Potential Effects of Remdesivir on Tacrolimus Exposure in Transplant Recipients With COVID-19 Infection

INTRODUCTION: Remdesivir has proven to have benefits against COVID-19 infection. However, data supporting drug-drug interactions are insufficient. Clinicians have noticed that calcineurin inhibitor (CNI) levels tend to change after starting remdesivir. This retrospective study aimed to evaluate the effect of remdesivir on CNI levels. METHODS: This study included adult solid organ transplant recipients hospitalized for COVID-19 who received remdesivir while on CNI. Patients were excluded if they started on other medications known to interact with CNI. The primary end point was the percentage of change in CNI levels after starting remdesivir. Secondary end points included the time until CNI levels reached a maximum increase in trough levels, the incidence of acute kidney injury (AKI), and the time until CNI levels normalized. RESULTS: Of the 86 patients screened, 61 were included (56 on tacrolimus and 5 on cyclosporine). Most patients received kidney transplants (44.3%), and baseline demographics were similar among the transplanted organs. The median increase in tacrolimus level after starting remdesivir was 84.8%, and only 3 patients had no significant change in CNI levels. The median increase in tacrolimus level was more pronounced in lung and kidney recipients than in heart recipients (96.5% vs. 93.9% vs. 64.6 %, respectively). The median time to maximum increase in tacrolimus trough levels was 3 days, and it took 10 days after the remdesivir course for levels to return to baseline. CONCLUSION: This retrospective analysis demonstrates that CNI levels were significantly elevated after starting remdesivir. However, future studies are warranted to evaluate this interaction further.