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

Abstract

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.

Yes We Can (Use Nirmatrelvir/Ritonavir Even in High Immunological Risk Patients Treated with Immunosuppressive Drugs)!

“…Given the half-life of tacrolimus when combined with ritonavir (117–232 h), it is unlikely further administration will be required during the final 4 days of nirmatrelvir/ritonavir treatment. A recent case series shows a mean tacrolimus trough concentration of 7.2 ng/mL before the introduction of nirmatrelvir/ritonavir and of 5.4 ng/mL afterwards, which is consistent with previous data for the tacrolimus half-life when combined with ritonavir [ 5 ]. The present strategy would also allow maintaining a comparable 5-day total exposure (i.e.…”

Update on COVID-19 Therapeutics for Solid Organ Transplant Recipients, Including the Omicron Surge

“…However, a recent report has described the safe use of nirmatrelvir/ritonavir in 25 adult SOT recipients who were taking tacrolimus (n = 21), cyclosporine (n = 4), everolimus (n = 3), or sirolimus (n = 1). 67 Patients were told to hold tacrolimus and mTOR inhibitors and reduce cyclosporine to 20% of their dose during the 5 d of treatment. Only 4 required hospitalization, and there were no deaths.…”

Supratherapeutic Tacrolimus Concentrations With Nirmatrelvir/Ritonavir in Solid Organ Transplant Recipients Requiring Hospitalization: A Case Series Using Rifampin for Reversal

“…Based on the cumulative data coupled with our cases, we recommend (1) holding tacrolimus during the 5-day NIM-RTV course; (2) checking tacrolimus concentrations on day 2–3 of therapy (transplant centers could implement mobile phlebotomy services that avoid violating Centers for Disease Control and Prevention quarantine guidance); and (3) implementing biweekly therapeutic drug monitoring following tacrolimus reinitiation, as residual CYP3A inhibition could last ≥3–7 days despite NIM-RTV discontinuation. Early data in 25 adult SOTRs suggests that this strategy does not compromise patient safety and that the majority can restart 82% of their daily baseline tacrolimus dose 3 days after NIM-RTV completion [ 19 ]. Importantly, 4 patients in this cohort experienced supratherapeutic concentrations after restarting, supporting an individualized, frequent monitoring plan.…”