Basic Information
ID DDInter2000 and DDInter1347
Interaction Coadministration of belzutifan with inhibitors of uridine diphosphate glucuronosyltransferase 2B17 (UGT2B17) and/or CYP450 2C19 may increase the plasma concentrations and the risk and severity of adverse effects, including anemia and hypoxia, of belzutifan. The proposed mechanism is inhibition of UGT 2B17 and/or CYP450 2C19, the isoenzymes responsible for the metabolic clearance of belzutifan. Patients who are dual UGT 2B17 and CYP450 2C19 poor metabolizers are at a greater risk of adverse reactions.
Management Close monitoring is recommended whenever belzutifan is used concomitantly with a UGT 2B17 and/or CYP450 2C19 inhibitor. Clinical and laboratory monitoring should be considered whenever a UGT 2B17 and/or CYP450 2C19 inhibitor is added to or withdrawn from therapy with belzutifan, and the dosage adjusted as necessary. Consult the manufacturer's product labeling for specific dose adjustment recommendations. Patients should be monitored for development of anemia and hypoxia.
References [1] Sten T, Finel M, Ask B, Rane A, Ekstrom L "Non-steroidal anti-inflammatory drugs interact with testosterone glucuronidation." Steroids 74 (2009): epub [2] "Product Information. Welireg (belzutifan)." Merck & Co., Inc (2021):
Alternative for Belzutifan L01X
Pertuzumab Olaparib Oxaliplatin Rucaparib Tisagenlecleucel Aminolevulinic acid
Omacetaxine mepesuccinate Altretamine Tagraxofusp Pegaspargase Ixazomib
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Alternative for Oritavancin J01X
Linezolid Bacitracin Polymyxin B Daptomycin Vancomycin Metronidazole
Telavancin Methenamine Spectinomycin Lefamulin Nitrofurantoin
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Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.