Inappropriate Prescribing of Nirmatrelvir/Ritonavir in Solid Organ Transplantation With COVID-19 Infection: A Multicenter Retrospective Study

Clin Ther. 2024 Nov 29:S0149-2918(24)00321-7. doi: 10.1016/j.clinthera.2024.10.013. Online ahead of print.

Abstract

Background: Nirmatrelvir-ritonavir (NR) has demonstrated effectiveness in halting the progression to severe coronavirus disease 2019 (COVID-19) among solid organ transplant recipients (SOTRs) infected with Severe Acute Respiratory Syndrome Coronavirus 2. However, it has a wide range of interactions, especially with immunosuppressants. The study aimed to comprehensively evaluate the Inappropriate prescribing of NR and immunosuppressants in SOTRs with COVID-19, while also highlighting the essential aspects.

Methods: We included hospitalized SOTRs who received NR at five tertiary hospitals between December 2022 and June 2023, and evaluated their prescription.

Results: A total of 211 patients were enrolled, of which 205 did not meet all criteria for appropriate prescribing (97.16%). Inappropriateness primarily stemmed from starting treatment more than 5 days after symptom onset (87.68%), followed by application in severe-to-critical cases of COVID-19 (52.13%), the inappropriate dosages based on renal function (47.87%). Contraindications encompassed 17.06% of patients with severe renal impairment and 5.69% with contraindicated drug interactions. Inappropriate resumption of immunosuppressants accounted for a larger proportion than inappropriate discontinuation or dose adjustment (30.16% vs 8.99%). More than one-third of patients neglected to monitor concentrations. About 8% experienced abnormal high concentrations.

Conclusion: Inappropriate prescribing of NR is widespread among hospitalized SOTRs. Adjusting doses based on patients' renal function and paying attention to concurrent use of immunosuppressive drugs are crucial, and therapeutic drug monitoring is necessary. Clinical practitioners should enhance their vigilance and attention.

Keywords: COVID-19; Immunosuppressive drugs; Inappropriate prescribing; Nirmatrelvir/ritonavir; Solid organ transplant recipients.