key: cord-0731929-q2mdd7gg
authors: Wang, Aileen X.; Koff, Alan; Hao, Diana; Tuznik, Natascha M.; Huang, Yihung
title: Effect of nirmatrelvir/ritonavir on calcineurin inhibitor levels: Early experience in four SARS‐CoV‐2 infected kidney transplant recipients
date: 2022-02-23
journal: Am J Transplant
DOI: 10.1111/ajt.16997
sha: 2b06c2c7847d2726e0acf4c48fee9a7d3f594d48
doc_id: 731929
cord_uid: q2mdd7gg

nan

To the Editor:

We read with great interest the recent letter by Lange and colleagues describing a proposed strategy of calcineurin inhibitors (CNI) management in COVID-19 positive solid organ transplant recipients (SOTR) treated with nirmatrelvir/ritonavir. 1 As ritonavir is a potent, irreversible CYP3A4 inhibitor, their strategy proposed immediate holding of tacrolimus or empiric dose reduction of cyclosporine upon initiation of nirmatrelvir/ritonavir, through to completion of the 5-day course. Measuring the CNI level on Day 3 and Days 6-7 from nirmatrelvir/ritonavir initiation was also recommended to assist with timing of CNI resumption. However, experience with this strategy in a real-world setting is limited.

We retrospectively reviewed our first four kidney transplant recipients on tacrolimus-based immunosuppressive therapy who received nirmatrelvir/ritonavir utilizing the strategy proposed by Based on our observations we agree with holding tacrolimus for SOTR treated with nirmatrelvir/ritonavir, along with close CNI monitoring. However, ascertaining the optimal timing and dose of tacrolimus re-introduction proved more challenging. During the 5-day course of nirmatrelvir/ritonavir while holding tacrolimus, levels only very gradually declined, but became sub-therapeutic several days after completion of the course. Based on these data, we anticipate tacrolimus can be reintroduced at partial or full dose between Days 8 and 10, ideally guided by drug levels. Given mild transaminitis observed it might also be prudent to discontinue statins on the day of nirmatrelvir/ritonavir initiation. While nirmatrelvir/ritonavir appears to possess potent antiviral activity against SARS-CoV-2, providers caring for SOTR on CNI should be very selective in its use, particularly in situations where access to phlebotomy for COVID-positive patients is limited, turnaround time for CNI levels is prolonged, or immunologic risk is high. 

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