Drug Interaction Report

MONITOR CLOSELY: 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Clinical and laboratory monitoring should be considered whenever a UGT 2B17 and/or CYP450 2C19 inhibitor is added to or withdrawn from therapy with belzutifan, and the dosage adjusted as necessary.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.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.