Drug Interaction Report

CONTRAINDICATED: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of doravirine, which is primarily metabolized by the isoenzyme. When a single 100 mg dose of doravirine was administered with the potent CYP450 3A4 inducer rifampin (600 mg once daily) in 10 study subjects, doravirine peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (C24hr) decreased by an average of 57%, 88% and 97%, respectively, compared to doravirine administered alone. Reduced efficacy of doravirine may occur.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, concomitant use of doravirine with potent CYP450 3A4 inducers is considered contraindicated. At least a 4-week cessation period is recommended prior to initiation of doravirine treatment.

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.