OXCARBAZEPINE MYLAN Film-coated tablet Ref.[7327] Active ingredients: Oxcarbazepine

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. In adjunctive therapy, as the total antiepileptic medicinal product load of the patient is increased, the dose of concomitant antiepileptic medicinal product(s) may need to be reduced and/or the Oxcarbazepine Mylan dose increased more slowly (see section 4.5).

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. However, it may be useful in situations where an alteration in MHD clearance is to be expected (see section 4.4). 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 2400 mg/day.

Controlled monotherapy trials in patients not currently being treated with antiepileptic medicinal products showed 1200 mg/day to be an effective dose; however, a dose of 2400 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 2400 mg/day.

Maximum recommended dose:

Daily doses from 600 to 2400 mg/day have been shown to be effective in a controlled adjunctive therapy trial, although most patients were not able to tolerate the 2400 mg/day dose without reduction of concomitant antiepileptic medicinal products, mainly because of CNS-related adverse events. Daily doses above 2400 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 <30 ml/min) (see ‘Patients with renal impairment’). Close monitoring of sodium levels is required inpatients at risk of hyponatraemia see (section 4.4).

Patients with hepatic impairment

No dosage adjustment is required for patients with mild to moderate hepatic impairment. Oxcarbazepine has not been studied in patients with severe hepatic impairment, therefore, caution should be exercised when dosing severely impaired patients (see section 5.2).

Patients with renal impairment

In patients with impaired renal function (creatinine clearance less than 30 ml/min) oxcarbazepine therapy should be initiated at half the usual starting dose (300 mg/day) and increased, in at least weekly intervals, to achieve the desired clinical response (see section 5.2).

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.

Maximum recommended dose:

If clinically indicated, the dose may be increased by a maximum of 10 mg/kg/day at approximately weekly intervals from the starting dose, to a maximum dose of 46 mg/kg/day, to achieve the desired clinical response (see section 5.2).

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. For children, who cannot swallow tablets or where the required dose cannot be administered using tablets, other oxcarbazepine containing pharmaceutical forms are available.

Isolated cases of overdose have been reported. The maximum dose taken was approximately 48,000 mg.

Signs and symptoms

Electrolyte and fluid balance conditions: hyponatraemia

Eye disorders: diplopia, miosis, blurred vision

Gastrointestinal disorders: nausea, vomiting, hyperkinesia

General disorders and administration site conditions: fatigue

Investigations: respiratory rate depression, QTc prolongation

Nervous system disorders: drowsiness and somnolence, dizziness, ataxia and nystagmus, tremor, disturbances in coordination (coordination abnormal), convulsion, headache, coma, loss of consciousness, dyskinesia

Psychiatric disorders: aggression, agitation, confusional state

Vascular disorders: hypotension

Respiratory, thoracic and mediastinal disorders: dyspnoea

Management

There is no specific antidote. Symptomatic and supportive treatment should be administered as appropriate. Removal of the medicinal product by gastric lavage and/or inactivation by administering activated charcoal should be considered.

30 months.

Do not store above 30°C.

Clear PVC-PVdC/aluminium blisters.

Pack sizes: 10, 20, 30, 50, 60, 100, 200 film-coated tablets.

Polypropylene tablet containers with tamper evident polyethylene caps and optional polyethylene ullage filler.

Pack sizes: 100, 200, 500 film-coated tablets.

Not all pack sizes may be marketed.

No special requirements for disposal.