Drug interactions between Mysoline and Tegretol

MONITOR: Coadministration with primidone may decrease the plasma concentrations of carbamazepine and increase concentrations of its active 10,11-epoxide metabolite. The mechanism is primidone induction of CYP450 3A4, the isoenzyme responsible for the metabolism of carbamazepine to carbamazepine-10,11-epoxide (CBZ-E). In one case report, carbamazepine levels were persistently low and subtherapeutic in a 15-year-old boy receiving carbamazepine and primidone for the treatment of partial complex seizures. Increasing the carbamazepine dosage only modestly increased serum levels but did not control the seizures. Adequate control was achieved only after gradual withdrawal of primidone, which led to a substantial increase in carbamazepine serum levels, a reduction in CBZ-E levels, and a 60% reduction in total carbamazepine clearance. Conversely, carbamazepine has also been reported to decrease the plasma concentrations of primidone and increase levels of phenobarbital derived from primidone. In clinical and pharmacokinetic studies, primidone levels were typically lower when the drug was administered with carbamazepine than when administered alone, and phenobarbital levels generally higher. The proposed mechanism is carbamazepine induction of the metabolism of primidone to phenobarbital.

MANAGEMENT: Serum drug levels and seizure control should be monitored more closely when carbamazepine or primidone is added to or withdrawn from a stabilized anticonvulsant regimen, and the dosages adjusted as necessary.