Oxcarbazepine for Treatment of Partial Epilepsy: A Review and Recommendations for Clinical Use.
Recent trials and extensive postmarketing use confirm the efficacy and safety of oxcarbazepine (OXC) as a first-line treatment for adults and children with simple partial seizures, complex partial seizures, and partial seizures evolving to secondarily generalized seizures. OXC undergoes reductive metabolism at its keto moiety to form 10-hydroxy-10,11-dihydro-10-oxo-5H-dibenz[b,f]azepine-5-carboxamide (MHD), which is glucuronidated and excreted in the urine, with minimal involvement of the hepatic cytochrome P450-dependent enzymes. OXC has some drug interactions, and does not require titration, allowing for better tolerability. Titration for monotherapy and adjunctive therapy of OXC could begin at 150 mg/day and be increased by 150 mg every 2-3 days until the target dose of 900-1200 mg/day is reached. If necessary, one can go faster and start with up to 600 mg/day and titrate with weekly increments up to 600 mg/day if necessary for seizure control. Conversion to monotherapy can be done overnight or gradually. For gradual conversion, use the recommended titration of OXC and withdraw the baseline antiepileptic drugs gradually by 25%, starting at Day 14 or earlier in case of baseline tolerability issues. Consider reducing the dose of the primary antiepileptic drug during adjunctive therapy in case of adverse events or increase the dose of OXC in case of incomplete seizure control. In children OXC should be started at 8-10 mg/kg/day in two or three divided doses. If clinically indicated the dose can then be increased by 10 mg/kg/day in weekly intervals with final doses up to 30-46 mg/kg/day. Dose adjustment may be necessary in very young children (age 2-5 years) and in patients with renal dysfunction, based on renal clearance. However no adjustment of OXC dose is needed in patients with mild to moderate hepatic dysfunction. OXC has a number of advantages which include rapid titration, no need for safety monitoring (except for uncommon and mostly asymptomatic hyponatremia), a low potential for drug-drug interactions (except for those possibly impairing the effectiveness of oral contraceptives and increasing the serum concentration of phenytoin), a rash rate of less than 5%, similar efficacy and similar or better tolerability and safety compared with first-generation antiepileptic drugs. OXC is a valuable alternative to current treatment options.
Epilepsy Research Group, Goethestrasse 5, D-14163, Berlin, Germany
Dieter
D
Schmidt
Rajesh
R
Sachdeo