Early clinical experience with nirmatrelvir/ritonavir for the treatment of COVID‐19 in solid organ transplant recipients

Nirmatrelvir/ritonavir (NR) use has not yet been described in solid organ transplant recipients (SOTRs) with mild COVID‐19. The objective was to evaluate outcomes among SOTR and describe the drug–drug interaction of NR. This is an IRB‐approved, retrospective study of all adult SOTR on a calcineurin inhibitor (CNI) or mammalian target of rapamycin inhibitor who were prescribed NR between December 28, 2021 and January 6, 2022. A total of 25 adult SOTR were included (n = 21 tacrolimus, n = 4 cyclosporine, n = 3 everolimus, n = 1 sirolimus). All patients were instructed to follow the following standardized protocol during treatment with 5 days of NR: hold tacrolimus or mTOR inhibitor or reduce cyclosporine dose to 20% of baseline daily dose. Four patients (16%) were hospitalized by day 30; one for infectious diarrhea and three for symptoms related to COVID‐19. No patients died within 30 days of receipt of NR. Median tacrolimus level pre‐ and post‐NR were 7.4 ng/ml (IQR, 6.6–8.6) and 5.2 (IQR, 3.6–8.7), respectively. Four patients experienced a supratherapeutic tacrolimus concentration after restarting tacrolimus post‐NR. Our results show the clinically significant interaction between NR and immunosuppressive agents can be reasonably managed with a standardized dosing protocol. Prescribers should carefully re‐introduce CNI after the NR course is complete. Clinically significant drug‐drug interaction between nirmatrelvir/ritonavir and immunosuppressive agents can be managed in solid organ transplant recipients using a standardized dosing protocol.