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Review
. 2023 Apr;25(2):e14037.
doi: 10.1111/tid.14037. Epub 2023 Feb 27.

"Saving lives with nirmatrelvir/ritonavir one transplant patient at a time"

Katherine A Belden  1 , Sarah Yeager  2 , Jamie Schulte  3 , Maria P Martinez Cantarin  4 , Sean Moss  1 , Tricia Royer  1 , Dagan Coppock  1
Affiliations
Review

"Saving lives with nirmatrelvir/ritonavir one transplant patient at a time"

Katherine A Belden et al. Transpl Infect Dis. 2023 Apr.

Abstract

Background: Solid organ transplant (SOT) recipients are at risk of complications from COVID-19. Nirmatrelvir/ritonavir (Paxlovid) can reduce mortality from COVID-19 but is contraindicated in patients receiving calcineurin inhibitors (CI), which depend on cytochrome p4503A (CY3PA). In this study, we aim to show the feasibility of nirmatrelvir/ritonavir administration to SOT recipients receiving CI with coordination of medication management and limited tacrolimus trough monitoring.

Methods: We reviewed adult SOT recipients treated with nirmatrelvir/ritonavir from 4/14 to 11/1/2022 and assessed for changes in tacrolimus trough and serum creatinine after therapy.

Results: Of 47 patients identified, 28 were receiving tacrolimus and had follow-up laboratory testing. Patients had a mean age of 55 years, 17 (61%) received a kidney transplant and 23 (82%) received three or more doses of SARS-CoV-2 mRNA vaccine. Patients had mild-moderate COVID-19 and started nirmatrelvir/ritonavir within 5 days of symptom onset. Median baseline tacrolimus trough concentration was 5.6 ng/mL (Interquartile range 5.1-6.7), while median follow-up tacrolimus trough concentration was 7.8 ng/mL (Interquartile range 5.7-11.5, p = 0.0017). Median baseline and follow-up serum creatinine levels were 1.21 mg/dL (Interquartile range 1.02-1.39) and 1.21 mg/dL (interquartile range 1.02-1.44, p = 0.3162), respectively. One kidney recipient had a follow up creatinine level >1.5 times baseline. No patients were hospitalized or died from COVID-19 in the follow up period.

Conclusion: While administration of nirmatrelvir/ritonavir resulted in a significant increase in tacrolimus concentration, this did not result in significant nephrotoxicity. Early oral antiviral treatment in SOT recipients is feasible with medication management, even with limited tacrolimus trough monitoring.

Keywords: COVID-19; SARS-CoV-2; nirmatrelvir/ritonavir; solid organ transplantation; tacrolimus.

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Conflict of interest statement

CONFLICT OF INTEREST STATEMENT

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Figures

FIGURE 1
FIGURE 1
Paxlovid workflow.
FIGURE 2
FIGURE 2
(A) Change in tacrolimus levels in liver transplant recipients before and after completion of nirmatrelvir/ritonavir. (B) Change in tacrolimus levels in kidney transplant recipients before and after completion of nirmatrelvir/ritonavir.
See this image and copyright information in PMC

References

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