Drug Interactions between belzutifan and Synalgos-DC

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as well as clinical and laboratory monitoring may be appropriate for some drugs whenever belzutifan is added to or withdrawn from therapy.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.

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.