Drug Interaction Report

Coadministration with doravirine may decrease the plasma concentrations and therapeutic effects of drugs that are metabolized by CYP450 3A4, particularly sensitive CYP450 3A4 substrates such as sirolimus and tacrolimus. Doravirine may be a weak inducer of CYP450 3A4. Until more information is available, caution is advised if doravirine is used concomitantly with drugs that are sensitive substrates of CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever doravirine is added to or withdrawn from therapy.

ADJUST DOSING INTERVAL: Consumption of food can decrease the rate and extent of gastrointestinal absorption of sirolimus. Also, the consumption of grapefruit juice may result in increased sirolimus trough concentrations.

MANAGEMENT: Experts recommend that this drug be taken either at least one hour prior to eating or consistently with or without food to avoid variations in sirolimus blood levels. The manufacturer recommends against using grapefruit juice for dilution of sirolimus doses. Patients should be monitored for clinical and laboratory evidence of altered immunosuppressant effects.