Coronavirus Disease 2019 Treatment: A Review of Early and Emerging Options

McCreary, Erin K; Pogue, Jason M

It is interesting to note that the adaptive clinical trial protocol originally stated "remdesivir is a prodrug that is metabolized to its active form as a substrate of CYP-3A4". This implies the existence of a drug-drug interaction with CYP3A4 substrate inhibitors such as ritonavir or voriconazole. However, the protocol also stated "although remdesivir is a substrate for CYP2C8, CYP2D6, and CYP3A4 in vitro, coadministration with inhibitors of these CYP isoforms is unlikely to markedly increase remdesivir levels, as its metabolism is likely to be predominantly mediated by hydrolase activity." Unlike the former, the latter statement is substantiated by well described chemistry of the molecule. The National Institute of Allergy and Infectious Diseases was contacted about this discrepancy and in collaboration with Gilead, this has been corrected. There is no reason to believe that any significant drug interactions between remdesivir and CYP3A4 inhibitors or inducers are likely [8] .