Drug Interaction Report

MONITOR: Coadministration with oxcarbazepine may increase the plasma concentrations of phenytoin. The proposed mechanism is inhibition by oxcarbazepine and its active metabolite (10-monohydroxy derivative, or MHD) of the CYP450 2C19-mediated metabolism of phenytoin. In vivo, the plasma levels of phenytoin increased by up to 40% when oxcarbazepine was given at dosages above 1200 mg/day. Conversely, phenytoin 250 to 500 mg/day can decrease the plasma concentrations of MHD by approximately 30% due to induction of CYP450 isoenzymes. Since MHD is responsible for much of the pharmacologic effects of oxcarbazepine, the potential for altered anticonvulsant activity should be considered.

MANAGEMENT: Pharmacologic effects and serum phenytoin levels should be monitored more closely following the addition, discontinuation or change of dosage of oxcarbazepine, and the phenytoin dosage adjusted as necessary. Particular caution is advised when oxcarbazepine is administered at dosages greater than 1200 mg/day. Patients should be advised to contact their physician if they experience signs and symptoms of phenytoin toxicity such as nausea, vomiting, tremors, ataxia, lethargy, slurred speech, visual disturbances, or changes in mental status. Likewise, patients stabilized on oxcarbazepine should be monitored more closely whenever phenytoin is added to or withdrawn from therapy and during the period of phenytoin titration.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.