Drug Interaction Report

MONITOR: Some anticonvulsants such as carbamazepine, phenobarbital, phenytoin, and primidone may reduce the systemic exposure of etoposide. The proposed mechanism is accelerated clearance of etoposide due to induction of hepatic CYP450 enzymes by these anticonvulsants. In one study, the median clearance of etoposide in seven pediatric patients receiving concomitant therapy with phenobarbital and/or phenytoin was 77% higher than that in a matched control group of patients receiving the same chemotherapeutic protocol without anticonvulsant therapy. The investigators noted that clearance estimates for control patients were similar to previously published values for pediatric patients. No data are available for other anticonvulsants, but agents with similar potential for induction of hepatic metabolism should be expected to participate in the interaction.

MANAGEMENT: During concomitant therapy with certain anticonvulsants, patients should be observed for potentially inadequate or altered response to etoposide, and the dosage adjusted accordingly as necessary.

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.