Drug Interaction Report

MONITOR: Carbamazepine may decrease serum concentrations of tricyclic antidepressants. The mechanism may be related to carbamazepine induction of CYP450 enzymes responsible for tricyclic antidepressant metabolism. Serum concentrations of carbamazepine may be increased by an unknown mechanism. Carbamazepine toxicity has been reported with desipramine. Additionally, tricyclic antidepressants may counteract the anticonvulsant effects of carbamazepine by lowering the seizure threshold.

MANAGEMENT: Clinical monitoring of serum concentrations, patient response, seizure control, and tolerance is recommended whenever either agent is added to or discontinued from an existing regimen, or when the dosage is changed.

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.