Adaptative Strategy of Immunosuppressive Drugs Dosage Adjustments When Combined With Nirmatrelvir/Ritonavir in Solid Organ Transplant Recipients With COVID-19.

Nirmatrelvir/ritonavir is a promising option for preventing severe COVID-19 in solid organ transplant recipients with SARS-CoV-2 infection. However, concerns have arisen regarding potential drug interactions with calcineurin inhibitors (CNI). This two-phase multicentre retrospective study, involving 113 patients on tacrolimus and 13 on cyclosporine A, aimed to assess the feasibility and outcomes of recommendations issued by The French societies of transplantation (SFT) and pharmacology (SFPT) for CNI management in this context. The study first evaluated adherence to recommendations, CNI exposure, and clinical outcomes. Notably, 96.5% of patients on tacrolimus adhered to the recommendations, maintaining stable tacrolimus trough concentrations (C ₀ ) during nirmatrelvir/ritonavir treatment. After reintroduction, most patients experienced increased C ₀ , with 42.9% surpassing 15 ng/mL, including three patients exceeding 40 ng/mL. Similar trends were observed in cyclosporine A patients, with no COVID-19-related hospitalizations. Moreover, data from 22 patients were used to refine the reintroduction strategy. Modelling analyses suggested reintroducing tacrolimus at 50% of the initial dose on day 8, and then at 100% from day 9 as the optimal approach. In conclusion, the current strategy effectively maintains consistent tacrolimus exposure during nirmatrelvir/ritonavir treatment, and a stepwise reintroduction of tacrolimus may be better suited to the low CYP3A recovery.
Competing Interests: AD reports consultancy fees from Alnylam and Merck outside the submitted work. CM reports research grants (paid to institution), financial support for participation in congresses, and expertise fees from Chiesi and Astellas. StB received lecture fees from Astellas. BG reports financial support for participation in congresses from Chiesi and Gilead, speaker for Gilead, outside the submitted work. LC received lecture fees from Astellas, Chiesi, Novartis, Sandoz, Ostuka, GSK, and Biotest, and participated in advisory boards for Biotest, Hansa, and Novartis. LE received fees from Astellas, Chiesi, and Sandoz. FL received research grants (paid to institution) from Astellas, Sandoz, and Chiesi and fees to attend meetings from Viiv, MSD, Janssen-Cilag, Pfizer, and Gilead. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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