Drug Interaction Report

GENERALLY AVOID: Coadministration with inducers of CYP450 3A4 may significantly decrease the plasma concentrations of doravirine, which is primarily metabolized by the isoenzyme. Some non-nucleoside reverse transcriptase inhibitors such as efavirenz, etravirine, and nevirapine are known inducers of CYP450 3A4. When doravirine 100 mg once daily was initiated following cessation of treatment with efavirenz 600 mg once daily in 17 study subjects, doravirine peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (C24hr) decreased by an average of 35%, 62% and 85%, respectively, on the first day and 14%, 32% and 50%, respectively, 14 days later. 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 efavirenz, etravirine, or nevirapine should generally be avoided.

ADJUST DOSING INTERVAL: Coadministration with food increases the oral bioavailability of etravirine. The mechanism is unknown. Compared to administration following a meal, the systemic exposure (AUC) to etravirine was decreased by about 50% when the drug was administered under fasting conditions. The types of meal studied (ranging from 345 kilocalories containing 17 grams fat to 1160 kilocalories containing 70 grams fat) did not appear to make a difference with respect to impact on etravirine bioavailability.

MANAGEMENT: Etravirine should always be administered following a meal.

The recommended maximum number of medicines in the 'NNRTIs' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'NNRTIs' category:

• doravirine
• etravirine

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.