Drug-drug interaction between remdesivir and immunosuppressant agents in a kidney transplant recipient

A 60-year-old man was treated with a regimen of controlled-release tacro-limus (2 mg once daily), everolimus (0.5 mg twice daily), methylprednisolone (4 mg once daily), and mizoribine (100 mg twice daily) as an anti-rejection regimen following liv-ing-donor kidney transplantation. One year after transplantation, the recipient was ad-mitted to Mie University Hospital (day X; admission date) to treat coronavirus disease 2019 pneumonia. The latest trough concen-trations of tacrolimus and everolimus before admission (day X-65) were 4.5 ng/mL and 4.4 ng/mL, respectively. Since tacrolimus concentration was 4.2 ng/mL on day X+3, the dose was adjusted to 1.5 mg once daily to reach the target concentration of 3.0 ng/ mL due to the introduction of remdesivir. After starting remdesivir on day X+4, the in-creased trough concentrations of tacrolimus on day X+6 (6.9 ng/mL) and everolimus on day X+7 (9.2 ng/mL) were observed, which resulted in dose reduction of tacrolimus (0.5 mg once daily) and discontinuation of everolimus. After discontinuation of remdes-ivir on day X+9, dose titration of controlled -release tacrolimus and restart of everolimus (0.5 mg twice daily) were performed from day X+15. The dose of controlled-release tacrolimus was titrated and fixed to 2 mg once daily at discharge (day X+21). There was no toxicity due to immunosuppressive agents during hospitalization. This case re-port indicated that remdesivir might interact with cytochrome P450 3A4 substrates, such as tacrolimus and everolimus, and elevate their blood concentrations under high in-flammatory conditions.