Drug Interactions between dofetilide and remdesivir

Coadministration with remdesivir may increase the plasma concentrations of drugs metabolized via CYP450 3A4, but many sources indicate that clinically significant interactions are unlikely. The proposed mechanism is inhibition of CYP450 3A4 by remdesivir. Two drug interaction studies were conducted using the sensitive CYP450 3A4 substrate, midazolam. In the first study, healthy volunteers (n=19) received a single dose of remdesivir (200 mg) and a single dose of midazolam (2.5 mg), which resulted in midazolam's maximum concentration (Cmax) and systemic exposure (AUC) increasing by 29% and 20%, respectively. In the second study, healthy volunteers (n=14) received remdesivir (200 mg once, followed by 100 mg daily) for a total of 10 doses and a single dose of midazolam (2.5 mg) administered with the last dose of remdesivir. Midazolam's Cmax and AUC increased by 45% and 30%, respectively. Both studies indicated that remdesivir is a weak in vivo inhibitor of CYP450 3A4; however, some authorities consider these findings to be clinically insignificant.