Drug Interactions between belzutifan and Omeclamox-Pak

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and laboratory monitoring should be considered whenever a UGT 2B17 and/or CYP450 2C19 inhibitor is added to or withdrawn from therapy with belzutifan, and the dosage adjusted as necessary.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

MONITOR: Coadministration with belzutifan may decrease the plasma concentrations and therapeutic effects of drugs that are substrates of CYP450 3A4. The extent of the decrease in concentration and effects may be more pronounced in patients who are dual uridine diphosphate glucuronosyltransferase (UGT) 2B17 and CYP450 2C19 poor metabolizers. The proposed mechanism is increased clearance due to belzutifan-mediated induction of CYP450 3A4. Concomitant use of belzutifan (120 mg once daily) with midazolam (a sensitive CYP450 3A4 substrate) decreased the midazolam systemic exposure (AUC) and peak plasma concentration (Cmax) by 40% and 34%, respectively. In patients with higher belzutifan concentrations (e.g., dual UGT 2B17 and CYP450 2C19 poor metabolizers) the AUC of midazolam is predicted to decrease by up to 70%.

MANAGEMENT: Caution is advised when belzutifan is used concomitantly with drugs that undergo metabolism by CYP450 3A4. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever belzutifan is added to or withdrawn from therapy. Patients should be monitored for diminished therapeutic effects.

Although some in vitro data indicate synergism between macrolide antibiotics and penicillins, other in vitro data indicate antagonism. When these drugs are given together, neither has predictable therapeutic efficacy. Data are available for erythromycin, although theoretically this interaction could occur with any macrolide. Except for monitoring of the effectiveness of antibiotic therapy, no special precautions appear to be necessary.

Clarithromycin may increase and prolong the omeprazole plasma concentration. The mechanism may be related to clarithromycin inhibition of hepatic cytochrome P450 enzymes responsible for omeprazole metabolism. Coadministration of omeprazole may result in an increase in clarithromycin and 14-(R)-hydroxyclarithromycin plasma concentrations. These increases may be due to the effect of omeprazole on gastric pH.