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: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.