Paxlovid Contraindications Prevalent in High-Risk Patients Hospitalized With COVID-19

Contraindications to Paxlovid for COVID-19 treatment were prevalent, suggesting some medications should be temporarily held during nirmatrelvir-ritonavir use.

Contraindications to treatment with Paxlovid (nirmatrelvir-ritonavir) is prevalent in patients hospitalized with COVID-19 infection, the most common of which include severe kidney impairment and the use of medications dependent on CYP3A clearance. These study findings were published in JAMA Network Open.

In this cohort study, researchers applied Food and Drug Administration-listed contraindications to Paxlovid to patients who were hospitalized with COVID-19 infection at 36 university hospitals in France between January 2020 and November 2021. The researchers assessed the number of patients with contraindications to Paxlovid, including among those who died within 28 days of hospitalization. Results were stratified by sex, age (≤65 years vs >65 years), and comorbidities.

Among a total of 62,525 patients included in the final analysis, the median age was 52.8 (IQR, 33.8-70.5) years, 50.5% were women, and contraindications to Paxlovid were noted in 14.6% of patients.

Results showed an increased prevalence of contraindications to Paxlovid among men vs women (18.0% vs 11.3%), with similar findings for older vs younger patients (26.9% vs 8.8%), and those with vs without comorbidities (37.0% vs 3.9%).

Contraindications to Paxlovid were most commonly observed among patients with severe kidney impairment (6.33%) and those receiving medications dependent on CYP3A for clearance (5.15%). Patients with conditions originating in the perinatal period (n=85), those with genitourinary-related diseases (n=5628), and those with congenital malformations, deformations, or chromosomal abnormalities (n=244) had the highest rate of at least 1 possible contraindication (82.4%, 77.6%, and 52.5%, respectively).

These findings support the need to anticipate supplies for alternative approved treatments and those that are under regulatory review (eg, SARS-CoV-2 main protease inhibitors).

Of 4861 patients who died within 28 days of hospitalization, contraindications to Paxlovid were present in 50.7%, and higher rates of contraindications were noted in those with vs without comorbidities. In contrast with the overall population, contraindication rates among these patients were similar between men vs women (49.0% vs 51.6%) and between younger vs older patients (49.6% vs 50.9%).

Study limitations include the possibility that Paxlovid may not have been administered to some patients even if it were not contraindicated, potentially owing to duration of COVID-19-related symptoms of more than 5 days or limited supply. Other limitations were the lack of data on COVID-19 vaccination, race or ethnicity, and patient weight.

According to the researchers, “These findings support the need to anticipate supplies for alternative approved treatments and those that are under regulatory review (eg, SARS-CoV-2 main protease inhibitors)…”


Hoertel N, Boulware DR, Sánchez-Rico M, Burgun A, Limosin F. Prevalence of contraindications to nirtmatrelvir-ritonavir among hospitalized patients with COVID-19 at risk for progression to severe disease. JAMA Netw Open. Published online November 15, 2022. doi:10.1001/jamanetworkopen.2022.42140