Drug Interaction Report

MONITOR: Some anticonvulsants such as carbamazepine, phenobarbital, phenytoin, and primidone may reduce the systemic exposure of teniposide. The proposed mechanism is accelerated clearance of teniposide due to induction of hepatic CYP450 enzymes by these anticonvulsants. In one study, the systemic clearance of teniposide in six pediatric patients receiving concomitant therapy with either phenobarbital or phenytoin was consistently increased two- to threefold compared to that in a matched control group of patients receiving the same chemotherapeutic protocol without anticonvulsant therapy (mean 32 mL/min/m2 vs. 13 mL/min/m2). The investigators noted that clearance estimates for control patients were similar to previously published values for pediatric patients. The investigators also studied one patient who demonstrated a similar change in teniposide clearance rate following coadministration of carbamazepine. Based on these findings, other 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 teniposide, and the dosage adjusted accordingly as necessary.

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

In a small, randomized, crossover study, the administration of carbamazepine with grapefruit juice (compared to water) increased plasma drug concentrations by approximately 40%. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients receiving carbamazepine should be advised to avoid or limit consumption of alcohol. Given the drug's narrow therapeutic index, patients receiving carbamazepine therapy should preferably avoid the regular consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels. Patients should be advised to report signs of carbamazepine toxicity (nausea, visual disturbances, dizziness, or ataxia) to their physicians.