Drug Interactions between belzutifan and nirmatrelvir / ritonavir

MONITOR: Coadministration of belzutifan with inducers of CYP450 2C19 may decrease the plasma concentrations and pharmacologic effects of belzutifan. The proposed mechanism is induction of CYP450 2C19, one of the primary pathways for the metabolic clearance of belzutifan. Clinical data are not available.

MANAGEMENT: Caution and clinical monitoring are recommended whenever belzutifan is prescribed in combination with a CYP450 2C19 inducer. Pharmacologic response to belzutifan should be monitored more closely whenever a CYP450 2C19 inducer is added to or withdrawn from therapy.

MONITOR: Coadministration with drugs that are inducers of CYP450 3A4 may decrease the plasma concentrations of nirmatrelvir which is primarily metabolized by the isoenzyme. According to the manufacturer, coadministration of nirmatrelvir-ritonavir (300 mg-100 mg twice daily for 5 doses) with the potent CYP450 3A4 inducer carbamazepine (300 mg twice daily for 16 doses) (n=9) decreased the systemic exposure (AUC) and peak plasma concentration (Cmax) of nirmatrelvir by approximately 55% and 43%, respectively. Data are unavailable for other, less potent inducers. In addition, the plasma concentrations and pharmacologic effects of the concomitant inducer may be affected; however, clinical data are lacking.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiviral drug levels, nirmatrelvir-ritonavir should be used cautiously with agents that induce CYP450 3A4. Antiviral response should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy.