Drug Interaction Report

MONITOR: Limited data suggest that coadministration with cisplatin and/or doxorubicin may decrease the plasma concentrations and pharmacologic effects of carbamazepine. The exact mechanism of interaction is unknown. In one case report, a young woman with a history of epilepsy developed tonic-clonic seizures during antineoplastic therapy with cisplatin and doxorubicin. Anticonvulsant levels were measured during two courses, and lower plasma levels of carbamazepine and valproate sodium were observed after 2 days of antineoplastic therapy. Levels returned to normal 2 to 3 days after the last cisplatin dose.

MANAGEMENT: Serum carbamazepine levels should be monitored more closely during therapy with cisplatin and/or doxorubicin. Dosage adjustments may be required.

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.