untreated women with RA (unadjusted OR 1.31, 95% CI 0.38-4.52), and 16/152 (10.5%) in women treated with adalimumab with CD and 3/32 (9,
  • The adjusted OR (considering baseline differences) was 1.10 (95% CI 0.45-2.73) for RA and CD combined. No notable difference was reported between women treated with adalimumab and women not treated with adalimumab for secondary endpoints of spontaneous abortion, minor congenital anomalies, preterm delivery, height. at birth and serious or opportunistic infections, and stillbirth or malignancy. Interpretation of the data may be affected due to methodological limitations of the study, including the small sample size and the non-randomized study design.
  • In a developmental toxicity study performed in monkeys, there were no signs of possible maternal toxicity, embryotoxicity or teratogenic potential.
  • Preclinical data on the postnatal toxicity of adalimumab are not available (see section Preclinical safety data).
  • Due to its inhibitory effect on TNFα, adalimumab administered during pregnancy may affect the normal immune responses of the newborn. Adalimumab should be used during pregnancy only if needed.
  • In women treated with adalimumab during pregnancy, adalimumab can cross the placenta and pass into the blood of their child. As a result, these children may have an increased risk of infections. The administration of live vaccines (eg BCG vaccine) to children who have been exposed to adalimumab in utero is not recommended for 5 months after the mother’s last injection during pregnancy.

Feeding with milk

  • Limited data from the published literature indicate that adalimumab is excreted in human milk at very low concentrations, with adalimumab present in human milk at concentrations equivalent to 0.1% -1% of maternal serum levels. .
  • When administered orally, immunoglobulin G proteins undergo intestinal proteolysis and exhibit low bioavailability. No effects on breastfed newborns / infants are expected. Therefore, adalimumab can be used during breast-feeding.

Fertility

  • Preclinical data on the effects of adalimumab on fertility are not available.

What happens if I overdose from HULIO  ?

No dose related toxicity was observed in clinical trials. The highest dose evaluated consisted of repeated doses of 10 mg / kg IV, which is approximately 15 times the recommended dose.

What is  Forms and Composition ?

Solution for injection (injection).

Clear or slightly opalescent, colorless to pale yellow-brownish solution.

Hulio 40 mg solution for injection in single-use pre-filled syringe with automatic needle guard.

The syringe is made of cycloolefin polymer with a stopper (chlorobutyl rubber) and a needle (stainless steel) with cap (butyl / diene polymer and polypropylene).

Package size:

  • 2 pre-filled syringes (with 2 alcohol swabs)

* per unit dose

  • Active ingredients: Adalimumab
  • Excipients with known effects Sorbitol
  • Other excipients: Monosodium glutamate , Methionine, Polysorbate 80, Hydrochloric acid (for pH adjustment), Water for injections, Original substrates: Hamster protein

NOT’s

Edrug-online contains comprehensive and detailed information about drugs available in the medical field, and is divided into four sections:

general information:

  • Includes a general description of the drug, its use, brand names, FAQs, and relevant news and articles

Additional information:

  • General explanation about dealing with the medicine: how to take the medicine, the doses and times of it, the start and duration of its effectiveness, the recommended diet during the period of taking the medicine, the method of storage and storage, recommendations in cases for forgetting the dose and instructions to stop taking the drug and take additional doses.

Special warnings:

  • For pregnant and breastfeeding women, the elderly, boys and drivers, and use before surgery.

Side effects:

  • It treats possible side effects and drug interactions that require attention and its effect on continuous use.
  • The information contained in this medicine is based on medical literature, but it is not a substitute for consulting a doctor.
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Enbrel Injection Uses, Dosage, Side Effects, Precautions https://edrug-online.com/134/enbrel-injection.html https://edrug-online.com/134/enbrel-injection.html#comments Tue, 18 Aug 2020 16:09:57 +0000 http://www.edrug-online.com/?p=134 Enbrel Injection Uses, Dosage, Side Effects, PrecautionsEnbrel Injection >> Generic drug of the therapeutic class: Immunology active ingredients: Etanercept what is enbrel? Etanercept suppresses body defenses and inhibits inflammation. In joint inflammation (rheumatoid arthritis, Bechterew’s disease) and psoriasis (scaling skin disease). Sometimes also with inflammatory bowel disease (Crohn’s disease) and Wegener’s disease (chronic vascular inflammation). You will usually notice that your illness will become calmer […]]]> Enbrel Injection Uses, Dosage, Side Effects, Precautions

Enbrel Injection >> Generic drug of the therapeutic class: Immunology
active ingredients: Etanercept

what is enbrel?

  • Etanercept suppresses body defenses and inhibits inflammation.
  • In joint inflammation (rheumatoid arthritis, Bechterew’s disease) and psoriasis (scaling skin disease). Sometimes also with inflammatory bowel disease (Crohn’s disease) and Wegener’s disease (chronic vascular inflammation).
  • You will usually notice that your illness will become calmer within a few weeks.
  • You can inject etanercept yourself. A nurse will explain how you do that.
  • Usually you use the injection twice a week, sometimes once.
  • Redness, itching and swelling at the injection site occur regularly. Therefore, always choose another injection site for example in the thigh, abdomen or back of the upper arm. Usually this local update takes 3 to 5 days. After a month you are less affected by this.
  • You are more likely to have infections such as colds, bronchitis and forehead inflammation. This is because the body’s defense is reduced. Always consult your doctor if you have a fever.

what is enbrel injection used for and indication?

Rheumatoid arthritis :

  • Enbrel Injection in combination with methotrexate is indicated for the treatment of moderate to severely active rheumatoid arthritis in adults with inadequate response to DMARDs, including methotrexate (unless contraindicated).
  • Enbrel Injection may be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is unsuitable.
  • Enbrel Injection is also indicated for the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate.
  • Enbrel Injection, alone or in combination with methotrexate, has been shown to slow the progression of structural joint damage as measured by X-ray and improve functional abilities.

Juvenile idiopathic arthritis :

  • Treatment of rheumatoid arthritis (positive or negative rheumatoid factor) and extensive oligoarthritis in children from 2 years of age and adolescents in case of inadequate response or proven intolerance to methotrexate.
  • Treatment of psoriatic arthritis of the adolescent from the age of 12 years in case of inadequate response or proven intolerance to methotrexate.
  • Treatment of enthesitis-related arthritis in adolescents from the age of 12 years in the event of an inadequate response or proven intolerance to the reference treatment.
  • Enbrel Injection has not been studied in children under 2 years old.

Psoriatic arthritis

  • Treatment of active and progressive psoriatic arthritis of the adult in case of inadequate response to previous background therapy.
  • Enbrel Injection has been shown to improve functional abilities in patients with psoriatic arthritis, and to slow the progression of peripheral joint structural damage as measured by radiography in patients with symmetrical polyarticular forms of the disease.

Axial spondyloarthritis

Ankylosing spondylitis (AS)

  • Treatment of severe and active ankylosing spondylitis in adults with inadequate response to conventional therapy.

Non-radiographic axial spondyloarthritis

Treatment of severe non-radiographic axial spondyloarthritis of the adult with objective signs of inflammation, resulting in high levels of C-reactive protein (CRP) and / or visible signs on magnetic resonance imaging (MRI), in case of inadequate response to nonsteroidal anti-inflammatory drugs (NSAIDs).

Plaque psoriasis

  • Treatment of moderate-to-severe plaque psoriasis in adults in the event of failure, contra-indication, or intolerance to other systemic treatments including ciclosporin, methotrexate or PUVA.

Psoriasis in plaques of the child

  • Treatment of severe chronic plaque psoriasis in children from 6 years of age and adolescents in case of inadequate control, or intolerance to other systemic treatments or phototherapy.

enbrel dosage

Treatment with Enbrel Injection must be initiated and supervised by a medical specialist experienced in the diagnosis and treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, plaque psoriasis or plaque psoriasis in the child. The Patient Monitor Card should be given to patients treated with Enbrel Injection.

Enbrel Injection is available in dosages of 10, 25 and 50 mg.

Enbrel Injection Dosage
Enbrel Injection Dosage

Dosage

Rheumatoid arthritis :

  • The recommended dose of Enbrel Injection is 25 mg twice weekly. However, the efficacy and safety of administration of 50 mg once a week has been demonstrated .
  • Psoriatic arthritis, ankylosing spondylitis and non-radiographic axial spondyloarthritis The recommended dose is 25 mg Enbrel Injection twice weekly or 50 mg once weekly.
  • For all the above indications, the available data suggest that a clinical response is usually obtained within 12 weeks of treatment. Further treatment should be carefully reconsidered in a patient who has not responded within this time frame.

Plaque psoriasis :

  • The recommended dose of Enbrel Injection is 25 mg twice daily or 50 mg once weekly. However, a dose of 50 mg twice a week may be used up to 12 weeks, followed, if necessary, by a dose of 25 mg twice a week or 50 mg once a week. Treatment with Enbrel Injection should be continued until remission is achieved, up to a maximum of 24 weeks. Continuous treatment beyond 24 weeks may be appropriate for some adult patients ( Pharmacodynamic properties ).
  • Treatment with Enbrel Injection should be discontinued in patients with no response after 12 weeks of treatment.
  • If re-treatment with Enbrel Injection is indicated, the same treatment duration schedule should be followed. The dose should be 25 mg given twice a week or 50 mg once a week.

Special populations

Patients with renal and hepatic impairment

  • No dosage adjustment is necessary.

Elderly patients

  • No dosage adjustment is necessary. The dosage and administration are identical to those of adults aged 18 to 64 years.

Pediatric population :

  • The dose of Enbrel Injection depends on the weight of pediatric patients. Patients weighing less than 62.5 kg should be given an exact dose calculated in mg / kg using the powder and solvent for solution for injection or the powder for solution for injection (see below for doses as indicated). Patients weighing 62.5 kg or more can receive a fixed dose using the pre-filled syringe or pre-filled pen (50 mg / week).

Juvenile idiopathic arthritis :

  • The recommended dose is 0.4 mg / kg (maximum 25 mg per injection) administered twice a week by subcutaneous injection, with an interval of 3-4 days between two injections or 0.8 mg / kg ( maximum 50 mg per injection) administered once a week. Discontinuation of treatment should be considered in non-responder patients after 4 months.
  • The 10 mg dosage is more suitable for administration to children with JIA less than 25 kg.
  • No clinical trials have been conducted in children aged 2 to 3 years. Limited safety data from a patient registry, however, suggests that the safety profile in children aged 2 to 3 years is similar to that of adults and children over 4 years of age, at a dose of 0, 8 mg / kg subcutaneously weekly (see section 5.1 Pharmacodynamic properties ).
  • Enbrel Injection is generally not recommended for use in children under 2 years of age for juvenile idiopathic arthritis.

Plaque psoriasis of the child (6 years old and over)

  • The recommended dose is 0.8 mg / kg (maximum 50 mg per injection) once a week up to 24 weeks. Treatment should be discontinued in patients who do not respond after 12 weeks of treatment.
  • If resumption of treatment with Enbrel Injection is indicated, the treatment duration schedule described above should be followed. The dose should be 0.8 mg / kg (maximum 50 mg per injection) once a week.
  • Enbrel Injection is generally not recommended for use in children under 6 years of age for plaque psoriasis.
  • Full instructions for administration are given in the package leaflet, section 7 “Instructions for the preparation and administration of an injection of Enbrel Injection”.

Contraindications

  • Etanercept hypersensitivity
  • Septicemia
  • Infection
  • Child under 2 years old
  • Lack of effective female contraception
  • Feeding with milk
  • Moderate to severe alcoholic hepatitis
  • Pregnancy

Hypersensitivity to the active substance or to any of the excipients listed in the Composition section. Sepsis or risk of sepsis.

Treatment with Enbrel should not be initiated in patients with active infection including chronic or localized infections.

how enbrel works?

Pharmacotherapeutic group: immunosuppressive agents, inhibitors Necrosis Factor alpha Tumors (TNF α ), ATC code: L04AB01

Tumor necrosis factor (TNF) is a dominant cytokine in the inflammatory process of rheumatoid arthritis. High levels of TNF are also found in the synovial membranes and psoriatic plaques of patients with psoriatic arthritis, and in the serum and synovial tissue of patients with ankylosing spondylitis. In psoriasis plaques, infiltration by inflammatory cells, including T cells, leads to an increase in TNF levels in psoriatic lesions, compared to levels seen in non-skin areas. Etanercept is a competitive inhibitor of TNF binding to its surface receptors thereby inhibiting the biological activity of TNF.

TNF and lymphotoxin are pro-inflammatory cytokines that bind two distinct receptors on the cell surface: tumor necrosis factor receptors (TNFRs) of 55-kilodalton (p55) and 75-kilodalton (p75). These two TNFRs naturally exist in membrane and soluble forms. Soluble TNFRs are thought to regulate the biological activity of TNF.

TNF and lymphotoxin exist mainly as homotrimers, their biological activity being dependent on the TNFR crosslinking at the cell surface. Soluble dimeric receptors such as etanercept have a greater affinity for TNF than monomeric receptors and are much more potent competitive inhibitors of TNF binding to its cellular receptors. In addition, the use of an immunoglobulin Fc region as a fusion element in the construction of a dimeric receptor confers on the molecule a longer plasma half-life.

Action mechanism

The majority of joint damage in rheumatoid arthritis and ankylosing spondylitis, and skin involvement of plaque psoriasis is mediated by pro-inflammatory molecules that belong to a TNF-controlled network. The supposed mechanism of action of etanercept is competitive inhibition of TNF binding to TNFR of the cell surface: TNF-mediated cellular responses are blocked by rendering TNF biologically inactive. Etanercept may also modulate the biological responses controlled by other molecules acting downstream (eg cytokines, adhesins or proteinases) whose activity is induced or regulated by TNF.

Clinical efficacy and safety

This section presents data from four randomized controlled trials in adults with rheumatoid arthritis, a study in adults with psoriatic arthritis, a study in adults with ankylosing spondylitis, a study in adults with non-radiographic axial spondyloarthritis, four studies in adults with plaque psoriasis, three studies in juvenile idiopathic arthritis, and one study in children with plaque psoriasis.

Adult patients with rheumatoid arthritis

The efficacy of Enbrel Injection was evaluated in a randomized, double-blind, placebo-controlled study. The study evaluated 234 adult patients with active rheumatoid arthritis who did not respond to at least one and at most four DMARDs. Doses of 10 mg or 25 mg of Enbrel Injection or placebo were administered subcutaneously twice a week for 6 consecutive months. The results of this controlled study were expressed as percentage improvement in rheumatoid arthritis, using the American College of Rheumatology (ACR) response criteria.

ACR 20 and ACR 50 responses were higher in Enbrel Injection-treated patients compared to placebo at 3 and 6 months (ACR 20: Enbrel Injection 62% and 59%, placebo 23% and 11% at 3 and 6 months respectively; ACR 50 : Enbrel Injection 41% and 40%, placebo 8% and 5% respectively at 3 and 6 months, p <0.01 Enbrel Injection vs placebo at all measurement times for the ACR 20 and ACR 50 responses).

Approximately 15% of patients receiving Enbrel Injection achieved an ACR 70 response at 3 months and at 6 months compared to less than 5% of placebo-treated patients. Among patients receiving Enbrel Injection, clinical responses generally started 1 to 2 weeks after initiation of treatment, and were almost always achieved within 3 months. A dose-dependent response was observed; results with 10 mg were intermediate between placebo and 25 mg. Enbrel Injection was significantly superior to placebo on all ACR criteria items, as well as other measures of rheumatoid arthritis activity not included in these ACR response criteria, such as duration of morning stiffness. The Health Assessment Questionnaire (HAQ) scale, including disability, activity, mental state, general condition, state of joint function, was evaluated every 3 months during the study. All areas of the HAQ scale were improved in patients treated with Enbrel Injection compared to placebo-treated patients at 3 and 6 months.

After the arrest of Enbrel Injection, arthritis symptoms usually reappeared in the following month. Based on the results of the open label studies, restarting treatment with Enbrel Injection after periods of up to 24 months resulted in the same range of response as in patients receiving Enbrel Injection without interruption of treatment. Stable and lasting responses have been observed in patients receiving Enbrel Injection continuously up to 10 years in open-label studies (extension phase of therapeutic studies).

The efficacy of Enbrel Injection was compared with methotrexate in a randomized, controlled-active study with blinded radiographic endpoints as a primary endpoint in 632 adult patients with active rheumatoid arthritis (<3 years duration). ) who had never received treatment with methotrexate. Enbrel Injection 10 mg or 25 mg doses were administered subcutaneously twice a week for up to 24 months. Methotrexate doses were increased from 7.5 mg / week to 20 mg / week maximum during the first 8 weeks of the trial and maintained for up to 24 months. With Enbrel Injection 25 mg clinical improvement, including the onset of action within two weeks, was similar to that seen in previous trials, and is maintained for up to 24 months. At inclusion, patients had a moderate degree of disability, with mean HAQ scores of 1.4 to 1.5. Treatment with Enbrel Injection 25 mg resulted in a significant improvement at 12 months, with approximately 44% of patients achieving a normal HAQ score (less than 0.5). This benefit was maintained in the second year of this study.

In this study, structural joint damage was assessed radiographically and expressed as a modification of the Sharp Total Score (STS) and its components; Erosion score and Articular Pinching Score (APS). X-rays of the hands / wrists and feet were read at inclusion and at 6, 12 and 24 months. The 10 mg dose of Enbrel Injection had consistently less effect on structural damage than the 25 mg dose. Enbrel Injection at 25 mg was significantly superior to methotrexate for erosion scores, at both 12 and 24 months. Differences between the methotrexate group and the 25 mg Enbrel Injection group for STS and SPA were not statistically significant.

In another controlled versus active, randomized, double-blind study, clinical efficacy, tolerability, and radiographic outcome in patients with RA treated with Enbrel Injection alone (25 mg twice weekly), or methotrexate alone (7.5 to 20 mg weekly, 20 mg median dose) or concurrently initiated Enbrel Injection plus methotrexate, were compared in 682 adult patients with active rheumatoid arthritis of 6 months to 20 years (median 5 years) and who had an inadequate response to at least one DMARD other than methotrexate.

Patients treated with Enbrel Injection plus methotrexate had ACR 20, ACR 50, and ACR 70 responses, and significantly improved DAS and HAQ scores at both 24 and 52 weeks, compared with patients in each of the monotherapy groups. (results presented in the table below). Significant benefits with Enbrel Injection plus methotrexate compared with Enbrel Injection monotherapy and methotrexate monotherapy were also observed after 24 months.

what are the enbrel side effects?

In addition to the desired effect, this can cause drug side effects.

The main side effects are the following.

Regularly (with more than 30 in 100 people)

  • Redness, itching and swelling at the site of injection. These symptoms usually last 3 to 5 days. You are particularly troubled by the first month. Thereafter, this side effect is usually less.

Sometimes (from 10 to 30 people in 100)

  • More risk of infections , such as colds, bronchitis, forehead inflammation, bladder infections or skin infections. Also tuberculosis can rarely occur.
  • Infections arise earlier because the body’s immune system is reduced. If you get a fever or signs of an infection, always consult your doctor. Rarely, a serious infection develops in the blood; this can sometimes only become noticeable after a few weeks of use.
  • Childrenthose treated with etanercept may be more likely to develop a childhood disease, such as chickenpox. Moreover, the childhood disease can be more serious. For children who have not yet received all vaccinations against childhood diseases, it is better to first get all vaccinations before they start etanercept.

Consult with the doctor about this.

Rarely (from 1 to 10 in 100 people)

  • Hypersensitivity to this medication. You will notice this by skin rash, itching, hives, fever, tightness or fainting. Then warn a doctor.
  •  In rare cases ‘angioedema’ develops: a swelling of the face, lips, mouth, tongue or throat. You can be very stuffy. If it occurs, you should immediately seek out a doctor or go to the First Aid Service.
  • In very rare cases a severe skin condition can develop with blistering. The blisters mainly develop on the lips and on the mucous membranes of the mouth and genitals. Then contact a doctor immediately.
  • If you are hypersensitive you should not use this medicine in the future.
  •  Therefore tell the pharmacist that you are hypersensitive to etanercept.
  • The pharmacy team can then ensure that you do not get this medication again.

Very rare (affects less than 1 in 100 people)

  • Worsening of psoriasis . Consult your doctor.
  • Less red and white blood cells or platelets. This can occur after a few weeks or months. Your doctor will therefore have your blood checked regularly. You notice extreme fatigue, sore throat, fever, blisters in the mouth, bruises or bloody noses and more chance of infections. In these cases, tell your doctor immediately.
  • Heart failure or more heart failure. In the event of increased fluid retention (thick ankles) or tightness, you should warn your doctor.
  • More risk of chronic diseases , such as lupus erythematodes (LE), blood vessel inflammation, inflamed muscles and skin (dermatomyositis), organ inflammation (sarcoidosis), liver inflammation (hepatitis), intestinal inflammation and ocular inflammation (uveitis).
  • More risk of certain types of cancer , such as lymphoma , blood cancer (leukemia), skin cancer, breast cancer or lung cancer.
  • Nervous abnormalities . In people with multiple sclerosis (MS) or optic nerve abnormalities, the symptoms can worsen.
  • People who have had hepatitis B before may be given this again. In people with epatitis C the symptoms may worsen. Consult your doctor.

Consult your doctor if you suffer too much from one of the above mentioned side effects or if you experience other side effects that you are worried about.

Enbrel Injection Interactions

Concomitant treatment with anakinra

Enbrel Injection Interactions
Enbrel Injection Interactions
  • Adult patients treated with Enbrel Injection and anakinra had a higher rate of serious infections compared to patients treated with either Enbrel Injection alone or anakinra alone (historical data).
  • In addition, in a double-blind, placebo-controlled trial in adult patients receiving methotrexate DMARD, patients treated with Enbrel Injection and anakinra experienced a higher rate of serious infections (7%). ) and neutropenia as patients treated with Enbrel Injection alone (see Warnings and Precautions and Adverse Reactions sections ). The combination of Enbrel Injection and anakinra has not demonstrated superior clinical benefit and is therefore not recommended.

Concomitant treatment with abatacept

  • Concomitant administration of abatacept and Enbrel Injection in clinical studies has resulted in an increased incidence of serious adverse events.
  • This association did not demonstrate additional clinical benefit; therefore this combination is not recommended (see Warnings and Precautions section ).

Concomitant treatment with sulfasalazine

  • In a clinical study in adult patients treated with stable doses of sulfasalazine and in which Enbrel Injection was added, patients in the group receiving this combination showed a significant decrease in mean white blood cell count, compared to the groups treated with Enbrel Injection or sulfasalazine alone.
  • The clinical significance of this interaction is unknown.
  • The use of Enbrel Injection in combination with sulfasalazine should be considered with caution.

No interactions

  • In clinical trials, no interaction was observed when Enbrel Injection was administered with glucocorticoids, salicylates (except sulfasalazine), nonsteroidal anti-inflammatory drugs (NSAIDs), analgesics or methotrexate. See Warnings and Precautions for Immunization Recommendations.
  • No significant pharmacokinetic drug interaction was observed in the methotrexate, digoxin and warfarin studies.

Warnings and Precautions

  • Infections should be investigated in patients before, during, and after treatment with Enbrel Injection, taking into account that the mean elimination half-life of etanercept is approximately 70 hours (between 7 and 300 hours).
  • Serious infections, septicemia, tuberculosis, and opportunistic infections, including invasive fungal infections, listeriosis and legionellosis, have been reported with Enbrel Injection (see section 4.8).). These infections were caused by bacteria, mycobacteria, fungi, viruses and parasites (including protozoa). In some cases, specific fungal infections and other opportunistic infections have not been diagnosed, resulting in delayed initiation of appropriate treatment and sometimes death. When assessing the risk of infection in a patient, exposure to risk factors specifically associated with certain opportunistic infections (eg exposure to endemic fungal infections) should be assessed and considered.
  • Careful monitoring should be exercised in patients treated with Enbrel Injection developing a new infection. Treatment with Enbrel Injection should be discontinued if the patient develops a serious infection. The safety and efficacy of Enbrel Injection in patients with chronic infections have not been evaluated. Physicians should prescribe Enbrel Injection with caution to patients with a history of recurrent or chronic infections, or having a predisposing course for infections such as severe or poorly balanced diabetes.

Tuberculosis

  • Cases of active tuberculosis including miliary tuberculosis and tuberculosis with extra-pulmonary localization have been reported in patients treated with Enbrel Injection.
  • Before initiating treatment with Enbrel Injection, a search for active or inactive (“latent”) TB should be performed in all patients. This research should include a detailed medical interview on the personal history of tuberculosis or any previous contacts with a TB patient and on previous and / or ongoing immunosuppressive therapy. Appropriate screening tests, such as a dermal tuberculin test and a chest X-ray, should be performed in all patients (in accordance with local recommendations). It is recommended that you write these exams on the Patient Monitor Card. Prescribers are reminded that dermal tuberculin testing may be falsely negative, particularly in a severely ill or immunocompromised patient.
  • If active TB is diagnosed, treatment with Enbrel Injection should not be initiated. In the case of diagnosis of inactive (“latent”) TB, appropriate prophylactic TB treatment should be initiated prior to initiating Enbrel Injection, and in accordance with recommendations.
  • local. In such a case, the benefit / risk ratio of treatment with Enbrel Injection should be carefully evaluated.
  • All patients should be made aware of the need to consult a physician if signs or symptoms suggestive of TB (eg, persistent cough, weight loss / weight loss, fever) occur during or after treatment with Enbrel Injection.

Reactivation of hepatitis B

  • Hepatitis B reactivation has been reported in patients previously infected with the hepatitis B virus (HBV) and treated with anti-TNF, including Enbrel Injection. This includes cases of reactivation of hepatitis B in patients positive for anti-HBc but negative for HBs.
  • Patients should be screened for HBV infection before initiating treatment with Enbrel Injection.
  • If the results of the screening are positive, it is recommended to consult a doctor specialized in the treatment of hepatitis B; precautions to be taken when administering Enbrel Injection to patients previously infected with HBV.
  • In these patients, the signs and symptoms of active infection with HBV throughout the course of treatment and for several weeks after the end of treatment.
  • No relevant data for treating HBV-positive patients with anti-TNF-related antiviral therapy is available. In patients who develop HBV infection, treatment with Enbrel Injection should be discontinued and effective antiviral therapy with symptomatic treatment should be initiated.

Aggravation of hepatitis C

  • Cases of worsening hepatitis C have been reported in patients receiving Enbrel Injection.
  •  Enbrel Injection should be used with caution in patients with a history of hepatitis C.

Concomitant treatment with anakinra

  • Concomitant administration of Enbrel Injection and anakinra has been associated with an increased risk of serious infections and neutropenia compared with Enbrel Injection when administered alone.
  • This association has not demonstrated superior clinical benefit.
  • Therefore the combination of Enbrel Injection and anakinra is not recommended (see sections Interactions with other medicinal products and other forms of interaction and side effects ).

Concomitant treatment with abatacept

  • Concomitant administration of abatacept and Enbrel Injection in clinical studies has resulted in an increased incidence of serious adverse events.
  • This association did not demonstrate additional clinical benefit; therefore this combination is not recommended (see section Interactions with other medicinal products and other forms of interaction ).

Allergic reactions

  • Allergic reactions associated with the administration of Enbrel Injection have been frequently reported. These allergic reactions included cases of angioedema and urticaria; serious reactions have occurred. In case of severe allergic reaction or anaphylactic reaction, treatment with Enbrel Injection should be discontinued immediately and appropriate treatment instituted.
  • The needle guard of the pre-filled syringe contains latex (natural rubber) that can cause hypersensitivity reactions when handled or when Enbrel Injection is administered in persons with known or potential latex sensitivity.

immunosuppression

  • Anti-TNFs, including Enbrel Injection, may alter the patient’s immune defenses against infections and malignancies, especially as TNF mediates inflammation and modulates the immune response. cells. In a study of 49 adult patients with rheumatoid arthritis treated with Enbrel Injection, no reduction in delayed hypersensitivity, immunoglobulin levels, or changes in blood count was observed.
  • Two patients with juvenile idiopathic arthritis developed chickenpox with signs and symptoms of aseptic meningitis followed by a cure without sequelae. Patients exposed to the chickenpox virus should temporarily discontinue Enbrel Injection and prophylaxis with specific immunoglobulins should be considered.
  • The safety and efficacy of Enbrel Injection in immunocompromised patients have not been evaluated.

Malignant neoplasms and lymphoproliferative disorders

Solid tumors and hematopoietic disorders (excluding skin cancer)

  • Various cases of malignant tumors (breast cancer, lung cancer, lymphoma) have been reported after marketing.
  • In the controlled phases of clinical trials with anti-TNF, more cases of lymphoma were observed in patients who received anti-TNF than in control patients. However, the occurrence was rare and the follow-up period for patients on placebo was shorter than that for patients receiving anti-TNF therapy. After marketing, cases of leukemia have been reported in patients treated with anti-TNF. There is an increased risk of developing lymphoma or leukemia in patients with rheumatoid arthritis when the disease is old, highly active and inflammatory, which complicates the risk assessment.
  • In the current state of knowledge, the possibility of developing lymphoma, leukemia or other solid or haematopoietic malignancies in patients treated with anti-TNF can not be ruled out. Precautions should be taken when using anti-TNF therapy in patients with a history of malignancy or when continuing treatment in patients who develop malignancy.
  • Malignancies, some of which have been fatal, have been reported post-marketing in children, adolescents and young adults (up to age 22) treated with anti-TNF including Enbrel Injection (initiation of treatment ≤ 18 years). About half of the cases were lymphomas. Other cases were other types of malignancies, including rare malignancies usually associated with immunosuppression. The risk of developing malignant tumors in children and adolescents treated with anti-TNF can not be ruled out.

Skin cancers

  • Cases of melanoma and non-melanoma skin cancer have been reported in patients treated with anti-TNF including Enbrel Injection. Cases of Merkel cell carcinoma have been rarely reported after marketing in patients treated with Enbrel Injection. Periodic skin examinations are recommended for all patients, especially those with a risk factor for skin cancer.
  • Combining the results of clinical trials, more cases of non-melanoma skin cancer were observed in patients receiving Enbrel Injection compared to the control group, particularly in patients with psoriasis.

immunizations

  • Live vaccines should not be administered to patients treated with Enbrel Injection. No data are available on infectious transmission secondary to the administration of live vaccines in patients treated with Enbrel Injection.
  • In a randomized, double-blind, placebo-controlled clinical trial in adult patients with psoriatic arthritis, 184 patients also received a multivalent pneumococcal polysaccharide vaccine at week 4.
  • In this study, most patients with psoriatic arthritis treated with Enbrel Injection were able to increase the immune response of activated B cells to pneumococcal polysaccharide vaccine; however the aggregates were moderately low and some patients had increased their titre a factor of 2 compared to patients who were not treated with Enbrel Injection.
  • The clinical significance of these findings is unknown.

Autoantibody formation

  • Enbrel Injection may cause the formation of autoimmune antibodies.

Hematologic reactions

  • Rare cases of pancytopenia and very rare cases of bone marrow aplasia, some of which have been fatal, have been reported in patients treated with Enbrel Injection. Special attention should be paid to patients treated with Enbrel Injection who have a history of haematological involvement.
  • All patients and parents / relatives should be informed that if signs or symptoms suggestive of hematological involvement or infection (such as persistent fever, pharyngeal pain, bruising, bleeding, pallor) occur in the patient under Enbrel Injection they must immediately consult a doctor.
  • In these patients, additional tests, including a blood count, should be performed urgently; if hematological involvement is confirmed, treatment with Enbrel Injection should be discontinued.

Neurological disorders

  • Rare cases of CNS demyelinating disorders have been reported in patients treated with Enbrel Injection .
  • Very rare cases of demyelinating peripheral polyneuropathies have also been reported (including Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, demyelinating polyneuropathy and multifocal motor neuropathy). Although no clinical trials have been conducted to study Enbrel Injection therapy in multiple sclerosis patients, trials with other TNF blocking agents in patients with multiple sclerosis have shown that an increase in the activity of the disease. It is recommended to carefully evaluate the benefit / risk ratio, with a neurological evaluation before prescribing Enbrel Injection in patients with a history of demyelinating disease or in the event of recent onset of demyelinating disease,

Associated treatment

  • In a 2-year controlled clinical trial in patients with rheumatoid arthritis, the combination of Enbrel Injection and methotrexate did not show unexpected safety data, and the safety profile of Enbrel Injection associated with Methotrexate was similar to the profiles reported in studies with Enbrel Injection and methotrexate used alone. Long-term studies evaluating the tolerance of this association are currently underway. The long-term safety of Enbrel Injection in combination with other DMARDs has not been established.
  • The use of Enbrel Injection in combination with other systemic treatments or phototherapy in the treatment of psoriasis has not been studied.

Renal and hepatic insufficiency

  • Based on pharmacokinetic data , no dose adjustment is required in patients with renal or hepatic impairment; clinical experience in such patients is limited.

Congestive heart failure

  • Physicians should use Enbrel Injection with caution in patients with congestive heart failure (CHF). Post-marketing reports of worsening CHF, with or without an identifiable enhancing factor, have been reported in Enbrel Injection patients. There have also been rare cases (<0.1%) of de novo onset of CHF, including in patients with no known cardiovascular history. Some of these patients were under 50 years old. Two large clinical studies evaluating Enbrel Injection in the treatment of CHF were interrupted early due to a lack of efficacy. Although inconclusive, data from one of these studies suggests a possible trend toward worsening CHF, in patients receiving Enbrel Injection.

Alcoholic hepatitis

  • In a randomized, placebo-controlled, placebo-controlled Phase II study of 48 hospitalized patients treated with Enbrel Injection or placebo for moderate to severe alcoholic hepatitis, Enbrel Injection was not effective and the mortality rate of patients treated with Enbrel Injection was significantly higher. after 6 months. Therefore, Enbrel Injection should not be used in patients with moderate to severe alcoholic hepatitis.

Wegener granulomatosis

  • A placebo-controlled trial, in which 89 adult patients were treated with Enbrel Injection added to standard therapy (including cyclophosphamide or methotrexate, and glucocorticoids) for a median of 25 months, did not demonstrate that Enbrel Injection is a treatment. effective in Wegener granulomatosis. The incidence of non-cutaneous malignancies of different types was significantly higher in patients treated with Enbrel Injection than in the control group. Enbrel Injection is not recommended for the treatment of Wegener’s granulomatosis.

Hypoglycaemia in patients treated for diabetes

  • Hypoglycemia has been reported following Enbrel Injection initiation in patients receiving antidiabetic therapy. These hypoglycaemia required a reduction in antidiabetic treatment in some of these patients.

Special populations

Elderly patients

  • In phase 3 studies in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, no overall differences in adverse events, serious adverse events and serious infections were observed in patients with 65 years or older receiving Enbrel Injection compared to younger patients. However, caution should be exercised when treating elderly patients and special attention should be paid to the occurrence of infections.

Pediatric population

immunizations

  • It is recommended that children have up-to-date vaccinations, if possible, in accordance with the vaccination schedule in force before initiating treatment with Enbrel Injection (see Vaccinations above).
  • Inflammatory bowel disease (IBD) and uveitis in patients with juvenile idiopathic arthritis (JIA)
  • Cases of IBD and uveitis have been reported in patients with JIA treated with Enbrel Injection .

Drive and use machines

Pregnancy / Breastfeeding / Fertility

Women of childbearing age

  • Women of childbearing potential should be informed that they must use effective contraception to prevent pregnancy during treatment with Enbrel Injection and up to 3 weeks after stopping treatment.

enbrel pregnancy

  • Reproductive toxicity studies in rats and rabbits have not shown any damage to the fetus or to the newborn rat due to etanercept.
  • A higher rate of major congenital malformations was observed in an observational study comparing pregnancies exposed to etanercept in the first trimester to pregnancies not exposed to etanercept or other TNF-blockers (adjusted odds ratio). 2.4, 95% CI 1.0-5.5).
  • The major congenital malformations corresponded to those most frequently encountered in the general population and no particular pattern of abnormality was identified.
  • There was no change in the incidence of spontaneous abortions, stillbirths, or minor malformations.
  • So,Etanercept crosses the placenta and has been detected in the serum of infants whose mothers had been treated with Enbrel Injection during pregnancy.
  • Clinical consequences are not known, but infants may be at increased risk of infection. It is generally not recommended to administer live vaccines to infants up to 16 weeks after the last dose of Enbrel Injection received by the mother.

feeding

  • It has been reported that following subcutaneous administration, etanercept was excreted in human breast milk.
  • In lactating rats, after subcutaneous administration, etanercept was excreted in milk and detected in serum of neonates.
  • Because immunoglobulins, like many drugs, can be excreted in breast milk, it must be decided either to discontinue breastfeeding or to discontinue treatment with Enbrel Injection, taking into account the benefit of breastfeeding for breastfeeding.
  • child and the benefit of treatment for the woman.

Fertility

  • There are no preclinical data available on the peri- and postnatal toxicity of etanercept or on the effects of etanercept on fertility and overall reproductive function.

What should I do if I miss a dose?

It is important to use this medication consistently. If you have forgotten a dose:

Does it take longer than 24 hours before you should use the next dose?

  •  Use the missed dose immediately.
  • The next dose you can simply administer at the usual time the day after.

Does it take less than 24 hours before you should use the next dose?

  •  Then talk to your doctor. Sometimes you have to skip the missed dose.
  • Sometimes you should use the missed dose and postpone the next dose for a day.
  • Never use a double dose in one day.

What happens if I overdose from Enbrel Injection ?

  • No toxic dose limits were observed during clinical trials in patients with rheumatoid arthritis. The highest dose tested was an intravenous challenge dose of 32 mg / m 2 , followed by subcutaneous doses of 16 mg / m 2administered twice weekly.
  • One patient with rheumatoid arthritis mistakenly self-administered Enbrel Injection 62 mg subcutaneously twice weekly for three weeks without adverse effects.
  • There is no known antidote for Enbrel Injection.

What is  Forms and Composition?

Solution for injection SC (clear, colorless or pale yellow) 25 mg and 50 mg:  Pack of 4 pre-filled syringes * + 4 alcoholic buffers.
*   The needle guard contains natural rubber (latex): see Warnings and Precautions for use . Solution for injection SC (clear, colorless or pale yellow) 50 mg:   Pack of 4 pre-filled pens (Myclic) * + 4 alcoholic tampons. *   The pen cap contains natural rubber (latex): see Warnings and Precautions for use . Powder (white) and solvent (clear and colorless) for 10 mg SC injection for pediatric use:  
Box of 4 vials of powder + 4 syringes pre-filled with solvent (water ppi) + 4 needles + 4 adapters for vial + 8 alcohol swabs.
Powder (white) and solvent (clear and colorless) for solution for injection SC 25 mg:   Set of 4 vials of powder + 4 pre-filled syringes of solvent (water ppi) + 4 needles + 4 adapters for vial + 8 alcohol swabs.

NOT’s

Edrug-online contains comprehensive and detailed information about drugs available in the medical field, and is divided into four sections:

general information:

  • Includes a general description of the drug, its use, brand names, FAQs, and relevant news and articles

Additional information:

  • General explanation about dealing with the medicine: how to take the medicine, the doses and times of it, the start and duration of its effectiveness, the recommended diet during the period of taking the medicine, the method of storage and storage, recommendations in cases for forgetting the dose and instructions to stop taking the drug and take additional doses.

Special warnings:

  • For pregnant and breastfeeding women, the elderly, boys and drivers, and use before surgery.

Side effects:

  • It treats possible side effects and drug interactions that require attention and its effect on continuous use.
  • The information contained in this medicine is based on medical literature, but it is not a substitute for consulting a doctor.
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Humira injection pen Uses, Dosage, Side Effects, Precautions & Warnings https://edrug-online.com/73/humira-pen.html https://edrug-online.com/73/humira-pen.html#respond Sun, 26 Jul 2020 08:54:33 +0000 http://www.edrug-online.com/?p=73 what is humiraHumira injection pen >>> Generic drug of the Therapeutic Class: Immunology Active ingredients: Adalimumab What exactly does Humira do? Adalimumab suppresses body defenses and inhibits inflammation. In joint inflammations (rheumatism, Bechterew’s disease), inflammatory bowel disease (Crohn’s disease, ulcerative colitis), the skin disease psoriasis and other skin conditions. Furthermore, in the eye disease uveitis and sometimes in […]]]> what is humira

Humira injection pen >>> Generic drug of the Therapeutic Class: Immunology
Active ingredients: Adalimumab

What exactly does Humira do?

  • Adalimumab suppresses body defenses and inhibits inflammation.
  • In joint inflammations (rheumatism, Bechterew’s disease), inflammatory bowel disease (Crohn’s disease, ulcerative colitis), the skin disease psoriasis and other skin conditions. Furthermore, in the eye disease uveitis and sometimes in sarcoidosis (Besnier-Boeck’s disease).
  • Usually you notice within a few weeks that the disease becomes calmer. Do you notice no effect within 2 to 4 months? Your doctor will then look for another medication for you.
  • You can administer the medication yourself. The doctor or nurse will explain to you how to do this.
  • You usually use an injection once every two weeks; sometimes once a week
  • You may experience redness, itching, pain and swelling at the site of the injection. Usually this will change automatically within a few days. Always give the injection in a different place.
  • Other side effects: respiratory or other infections, gastrointestinal complaints and headache. Blood disorders can occur after a few weeks to months. The doctor will therefore regularly check your blood. Do you get sore throat, fever or do you get bruises quickly? Then tell your doctor.

what is humira used for and

indication?

Rheumatoid arthritis

Humira in combination with methotrexate is indicated for:

  1. the treatment of moderate to severely active rheumatoid arthritis in adults when the response to DMARDs, including methotrexate, is inadequate.
  2. the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate.
  3. Humira may be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate.
  4. Humira has been shown to slow the progression of X-ray structural joint damage and improve functional abilities when administered in combination with methotrexate.

Juvenile idiopathic arthritis

Polyarticular juvenile idiopathic arthritis

  1. Humira in combination with methotrexate is indicated for the treatment of progressive polyarticular juvenile idiopathic arthritis in patients from 2 years of age in case of insufficient response to one or more DMARDs.
  2. Humira can be given as monotherapy in case of intolerance to methotrexate or when continuation of treatment with methotrexate is inappropriate (for efficacy in monotherapy, ). Humira has not been studied in patients less than 2 years old.

Arthritis related to enthesitis

  1. Humira is indicated for the treatment of active arthritis related to enthesitis in patients from 6 years of age in case of insufficient response or intolerance to conventional therapy .

Axial spondyloarthritis

Ankylosing spondylitis (AS)

  • Humira is indicated for the treatment of severe and active ankylosing spondylitis in adults who have had an inadequate response to conventional therapy.

Axial spondyloarthritis without radiographic signs of SA

  • Humira is indicated for the treatment of severe axial spondyloarthritis without radiographic evidence of SA, but with objective signs of inflammation on MRI and / or elevated CRP in adults with inadequate response or intolerance to -non-steroidal inflammatory drugs.

Psoriatic arthritis

  • Humira is indicated for the treatment of active and active psoriatic arthritis in adults when the response to previous background therapy has been inadequate. Humira has been shown to slow the progression of peripheral joint structural damage as measured by radiography in patients with symmetrical polyarticular forms of the disease (see section 5.1 ) and improves functional abilities.

Psoriasis

  • Humira is indicated for the treatment of moderate to severe plaque psoriasis in adult patients requiring systemic therapy.

Plaque psoriasis of the child and teenager

  • Humira is indicated for the treatment of chronic severe plaque psoriasis in children from 4 years of age and adolescents in case of insufficient response to topical treatment and phototherapy or when these treatments are inappropriate.

Suppurative hidrosadenitis (HS)

  • Humira is indicated for the treatment of active, moderate to severe suppurative hidrosadenitis (Verneuil’s disease) in adults and adolescents from 12 years of age when there is insufficient response to conventional systemic treatment of HS (see sections Property pharmacodynamicsand pharmacokinetic properties ).

Crohn’s disease

  • Humira is indicated for the treatment of moderate to severe active Crohn’s disease in adult patients who have not responded despite appropriate and well-managed corticosteroid and / or immunosuppressive therapy; or in whom this treatment is contraindicated or poorly tolerated.

Crohn’s disease in children and adolescents

  • Humira is indicated for the treatment of moderate to severe active Crohn’s disease in children and adolescents from 6 years of age who have not responded to conventional therapy including first-line and corticosteroid or an immunomodulator, or in which these treatments are poorly tolerated or contraindicated.

Hemorrhagic rectocolitis

  • Humira is indicated for the treatment of moderate to severe active ulcerative colitis in adult patients who have had an inadequate response to conventional therapy, including corticosteroids and 6-mercaptopurine (6-MP) or azathioprine (AZA), or in which this treatment is contraindicated or poorly tolerated.

uveitis

  • Humira is indicated for the treatment of non-infectious, intermediate, posterior uveitis and panuveitis in adult patients who have had an inadequate response to corticosteroid therapy, in patients requiring cortisone sparing, or in whom corticosteroid therapy is inappropriate.

what is the dosage of humira pen?

  • Treatment with Humira should be initiated and supervised by a specialist physician qualified in the diagnosis and treatment of the conditions in which Humira is indicated.
  • Ophthalmologists are advised to consult an appropriate specialist before initiating Humira therapy (see Warnings and Precautions , Neurological Events section).
  • A special surveillance card will be given to patients treated with Humira.
  • After proper training in the injection technique, patients can self-inject Humira, if their doctor considers it possible, under the guise of appropriate medical follow-up.
  • During treatment with Humira, other concomitant treatments (such as corticosteroids and / or immunomodulators) should be optimized.

Dosage

Rheumatoid arthritis

  • In adult patients with rheumatoid arthritis, the recommended dose of Humira is a single dose of 40 mg adalimumab administered every two weeks, subcutaneously. Methotrexate should be continued during treatment with Humira.
  • Glucocorticoids, salicylates, nonsteroidal anti-inflammatory drugs or analgesics may be continued during treatment with Humira. For combination with other non-rheumatic drugs other than methotrexate (see sections Warnings and Precautions and Pharmacodynamic Properties ).
  • As monotherapy, some patients who experience a decrease in their response to Humira may benefit from an increase in dosage to 40 mg adalimumab weekly.
  • Available data suggest that the clinical response is usually achieved by
  • 12 weeks of treatment. Further treatment should be reconsidered in a patient who has not responded within this time frame.

Interruption of treatment

  • It may be necessary to stop treatment, for example before surgery or in case of severe infection.
  • Available data suggest that re-introduction of Humira after stopping for 70 days or longer results in a similar clinical response and a similar safety profile to that observed before discontinuation of treatment.
  • Ankylosing spondylitis, axial spondyloarthritis without radiographic signs of AS and psoriatic arthritis
  • The recommended dose of Humira for patients with ankylosing spondylitis, axial spondyloarthritis without radiographic evidence of AS and for patients with psoriatic arthritis is 40 mg adalimumab single dose every two weeks, by subcutaneous injection. .

Available data suggest that the clinical response is usually achieved by

12 weeks of treatment. Further treatment should be reconsidered in a patient who has not responded within this time frame.

Psoriasis

  • The recommended dose of Humira for starting treatment in adults is 80 mg subcutaneously. The dosage will be continued one week later by 40 mg subcutaneously every other week.
  • Continuation of treatment beyond 16 weeks should be carefully reconsidered in a patient who has not responded within this time frame.
  • Beyond 16 weeks, in case of insufficient response, patients can benefit from an increase in the frequency of administration to 40 mg every week. The benefits and risks of continuous treatment with Humira every week should be carefully reconsidered in a patient if there is insufficient response after increasing the frequency of administration (see section 5.1 ). If a sufficient response is obtained after increasing the frequency of administration, the dose may then be reduced to 40 mg every 2 weeks.

Suppurative hidrosadenitis

  • The recommended dosing regimen for Humira in adult patients with suppurative hidrosadenitis (HS) is an initial dose of 160 mg on Day 1 (given as four 40 mg injections on one day or two injections of 40 mg daily for two consecutive days), followed by a dose of 80 mg two weeks later, on Day 15 (given as 2 injections of 40 mg on a day). Two weeks later (Day 29), continue with a dose of 40 mg weekly. If necessary, antibiotics may be continued during treatment with Humira. During treatment with Humira, it is recommended that the patient cleanse their lesions daily with a topical antiseptic.
  • Continuation of treatment beyond 12 weeks should be carefully reconsidered in patients with no improvement during this period.
  • If treatment is interrupted, Humira 40 mg weekly may be reintroduced .
  • The benefit and risk of continued long-term treatment should be regularly evaluated .

Crohn’s disease

  • In adult patients with moderate to severe active Crohn’s disease, the recommended induction regimen of Humira is 80 mg at week 0, followed by 40 mg at week 2. If it is necessary to obtain a faster response to treatment, the 160 mg schedule at week 0 (the dose can be given as 4 injections per day or 2 injections per day for two consecutive days), 80 mg at week 2, can be used knowing that the risk of adverse events is higher during this induction phase.
  • After induction therapy, the recommended dose is 40 mg administered every two weeks as a subcutaneous injection. If a patient has stopped taking Humira and the signs and symptoms of the disease recur, Humira can be re-administered. The experience of re-administration of treatment beyond 8 weeks after the previous dose is limited.
  • During maintenance therapy, corticosteroids may be progressively decreased as recommended by clinical practice.
  • Some patients who experience a decrease in the response to treatment may benefit from an increase in the frequency of administration to 40 mg Humira weekly.
  • Some patients who did not respond to treatment at week 4 may continue maintenance treatment until week 12. Continuation of treatment should be carefully reconsidered in a patient who has not responded within this time frame.

Hemorrhagic rectocolitis

  • In adult patients with moderate to severe ulcerative colitis, the recommended induction regimen of Humira is 160 mg at week 0 (the dose may be administered as 4 injections per day or 2 injections per day two consecutive days) and 80 mg at week 2. After induction therapy, the recommended dose is 40 mg given every two weeks as a subcutaneous injection.
  • During maintenance therapy, corticosteroids may be progressively decreased as recommended by clinical practice.
  • Some patients who experience a decrease in the response to treatment may benefit from an increase in the frequency of administration to 40 mg Humira weekly.

Available data suggest that the clinical response is usually

8 weeks of treatment. Humira treatment should not be continued in patients who have not responded within this time frame.

uveitis

  • In adult patients with uveitis, the recommended dose of Humira is an initial dose of 80 mg followed by a dose of 40 mg every two weeks starting one week after the first dose. Experience with initiation of Humira therapy as monotherapy is limited. Treatment with Humira may be started in combination with corticosteroids and / or other non-biological immunomodulatory therapies. The associated corticosteroid dose may be progressively decreased according to clinical practice, starting two weeks after initiation of Humira treatment.
  • An annual reassessment of the benefits and risks associated with long-term continuous therapy is recommended.

Elderly

  • No adjustment of the dosage is necessary. Patients with renal and / or hepatic impairment
  • Humira has not been studied in these patient populations. It is not possible to recommend dosages.

Pediatric population

Juvenile idiopathic arthritis

Polyarticular Juvenile Idiopathic Arthritis 2-12 Years

  • The recommended dose of Humira for patients aged 2 to 12 years with polyarticular juvenile idiopathic arthritis is 24 mg / m 2 body surface area up to a single maximum dose of 20 mg adalimumab (for 2-4 years) and up to a single maximum dose of 40 mg adalimumab (for patients aged 4 to 12 years) every two weeks by subcutaneous injection.
  • The injection volume is determined according to the size and weight of the patient (Table 1). A pediatric vial of 40 mg / 0.8 ml is available for patients who require a dose lower than a full dose of 40 mg.

Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in the Composition section.

Active tuberculosis or other severe infections such as sepsis and opportunistic infections.

Moderate to severe heart failure (NYHA classes III / IV) (see section Special warnings and precautions for use ).

What are the most common side effects of Humira?

In addition to the desired effect, this can cause drug side effects.

The main side effects are the following.

Sometimes (from 10 to 30 people in 100)

  • Redness , itching, pain and swelling at the site of injection. This usually changes after a few days.
  • Gastrointestinal complaints such as nausea, vomiting and abdominal pain. Rarely bloating, heartburn, belching or bleeding in the stomach or intestines.
  • Less red and white blood cells and fewer platelets . You therefore have a higher risk of infections , anemia and bleeding .
    Warn the doctor by sore throat, fever, blisters in the mouth, bruises, nose bleeds, pale skin, severe tiredness, shortness of breath, persistent cough or blood in the urine. Furthermore, if you have an infection, such as boils, shingles, fungal infections on a bladder infection.
    Tuberculosis can occur in rare cases. Before, during and up to 6 months after the last injection, the doctor will have your lungs checked for, among other things, tuberculosis.
  • Headache , rarely migraine. In rare cases, headache is the result of meningitis (neck catastrophe, meningitis). Consult your doctor for headaches that last longer than a day.
  • Muscle pain or muscle cramp . Usually the muscle pain is harmless, but in very rare cases a serious side effect can occur on the muscles. The symptoms of this serious side effect are muscle pain, muscle weakness, general feeling sick, fever, nausea and vomiting. The muscle pain is usually in the calves or lower back, but the whole body can also do a lot. If you experience these symptoms, you should consult your doctor as soon as possible.
  • Too much cholesterol and other fats in the blood. Your doctor will check your blood regularly for this.
  • Dry skin , skin rash , itching, hives, inflammation of the skin, sweating and breaking of the nails. Skin rash may be due to hypersensitivity (see Rare ). Consult the doctor for a rash.

Rarely (from 1 to 10 in 100 people)

  • Psychological complaints such as anxiety, depression, mood swings and insomnia.
  • Spirky feeling . Very rare ringing in the ears, deafness.
  • Nervous abnormalities . Warn your doctor if you notice a numb or tingling sensation in the arms or legs. In people with multiple sclerosis (MS) or optic nerve abnormalities, the symptoms can worsen.
  • Eye complaints such as painful eyes and inflamed eyes. Very rare double vision and inflammation of the eyelids. It can also reduce vision. Then tell your doctor.
  • Dry mucous membranes . This is most noticeable in dry eyes and dry mouth.
  • Flushing and dizziness of . These side effects are the result of the blood vessels becoming wider.
  • Increased blood pressure, accelerated heartbeat, chest pain and palpitations. Very rarely, a heart attack or stroke can occur. In people with high blood pressure , the doctor will check blood pressure regularly.
  • Hypersensitivity . You can notice this by skin rash, hives and itching. Severe hypersensitivity can be seen from chest tightness or a swollen face, lips, mouth, tongue or throat. You can be very stuffy.
    Very rarely, a severe hypersensitivity reaction occurs with red spots and blisters on the skin. In these cases, you should immediately seek out a doctor or go to the First Aid Service. If you are hypersensitive, you should not use adalimumab. Therefore, pass this on to the pharmacist. The pharmacy team can then ensure that you do not get this medication again.

Very rare (affects less than 1 in 100 people)

  • People with heart failure may suffer more from their complaints. In the event of increased fluid retention (thick ankles) or shortness of breath, you should warn the doctor.
  • Disorders of the liver , pancreas , gallbladder or spleen . Tell your doctor immediately if you have a fever, night sweats, weight loss, abdominal pain, swollen belly, yellow skin color and whites, nausea and dark urine. People who have had hepatitis B before may be given this again.
  • Lung disorders . You may notice this by shortness of breath, cough or fever. In some cases severe pneumonia can develop. Consult your doctor when these symptoms occur.
  • More risk of chronic diseases , such as lupus erythematodes (LE), blood vessel inflammation (vasculitis), organ inflammation (sarcoidosis), intestinal inflammation.
  • More risk of certain types of cancer , such as lymphoma , blood cancer (leukemia), skin cancer, breast cancer, cervical cancer or lung cancer.

Consult your doctor if you suffer too much from one of the above mentioned side effects or if you experience other side effects that you are worried about.

humira drug interactions

  • Humira has been studied in patients with rheumatoid arthritis, polyarticular juvenile idiopathic arthritis and psoriatic arthritis taking Humira monotherapy and those taking concomitant methotrexate.
  •  Antibody formation was lower when Humira was administered concurrently with methotrexate compared to its use as monotherapy.Administration of Humira without methotrexate resulted in increased antibody formation, increased clearance, and decreased efficacy of adalimumab .
  • The combination of Humira and anakinra is not recommended ( Special warnings and precautions for use “Simultaneous administration of biological first-line drugs or α -TNF antagonists “).
  • The combination of Humira and abatacept is not recommended. Special warnings and precautions for use “Simultaneous administration of biological DMARDs or TNFα antagonists “.

Humira pen Warnings and Precautions

In order to improve the traceability of biological drugs, the brand name and lot number of the product administered must be clearly recorded.

infections

  • Patients receiving TNF antagonists are more prone to severe infections. Impaired lung function may increase the risk of developing infections. Patients should therefore be closely monitored for infections (including tuberculosis) before, during and after treatment with Humira. The duration of elimination of adalimumab can be up to four months, the monitoring should be continued throughout this period.
  • Humira treatment should not be initiated until progressive infections, including chronic or localized infections, are controlled. In patients who have been exposed to tuberculosis or who have traveled to areas at high risk of tuberculosis or endemic mycoses, eg histoplasmosis, coccidioidomycosis or blastomycosis, the risks and benefits of Humira treatment should be considered before initiation. treatment (see opportunistic infections).
  • Patients who develop a new infection during treatment with Humira should be carefully monitored and a complete diagnostic assessment should be performed. If a new severe infection or sepsis develops, Humira should be discontinued and appropriate antimicrobial or antifungal therapy initiated until the infection is controlled. The physician should exercise caution before using Humira in patients with a history of recurrent infection or under underlying conditions that may predispose them to infections, including concomitant treatment with immunosuppressive drugs.

Serious infections

  • Serious infections, including septicemia due to bacterial, mycobacterial, invasive fungal, parasitic, viral or other opportunistic infections, such as listeriosis, legionellosis and pneumocystosis, have been reported in patients treated with Humira.
  • Other serious infections observed in clinical trials include pneumonia, pyelonephritis, septic arthritis and sepsis Cases of infections requiring hospitalization or having a fatal outcome have been reported.

Tuberculosis

  • Cases of tuberculosis, including cases of reactivation of tuberculosis and primary tuberculosis infection, have been reported in patients receiving Humira. Cases of pulmonary and extra-pulmonary (ie disseminated) tuberculosis have been reported.
  • Before initiating Humira treatment, all patients should be screened for TB infection, active or otherwise (“latent”). This assessment should include a detailed medical assessment in patients with a history of tuberculosis or possible previous exposure to patients with active TB and / or current or past immunosuppressive therapy. Appropriate screening tests (eg, dermal tuberculin test and chest x-ray) should be performed in all patients (according to local recommendations). It is advisable to note the achievement and results of these tests in the patient’s monitoring card.
  • If active TB is diagnosed, treatment with Humira should not be initiated.
  • In all the situations described below, the benefit / risk ratio of the treatment should be very carefully evaluated.
  • In case of suspicion of latent tuberculosis, the consultation of a medical specialist, qualified in the treatment of tuberculosis, should be considered.
  • If latent TB is diagnosed, appropriate TB prophylaxis consistent with local recommendations should be initiated prior to initiation of Humira therapy.
  • Antituberculosis prophylaxis should also be considered prior to the initiation of Humira in patients with multiple or significant risk factors for tuberculosis despite a negative tuberculosis test and in patients with a history of latent or active tuberculosis. that the administration of appropriate anti-tuberculosis treatment can not be confirmed.
  • Cases of reactivation of tuberculosis despite prophylaxis have occurred in patients treated with Humira.Some patients who had been successfully treated for active TB developed the disease again during treatment with Humira.
  • Patients should be informed that they should consult their physician if signs or symptoms suggestive of TB infection (eg persistent cough, weight loss / weight loss, fever, apathy) occur during or after treatment with the doctor. Humira.

Other opportunistic infections

  • Opportunistic infections, including invasive fungal infections, have been observed in patients treated with Humira. These infections have not always been detected in patients receiving TNF antagonists, which has delayed the initiation of appropriate treatment, sometimes with a fatal outcome.
  • In patients with signs and symptoms such as fever, malaise, weight loss, sweating, coughing, dyspnoea and / or pulmonary infiltrates or other severe systemic disease with or without concomitant shock, an invasive fungal infection should be suspected; in this case, the administration of Humira should be stopped immediately. Diagnosis and initiation of empirical antifungal therapy in these patients should be made in consultation with a physician experienced in the management of patients with invasive fungal infections.

Reactivation of hepatitis B

Hepatitis B reactivation occurred in patients who received a TNF antagonist y Comris Humira and who were chronic carriers of this virus (ie, positive surface antigen – HBsAg positive). Some cases have had a fatal outcome. Patients should be screened for HBV infection before initiating Humira treatment. 

For patients for whom the hepatitis B test is positive, it is recommended that you consult a doctor who specializes in the treatment of hepatitis B. HBV carriers who require treatment with Humira should be observed carefully.

signs and symptoms of active HBV infection throughout treatment and for several months after discontinuation. 

He does not There is insufficient data available to treat antiviral-treated HBV patients to prevent reactivation of HBV and treated with a TNF antagonist. 

In patients who develop HBV reactivation, Humira should be discontinued and effective antiviral therapy and appropriate adjunctive therapy initiated.\

Neurological events

TNF antagonists, including Humira, have been associated in rare circumstances with the onset or exacerbation of clinical symptoms and / or radiological signs of demyelinating central nervous system disease including multiple sclerosis, optic neuritis and peripheral demyelinating disease, including Guillain-Barré syndrome. 

Caution should be exercised with prescribers prior to treatment with Humira in patients with demyelinating central or peripheral nervous system disease, pre-existing or recent onset; discontinuation of treatment should be considered if any of these disorders occur.

The association between intermediate uveitis and demyelinating diseases of the central nervous system is known.

Allergic reactions

In clinical trials, serious allergic reactions associated with Humira have been reported rarely and non-serious allergic reactions attributable to Humira have been infrequent. Cases of serious allergic reactions including anaphylactic reactions have been reported after administration of Humira. If an anaphylactic reaction or other severe allergic reaction occurs, the administration of Humira should be stopped immediately and appropriate treatment instituted.

immunosuppression

In a study of 64 patients with rheumatoid arthritis treated with Humira, there was no evidence of delayed-type hypersensitivity depression, decreased immunoglobulin levels, or a change in T and B effector lymphocyte counts, NK lymphocytes, monocytes / macrophages and neutrophil granulocytes.

Malignant neoplasms and lymphoproliferative disorders

  • In the controlled part of clinical trials with anti-TNF, more cases of cancer, including lymphoma, were observed in patients treated with anti-TNF than in patients in the control group. However, the incidence was rare. During post-marketing surveillance, cases of leukemia have been reported in patients treated with anti-TNF. In addition, there is a context of increased risk of lymphoma and leukemia in patients with old, inflammatory and highly active rheumatoid arthritis, which complicates the risk assessment. In the current state of knowledge, the possibility of a risk of developing lymphoma, leukemia or other malignant diseases in patients treated with anti-TNF can not be ruled out.
  • Malignant tumors, some of them fatal, have been reported post-marketing in children, adolescents, and young adults (up to the age of 22 years) treated with anti-TNF agents (initiation of pre-treatment). 18 years old), including adalimumab. About half of these cases were lymphomas. The other cases corresponded to other types of malignancies, including rare cancers generally associated with an immunosuppressive context. The risk of developing malignant tumors can not be ruled out in children and adolescents treated with anti-TNF.
  • During post-marketing surveillance, rare cases of T-cell hepatosplenic lymphoma have been identified in patients treated with adalimumab. This rare form of T lymphoma has a very aggressive evolution and is often fatal. Some of these T-cell hepatosplenic lymphomas have occurred in young adults with concomitant treatment with azathioprine or 6-mercaptopurine for inflammatory bowel disease. The potential risk of combining azathioprine or 6-mercaptopurine with Humira should be carefully considered.).
  • There are no studies in patients with a history of malignancy or in whom Humira treatment is continued after the development of cancer. Therefore, increased caution should be observed when considering treatment of these patients with Humira .
  • All patients, especially those with a history of intense immunosuppressive therapy or psoriasis and a history of puvathérapie, should be screened for non-melanoma skin cancer before and during treatment with Humira. Cases of melanoma and Merkel cell carcinoma have also been reported in patients treated with anti-TNF including adalimumab .
  • In a prospective clinical study evaluating the use of another anti-TNF agent, infliximab, in patients with chronic obstructive pulmonary disease (COPD), moderate to severe, more cancers, mainly lung cancer, were reported. head and neck, among patients treated with infliximab compared to patients in the control group. All patients had a history of heavy smoking. For this reason, care should be taken in the use of TNFα antagonist in patients with COPD, and also in patients at risk of cancer due to heavy smoking.
  • Based on current data, it is not known whether adalimumab treatment influences the risk of developing dysplasia or colon cancer. All patients with ulcerative colitis who are at high risk for dysplasia or colon cancer (eg, patients with early bleeding ulcerative colitis or primary sclerosing cholangitis) or who have a history of dysplasia or colon cancer should be referred to regular screening for dysplasia before treatment and throughout the course of their disease. This assessment should include colonoscopy and biopsies according to local recommendations.

Hematologic reactions

Rare cases of pancytopenia including aplastic anemia have been reported with TNF blockers. Undesirable effects of the blood system including medically significant cytopenias (eg thrombocytopenia, leukopenia) have been observed with Humira. All patients should be advised to seek immediate medical attention if they have signs or symptoms suggestive of blood disorders (eg, persistent fever, bruising, bleeding, pallor) under Humira. Discontinuation of Humira should be considered for patients who have significant blood abnormalities confirmed.

immunizations

  • Antibody responses similar to the standard 23-valent pneumococcal vaccine and vaccination against trivalent influenza virus were observed in 226 adults with rheumatoid arthritis treated with adalimumab or placebo. There are no data available on the secondary transmission of infection with live vaccines in patients receiving Humira.
  • In children and adolescents, it is recommended, if possible, that all vaccinations be up-to-date in accordance with the vaccination recommendations in force before the start of treatment with Humira.
  • Humira patients can receive multiple vaccines simultaneously, except for live vaccines. The administration of live vaccines to infants who have been exposed to adalimumab in utero is not recommended for 5 months following the last injection of adalimumab into the mother during pregnancy.

Congestive heart failure

  • In a clinical trial with another TNF antagonist, aggravation of congestive heart failure and increased mortality from congestive heart failure were observed. Cases of aggravation of congestive heart failure have also been reported in patients taking Humira. 
  • Humira should be used with caution in patients with mild heart failure (NYHA Class I / II). 
  • Humira is contraindicated in moderate to severe heart failure.
  • Humira treatment should be discontinued in patients with new or worsening symptoms of congestive heart failure.

Autoimmune processes

  • Humira treatment may result in the formation of autoimmune antibodies.
  • The impact of long-term Humira treatment on the development of autoimmune diseases is unknown. If a patient develops symptoms suggestive of lupus syndrome following Humira treatment and has a positive anti-double-stranded DNA reaction, treatment with Humira should not be continued .

Simultaneous administration of biological DMARDs or TNF antagonists

  • Serious infections have been observed in clinical studies when simultaneous administration of anakinra and another TNF-antagonist, etanercept, did not provide additional clinical benefit compared with etanercept alone. Due to the nature of the adverse effects observed with etanercept and anakinra combination therapy, similar adverse effects may also result from the combination of anakinra and other TNF antagonists.Therefore the combination of adalimumab and anakinra is not recommended (see section Interactions with other medicinal products and other forms of interaction ).
  • Concomitant administration of adalimumab with other biological DMARDs (eg anakinra and abatacept) or other TNF antagonists is not recommended because of the potential increase in the risk of infections, including serious infections, and other potential pharmacological interactions.

Surgery

  • Experience with tolerance during surgical procedures in patients treated with Humira is limited.
  •  The long half-life of adalimumab should be taken into account if surgery is planned. A Humira-treated patient requiring surgery should be carefully monitored for infections and appropriate actions should be undertaken.
  • Experience with Humira tolerance in patients undergoing arthroplasty is limited.

Occlusion of hail

  • In Crohn’s disease, treatment failure may indicate the presence of fixed fibrotic stenoses that may require surgical treatment. Available data suggest that Humira does not worsen or cause stenosis.

Elderly

The frequency of serious infections in Humira treated subjects over 65 years (3.7%) is higher than in patients younger than 65 years (1.5%). 

Some cases have had a fatal outcome. Special attention to the risk of infection should be given when treating elderly subjects.

Pediatric population

See Vaccinations above.

Drive and use machines

Humira may have a minor influence on the ability to drive and use machines. Vertigo and visual disturbances may occur after administration of Humira.

Humira and PREGNANCY / BREAST FEEDING / FERTILITY

Women of childbearing age, contraception in men and women

It is strongly recommended that women of childbearing potential use an effective method of contraception while taking Humira and continue for at least five months after the last Humira administration.

humira injection and pregnancy

  • For Humira, there is limited data on the use of this drug in pregnant women.
  • In a developmental toxicity study in monkeys, there was no evidence of maternal toxicity, embryo-toxicity, or teratogenic potential. There are no preclinical data on the postnatal toxicity of adalimumab.
  • Because of its inhibitory effect on TNFα, adalimumab administered during pregnancy may affect the normal immune responses of the newborn. Administration of adalimumab is not recommended during pregnancy.
  • In women who take adalimumab during pregnancy, adalimumab can cross the placenta and pass into their child’s blood. As a result, these children may have an increased risk of infections.
  •  The administration of live vaccines to children who have been exposed to adalimumab in utero is not recommended for 5 months following the mother’s last injection during pregnancy.

feeding

  • It is not known whether adalimumab is excreted in breast milk or passes into the systemic circulation after administration.
  • However, since human immunoglobulins pass into breast milk, women should not breastfeed for at least five months after the last Humira administration.

Fertility

  • There are no preclinical data on the effects of adalimumab on fertility.

What should I do if I miss a dose?

You usually use this medication once every 2 weeks. In some cases you use this medicine once a week: give the forgotten dose as soon as you remember.

Take the next dose on the normal day of the administration schedule.

What happens if I overdose from Humira ?

No dose-related toxicity was observed in the clinical trials. The highest dose evaluated was repeated doses of 10 mg / kg IV, which is approximately 15 times the recommended dose.

What is  Forms and Composition?

  • Solution for injection (clear, colorless) 40 mg SC:  0.4 ml pre-filled single-dose syringes + 1 alcohol swab, box of 2, in blister pack.
  • Pre-filled single-dose pens of 0.4 ml + 1 alcohol swab, box of 2, under blister. Solution for injection (clear, colorless) SC for pediatric use at 40 mg / 0.8 ml: 0.8 ml   vials for single use + 1 sterile syringe for injection + 1 needle + 1 adapter for vial + 2 alcohol swabs, box of 2.

NOT’s

Edrug-online contains comprehensive and detailed information about drugs available in the medical field, and is divided into four sections:

general information:

  • Includes a general description of the drug, its use, brand names, FAQs, and relevant news and articles

Additional information:

  • General explanation about dealing with the medicine: how to take the medicine, the doses and times of it, the start and duration of its effectiveness, the recommended diet during the period of taking the medicine, the method of storage and storage, recommendations in cases for forgetting the dose and instructions to stop taking the drug and take additional doses.

Special warnings:

  • For pregnant and breastfeeding women, the elderly, boys and drivers, and use before surgery.

Side effects:

  • It treats possible side effects and drug interactions that require attention and its effect on continuous use.
  • The information contained in this medicine is based on medical literature, but it is not a substitute for consulting a doctor.
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Remicade Uses, Dosage, Side Effects, Precautions & Warnings https://edrug-online.com/153/what-is-remicade.html https://edrug-online.com/153/what-is-remicade.html#respond Thu, 23 Jul 2020 08:04:38 +0000 http://www.edrug-online.com/?p=153 what is remicaderemicade >>> Generic drug of the therapeutic class: Immunology active ingredients: Infliximab what is remicade? Infliximab suppresses body defenses and inhibits inflammation. In joint inflammations (rheumatoid arthritis, Bechterew’s disease), psoriasis (scaling skin disease) and in chronic inflammatory bowel disease (Crohn’s disease, ulcerative colitis). You will usually receive a second infusion 2 weeks after the first […]]]> what is remicade

remicade >>> Generic drug of the therapeutic class: Immunology
active ingredients: Infliximab

what is remicade?

  • Infliximab suppresses body defenses and inhibits inflammation.
  • In joint inflammations (rheumatoid arthritis, Bechterew’s disease), psoriasis (scaling skin disease) and in chronic inflammatory bowel disease (Crohn’s disease, ulcerative colitis).
  • You will usually receive a second infusion 2 weeks after the first infusion and a third infusion 4 weeks later. You will then receive it every 6 to 8 weeks, depending on the course of your illness.
  • After the second or third infusion, you must notice the effect. Do you notice any effect after the third infusion? Your doctor will then look for another medication for you.
  • You get the infusion in the hospital. This takes 2 hours. After that you have to stay under control for 1 to 2 hours, because you can get fever, headaches, itching or rashes or can get anxious. The doctor can then quickly give you medication for this.
  • You can also react hypersensitive 3 to 12 days after the infusion, with swelling, fever, pain and skin rash. Then immediately notify a doctor.
  • You can also get infections more often, for example from the nose, throat, sinuses, bladder or skin. This is because the body defenses are reduced. Always consult your doctor if you have a fever.

what is the drug remicade used for and indication?

Rheumatoid arthritis

Remicade, in combination with methotrexate, is indicated for the reduction of signs and symptoms but also the improvement of functional abilities in:

  • adult patients with active disease when the response to anti-rheumatic drugs (DMARDs), including methotrexate, has been inappropriate.
  • adult patients with active, severe and progressive disease not previously treated with methotrexate or other DMARDs.

In these patient populations, a reduction in joint destruction, measured by radiography, has been demonstrated .

Crohn’s disease in adults:

Remicade is indicated in:

  • the treatment of moderate to severe active Crohn’s disease in adult patients who have not responded despite appropriate treatment and are well-managed with a corticosteroid and / or immunosuppressant;or in whom this treatment is contraindicated or poorly tolerated.
  • the treatment of fistulized active Crohn’s disease in adult patients who have failed to respond despite appropriate and well-conducted conventional therapy (including antibiotics, drainage and immunosuppressive therapy).

Crohn’s disease in children:

  • Remicade is indicated for the treatment of severe, active Crohn’s disease in children and adolescents aged 6 to 17 who have not responded to conventional therapy including a corticosteroid, an immunomodulatory agent and a first-line nutritional treatment. intention; or where these treatments are poorly tolerated or contraindicated. Remicade has only been studied in combination with conventional immunosuppressive therapy.

Hemorrhagic rectocolitis:

  • Remicade is indicated for the treatment of moderate to severe active ulcerative colitis in adult patients who have not responded adequately to conventional therapy including corticosteroids and 6-mercaptopurine (6-MP) or azathioprine ( AZA), or where this treatment is poorly tolerated or contraindicated.

 Hey colitis rragique in thechild:

Re cade is indicated for the treatment of colitis hey rragique severe active in children and adolescents aged 6 to 17 years q i have not replied to adequate ay to a milking nt conventional core ant corticosteroids and 6 – MP or the ‘ AZA, or in whom these mainten ts are poorly tolerated uagainst-ind c.Ankylosing spondylitis :

  • Remicade is indicated for the treatment of active, severe ankylosing spondylitis in adults who have not responded adequately to conventional therapy.

Psoriatic arthritis:

  • Remicade is indicated for the treatment of active and active psoriatic arthritis in adult patients when the response to previous treatment with DMARDs has been inadequate.

Remicade must be administered

  • – in combination with methotrexate
  • – or only in patients who have shown intolerance to methotrexate or in whom methotrexate is contraindicated

Remicade has been shown to improve physical function in patients with psoriatic arthritis and to slow the progression of peripheral arthritis on radiography in patients with symmetrical polyarticular forms of the disease.

Psoriasis:

  • Remicade is indicated for the treatment of moderate to severe plaque psoriasis in adult patients in the event of failure, contraindication, or intolerance to other systemic treatments including ciclosporin, methotrexate, or PUVA). pharmacodynamics ).

Remicade Dosage

Remicade must be initiated under the supervision of qualified physicians experienced in the diagnosis and treatment of rheumatoid arthritis, inflammatory bowel disease, ankylosing spondylitis, psoriatic arthritis or psoriasis. Remicade must be administered intravenously. Remicade infusions should be administered by qualified health professionals who are trained to detect infusion complications. Patients treated with Remicade should receive the package leaflet and the report card.

During treatment with Remicade, other concomitant treatments such as corticosteroids and immunosuppressants should be optimized.

remicade dosage for adults

In adults ( ≥ 18 years old)

Rheumatoid arthritis

  • 3 mg / kg administered as an intravenous infusion followed by additional infusions of 3 mg / kg at weeks 2 and 6 after the first infusion, and then every 8 weeks thereafter.
  • Remicade should be administered in combination with methotrexate.
  • Available data suggest that the clinical response is usually achieved within 12 weeks of treatment. If a patient responds inadequately or no longer responds after this period, a dose escalation of approximately 1.5 mg / kg can be considered, up to a maximum of 7.5 mg / kg every 8 months. weeks. Alternatively, administration of 3 mg / kg as often as every 4 weeks may be considered. If an adequate response is obtained, patients should be maintained at the dose or frequency of administration selected. Continuation of this treatment should be carefully reconsidered in patients for whom no therapeutic benefit has been demonstrated during the first 12 weeks of treatment or after dose adjustment.

Active Crohn’s disease, moderate to severe

  • 5 mg / kg administered by intravenous infusion, followed by an additional infusion of 5 mg / kg 2 weeks after the first infusion. If a patient does not respond after 2 doses, no additional treatment with infliximab should be given. Available data do not allow continuation of treatment with infliximab in non-responder patients within 6 weeks of initial infusion.

In responder patients, alternative strategies for continuing treatment are:

  1. Maintenance treatment: an additional infusion of 5 mg / kg at week 6 after the initial dose, followed by infusions every 8 weeks or
  2. Re-administration: An infusion of 5 mg / kg if the signs and symptoms of the disease reappear (see “Re-administration” below and Warnings and Precautions ).
  3. Although comparative data are lacking, limited data obtained from patients who initially responded to 5 mg / kg, but whose response was subsequently lost, indicate that some patients may regain a response after dose escalation (see section 4.2). Pharmacodynamic properties ). Continued treatment should be seriously questioned in patients showing no evidence of therapeutic benefit after dose adjustment.

Fistulized active Crohn’s disease

  • 5 mg / kg administered by intravenous infusion followed by additional infusions of 5 mg / kg at weeks 2 and 6 after the first infusion. If the patient does not respond after 3 doses, no additional treatment with infliximab should be given.

In responder patients, alternative strategies for continuing treatment are:

  • Maintenance treatment: additional infusions of 5 mg / kg every 8 weeks or
  • Re-administration: infusion of 5 mg / kg if the signs and symptoms of the disease recur, followed by infusions of 5 mg / kg every 8 weeks (see “Re-administration” below and Warnings section). and precautions for use ).
  • Although comparative data are lacking, limited data obtained from patients who initially responded to 5 mg / kg, but whose response was subsequently lost, indicate that some patients may regain a response after dose escalation (see section 4.2). Pharmacodynamic properties ). Continued treatment should be seriously questioned in patients showing no evidence of therapeutic benefit after dose adjustment.
  • In Crohn’s disease, the experience of re-administration in case of reappearance of the signs and symptoms of the disease is limited and comparative data on the benefit / risk ratio of alternative strategies for continued treatment are insufficient.

Hemorrhagic rectocolitis

  • 5 mg / kg administered as an intravenous infusion followed by additional infusions of 5 mg / kg at weeks 2 and 6 after the first infusion and then every 8 weeks thereafter.
  • Available data suggest that the clinical response is usually achieved within 14 weeks of treatment, ie after three doses. Continuation of this treatment should be carefully reconsidered in patients for whom no therapeutic benefit has been demonstrated during this time interval.

Ankylosing spondylitis

  • 5 mg / kg administered as an intravenous infusion followed by additional infusions of 5 mg / kg at weeks 2 and 6 after the first infusion, and then every 6 to 8 weeks thereafter. If a patient does not respond to week 6(ie after 2 doses), no additional treatment with infliximab should be given.

Psoriatic arthritis

  • 5 mg / kg administered as an intravenous infusion, followed by additional infusions of 5 mg / kg at weeks 2 and 6 after the first infusion, and then every 8 weeks thereafter.

Psoriasis

5 mg / kg administered as an intravenous infusion, followed by additional infusions of 5 mg / kg at weeks 2 and 6 after the first infusion, and then every 8 weeks thereafter. If a patient does not respond after week 14(ie after 4 doses), no additional treatment with infliximab should be given.

Re-administration for Crohn’s disease and rheumatoid arthritis

If the signs and symptoms of the disease recur, Remicade can be re-administered within 16 weeks of the last infusion. In clinical studies, delayed hypersensitivity reactions have been infrequent and occurred after Remicade-free intervals of less than 1 year (see sections Warnings and Precautions and Adverse Reactions). The safety and efficacy of re-administration after a Remicade-free interval of more than 16 weeks has not been established. This applies to both patients with Crohn’s disease and patients with rheumatoid arthritis.

Re-administration for ulcerative colitis

The safety and efficacy of re-administration, other than every 8 weeks, have not been established (seeWarnings and Precautions and Adverse Reactions sections ).

Re-administration for ankylosing spondylitis

The safety and efficacy of re-administration, other than every 6 to 8 weeks, have not been established (seeWarnings and Precautions and Adverse Reactions sections ).

Re-administration for psoriatic arthritis

The safety and efficacy of re-administration, outside the regimen every 8 weeks, have not been established (see Warnings and Precautions and Adverse Reactions sections ).

Re-administration for psoriasis

The limited experience of re-treatment of psoriasis with a single dose of Remicade after a 20-week interval suggests reduced efficacy and a higher incidence of mild-to-moderate perfusion reactions compared to an initial induction regimen (see section Pharmacodynamic properties ).

The limited experience of reintroduction of treatment following disease recovery suggests a greater incidence of infusion reactions, including severe reactions, compared to those seen with regularly administered maintenance therapy. every 8 weeks.

Re-administration for all indications

In the event of interruption of the maintenance treatment and the need to resume treatment, the use of the induction regimen is not recommended (see section 4.8 ). In this situation, Remicade should be re-initiated as a single administration followed by the maintenance dose as recommended above.

Elderly ( ≥ 65 years old)

  • Remicade has not been studied in elderly subjects. No major age-related differences were observed in clinical studies with respect to clearance or volume of distribution. No dose adjustment is necessary (see section Pharmacokinetic properties ). For more information on the safety of Remicade in elderly patients, see Warnings and Precautions and Adverse Reactions .

Renal and / or hepatic insufficiency

  • Remicade has not been studied in this patient population. No dose recommendation can be made (see section Pharmacokinetic properties ).

remicade pediatric dosage

Crohn’s disease (6 to 17 years old)

  • 5 mg / kg administered as an intravenous infusion followed by additional infusions of 5 mg / kg at weeks 2 and 6 after the first infusion and then every 8 weeks thereafter. The available data do not allow continuation of infliximab therapy in children and adolescents who have not responded within the first 10 weeks of treatment (see section 5.1 Pharmacodynamic properties ).
  • For some patients a shorter administration interval may be necessary to maintain the clinical benefit while for others a longer dose interval seems sufficient. The risk of adverse events is increased in patients for whom the interval of administration has been reduced to less than 8 weeks. Continuation of treatment in patients for whom a shorter administration interval is required should be carefully reconsidered if no additional therapeutic benefit is provided after a change in the dose range.
  • The safety and effectiveness of Remicade in children under 6 years of age with Crohn’s disease have not been established. The pharmacokinetic data currently available are described under Pharmacokinetic properties, but no dosage recommendation can be made for children under 6 years of age.

Hemorrhagic rectocolitis (6 to 17 years)

5 mg / kg administered as an intravenous infusion, followed by additional infusions of 5 mg / kg at weeks 2 and 6 after the first infusion, and then every 8 weeks thereafter. The available data do not allow continuation of infliximab treatment in children and adolescents who have not responded within the first 8 weeks of treatment.

The safety and effectiveness of Remicade in children under 6 years of age with ulcerative colitis has not been established. The pharmacokinetic data currently available are described under Pharmacokinetic properties, but no dosage recommendation can be made for children under 6 years of age.

Psoriasis

  • The safety and effectiveness of Remicade in children and adolescents under 18 years of age for the indication of psoriasis have not been established. Currently available data are described underPharmacokinetic properties, but no dosage recommendation can be issued.

Juvenile idiopathic arthritis, psoriatic arthritis and ankylosing spondylitis

  • The safety and efficacy of Remicade in children and adolescents under 18 years of age in the indications for juvenile idiopathic arthritis, psoriatic arthritis and ankylosing spondylitis have not been established. Currently available data are described under Pharmacokinetic properties, but no dosage recommendation can be issued.

Juvenile rheumatoid arthritis

  • The safety and effectiveness of Remicade in children and adolescents under 18 years of age for the indication of juvenile rheumatoid arthritis have not been established. Currently available data are described under Adverse Reactions and Pharmacokinetic Properties but no dosage recommendations can be made.

Renal and / or hepatic insufficiency

  • Remicade has not been studied in this patient population. No dose recommendation can be made (see section Pharmacokinetic properties ).

Administration mode

Remicade should be administered intravenously over a period of 2 hours. All patients receiving Remicade should be observed for at least 1 to 2 hours post-infusion because of the risk of acute infusion reactions.Emergency equipment such as adrenaline, antihistamines, corticosteroids and respiratory support should beavailable. Patients may be pretreated with, for example, an antihistamine, hydrocortisone and / or paracetamol and the infusion rate may be slowed down to reduce the risk of infusion reactions especially if there has already been antecedents (see Warnings and Precautions section ).

Infusion of shortened duration, for all indications in adults

In some carefully selected adult patients who have tolerated at least 3 initial Remicade infusions, each lasting 2 hours (induction therapy) and receiving maintenance therapy, administering the following infusions for a duration not to to be less than 1 hour, can be considered. If an infusion reaction occurs during a shortened infusion and if treatment is continued, a decrease in infusion rate should be considered for subsequent infusions. The shorter infusions at doses> 6 mg / kg have not been studied .

For preparation and administration instructions, see the Instructions for Use, Handling and Disposal section .

Contraindications

  • Infliximab hypersensitivity
  • Murine protein hypersensitivity
  • Tuberculosis
  • Severe infection
  • Stage III or IV heart failure
  • Child under 6
  • Feeding with milk
  • Lack of effective female contraception
  • Pregnancy

Hypersensitivity to the active substance, to other murine proteins, or to any of the excipients listed in the Composition section.

Patients with tuberculosis or other severe infections such as sepsis, abscesses, and opportunistic infections.

Patients with moderate or severe heart failure (class III / IV in the NYHA classification) (see sections Warnings and precautions for use and Undesirable effects).

how does remicade work?

Pharmacotherapeutic: Inhibitors Necrosis Factor alpha Tumors (TNF α ), code

ATC: L04AB02.

Action mechanism

  • Infliximab is a chimeric human monoclonal antibody / mouse that binds with high affinity to both soluble and transmembrane forms of TNF α but not to lymphotoxin  α (TNF β ).

Pharmacodynamic effects

  • Infliximab inhibits the functional activity of TNF α in a wide variety of biological assays in vitro. Infliximab prevented the disease in transgenic mice that develop polyarthritis following the expression of human TNFαand when administered after the onset of the disease, it allowed the injured joints to heal. In vivo, infliximab rapidly forms stable complexes with TNF α human, a process that parallels the loss of bioactivity of TNF α .
  • High concentrations of α- TNFhave been found in the joints of patients with rheumatoid arthritis and these are correlated with high activity of the disease. In rheumatoid arthritis, treatment with infliximab decreases the infiltration of inflammatory cells into the inflammatory parts of the joint as well as the expression of cell adhesion molecules, chemo-attraction and tissue degradation. After infliximab treatment, patients experienced decreased serum levels of interleukin-6 (IL-6) and C-reactive protein (CRP), and increased hemoglobin levels in patients with rheumatoid arthritis who had reduced hemoglobin. , compared to the basic values. Moreover, there was no decrease in the circulating lymphocyte level,in vitro compared to the cells of untreated patients. In patients with psoriasis, treatment with infliximab led to a decrease in epidermal inflammation and a normalization of keratinocyte differentiation in psoriatic plaques. In psoriatic arthritis, short-term treatment with Remicade reduces the number of T cells and blood vessels in the synovium and psoriatic skin.
  • Histological evaluation of colonic biopsies, obtained before and 4 weeks after administration of infliximab, revealed a substantial reduction of TNF αdetectable. Infliximab treatment of patients with Crohn’s disease is also accompanied by a significant reduction in the generally high serum marker of inflammation, CRP. Total peripheral leukocyte counts were only slightly affected in infliximab-treated patients, although changes from normal values ​​of lymphocytes, monocytes, and neutrophils were observed. Peripheral blood mononuclear cell count (PBMC) in infliximab-treated patients showed a stable proliferative response to stimuli compared to untreated patients, and no significant alterations in mononuclear cytokine production (PBMC) were observed. observed following treatment with infliximab. According toα and interferon- g . Additional histological studies have shown that infliximab treatment reduces the infiltration of inflammatory cells in the affected areas of the intestine as well as the presence of inflammation markers on these sites. Endoscopic studies on the intestinal mucosa have demonstrated mucosal healing in infliximab-treated patients.

Efficacy and clinical safety

Rheumatoid arthritis in adults

  • The efficacy of infliximab was evaluated in two pivotal, multicenter, randomized, double-blind clinical trials: ATTRACT and ASPIRE. In both studies, concomitant use of stable doses of folic acid, oral corticosteroids ( ≤10 mg / day) and / or nonsteroidal anti-inflammatory drugs (NSAIDs) was permitted.
  • The primary endpoints were the reduction of signs and symptoms assessed according to those of the American College of Rheumatology (ACR20 in ATTRACT, ACR-N landmark for ASPIRE), prevention of joint destruction, and improvement of functional abilities. 
  • A reduction in signs and symptoms was defined as at least equivalent to a 20% improvement (ACR20) in the number of swollen and painful joints, and to 3 of the following 5 criteria: (1) overall assessment by the physician, (2) overall assessment by the patient, (3) functional capacity measurement, (4) visual analogue scale of pain and (5) sedimentation rate of erythrocytes or C-reactive protein. The ACR-N uses the same criteria as the ACR20, calculated by taking the lowest percentage of improvement in the number of swollen joints, painful joints and the median value of the remaining 5 components of the ACR response. Articular destruction (erosion and narrowing of the joint space) of the hands and feet was measured by the change from the initial values ​​of van der Heijde’s modified Sharp total score (0-440). The Health Assessment Questionnaire (HAQ, scale 0-3) was used to measure average changes in functional abilities compared to baseline values. change from initial values ​​of van der Heijde’s modified Sharp total score (0-440). The Health Assessment Questionnaire (HAQ, scale 0-3) was used to measure average changes in functional abilities compared to baseline values. change from initial values ​​of van der Heijde’s modified Sharp total score (0-440). The Health Assessment Questionnaire (HAQ, scale 0-3) was used to measure average changes in functional abilities compared to baseline values.
  • The ATTRACT study evaluated responses at weeks 30, 54, and 102 in a placebo-controlled study in 428 patients with active rheumatoid arthritis despite methotrexate therapy. About 50% of the patients had a class III functional capacity. Patients received either placebo or 3 mg / kg or 10 mg / kg infliximab at weeks 0, 2 and 6 and then every 4 or 8 weeks. All patients received stable doses of methotrexate (average 15 mg / week) for 6 months prior to inclusion and were maintained at stable doses during the study.
  • The results at week 54 (ACR20, van der Heijde’s modified total score of Sharp and HAQ) are shown in Table 3. Improved clinical responses (ACR50 and ACR70) were observed in all infliximab-treated groups. weeks 30 and 54 compared with methotrexate alone.
  • A reduction in the rate of progression of joint destruction (erosion and narrowing of joint space) was observed in all infliximab treated groups at week 54 (Table 3).\
  • The effects observed at week 54 were maintained until week 102. Due to a number of study discontinuations, the significance of the difference in effects seen in infliximab-treated groups compared to methotrexate alone can not be defined.

remicade side effects

In addition to the desired effect, this can cause drug side effects.and many pepole wanna know  the most common side effects of remicade ,so let’s know it

what are the most common side effects of remicade

The most important side effects are the following.

Sometimes (from 10 to 30 people in 100)

  • Violent reaction to the infusion , directly or within 2 hours after the infusion. Symptoms include fever, shivering, headache, skin rash, itching, fatigue, chest pain, wheezing or shortness of breath . These infusion reactions are most common with the first and second infusions. The symptoms usually decrease with subsequent infusions. If it occurs during an infusion, the infusion must be stopped immediately. With a subsequent infusion, the doctor can prescribe medication to use in advance, so that you will suffer less from these complaints. It concerns the painkiller paracetamol, medicines for allergies, inhalers for shortness of breath and adrenal cortex hormones (corticosteroids).
  • Hypersensitivity symptoms, a few days after the infusion. This is especially common in people who have ever used infliximab and who now get infliximab again after a break of a few months. Muscle pain, joint pain, fever, skin rash, itching, hives, hoarseness, dry throat, swallowing disorders, headaches and swelling of the face, lips or hands may develop three to 12 days after treatment . Tell your doctor immediately if you experience this.
    In very rare cases a severe skin condition can develop with blistering. The blisters mainly develop on the lips and on the mucous membranes of the mouth and genitals. Then contact a doctor immediately.
  • More risk of infections , such as colds, bronchitis, forehead inflammation, bladder infections or skin infections. Also tuberculosis can rarely occur. Infections arise earlier because the body’s immune system is reduced. If you get a fever or signs of an infection, always consult your doctor. Lung examinations for, among other things, tuberculosis take place before, during and up to 6 months after the last infusion. In severe infections, use should be stopped.
    Rarely, a serious infection develops in the blood . This can sometimes only become noticeable after a few weeks of use.
  • Gastrointestinal complaints such as nausea and abdominal pain, rarely heartburn, constipation, abdominal pain or diarrhea.
  • Headache.

Rarely (from 1 to 10 in 100 people)

  • Blushing and dizziness because the blood vessels temporarily spread.
  • Increased blood pressure , therefore the doctor will regularly check your blood pressure.
  • Insomnia and fatigue.
  • Dry skin , itching, skin rash and sweating. Very rare hair loss, increased scaling. More chance of fungal nails.
  • Reduced production of red and white blood cells or platelets. This can occur after a few weeks or months. Your doctor will therefore have the blood checked regularly. You notice extreme fatigue, sore throat, fever, blisters in the mouth, bruises or bloody noses and more chance of infections. In these cases, tell your doctor immediately.
  • Nervous abnormalities . Warn your doctor if you notice a numb or tingling sensation in the arms or legs. In people with multiple sclerosis (MS) or optic nerve abnormalities, the symptoms can worsen.
  • Eye complaints such as irritated red eyes. Very rare corneal inflammation, Also the vision during the infusion up to 2 hours after it can temporarily deteriorate.
  • Joint pain or muscle pain.

Very rare (affects less than 1 in 100 people)

  • People with heart failure may be more affected by their symptoms. In the event of increased fluid retention (thick ankles) or shortness of breath, you should warn your doctor.
  • Psychological symptoms such as depression, confusion, restlessness and memory loss.
  • More risk of chronic diseases , such as lupus erythematodes (LE), blood vessel inflammation, inflamed muscles and skin (dermatomyositis), organ inflammation (sarcoidosis), liver inflammation (hepatitis), intestinal inflammation and ocular inflammation (uveitis).
  • More risk of certain types of cancer , such as lymphoma , blood cancer (leukemia), skin cancer, breast cancer, cervical cancer or lung cancer. For women: it is important to continue to participate in population screening for uterine cancer, even if you are over 60 years of age.
  • Inflammation of the liver or pancreas . In case of sudden severe pain in the abdomen or yellow discoloration of the skin or mucous membranes, immediately inform your doctor. People who have had hepatitis B before may be given this again.

Consult your doctor if you suffer too much from one of the above mentioned side effects or if you experience other side effects that you are worried about.

remicade drug interactions

No interaction studies were performed.

  • In patients with rheumatoid arthritis, psoriatic arthritis or Crohn’s disease, there is evidence that concomitant use of methotrexate or other immunosuppressants reduces the formation of anti-infliximab antibodies and increases plasma concentrations of infliximab. However, the results are uncertain because of the limitations of the methods used for serum testing of infliximab and anti-infliximab antibodies.
  • Corticosteroids do not appear to affect the pharmacokinetic parameters of infliximab clinically significantly.
  • The combination of Remicade with other biotherapies used to treat the same conditions as Remicade, including anakinra and abatacept is not recommended (see Warnings and Precautions ). 
  • Concomitant administration of live vaccines with Remicade is not recommended (see Warnings and Precautions ).
  • It is recommended not to concomitantly administer therapeutic infectious agents with Remicade (seeWarnings and Precautions ).

Remicade Warnings and Precautions

In order to improve the traceability of biological drugs, the brand name and lot number of the administered product must be clearly recorded (or recorded) in the patient’s chart.

Infusion-related reactions and hypersensitivity

  1. Infliximab has been associated with acute infusion-related reactions including anaphylactic shock and delayed hypersensitivity reactions.
  2. Acute infusion-related reactions with anaphylactic reactions that may occur at the time (within the first few seconds) of the infusion or within a few hours of the start of the infusion. When these acute infusion reactions occur, the infusion should be discontinued immediately. Emergency equipment such as adrenaline, antihistamines, corticosteroids and respiratory support should be available. Patients may be pretreated with, for example, an antihistamine, hydrocortisone and / or paracetamol to prevent the occurrence of mild and transient adverse effects.
  3. Anti-infliximab antibodies may develop and have been associated with an increase in the frequency of infusion-related reactions. A small proportion of these infusion-related reactions were severe allergic reactions. A relationship between the development of anti-infliximab antibodies and the decrease in response time was also observed. Co-administration of immunosuppressants has been associated with a lower incidence of anti-infliximab antibodies and a reduction in the frequency of infusion-related reactions.The effect of concomitant therapy with immunosuppressants was more marked in patients treated on demand than in patients under maintenance treatment. Patients who stop immunosuppressors before or during Remicade treatment have a higher risk of developing these antibodies. Anti-infliximab antibodies can not always be detected by taking blood. If severe reactions occur, symptomatic treatment should be given and Remicade should not be re-administered Side effects ).
  4. In clinical studies, delayed hypersensitivity reactions have been reported. The available data suggest an increased risk of delayed hypersensitivity with a prolongation of the remicade-free interval . Patients should be made aware of the need for immediate medical advice in the event of any delayed adverse event (see section 4.8 ). If after a long period of time without treatment with infliximab, patients are re-treated, they should be closely monitored for signs and symptoms of a delayed hypersensitivity reaction.

infections

  1. Patients should be carefully monitored for infections including tuberculosis before, during and after treatment with Remicade. Since the elimination of infliximab may take up to 6 months, surveillance should be maintained throughout this period. Remicade should not be re-administered if the patient develops a severe infection or sepsis.
  2. Caution should be exercised when the use of Remicade is considered in patients with chronic infection, a history of recurrent infections, or concomitant immunosuppressive therapy. Patients should be warned of the risk of infection and avoid exposure to any potential risk factors for infection.
  3. Alpha tumor necrosis factor (TNF α ) mediates inflammation and cell-mediated immune responses module.Experimental data show that TNF α is essential to fight against intracellular infections. Clinical experience has shown that host defenses against infection are impaired in some infliximab-treated patients.
  4. It should be emphasized that suppression of TNF α may mask the symptoms of an infection, such as fever.Early recognition of atypical clinical pictures of serious infections and clinical pictures typical of rare and unusual infections is important in order to reduce delays in diagnosis and treatment.
  5. Patients treated with anti-TNF are more exposed to severe infections.
  6. Tuberculosis, bacterial infections, including sepsis and pneumonia, invasive fungal infections, viral infections and other opportunistic infections have been observed in patients treated with infliximab. Some of these infections have had a fatal outcome; the most commonly reported opportunistic infections with a mortality rate> 5% include pneumocystosis, candidiasis, listeriosis and aspergillosis.
  7. Patients who develop a new infection during Remicade therapy should be closely monitored and fully diagnosed. Remicade administration should be discontinued if a patient develops a new serious infection or sepsis, and appropriate antimicrobial or antifungal therapy should be initiated until the infection is controlled.

Tuberculosis

  1. Cases of active TB have been reported in patients receiving Remicade. It should be noted that in the majority of these cases, tuberculosis was extra-pulmonary, presenting either as a local disease or a disseminated disease.
  2. Before initiating treatment with Remicade, active or inactive (“latent”) TB should be sought in all patients.This research should include a detailed medical interview detailing the personal history of tuberculosis, possible previous contacts with a TB patient, and previous and / or ongoing immunosuppressive therapies.Appropriate tests, that is to say, intradermal reaction to tuberculin and chest x-ray should be performed in all patients (without prejudging any local recommendations). It is recommended that the dates of these examinations be recorded on the patient’s report card. Prescribers are reminded that an intradermal reaction may be falsely negative, especially in a severely ill or immunocompromised patient.
  3. If active TB is diagnosed, treatment with Remicade should not be initiated .
  4. In case of suspicion of latent tuberculosis, it is advisable to consult a doctor specialized in the treatment of tuberculosis. In all the cases described below, the benefit / risk ratio of Remicade treatment should be carefully evaluated.
  5. If inactive (“latent”) TB is diagnosed, TB treatment adapted to latent TB should be started with a TB drug before initiating Remicade treatment, in accordance with national recommendations.
  6. In patients who have multiple or significant risk factors for tuberculosis and whose test for latent tuberculosis is negative, antituberculosis treatment should be considered before initiation of Remicade therapy.
  7. Anti-TB treatment should also be considered prior to initiating Remicade therapy in patients with a history of latent or active TB for whom the course of treatment can not be confirmed.
  8. Cases of active TB have been reported in patients treated with Remicade during and after treatment for latent TB.
  9. All patients should be made aware of the need to consult a physician if signs or symptoms suggestive of TB (eg, persistent cough, asthenia / weight loss, fever) occur during or after treatment with Remicade.

Invasive fungal infections

  1. In patients treated with Remicade, an invasive fungal infection such as aspergillosis, candidiasis, pneumocystosis, histoplasmosis, coccidiomycosis or blastomycosis should be suspected if they develop a serious systemic disease, and a doctor specializing in the diagnosis and treatment of fungal infections should be consulted early when auscultation of these patients. Invasive fungal infections may be in disseminated form rather than local form, and the antigen-antibody test may be negative in some patients with active infection. Appropriate empirical antifungal therapy should be considered as long as the diagnosis has been made taking into account both the risk of severe fungal infection and antifungal therapy.
  2. For patients who have stayed or traveled to endemic areas for invasive fungal infections such as histoplasmosis, coccidiomycosis or blastomycosis, the benefit / risk ratio of Remicade treatment should be carefully considered before initiation.

Crohn’s disease fistulized

  • Treatment with Remicade should not be initiated in patients with Crohn’s disease with acute suppurative fistula until all infectious sites, particularly abscesses, have been eliminated .

Reactivation of hepatitis B (HBV)

  • A reactivation of hepatitis B occurred in patients who received anti-TNF, including infliximab and who were chronic carriers of this virus. Some cases have been fatal.

The search for HBV infection should be made before initiating treatment with Remicade. For patients with a positive HBV test, consultation with a Hepatitis B specialist is recommended. Patients with HBV requiring Remicade therapy should be closely monitored for signs or symptoms. revealing active HBV infection throughout Remicade treatment and several months after the end of Remicade treatment. No relevant data to treat HBV-positive patients with antiviral therapy in conjunction with anti-TNF is available to prevent reactivation of HBV. In patients who develop HBV reactivation,

Hepatobiliary disorders

  • Very rare cases of jaundice and non-infectious hepatitis, some of which have the characteristics of autoimmune hepatitis, have been observed since the marketing of Remicade. Isolated cases of liver failure leading to liver transplantation or death have occurred. Evidence of liver injury should be sought in patients with symptoms or signs of hepatic dysfunction. If jaundice and / or elevation of ALT ≥ 5 times the upper normal limit develops, Remicade should be discontinued, and further investigation of abnormal signs should be conducted.

Concomitant administration of an inhibitory agent of TNF-alpha and anakinra

  • Of severe neutropenia and infections were seen in clinical trials in which anakinra and another agent anti-TNF- α , etanercept were administered concomitantly, no added clinical benefit compared to etanercept alone. Due to the nature of adverse effects reported during combination therapy of anakinra and etanercept, similar toxicities can result from the combination of anakinra with another agent anti- TNF α . Therefore, the combination of Remicade and anakinra is not recommended.

Concomitant administration of an inhibitor of TNF α , and abatacept

  • In clinical studies, concomitant administration of anti- TNF α and abatacept has been associated with an increased risk of infections including serious infections without increased clinical benefit compared to TNF alone . The combination of Remicade and abatacept is not recommended.

Concomitant administration with other biotherapies

  • There is insufficient information regarding the concomitant use of infliximab with other biotherapies used to treat the same conditions as infliximab. Concomitant administration of infliximab with these biotherapies is not recommended because of the potential increase in the risk of infections, and other potential pharmacological interactions.

Change of biological antirhistice treatments (DMARD)

Some precautions must be taken when changing a biological agent by another, and patients should be supervised, as the risk of adverse events including infections, may be increased.

Live vaccines and other therapeutic infectious agents

  • In patients receiving anti-TNF therapy, limited data are available on the response to vaccination with live vaccines or on the secondary transmission of infection by live vaccines. The use of live vaccines can lead to clinical infections, including disseminated infections. It is recommended not to administer live vaccines concomitantly with Remicade.
  • Other uses of therapeutic infectious agents such as live attenuated bacteria (eg, bladder instillation of BCG for the treatment of cancer) could lead to clinical infections, including disseminated infections. It is recommended not to administer therapeutic infectious agents concomitantly with Remicade.

Autoimmune processes

  • The relative deficiency of TNF α caused by anti-TNF therapy may result in the initiation of an autoimmune process. If symptoms suggestive of lupus-like lupus syndrome develop in a patient following treatment with Remicade and if the patient has anti-double-stranded DNA antibodies, a new treatment with Remicade should not be given ( see section on side effects ).

Neurological attacks

  • The use of TNF blocking agents, including infliximab, has been associated with reports of new or worsening clinical symptoms and / or radiographic evidence of central demyelinating disease, including multiple sclerosis. , and peripheral demyelinating disorders, including Guillain-Barré syndrome. In patients with a history or recent manifestations of demyelinating disease, the benefit / risk ratio of anti-TNF therapy should be carefully assessed before initiation of Remicade therapy. Remicade should be considered if these disorders occur.

Malignant neoplasms and lymphoproliferative disorders

  • In the controlled phases of clinical studies with TNF antagonists, more cases of tumors, including lymphomas, were observed among patients who received anti-TNF than in patients in the control group. In Remicade clinical studies covering all approved indications, the incidence of lymphoma in patients treated with Remicade was higher than that expected in the general population, but the frequency of lymphoma was rare. After marketing, cases of leukemia have been reported in patients treated with anti-TNF. There is an increased risk of developing lymphoma or leukemia in patients with long-standing, highly active and inflammatory rheumatoid arthritis, which complicates the risk assessment.
  • In an exploratory clinical study evaluating the use of Remicade in patients with moderate to severe chronic obstructive pulmonary disease (COPD), more malignancies have been reported in patients treated with Remicade than in patients in the control group. All patients had a history of heavy smoking. Precautions should be taken in patients at increased risk of tumors as a result of heavy smoking.
  • In the current state of knowledge, a risk of developing lymphomas or other malignancies in patients treated with an anti-TNF agent can not be ruled out (see section 4.8 ). Care should be taken when treatment with an anti-TNF agent is considered in patients with a history of malignancy or when continuing treatment in patients who develop a tumor.
  • Precautions should also be taken in patients with psoriasis who have a medical history of sustained immunosuppressive therapy or prolonged therapy with PUVA.
  • Malignant tumors, some of which have been fatal, have been reported post-marketing in children, adolescents, and young adults (up to age 22) treated with anti-TNF agents (initiation of treatment ≤ 18 years of age), such as Remicade. About half of the cases were lymphomas. The other cases corresponded to a different type of malignancy, including rare malignancies usually associated with immunosuppression. The risk of developing malignancies in patients treated with anti-TNF can not be ruled out.
  • Since the commercialization of Remicade, rare cases of hepatosplenic T-cell lymphoma have been reported in patients treated with anti-TNF including infliximab. This type of T lymphoma, a rare occurrence, is characterized by a very aggressive evolution and a usually fatal outcome. Almost all patients had been treated with AZA or 6-MP in combination or just before taking an anti-TNF. The vast majority of cases reported with Remicade occurred in patients with Crohn’s disease or ulcerative colitis and most of them were adolescent or young adult males. The potential risk of the combination of AZA or 6-MP with Remicade should be carefully considered.Side effects ).
  • Melanomas and carcinomas of Merkel cells have been reported in patients treated with anti-TNF agents, including Remicade Periodic skin examinations are recommended, especially for patients who have risk factors for skin cancer.
  • All patients with ulcerative colitis who are at high risk of developing dysplasia or colon carcinoma (for example, patients with long-standing ulcerative colitis or primary sclerosing cholangitis), or who have a history of dysplasia or colon carcinoma, should be be examined regularly for dysplasia before treatment and during the course of their disease. This evaluation should include colonoscopy and biopsies according to local recommendations. Current data do not indicate the influence of treatment with infliximab on the risk of developing dysplasia or colon cancer.
  • Since Remicade treatment has not been shown to increase the risk of developing cancer in patients treated with Remicade with newly diagnosed dysplasia, the risks and benefits should be carefully evaluated for each patient and the patient. discontinuation of the proposed treatment.

Heart failure

  • Remicade should be used with caution in patients with mild heart failure (NYHA Class I / II). Patients should be closely monitored and treatment with Remicade should not be continued in patients who develop new or worsening symptoms of heart failure (see Contraindications and Adverse Reactions sections ).

Hematologic reactions

  • Pancytopenia, leukopenia, neutropenia, and thrombocytopenia have been reported in patients receiving anti-TNF agents, such as Remicade. All patients should be informed of the need for immediate medical advice if signs and symptoms suggestive of blood dyscrasia (such as persistent fever, bruising, haemorrhage, pallor) occur. Discontinuation of Remicade should be considered in patients with confirmed significant haematological abnormalities.

Other

  • The safety of use in Remicade patients who have undergone surgery, including arthroplasty, is limited. The long half-life of infliximab should be considered when surgery is planned. If a patient requires surgery during treatment with Remicade, they should be closely monitored for infections and appropriate measures should be taken.
  • In Crohn’s disease, treatment failure may indicate the presence of fixed fibrotic stenoses that may require surgical treatment. Available data suggest that infliximab does not worsen or cause stenosis.

Special populations

Elderly (≥ 65 years old)

  • The incidence of serious infections in patients 65 years of age or older treated with Remicade was higher than in patients under 65 years of age. Some of them had a fatal outcome. Special precautions regarding the risk of infection should be taken in the elderly .

Pediatric population

infections

  • In clinical studies, infections have been reported more frequently in pediatric populations than in adult populations.

immunizations

  • It is recommended that children, if possible, be up-to-date with current vaccination recommendations before initiating treatment with Remicade.

Malignant neoplasms and lymphoproliferative disorders

  • Malignancies, including some fatal ones, have been reported post-marketing in children, adolescents, and young adults (up to age 22) treated with anti- TNF agents (initiation of treatment ≤ 18 years of age), such as Remicade. About half of the cases were lymphomas. The other cases corresponded to a different type of malignancy, including rare malignancies usually associated with immunosuppression. The risk of developing malignant tumors in children and adolescents treated with anti-TNF can not be ruled out.
  • Since the commercialization of Remicade, rare cases of hepatosplenic T-cell lymphoma have been reported in patients treated with anti-TNF including infliximab. This type of T lymphoma, a rare occurrence, is characterized by a very aggressive evolution and a usually fatal outcome. Almost all patients had been treated with AZA or 6-MP in combination or just before taking an anti-TNF. The vast majority of cases reported with Remicade occurred in patients with Crohn’s disease or ulcerative colitis and most of them were adolescent or young adult males. The potential risk of the combination of AZA or 6-MP with Remicade should be carefully considered.Side effects ).

Drive and use machines

Remicade may have a minor influence on the ability to drive and use machines. Dizziness may occur following administration of Remicade .

Remicade and PREGNANCY / BREAST FEEDING / FERTILITY

Women of childbearing age

Women of childbearing potential should use appropriate contraception to prevent pregnancy and continue using it for at least 6 months after the last Remicade treatment.

Pregnancy

  • The moderate number of pregnancies (about 450) under infliximab collected prospectively and with known outcomes, including a limited number of pregnancies with exposure during the first trimester of pregnancy (approximately 230), did not reveal any effects. unexpected about the progress of the pregnancy. Due to its inhibition of TNF α , infliximab administered during pregnancy could affect normal immune responses in the newborn. No evidence of maternal toxicity, embryotoxicity, or teratogenicity was reported in a mouse developmental toxicity study using a similar antibody that selectively inhibits). The clinical experience available is too limited to exclude any risk, therefore administration of infliximab is not recommended during pregnancy.
  • Infliximab crosses the placental barrier and has been detected up to 6 months in the serum of infants whose mothers had been treated with infliximab during pregnancy. As a result, these infants may be at increased risk for infections. It is not recommended to administer live vaccines to infants exposed in utero to infliximab in the 6 months following the last dose administered to the mother during pregnancy (see section Warnings and precautions and Interactions with other drugs and other forms of interaction ).

feeding

  • It is not known whether infliximab is excreted in breast milk or systemically absorbed after ingestion. Because human immunoglobulins are excreted in breast milk, women should not breastfeed for at least 6 months after treatment with Remicade.

Fertility

  • Preclinical data are insufficient to establish conclusions about the effects of infliximab on fertility and general reproductive functions .

What should I do if I miss a dose?

If you have forgotten the appointment with the hospital, you must make a new appointment as soon as possible.

What happens if I overdose from Remicade ?

No case of overdose has been reported. Single doses up to 20 mg / kg have been administered without toxic effects.

What is  Forms and Composition ?

  • Powder (freeze-dried white granule) for concentrate for IV infusion 100 mg:  Single-use vial, single box.

NOT’s

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Additional information:

  • General explanation about dealing with the medicine: how to take the medicine, the doses and times of it, the start and duration of its effectiveness, the recommended diet during the period of taking the medicine, the method of storage and storage, recommendations in cases for forgetting the dose and instructions to stop taking the drug and take additional doses.

Special warnings:

  • For pregnant and breastfeeding women, the elderly, boys and drivers, and use before surgery.

Side effects:

  • It treats possible side effects and drug interactions that require attention and its effect on continuous use.
  • The information contained in this medicine is based on medical literature, but it is not a substitute for consulting a doctor.
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