Drug-induced Liver Injury in a Patient With Coronavirus Disease 2019: Potential Interaction of Remdesivir With P-Glycoprotein Inhibitors
This case report describes a critically-ill patient with Covid-19 who developed hepatotoxicity 5 days after remdesivir was started; rapid decreases in ALT and AST were seen upon its discontinuation. An interaction with amiodarone (started 2 days after remdesivir) is proposed.
Source:
Clinical Infectious Diseases
SPS commentary:
The authors propose a drug-drug interaction between remdesivir and P-glycoprotein inhibitors, and suggest use of amiodarone and prior use of chloroquine (both P-glycoprotein inhibitors) could have increased the intrahepatocellular concentration of remdesivir above the toxicity threshold.
A letter in another journal commenting on this research notes that amiodarone is also a moderate CYP3A4 inhibitor, and that the proposed remdesivir-amiodarone interaction may result from amiodarone inhibiting both P-glycoprotein and CYP3A4. As remdesivir is a substrate for both P-glycoprotein and CYP3A4, the authors call for studies to demonstrate the safety of its simultaneous use with inhibitors of one or both, and recommend caution when using remdesivir concomitantly with such drugs, with close clinical monitoring for drug toxicity.