Drug Interactions between oxcarbazepine and phenobarbital

MONITOR: Coadministration with potent CYP450 inducers may decrease the plasma concentrations of the pharmacologically active 10-monohydroxy metabolite of oxcarbazepine known as MHD. Administration of oxcarbazepine 900 mg/day in combination with carbamazepine 400 to 2000 mg/day has resulted in an average reduction of MHD plasma concentrations by approximately 40%. Phenytoin 250 to 500 mg/day and phenobarbital 100 to 150 mg/day have reduced the plasma concentrations of MHD on average by approximately 30% and 25%, respectively, when oxcarbazepine was coadministered at 600 to 1800 mg/day. Since MHD is responsible for much of the pharmacologic effects of oxcarbazepine, the potential for altered anticonvulsant activity should be considered. Oxcarbazepine had no significant effect on the pharmacokinetics of carbamazepine and phenobarbital, but increased the plasma concentrations of phenytoin by 40% when administered at dosages greater than 1200 mg/day.

MANAGEMENT: The possibility of diminished therapeutic effects of oxcarbazepine should be considered when used in combination with potent CYP450 inducers such as carbamazepine, phenobarbital, phenytoin, primidone (which is metabolized to phenobarbital), rifampin, and St. John's wort. Close clinical and laboratory monitoring is recommended whenever a CYP450 inducer is added to or withdrawn from oxcarbazepine therapy, and the dosage adjusted as necessary.