Yes We Can (Use Nirmatrelvir/Ritonavir Even in High Immunological Risk Patients Treated with Immunosuppressive Drugs)!

Lemaître, F.

doi:10.1007/s40262-022-01158-7

Cited by 8 publications

(11 citation statements)

References 9 publications

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“…For this high-risk group, measuring an additional tacrolimus trough level around day 6 may be critical to accurately assess the tacrolimus elimination slope if concern for rejection exists. 14 …”

Section: Discussionmentioning

confidence: 99%

Nirmatrelvir/ritonavir Use With Tacrolimus in Lung Transplant Recipients: A Single-center Case Series

et al. 2022

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Background. Limited data and guidelines exist for using nirmatrelvir/ritonavir in solid organ transplant recipients stabilized on tacrolimus for the treatment of mild-to-moderate coronavirus disease. Concern exists regarding the impact of utilizing a 5-d course of nirmatrelvir/ritonavir with calcineurin inhibitors because of significant drug–drug interactions between ritonavir, a potent cytochrome P450 3A inhibitor, and other cytochrome P450 3A substrates, such as tacrolimus. Methods. We report the successful use of nirmatrelvir/ritonavir in 12 outpatient lung transplant recipients with confirmed severe acute respiratory syndrome coronavirus 2 infection stabilized on tacrolimus immunosuppression. All patients stopped tacrolimus and started nirmatrelvir/ritonavir 10 to 14 h after the last dose of tacrolimus. Tacrolimus was withheld and then reinitiated at a modified dose 48 h following the completion of nirmatrelvir/ritonavir therapy. Tacrolimus trough levels were checked during nirmatrelvir/ritonavir therapy and tacrolimus reinitiation. Results. Ten (10/12) patients were able to resume their original tacrolimus dose within 4 d of completing nirmatrelvir/ritonavir therapy and maintain therapeutic levels of tacrolimus. No patients experienced tacrolimus toxicity or acute rejection during the 30-d postcompletion of nirmatrelvir/ritonavir therapy. Conclusions. In this cohort of lung transplant recipients on tacrolimus, we demonstrated that nirmatrelvir/ritonavir can be safely used with close monitoring of tacrolimus levels and appropriate dose adjustments of tacrolimus. Further confirmatory studies are needed to determine the appropriate use of therapeutic drug monitoring and tacrolimus dose following completion of nirmatrelvir/ritonavir in the solid organ transplant population.

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Section: Discussionmentioning

confidence: 99%

Nirmatrelvir/ritonavir Use With Tacrolimus in Lung Transplant Recipients: A Single-center Case Series

et al. 2022

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“…Pharmacokinetic parameters were estimated using the MWPHARM ++ software (Mediware, Prague, Czech Republic) with a 5-d area under the curve (AUC) of tacrolimus blood concentrations (AUC 0-120 h ) of 1382 ng•h/mL during nirmatrelvir/ritonavir compared with the 1607 ng•h/mL AUC 0-120 h estimated before the antiviral treatment. 4 Tacrolimus exposure was then decreased by 14% during the nirmatrelvir/ritonavir 5-d treatment. During the ritonavir inhibition phase of tacrolimus metabolism, the half-life was estimated to be 161 h and the elimination constant was 0.00432 h -1 , which are values close to what is reported in the literature.…”

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confidence: 99%

“…First Experience of Optimization of Tacrolimus Therapeutic Drug Monitoring in a Patient Cotreated With Nirmatrelvir/Ritonavir: How Microsampling Approach Changes Everything Léonard Golbin, MD, 1,2 Camille Tron, MD, 2,3,4 Bénédicte Franck, MD, PhD, 2,3,4 Cécile Vigneau, MD, PhD, 1,2,3,4 Marie-Clémence Verdier, MD, 2,3,4 and Florian Lemaitre, MD, PhD 2,3,4 N irmatrelvir/ritonavir is approved for patients with high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Few experiences are reported with nirmatrelvir/ritonavir in solid organ recipients 1 and prescribing it in these patients can be challenging for clinicians because of expected drug-drug interactions between immunosuppressive drugs and the antiviral.…”

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confidence: 99%

First Experience of Optimization of Tacrolimus Therapeutic Drug Monitoring in a Patient Cotreated With Nirmatrelvir/Ritonavir: How Microsampling Approach Changes Everything

et al. 2023

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“…A simulation study of lopinavir/ritonavir treatment cessation showed a gradual decrease in drug transport and CYP3A inhibition, with 50% recovery of metabolism after 24 hours and 75% after 48 hours (30). Therefore, Lemaitre et al proposed reintroducing tacrolimus at 50% of the daily dose on Day 6 (Day 1 for the initiation of NR) and increasing it to 75% on day 7 before resuming the usual daily dose on day 8 (29). Along with monitoring whole blood tacrolimus concentrations, qualified institutions can measure nirmatrelvir and ritonavir plasma concentrations to better determine metabolic status and the appropriate timing of tacrolimus administration.…”

Section: Discussionmentioning

confidence: 99%

Optimizing the use of nirmatrelvir/ritonavir in solid organ transplant recipients with COVID-19: A review of immunosuppressant adjustment strategies

Tang

Song

2023

Front. Immunol.

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The coronavirus disease 2019 (COVID-19) pandemic has caused a significant burden of morbidity and mortality worldwide, with solid organ transplant recipients (SOTRs) being particularly vulnerable. Nirmatrelvir and ritonavir have demonstrated the potential for reducing the risk of hospitalization and death in patients with mild-to-moderate COVID-19. However, ritonavir has a strong drug–drug interaction with CYP3A-dependent drugs such as calcineurin inhibitors, potentially leading to rapid increases in blood concentration. As SOTRs are commonly prescribed immunosuppressants, co-administration with nirmatrelvir/ritonavir requires careful consideration. To address this issue, we conducted a literature review to evaluate the use and adverse effects of nirmatrelvir/ritonavir in SOTRs and explore feasible immunosuppressant adjustment regimens. Our findings suggest that nirmatrelvir/ritonavir could be a feasible treatment option for COVID-19 in SOTRs, provided that appropriate immunosuppressive drug management is in place during co-administration. Although prescribing the novel anti-SARS-CoV-2 drug to transplant recipients poses challenges, potential strategies to overcome these issues are discussed. Further studies are needed to determine the optimal dosing strategies of nirmatrelvir/ritonavir, immunosuppressant adjustment, and monitoring in this patient population.

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Yes We Can (Use Nirmatrelvir/Ritonavir Even in High Immunological Risk Patients Treated with Immunosuppressive Drugs)!

Cited by 8 publications

References 9 publications

Nirmatrelvir/ritonavir Use With Tacrolimus in Lung Transplant Recipients: A Single-center Case Series

Nirmatrelvir/ritonavir Use With Tacrolimus in Lung Transplant Recipients: A Single-center Case Series

First Experience of Optimization of Tacrolimus Therapeutic Drug Monitoring in a Patient Cotreated With Nirmatrelvir/Ritonavir: How Microsampling Approach Changes Everything

Optimizing the use of nirmatrelvir/ritonavir in solid organ transplant recipients with COVID-19: A review of immunosuppressant adjustment strategies

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