OXCARBAZEPINE MYLAN

Posology:

In mono- and adjunctive therapy, treatment with Oxcarbazepine Mylan is initiated with a clinically effective dose given in two divided doses. The dose may be increased depending on the clinical response of the patient. When other antiepileptic medicinal products are replaced by Oxcarbazepine Mylan, the dose of the concomitant antiepileptic medicinal products(s) should be reduced gradually on initiation of Oxcarbazepine Mylan therapy.

5). Therapeutic drug monitoring The therapeutic effect of oxcarbazepine is primarily exerted through the active metabolite 10-monohydroxy derivative (MHD) of oxcarbazepine (see section 5). Plasma level monitoring of oxcarbazepine or MHD is not routinely warranted.

4). In such situations, the dose of oxcarbazepine may be adjusted (based on plasma levels measured 2-4 hours post dose) to maintain peak MHD plasma levels< 35 mg/L. Adults Monotherapy Recommended initial dose Oxcarbazepine Mylan should be initiated with a dose of 600 mg/day (8-10 mg/kg/day) given in 2 divided doses.

Maintenance dose If clinically indicated, the dose may be increased by a maximum of 600 mg/day at approximately weekly intervals from the starting dose to achieve the desired clinical response. Therapeutic effects are seen at doses between 600 mg/day and 2,400 mg/day.

Controlled monotherapy trials in patients not currently being treated with antiepileptic medicinal products showed 1,200 mg/day to be an effective dose; however, a dose of 2,400 mg/day has been shown to be effective in more refractory patients converted from other antiepileptic medicinal products to oxcarbazepine monotherapy.

Maximum recommended dose In a controlled hospital setting, dose increases up to 2400 mg/day have been achieved over 48 hours. Adjunctive therapy Recommended initial dose Oxcarbazepine Mylan should be initiated with a dose of 600 mg/day (8-10 mg/kg/day) given in 2 divided doses.

Maintenance dose If clinically indicated, the dose may be increased by a maximum of 600 mg/day at approximately weekly intervals from the starting dose to achieve the desired clinical response. Therapeutic responses are seen at doses between 600 mg/day and 2,400 mg/day.

Maximum recommended dose Daily doses from 600 to 2,400 mg/day have been shown to be effective in a controlled adjunctive therapy trial, although most patients were not able to tolerate the 2,400 mg/day dose without reduction of concomitant antiepileptic medicinal products, mainly because of CNS-related adverse events.

Daily doses above 2,400 mg/day have not been studied systematically in clinical trials. Elderly (65 years old and above) No special dose recommendations are necessary in elderly patients because therapeutic doses are individually adjusted.

Dosage adjustments are recommended in elderly patients with renal impairment (creatinine clearance less than 30 ml/min) (see information below on dosage in renal impairment). Close monitoring of sodium levels is required inpatients at risk of hyponatraemia see section

Summary of the safety profile The most commonly reported adverse reactions are somnolence, headache, dizziness, diplopia, nausea, vomiting and fatigue occurring in more than 10% of patients. The safety profile is based on adverse events (AEs) from clinical trials assessed as related to oxcarbazepine.

In addition, clinically meaningful reports on adverse experiences from named patient programs and post-marketing experience were taken into account. Adverse drug reactions are listed by MedRA system organ class. Tabulated list of adverse reactions Frequency estimate*:- very common: ≥ 1/10; common: ≥1/100 - <1/10; uncommon: ≥1/1,000 - <1/100; rare: ≥ 1/10,000 - < 1/1,000; very rare: < 1/10,000 Within each system organ class, the adverse drug reactions are ranked by frequency, with the most frequent reactions first.

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Blood and lymphatic system disorders Uncommon:

Rare: Very rare: Leucopenia Bone marrow depression, aplastic anaemia, agranulocytosis, pancytopenia, neutropenia.

Thrombocytopenia Immune system disorders Rare:

Very rare: Anaphylactic reactions Hypersensitivity# Endocrine disorders Common: Uncommon: Weight increased Hypothyroidism Metabolism and nutrition disorders Common: Rare: Hyponatraemia† Inappropriate ADH secretion like syndrome with signs and symptoms of lethargy, nausea, dizziness, decrease in serum (blood) osmolality, vomiting, headache, confusional state or other neurological signs and symptoms.

g. nervousness), affect lability, confusional state, depression, apathy.

Nervous system disorders Very common:

Common: Somnolence, headache, dizziness. Ataxia, tremor, nystagmus, disturbance in attention, amnesia, speech disorders (including dysarthria); more frequent during up titration of oxcarbazepine dose Eye disorders Very common: Common: Diplopia.

Vision blurred, visual disturbance. Ear and labyrinth disorders Common: vertigo.

Cardiac disorders Very rare:

Atrioventricular block, arrhythmia.

Vascular disorders Uncommon:

Hypertension Gastrointestinal disorders Very common: Common: Very rare: Vomiting, nausea Diarrhoea, abdominal pain, constipation. Pancreatitis and/or lipase and/or amylase increase.

Hepatobiliary disorders Very rare:

Hepatitis.

Skin and subcutaneous tissue disorders Common:

Uncommon: Rare: Very rare: Rash, alopecia, acne. Urticaria. 4).

Musculoskeletal and connective tissue disorders Rare:

Very rare: There have been reports of decreased bone mineral density, osteopenia, osteoporosis and fractures in patients on long-term therapy with oxcarbazepine. The mechanism by which oxcarbazepine affects bone metabolism has not been identified.

Systemic lupus erythematosus.

General disorders and administration site conditions Very common:

Common: Fatigue. Asthenia.

Investigations Uncommon:

Rare: Hepatic enzymes increased, blood alkaline phosphatase increased. Decrease in T4 (with unclear clinical significance). Injury, poisoning and procedural complications Uncommon Fall Description of selected adverse reactions #Hypersensitivity (including multi-organ hypersensitivity) characterised by features such as rash, fever.

g. g. g. g. g. g. pulmonary oedema, asthma, bronchospasms, interstitial lung disease, dyspnoea), angioedema. 4). In most cases, the hyponatriaemia is asymptomatic and does not require adjustment of therapy. g. blurred vision), hypothyroidism, vomiting, and nausea.

4). 1).

Reporting of suspected adverse reactions:

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4. Patients with hepatic impairment No dosage adjustment is required for patients with mild to moderate hepatic impairment. 2). 2). Dose escalation in renally impaired patients may require more careful observation. Paediatric population Recommended initial dose In mono- and adjunctive therapy, Oxcarbazepine Mylan should be initiated with a dose of 8-10 mg/kg/day given in 2 divided doses.

Maintenance dose In adjunctive therapy trials, a maintenance dose of 30-46 mg/kg/day, achieved over two weeks, is shown to be effective and well tolerated in children. Therapeutic effects were seen at a median maintenance dose of approximately 30 mg/kg/day.

2). Oxcarbazepine Mylan is recommended for use in children of 6 years of age and above. Safety and efficacy have been evaluated in controlled clinical trials involving approximately 230 children aged less than 6 years (down to 1 month).

Oxcarbazepine is not recommended in children aged less than 6 years since safety and efficacy have not been adequately demonstrated. All the above dosing recommendations (adults, elderly and children) are based on the doses studied in clinical trials for all age groups.

However, lower initiation doses may be considered where appropriate. Method of administration Oral use. Oxcarbazepine Mylan can be taken with or without food. The tablets are scored and can be broken in two halves in order to make it easier for the patient to swallow the tablet.

However, the tablet cannot be divided into equal doses. For children, who cannot swallow tablets or where the required dose cannot be administered using tablets, other oxcarbazepine containing pharmaceutical forms are available. 1. 4 Special warnings and precautions for use Hypersensitivity Class I (immediate) hypersensitivity reactions including rash, pruritus, urticaria, angioedema and reports of anaphylaxis have been received in the post-marketing period.

Cases of anaphylaxis and angioedema involving the larynx, glottis, lips and eyelids have been reported in patients after taking the first or subsequent doses of oxcarbazepine. If a patient develops these reactions after treatment with oxcarbazepine, the drug should be discontinued and an alternative treatment started.

g. 8). Hypersensitivity reactions, including multi-organ hypersensitivity reactions, may also occur in patients without a history of hypersensitivity to carbamazepine. 8). In general, if signs and symptoms suggestive of hypersensitivity reactions occur Oxcarbazepine Mylan should be withdrawn immediately.

Dermatological effects Serious dermatological reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome) and erythema multiforme, have been reported very rarely in association with the use of oxcarbazepine.

Patients with serious dermatological reactions may require hospitalisation, as these conditions may be life- threatening and very rarely be fatal. Oxcarbazepine associated cases occurred in both children and adults. The median time to onset was 19 days.

Several isolated cases of recurrence of the serious skin reaction when rechallenged with oxcarbazepine were reported. Patients who develop a skin reaction with oxcarbazepine should be promptly evaluated and oxcarbazepine withdrawn immediately unless the rash is clearly not drug related.

In case of treatment withdrawal, consideration should be given to replacing oxcarbazepine with other antiepileptic drug therapy to avoid withdrawal seizures. 3). HLA-B*1502 allele – in Han Chinese, Thai and other Asian populations HLA-B*1502 in individuals of Han Chinese and Thai origin has been shown to be strongly associated with the risk of developing the severe cutaneous reactions known as Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), when treated with carbamazepine.

The chemical structure of oxcarbazepine is similar to that of carbamazepine, and it is possible that patients who are positive for HLA
B*1502 may also be at risk for SJS/TEN after treatment with oxcarbazepine. There are some data that suggest that such an association exists for oxcarbazepine.

The prevalence of HLA-B*1502 carrier is about 10% in Han Chinese and Thai populations. Whenever possible, these individuals should be screened for this allele before starting treatment with carbamazepine or a chemically-related active substance.

If patients of these origins are tested positive for HLA
B*1502 allele, the use of oxcarbazepine may be considered if the benefits are thought to exceed risks. g. above 15% in the […]

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