Drug Interaction Report

ADJUST DOSE: Carbamazepine, when coadministered with topiramate may lead to a 40% decrease in the plasma concentration of topiramate. The mechanism appears to be hepatic enzyme induction with subsequent increased metabolism of topiramate. In contrast, some evidence suggests that toxicity may occur when topiramate is added to the maximum tolerated doses of carbamazepine.

MANAGEMENT: If dosages of topiramate have been adjusted upward, reduction or withdrawal of carbamazepine during adjunctive therapy may require a downward dose adjustment of topiramate. In general, no adjustment in carbamazepine dosage is required when topiramate adjunctive therapy is started; however, if toxicity develops when topiramate is added to the maximum tolerated dose of carbamazepine, a reduction in the carbamazepine dose should be considered. Patients should be monitored for altered efficacy and safety and should be advised to notify their physician if seizure control worsens or adverse effects occur.

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.