Karbagen

Pharmacotherapeutic group: Antiepileptics ATC Code: N03A F02 Pharmacodynamic effects The pharmacological activity of oxcarbazepine is primarily exerted through the metabolite (MHD) (see section 5.2).‍‍‍‍‍‍​​​‍​​​​​​ The mechanism of action of oxcarbazepine and MHD is thought to be mainly based on blockade of voltage-sensitive sodium channels, thus resulting in stabilisation of hyperexcited neural membranes, inhibition of repetitive neuronal firing, and diminishment of propagation of synaptic impulses. In addition, increased potassium conductance and modulation of high-voltage activated calcium channels may also contribute to the anticonvulsant effects. No significant interactions with brain neurotransmitter or modulator receptor sites were found. Oxcarbazepine and its active metabolite (MHD), are potent and efficacious anticonvulsants in animals. They protected rodents against generalised tonic-clonic and, to a lesser degree, clonic seizures, and abolished or reduced the frequency of chronically recurring partial seizures in Rhesus monkeys with aluminium implants. No tolerance (i.e. attenuation of anticonvulsive activity) against tonic-clonic seizures was observed when mice and rats were treated daily for 5 days or 4 weeks, respectively, with oxcarbazepine or MHD. A prospective, open-label, multicentre, non-comparative, 24 week observational post marketing study has been conducted in India. Out of a study population of 816 patients, 256 pediatric patients (1 month to 19 years) with generalised tonic-clonic seizures (either secondary or primary) were treated with oxcarbazepine monotherapy. The initial oxcarbazepine dose for all patients > 6 years was 8-10 mg/kg/day given in 2 divided doses. For the 27 subjects aged 1 month to 6 years, the dose range for the initial dose was 4.62 - 27.27 mg/kg/day and 4.29 - 30.00 mg/kg/day maintenance dose. The primary endpoint was reduction in seizure frequency from baseline at week 24. In the age group 1 month to 6 years (n=27) the number of seizures changed from 1 [range] [1-12] to 0 [0-2], in the age group 7 years to 12 years (n=77) the frequency changed from 1 [1-22] to 0 [0-1] and in the age group 13-19 years (n=152), the frequency changed from 1 [1-32] to 0 [0-3]. No specific safety concerns in the pediatric patients were identified. Data supporting benefit/risk from the study regarding children under the age of 6 are inconclusive (see section 4.2). Based on the data from the randomized controlled trials, the use of oxcarbazepine is not recommended in children below the age of 6 since safety and efficacy have not been adequately demonstrated (see section 4.2). Paediatric population Two randomised, rater-blinded, dose-controller efficacy studies (Study 2339 and Study 2340) were conducted in paediatric patients aged 1 month to <17 years of age (n=31 patients aged 6 to <17 years; n=189 patients aged <6 years old). In addition, a number of open-label studies that enrolled children were conducted. In general, the safety profile of oxcarbazepine in younger children (<6 years old) was similar to that in older children (≥6 years old). However, in some studies in younger children (<4 years old) and older children (≥4 years old), a ≥ 5-fold difference in the proportion of patients with convulsions (7.9% vs. 1.0%, respectively) and status epilepticus (5% vs. 1%, respectively) was observed.