Early experience with modified dose nirmatrelvir/ritonavir in dialysis patients with coronavirus disease-2019

  1. Pierre Antoine Brown
  2. Michaeline McGuinty
  3. Christos Argyropoulos
  4. Edward G Clark
  5. David Colantonio
  6. Pierre Giguere
  7. Swapnil Hiremath

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Abstract

Introduction

Nirmatrelvir/Ritonavir was approved for use in high risk outpatients with coronavirus disease (COVID-19). However, patients with severe chronic kidney disease, including patients on dialysis, were excluded from the phase 3 trial, and currently the drug is not recommended below a glomerular filtration rate of 30 ml/min/1.73m 2 . Based on available pharmacological data and principles, we developed a modified dose which was lower, and administered at longer intervals.We administered nirmatrelvir/ritonavir as 300/100 mg on day one, followed by 150/100 mg daily from day two to day five. In this case series, we report the initial experience with this modified dose regimen.

Methods

This is a retrospective chart review, conducted after obtaining institutional board approval. Demographic and outcome data was abstracted from the electronic medical record for dialysis patients who developed COVID-19 during the period of study and received nirmatrelvir/ritonavir. The principal outcomes we describe are symptom resolution, and safety data with the modified dose regimen in the dialysis patients.

Results

19 patients developed COVID-19 during the period of study of whom 15 received nirmatrelvir/ritonavir. 47% of them were female and 67% had diabetes. Most patients had received three doses of the vaccine (80%) while 13% were unvaccinated. Potential drug interactions concerns were common (median 2 drugs per patient) with amlodipine and atorvastatin being the commonest drugs requiring dose modification. Nirmatrelvir/ritonavir use was associated with symptom resolution in all patients, and was well tolerated. One patient had a rebound of symptoms, which improved in 2 more days. There were no COVID-19 related hospitalizations or deaths in any of the patients.

Conclusion

In this case series of 15 hemodialysis patients with COVID-19, a modified dose of nirmatrelvir/ritonavir use, with pharmacist support for drug interaction management, was associated with symptom resolution, and was well tolerated with no serious adverse effects.

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  1. ScreenIT

    SciScore for 10.1101/2022.05.18.22275234: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: Procedures: Until April 11, 2022, eligibility for outpatient COVID therapy required adjudication and approval by an institutional committee which included an infectious diseases physician (MM).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    This study does have limitations. Most importantly, this is not a randomized controlled trial, and we do not have controls for comparison. Comparing these data with historical controls would be biased, given changing vaccination status, variants, and therapeutic options over time. A comparison with patients who did not receive nirmatrelvir/ritonavir also would be biased, as these patients would be importantly different from the treated group.. Lastly, the purpose of this case series is not to demonstrate the efficacy of nirmatrelvir/ritonavir, rather to report that a modified dose is well tolerated in this population. The importance of our experience is to allow faster implementation of modified dose protocol of nirmatrelvir/ritonavir for dialysis patients and shorten the period of therapeutic nihilism. Though monoclonal antibodies are easier and considered safer to use in the dialysis population, since there is no need for dose adjustment, their efficacy also changes as newer and resistant variants arise with mutations in the receptor binding domain (RBD) of the spike protein. This is less likely to happen with antiviral drugs, and the experience we describe will be useful for management of dialysis patients in the next few waves. We do not have robust evidence in the form of a randomized controlled trial. It should be noted that the phase 3 trial which led to the drug approval included 2246 patients, and to do such a large trial specifically in dialysis patients may not be ...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a protocol registration statement.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  2. Version published to 10.1101/2022.05.18.22275234v1 on medRxiv