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

Am J Transplant. 2022 Aug;22(8):2083-2088. doi: 10.1111/ajt.17027. Epub 2022 Mar 21.


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.

Keywords: clinical research/practice; drug interaction; immunosuppressant; immunosuppression/immune modulation; infection and infectious agents-viral: SARS-CoV-2/COVID-19; pharmacology; solid organ transplantation.

MeSH terms

  • Adult
  • COVID-19 Drug Treatment*
  • Calcineurin Inhibitors / therapeutic use
  • Cyclosporine / therapeutic use
  • Graft Rejection / drug therapy
  • Graft Rejection / prevention & control
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Lactams* / therapeutic use
  • Leucine* / therapeutic use
  • Nitriles* / therapeutic use
  • Organ Transplantation
  • Proline* / therapeutic use
  • Retrospective Studies
  • Ritonavir* / therapeutic use
  • Sirolimus / therapeutic use
  • Tacrolimus / therapeutic use
  • Transplant Recipients*


  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Lactams
  • Nitriles
  • nirmatrelvir
  • Cyclosporine
  • Proline
  • Leucine
  • Ritonavir
  • Sirolimus
  • Tacrolimus