amgevita Uses, Dosage, Side Effects, Precautions & Warnings

 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.

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 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

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

Feeding with milk

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 ?

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 ).

• 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.