Drug Interaction Report

ADJUST DOSE: Coadministration with potent inducers of CYP450 3A4 such as carbamazepine may significantly decrease the plasma concentrations of maribavir, which is primarily metabolized by the isoenzyme. According to physiologically-based pharmacokinetic modeling, maribavir peak plasma concentration (Cmax) and systemic exposure (AUC) were 1.5- and 1.4-fold higher, respectively, when dose-adjusted maribavir (800 mg twice daily) was administered with carbamazepine (400 mg once daily) compared to standard-dose maribavir (400 mg twice daily) alone. Studies evaluating the effect of concomitant use of carbamazepine with standard-dose maribavir are not available. However, when standard-dose maribavir was administered with another potent CYP450 3A4 inducer, rifampin (600 mg once daily), maribavir peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 39% and 60%, respectively. Reduced virologic response may occur.

MANAGEMENT: If concomitant use of carbamazepine is required, the manufacturer recommends that the dosage of maribavir should be increased to 800 mg twice daily.

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.