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...

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Published in:Transplant international 2024-03, Vol.37, p.12360-12360
Main Authors: Boland, Lidvine, Devresse, Arnaud, Monchaud, Caroline, Briol, Sébastien, Belaiche, Stéphanie, Giguet, Baptiste, Couzi, Lionel, Thaunat, Olivier, Esposito, Laure, Meszaros, Magdalena, Roussoulieres, Ana, Haufroid, Vincent, Le Meur, Yannick, Lemaitre, Florian
Format: Article
Language:English
Subjects:
Antiviral Agents - therapeutic use
Calcineurin Inhibitors - therapeutic use
COVID-19
COVID-19 Drug Treatment
Cyclosporine - therapeutic use
drug monitoring
drug-drug interactions
Health Archive
Humans
Immunosuppressive Agents
Lactams
Leucine
Life Sciences
nirmatrelvir/ritonavir
Nitriles
Organ Transplantation
pharmacokinetic modelling
Proline
Retrospective Studies
Ritonavir - pharmacology
Ritonavir - therapeutic use
SARS-CoV-2
Tacrolimus
Transplant Recipients
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Summary: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 ) during nirmatrelvir/ritonavir treatment. After reintroduction, most patients experienced increased C , 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.
ISSN:1432-2277
0934-0874
1432-2277
DOI:10.3389/ti.2024.12360