Transplant International (Mar 2024)

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

  • Lidvine Boland,
  • Lidvine Boland,
  • Arnaud Devresse,
  • Caroline Monchaud,
  • Caroline Monchaud,
  • Caroline Monchaud,
  • Sébastien Briol,
  • Stéphanie Belaiche,
  • Stéphanie Belaiche,
  • Stéphanie Belaiche,
  • Baptiste Giguet,
  • Lionel Couzi,
  • Olivier Thaunat,
  • Laure Esposito,
  • Magdalena Meszaros,
  • Ana Roussoulieres,
  • Vincent Haufroid,
  • Vincent Haufroid,
  • Yannick Le Meur,
  • Yannick Le Meur,
  • Florian Lemaitre,
  • Florian Lemaitre

DOI
https://doi.org/10.3389/ti.2024.12360
Journal volume & issue
Vol. 37

Abstract

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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 (C0) during nirmatrelvir/ritonavir treatment. After reintroduction, most patients experienced increased C0, 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.

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