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Clinical and laboratory monitoring should be considered whenever a UGT 2B17 and/or CYP450 2C19 inhibitor is added to or withdrawn from therapy with belzutifan, and the dosage adjusted as necessary.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 cause hypoglycemia or hyperglycemia in patients with diabetes. Hypoglycemia most frequently occurs during acute consumption of alcohol. Even modest amounts can lower blood sugar significantly, especially when the alcohol is ingested on an empty stomach or following exercise. The mechanism involves inhibition of both gluconeogenesis as well as the counter-regulatory response to hypoglycemia. Episodes of hypoglycemia may last for 8 to 12 hours after ethanol ingestion. By contrast, chronic alcohol abuse can cause impaired glucose tolerance and hyperglycemia. Moderate alcohol consumption generally does not affect blood glucose levels in patients with well controlled diabetes. A disulfiram-like reaction (e.g., flushing, headache, and nausea) to alcohol has been reported frequently with the use of chlorpropamide and very rarely with other sulfonylureas.

MANAGEMENT: Patients with diabetes should avoid consuming alcohol if their blood glucose is not well controlled, or if they have hypertriglyceridemia, neuropathy, or pancreatitis. Patients with well controlled diabetes should limit their alcohol intake to one drink daily for women and two drinks daily for men (1 drink = 5 oz wine, 12 oz beer, or 1.5 oz distilled spirits) in conjunction with their normal meal plan. Alcohol should not be consumed on an empty stomach or following exercise.