- 1 what is ixprim ?
- 2 what are ixprim tablets for and indication ?
- 3 IXPRIM Dosage
- 4 Contraindications
- 5 How it works IXPRIM?
- 6 IXPRIM Side Effects
- 7 IXPRIM Interactions
- 8 IXPRIM Warnings and Precautions
- 9 Drive and use machines
- 10 IXPRIM and PREGNANCY / BREAST FEEDING / FERTILITY
- 11 What should I do if I miss a dose?
- 12 What happens if I overdose from IXPRIM ?
- 13 What is Forms and Composition?
what is ixprim ?
- IXPRIM is a combination of 2 analgesics, tramadol and paracetamol, which work together to relieve your pain.
- IXPRIM is indicated for the treatment of moderate to severe pain when your doctor thinks that a combination of tramadol and paracetamol is needed.
- IXPRIM is reserved for adults and adolescents from 12 years old.
what are ixprim tablets for and indication ?
- Symptomatic treatment of moderate to severe pain.
- The use of Ixprim should be limited to patients whose moderate to severe pain requires treatment with a combination of paracetamol and tramadol ( see Pharmacodynamics ).
- RESERVED FOR ADULTS and ADOLESCENTS (from 12 years old).
- The use of IXPRIM should be limited to patients with moderate to severe pain requiring treatment with a combination of paracetamol and tramadol hydrochloride.
- The dose should be individually adjusted according to the intensity of the pain and the individual sensitivity of the patient.
- The recommended starting dose is 2 effervescent tablets of IXPRIM (75 mg tramadol hydrochloride and 650 mg paracetamol). Additional doses may be administered as needed, without exceeding 8 effervescent tablets per day (ie 300 mg tramadol hydrochloride and 2600 mg paracetamol).
- The catches must be spaced at least 6 hours apart.
- In no case should IXPRIM be administered longer than is strictly necessary (see Warnings and Precautions for Use section ). If the nature or severity of the disease require repeated treatment or prolonged treatment, careful and regular monitoring should be performed (with therapeutic breaks, if possible) to check if the further processing is required.
- The safety and efficacy of IXPRIM have not been established in children under 12 years of age. Treatment is not recommended in this population.
- The usual dosage may be used although a 17% increase in the elimination half-life of tramadol has been observed in healthy subjects over 75 years of age after oral administration. In patients over 75 years of age, a minimum interval of 6 hours between dosages is recommended due to the presence of tramadol.
Renal insufficiency :
- Due to the presence of tramadol, the use of IXPRIM is not recommended in cases of severe renal impairment (creatinine clearance <10 ml / min).
- In patients with moderate renal impairment (creatinine clearance between 10 and 30 ml / min), the interval between doses should be 12 hours. Since tramadol is eliminated very slowly by hemodialysis or haemofiltration, post-dialysis is not usually necessary to maintain analgesia.
- IXPRIM should not be used in patients with severe hepatic impairment (see section 4.3 ). In patients with moderate hepatic impairment, an increase in the interval between doses should be carefully considered (see Warnings and Precautions for Use section ).
Administration mode :
Oral way .
- The effervescent tablets should be dissolved in a glass of water.
- Tramadol hypersensitivity
- Paracetamol hypersensitivity
- Yellow-orange hypersensitivity S
- Acute poisoning with CNS depressants
- Severe hepatic impairment
- Uncontrolled epilepsy
- Feeding with milk
- Severe respiratory failure
- Severe renal failure (Clcr <10 ml / min)
- Alcohol consumption
- Child under 12
Hypersensitivity to the active substances, to orange yellow S dye or any of the excipients listed in Section Composition
Acute intoxication with alcohol, hypnotics, central analgesics, opioids or psychotropic drugs.
IXPRIM should not be given to patients who are being treated simultaneously or who have been treated within the previous 2 weeks with MAOIs.
Severe hepatic impairment.
Epilepsy not controlled by treatment (see Warnings and Precautions.).
How it works IXPRIM?
Tramadol hydrochloride is administered in a racemic form and the [-] and [+] forms of tramadol and its metabolite M1 are detected in the bloodstream. Although tramadol is absorbed rapidly after administration, its absorption is slower (and its half-life longer) than that of paracetamol.
After single oral administration of an effervescent tablet of tramadol hydrochloride / paracetamol (37.5 mg / 325 mg), peak plasma concentrations of 94.1 ng / ml [(+) – tramadol / (-) – tramadol] and 4 μg / ml (paracetamol) are respectively reached after 1.1 h [(+) – tramadol / (-) – tramadol] and 0.5 h (paracetamol). The average elimination half-lives t 1/2 are 5.7 h [(+) – tramadol / (-) – tramadol] and 2.8 h (paracetamol).
In pharmacokinetic studies in healthy volunteers after single and repeated oral administration of IXPRIM, no significant change in the kinetic parameters of each active ingredient was observed compared to the parameters observed after administration of each active ingredient used alone.
- Racemic tramadol is absorbed rapidly and almost entirely after oral administration. The average absolute bioavailability of a single dose of 100 mg is approximately 75%. After repeated administrations, the bioavailability increases to about 90%.
- After administration of IXPRIM the oral absorption of paracetamol is rapid and almost complete and occurs mainly in the small intestine. The peak plasma concentrations of paracetamol are reached within 1 hour and are not modified by the concomitant administration of tramadol hydrochloride.
- Oral administration of IXPRIM with food has no significant effect on peak plasma concentrations and absorption rate of tramadol or paracetamol; thus, IXPRIM can be administered independently of meals.
- Tramadol has a high tissue affinity (Vd, b = 203 ± 40 liters). The plasma protein binding is of the order of 20%.
- Paracetamol appears to be widely distributed to major tissues with the exception of fat. Its apparent volume of distribution is about 0.9 l / kg. A relatively small fraction (about 20%) of paracetamol binds to plasma proteins.
- Tramadol is extensively metabolised after oral administration. About 30% of the dose is excreted unchanged in the urine while 60% of the dose is excreted as metabolites.
- Tramadol is metabolized by O- demethylation (catalysed by the CYP2D6 enzyme) to the M1 metabolite, and by N- demethylation (catalyzed by the enzyme CYP3A) to the M2 metabolite. The metabolite M1 is then metabolized by N- demethylation and conjugation with glucuronic acid. The plasma elimination half-life of metabolite M1 is 7 hours. The metabolite M1 has antalgic properties and is more potent than the parent molecule. Plasma concentrations of the M1 metabolite are several times lower than those of tramadol and its contribution to the clinical effect is probably not modified during repeated administrations.
- Paracetamol is mainly metabolized in the liver according to 2 major liver pathways: glucuronidation and sulfoconjugation. This latter route can be rapidly saturated at dosages higher than the therapeutic doses. A small proportion (less than 4%) is transformed by cytochrome P 450 into an active metabolite (N-acetyl benzoquinone imine) which, under normal conditions of use, is rapidly detoxified by reduced glutathione and eliminated in the urine after conjugation with cysteine and mercaptopuric acid. On the other hand, during massive intoxications, the quantity of this toxic metabolite is increased.
- Tramadol and its metabolites are mainly eliminated by the kidneys. The half-life of paracetamol is approximately 2 to 3 hours in adults. It is a little shorter in children and a little longer in neonates and cirrhotic patients.
- Paracetamol is primarily eliminated by dose-dependent formation of glucuro- and sulfo-conjugated derivatives. Less than 9% of paracetamol is excreted unchanged in the urine.
In renal failure, the half-life of both substances is increased.
IXPRIM Side Effects
Like all medicines, IXPRIM 37.5 mg / 325 mg film-coated tablets can cause side effects, although not everybody gets them.
Very Frequent (more than 1 in 10 patients):
- feeling dizzy, drowsy.
Frequent (less than 1 in 10, but more than 1 in 100 patients):
- vomiting, difficult digestion (constipation, bloating, diarrhea), abdominal pain, dryness of mouth,
- itching, sweating,
- headache, tremors,
- confusion, sleep disturbances, changes in mood (anxiety, nervousness, euphoria).
Uncommon (less than 1 in 100 patients, but more than 1 in 1000 patients):
- increased blood pressure, heart rhythm disorders,
- difficulty or pain when you urinate,
- skin reactions (rashes, urticaria for example),
- tingling, numbness, tingling sensation in the limbs, tinnitus, involuntary muscle contractions,
- depression, nightmares, hallucinations (perception of things that do not exist in reality), amnesia,
- difficulty swallowing, blood in the stool,
- chills, hot flashes, chest pains,
- difficulty breathing.
Rare (less than 1 in 1,000 patients, but more than 1 in 10,000 patients):
- convulsions, difficulty coordinating movements,
- drug dependence,
- visual disturbances,
- transient loss of consciousness (syncope).
The following side effects have been reported in people taking medicines containing only tramadol or paracetamol. Contact your doctor if you experience any of these effects while taking IXPRIM 37.5 mg / 325 mg film-coated tablets:
- feeling weak when you get up after lying down or sitting down, heart rate decreases, appetite changes, muscle weakness, slowed or weakened breathing, mood changes, activity changes, changes in perception , aggravation of existing asthma.
- in rare cases, a rash, a sign of an allergic reaction, may develop with sudden swelling of the face and neck, difficulty breathing or decreased blood pressure and fainting. If you are concerned, stop your treatment and consult your doctor immediately. You must not continue taking this treatment.
In rare cases, taking a drug containing tramadol may cause dependence and make it difficult to stop treatment.
In rare cases, people who have been taking tramadol for some time may feel uncomfortable if treatment is stopped abruptly. They may feel restless, anxious, nervous or trembling. These people may be overactive, have trouble sleeping and have gastrointestinal disorders.
Some people have also had panic attacks, hallucinations, unusual sensations such as itching, tingling or numbness, and a ringing of ears. If you experience this type of symptoms after stopping IXPRIM 37.5 mg / 325 mg film-coated tablet, contact your doctor.
Exceptionally, blood tests may have revealed abnormalities, such as an abnormally low platelet count, which can cause bleeding from the nose or gums.
Use IXPRIM 37.5 mg / 325 mg, film-coated tablet with a thinning treatment (eg coumarin derivatives, warfarin) may increase the risk of bleeding. You should immediately report to your doctor any prolonged or unexpected bleeding.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This also applies to any undesirable effect that is not mentioned in this leaflet. You can also report side effects directly via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Pharmacovigilance Centers – Website:. By reporting side effects, you can help provide more information about the safety of the medicine.
Keep out of the reach and sight of children.
- Risk of serotonin syndrome: diarrhea, tachycardia, sweating, tremors, confusion or coma.
MAOI selective A
- By extrapolation from non-selective MAOIs
- Risk of serotonin syndrome: diarrhea, tachycardia, sweating, tremors, confusion or coma.
Selective MAOI B
- Manifestations of central excitement evoking serotonin syndrome: diarrhea, tachycardia, sweating, tremors, confusion, even coma.
- In case of recent treatment by MAOIs, observe a delay of 2 weeks before start of treatment with tramadol hydrochloride.
Associations advised against
- Alcohol enhancement of the sedative effect of opioid analgesics.
- Altered alertness can make driving dangerous and the use of machinery dangerous.
- Avoid taking alcoholic drinks and drugs containing alcohol.
Carbamazepine and other enzyme inducers
- Risk of decreased efficacy and duration of action due to decreased plasma concentrations of tramadol.
Morphine agonist-antagonists (buprenorphine, nalbuphine, pentazocine).
Decrease of the analgesic effect by competitive blocking of the receptors, with the risk of appearance of a withdrawal syndrome.
Associations to consider
- Isolated cases of serotonin syndrome with a chronological relationship to therapeutic doses of tramadol hydrochloride have been reported in association with other serotoninergic drugs such as selective serotonin reuptake inhibitors (SSRIs) and triptans. Signs of serotonin syndrome may include confusion, agitation, fever, sweating, ataxia, hyperreflexia, myoclonus, and diarrhea.
- Other morphine derivatives (including antitussive drugs and substitution treatments), benzodiazepines, barbiturates.
- Increased risk of respiratory depression, which can be fatal in case of overdose.
- Other central nervous system depressants, such as other morphine derivatives (including antitussive drugs and substitution treatments), barbiturates, benzodiazepines, other anxiolytics, hypnotics, sedative antidepressants, sedative antihistamines, neuroleptics, central antihypertensive drugs, thalidomide, baclofen .
- These medications may increase the central depression. Altered alertness can make driving dangerous and the use of machinery dangerous.
- Based on clinical need, an evaluation of the prothrombin level should be performed periodically with co-administration of IXPRIM with warfarin derivatives, with INR prolongations reported.
- Other active substances known to inhibit CYP3A4, such as ketoconazole and erythromycin, may inhibit the metabolism of tramadol (N-demethylation) and probably also the metabolism of the O-demethylated active metabolite. The clinical significance of this interaction has not been studied.
Drugs that lower the epileptogenic threshold, such as bupropion, antidepressants, serotonin reuptake inhibitors, tricyclic antidepressants and neuroleptics.
- Concomitant use of tramadol hydrochloride with these drugs may increase the risk of seizures. The rate of absorption of paracetamol can be increased by metoclopramide or domperidone and the absorption rate decreased by cholestyramine.
- In a limited number of studies, pre- or post-operative use of the anti-emetic 5HT3 receptor antagonist (ondansetron) has necessitated increased doses of tramadol hydrochloride in patients treated for post-operative pain. operating.
IXPRIM Warnings and Precautions
- In adults and adolescents from 12 years old. The maximum dose of 8 tablets ofIXPRIM should not be exceeded. To avoid the risk of accidental overdose, patients should be advised not to exceed the recommended dose and not to use other medicines containing paracetamol (including over-the-counter medications) or tramadol without doctor’s advice. .
- IXPRIM is not recommended for severe renal impairment (creatinine clearance <10 ml / min).
- IXPRIM should not be used in patients with severe hepatic impairment (see section 4.3). The risks associated with paracetamol overdose are higher in patients with non-cirrhotic alcoholic liver injury. In patients with moderate hepatic impairment, a prolongation of the dosing interval should be carefully discussed.
- IXPRIM is not recommended for severe respiratory failure.
- Tramadol hydrochloride is not suitable for substitution treatment in patients with opioid dependence. Indeed, although opioid agonist, tramadol hydrochloride can not correct the withdrawal symptoms of opioids.
- Seizures have been reported mainly in susceptible patients treated with tramadol hydrochloride and / or treated with drugs that may lower the seizure threshold, particularly selective serotonin reuptake inhibitors, tricyclic antidepressants, antipsychotics, central analgesics or local anesthetics. . Treatment-experienced epileptic patients or patients with seizures should be treated with IXPRIM only when absolutely necessary. Seizures have been reported in patients receiving tramadol hydrochloride at the recommended doses. The risk may be increased when doses of tramadol hydrochloride exceed the maximum recommended dose.
- Concomitant administration of agonist-antagonist opioids (nalbuphine, buprenorphine, pentazocine) is not recommended .
Precautions for use:
- Habituation and physical and / or mental dependence can develop, even at therapeutic doses. The clinical need for analgesic treatment should be reassessed on a regular basis (see section 4.2). In patients with opioid dependence and in patients with a history of abuse or dependence, treatment should be short-term and under strict medical supervision.
- IXPRIM should be used with caution in opioid-dependent patients, in patients with head trauma, in patients prone to seizures, in patients with bile duct dysfunction, in shock, with impaired consciousness. unknown origin, central or peripheral disorders of the respiratory function or an increase in intracranial pressure.
- Overdosage with paracetamol may cause liver toxicity in some patients.
- Withdrawal symptoms similar to those seen during opioid withdrawal may occur even at therapeutic doses and for short-term treatment (see section 4.8). Withdrawal symptoms can be avoided by gradually decreasing the doses at the end of treatment, especially after long periods of administration. Rare cases of dependence and abuse have been reported (see section 4.8).
- In one study, the use of tramadol during a general anesthesia with enflurane and nitrous oxide promoted intraoperative memory. Pending further new data, the use of tramadol during shallow anesthesia should be avoided.
- S orange yellow dye (E110) may cause allergic reactions.
- This medicine contains 7.8 mmol (179.4 mg) of sodium per effervescent tablet and should be taken into consideration in patients on a strict sodium diet.
Drive and use machines
- Tramadol hydrochloride may cause drowsiness or dizziness, which may be exacerbated by alcohol or other central nervous system depressants. In the event of these symptoms, the patient must not drive or use machines.
IXPRIM and PREGNANCY / BREAST FEEDING / FERTILITY
Since IXPRIM is a fixed combination of active ingredients based on tramadol hydrochloride, this medicine should not be administered during pregnancy.
Data on paracetamol :
- The results of the epidemiological studies have not revealed the deleterious effect of paracetamol used at the recommended doses.
Data on tramadol hydrochloride:
- Tramadol hydrochloride should not be used during pregnancy as there are no data of sufficient relevance to evaluate the safety of tramadol hydrochloride in pregnant women.
- Administered before or during delivery, tramadol hydrochloride does not affect uterine contractility. In neonates, it can induce changes in respiratory rate usually not clinically significant. Prolonged use during pregnancy may result in withdrawal syndrome in the newborn.
- Since IXPRIM is a fixed combination of active ingredients containing tramadol hydrochloride, this medicine should not be administered during breastfeeding.
Data on paracetamol :
Paracetamol is excreted in breast milk in non-clinically significant amounts. To date, published data do not contraindicate breastfeeding in women using drugs containing only paracetamol.
Data on tramadol hydrochloride :
Tramadol and its metabolites are found in low amounts in breast milk. During breastfeeding, approximately 0.1% of the dose administered to the mother could be ingested by the newborn. Tramadol hydrochloride should not be administered during breastfeeding.
What should I do if I miss a dose?
If you forget to take the tablets, the pain may reappear. Do not double the dose you forgot to take. Continue your treatment as before.
What happens if I overdose from IXPRIM ?
Ixprim is a fixed association of active ingredients. In case of overdose, the symptomatology may include the signs and symptoms of toxicity of tramadol, paracetamol or both active ingredients.
Symptoms related to tramadol overdose:
- In principle, during tramadol intoxication, symptoms similar to those caused by other centrally acting analgesics (opioids) are expected. These include, but are not limited to, miosis, vomiting, cardiovascular collapse, disturbances of consciousness to coma, convulsions and respiratory depression that may lead to respiratory arrest.
Symptoms related to paracetamol overdose:
- Intoxication is particularly feared in young children. During the first 24 hours, symptoms of paracetamol overdose manifest as pallor, nausea, vomiting, anorexia, and abdominal pain. Hepatic injury may occur within 12 to 48 hours after ingestion. Abnormalities of carbohydrate metabolism and metabolic acidosis may occur. In cases of massive overdose, hepatic failure may progress to encephalopathy, coma and death. Acute renal failure with acute tubular necrosis may occur even in the absence of severe hepatic impairment. Cases of cardiac arrhythmia and pancreatitis have been reported.
- Hepatic impairment may occur in adults after ingestion of 7.5 to 10 g or more of paracetamol. Excess toxic metabolites (usually degraded by glutathione oxidase when paracetamol is used at a therapeutic dose) could irreversibly bind to liver tissue.
- Emergency driving:
- Immediate transfer to a specialized environment.
- Maintaining respiratory and circulatory functions.
- Before starting treatment, a blood sample should be taken as soon as possible after overdose in order to measure plasma concentrations of paracetamol and tramadol and to perform liver tests.
- Liver tests should be performed initially (overdose) and repeated every 24 hours. Usually, there is an increase in liver enzymes (ASAT, ALAT), which normalize after one or two weeks.
- Perform gastric emptying by vomiting the patient (conscious patient), irritation or gastric lavage.
- The maintenance of vital functions, in particular the maintenance of freedom of the airways and cardiovascular function, must be put in place; naloxone is the antidote for respiratory depression; convulsions should be treated with diazepam.
- Tramadol is very poorly removed by hemodialysis or haemofiltration. The treatment of acute intoxication with Ixprim by hemodialysis or haemofiltration alone is not suitable for detoxification.
- Immediate treatment is essential in the management of overdosage with paracetamol. Even in the absence of clinically significant early symptoms, patients must be urgently transferred to hospital and placed under medical supervision. Gastric lavage should be performed in any adult or adolescent who has ingested approximately 7.5 g or more of paracetamol in the previous 4 hours or in a child who has been ingested ≥ 150 mg / kg paracetamol within 4 hours. Plasma paracetamol concentrations should be measured more than 4 hours after overdose to assess the risk of liver injury (using the paracetamol overdose nomogram). The administration of oral methionine or N-acetylcysteine IV (NAC), which may have a beneficial effect until at least 48 hours after overdose, may be necessary. Intravenous administration of NAC is more effective when initiated within 8 hours of overdose. However, N-acetylcysteine must be administered even if the management takes place more than 8 hours after the overdose and must be continued for the duration of the treatment. Treatment with N-acetylcysteine should be started immediately when massive overdose is suspected. Measures to maintain vital functions must be implemented. However, N-acetylcysteine must be administered even if the management takes place more than 8 hours after the overdose and must be continued for the duration of the treatment. Treatment with N-acetylcysteine should be started immediately when massive overdose is suspected. Measures to maintain vital functions must be implemented. However, N-acetylcysteine must be administered even if the management takes place more than 8 hours after the overdose and must be continued for the duration of the treatment. Treatment with N-acetylcysteine should be started immediately when massive overdose is suspected. Measures to maintain vital functions must be implemented.
- Regardless of the amount of paracetamol reported to have been ingested, the paracetamol antidote, N-acetylcysteine, should be administered orally or intravenously as soon as possible, preferably within 8 hours of intoxication.
What is Forms and Composition?
|Coated tablet :||p cp|
|Tramadol (DCI) hydrochloride||37.5 mg|
|Paracetamol (INN)||325 mg|
- Excipients: cellulose powder, pregelatinized starch, sodium carboxymethyl starch (type A), corn starch, magnesium stearate.
- Film coating : hypromellose, lactose monohydrate, titanium dioxide (E 171), macrogol 6000, yellow iron oxide (E 172), propylene glycol, talc.
- Lactose content: 1.784 mg / cp (as lactose monohydrate: 1.878 mg / cp).
|Effervescent tablet :||p cp|
|Tramadol (DCI) hydrochloride||37.5 mg|
|Paracetamol (INN)||325 mg|
- Excipients: dry sodium citrate, anhydrous citric acid, povidone K30, sodium bicarbonate, macrogol 6000, anhydrous colloidal silica, magnesium stearate, orange flavor (maltodextrin [corn], modified starch [E 1450], natural and artificial flavors), acesulfame potassium, saccharin sodium, orange yellow S (E 110).
- Sodium content (as monosodium citrate, sodium bicarbonate and sodium saccharin): 7.8 mmol (179.4 mg) / cp.
- Yellow orange content S: 0.4 mg / cp.
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