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.

GENERALLY AVOID: Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system. No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load. However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.

MANAGEMENT: Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.