Drug Interaction Report

MONITOR: Based on in vitro data, coadministration with tafamidis may increase the plasma concentrations and the risk of toxicity of drugs that are substrates of the transport protein breast cancer resistance protein (BCRP) (e.g., methotrexate, rosuvastatin, imatinib), uridine diphosphate glucuronosyltransferase (UGT) 1A1 (e.g., bictegravir, irinotecan, raltegravir), and/or uptake transporters OAT1 and OAT3 (organic anion transporters) (e.g., bumetanide, furosemide, lamivudine, methotrexate, oseltamivir, tenofovir, ganciclovir, adefovir, cidofovir, zidovudine, zalcitabine) at clinically relevant concentrations. The proposed mechanism is decreased clearance due to tafamidis-mediated inhibition of the corresponding transport protein.

MANAGEMENT: Caution is advised if tafamidis is used concomitantly with drugs that are substrates of these transport proteins, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever tafamidis is added to or withdrawn from therapy with these drugs. Patients should be monitored for the development of adverse effects.

Food increases the extent of absorption and slows the rate of absorption of dolutegravir. When administered with a low-, moderate- or high-fat meal, dolutegravir peak plasma concentration (Cmax) increased by 46%, 52% and 67%, systemic exposure (AUC) increased by 33%, 41% and 66%, and time to reach Cmax (Tmax) increased from 2 hours to 3, 4 and 5 hours, respectively, compared to administration under fasted conditions. Dolutegravir may be taken with or without food.