What Do We Know About Remdesivir Drug Interactions?

• Published in: Clinical and translational science Vol. 13; no. 5; pp. 842 - 844
• Main Author: Yang, Katherine
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01-09-2020; John Wiley and Sons Inc; Wiley
• Subjects: Adenosine; Antiviral drugs; Bioavailability; Coronaviruses; COVID-19; DNA-directed RNA polymerase; Epithelial cells; Intracellular; Metabolites; Mortality; Multidrug resistance; Oral administration; Pandemics; Voriconazole
• ISSN: 1752-8054; 1752-8062
• DOI: 10.1111/cts.12815

Since the start of the pandemic, information on potential therapeutic options have been rapidly disseminated on an almost daily basis, often with incomplete or conflicting results and without adequate peer review. Due to the high first‐pass hepatic extraction of phosphoramidates and expected low bioavailability, oral administration of remdesivir was not explored. 9 In respiratory epithelial cells, GS‐441524 is further converted by intracellular esterases into the pharmacologically active nucleoside triphosphate (GS‐443902), which competes with naturally occurring adenosine phosphate and functions as a delayed RNA‐dependent RNA polymerase inhibitor. 7 Although the plasma half‐lives of remdesivir and the intermediate metabolite are short (~ 0.5–1 hour), the plasma and intracellular half‐lives of the GS‐441524 are long (~ 24 and 40 hours, respectively) allowing for once‐daily dosing. Remdesivir is also a weak inhibitor of CYP3A4, OATP1B1, OATP1B3, bile acid export pump, multidrug resistance‐associated protein 4, and sodium‐taurocholate cotransporter protein. According to the website (accessed May 4, 2020), co‐administration of strong CYP3A4 inhibitors, such as voriconazole, is labeled as “no clinically significant interaction expected.”