Prevalence of Medical Contraindications to Nirmatrelvir/Ritonavir in a Cohort of Hospitalized and Nonhospitalized Patients With COVID-19
et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofac389, Aug 2022
Analysis of 66,007 hospitalized and non-hospitalized patients showing a 14% prevalence of medical contraindications with nirmatrelvir/ritonavir for outpatients, 21% for inpatients, and 35% for patients that died.
Resistance. Variants may be resistant to paxlovid1-8. Use may promote the emergence of variants that weaken host immunity and potentially contribute to long COVID9. Confounding by contraindication. Hoertel et al. find that over 50% of patients that died had a contraindication for the use of Paxlovid10. Retrospective studies that do not exclude contraindicated patients may significantly overestimate efficacy. Black box warning. The FDA notes that severe, life-threatening, and/or fatal adverse reactions due to drug interactions have been reported in patients treated with paxlovid11. Kidney and liver injury. Studies show significantly increased risk of acute kidney injury12 and liver injury13,14. Viral rebound. Studies show significantly increased risk of replication-competent viral rebound15-17.
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Lim et al., 1 Aug 2022, retrospective, USA, peer-reviewed, 5 authors, study period 4 March, 2020 - 22 March, 2022.
Contact: sarah.lim@state.mn.us, permissions@oup.com.
Abstract: Open Forum Infectious Diseases
BRIEF REPORT
Prevalence of Medical
Contraindications to Nirmatrelvir/
Ritonavir in a Cohort of Hospitalized
and Nonhospitalized Patients With
COVID-19
Sarah Lim,1 Christopher J. Tignanelli,2, Nicolas Hoertel,3, David R. Boulware,4,
and Michael G. Usher4
1
This analysis describes the prevalence of contraindications
to nirmatrelvir/ritonavir among 66 007 patients with
coronavirus disease 2019 in a large health care system. A
possible contradiction was present in 9830 patients (14.8%),
with the prevalence of contraindications increasing with
higher acuity of illness.
Keywords. nirmatrelvir/ritonavir; COVID-19; contraindications; Palovid.
The authorization of 2 novel oral antiviral therapies for severe
acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by
the US Food and Drug Administration (FDA) in December
2021, nirmaltrelvir/ritonavir and molnupiravir [1, 2], has re
sulted in broader availability of effective coronavirus disease
2019 (COVID-19) early treatments in high-income countries
and has spurred new initiatives for improved access, such as
the Test to Treat program [3]. Other therapeutics such as
monoclonal antibodies and intravenous remdesivir are avail
able but require skilled health care personnel resources to ad
minister. Of these 2 oral antivirals, nirmaltrelvir/ritonavir
reduced the risk of hospitalization by 89%, as compared with
30% with molnupiravir [4, 5], and is the preferred therapy
for mild to moderate COVID-19 in nonhospitalized high-risk
adults [6].
Received 19 May 2022; editorial decision 28 July 2022; accepted 01 August 2022; published
online 3 August 2022
Correspondence: S. Lim, MBBCh, MPH, Minnesota Department of Health, 625 North Robert
Street, St. Paul, MN 55155 (sarah.lim@state.mn.us).
Open Forum Infectious Diseases®
© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases
Society of America. This is an Open Access article distributed under the terms of the
Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.
org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of
the work, in any medium, provided the original work is not altered or transformed in any
way, and that the work is properly cited. For commercial re-use, please contact journals.
permissions@oup.com
https://doi.org/10.1093/ofid/ofac389
METHODS
We conducted a retrospective review of all patients evaluated
for a diagnosis of COVID-19 in an integrated health system
consisting of 11 hospitals and 55 clinics, between March 4,
2020, and March 22, 2022. This health system provides care
for ∼20% of the population of Minnesota. Approval was ob
tained from the institutional review board at the University
BRIEF REPORT • OFID • 1
Minnesota Department of Health, St. Paul, Minnesota, USA, 2Department of Surgery,
University of Minnesota, Minneapolis, Minnesota, USA, 3Université Paris Cité, AP-HP, Hôpital
Corentin-Celton, DMU Psychiatrie et Addictologie, INSERM U1266, Institut de Psychiatrie et
Neuroscience de Paris, Paris, France, and 4Department of Medicine, University of Minnesota,
Minneapolis, Minnesota, USA
However, nirmaltrelvir/ritonavir is not suitable for all
patients, including many who are at high risk for severe illness.
Ritonavir strongly inhibits cytochrome P450 (CYP) 3A4 me
tabolism, which results in..
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Late treatment
is less effective
is less effective
