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Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever tafamidis is added to or withdrawn from therapy with these drugs.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.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of axitinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

MANAGEMENT: Patients treated with axitinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Axitinib may be administered with or without food.