Prevalence of contraindications to Paxlovid in hospitalized patients with COVID-19

Nirmatrelvir–ritonavir (Paxlovid)1 may be the preferred outpatient treatment option for COVID-19 for most high-risk patients because of the convenience of oral dosing and its high efficacy versus placebo in reducing hospitalization or death (based on results in a phase 2/3 trial). However, nirmatrelvir–ritonavir should not be used in certain circumstances, because of the effect of ritonavir.1 Ritonavir may raise the concentrations of drugs highly dependent on hepatic CYP3A metabolism, potentially resulting in serious reactions. On the other hand, coadministration with potent CYP3A inducers can significantly reduce nirmatrelvir concentrations, potentially leading to the loss of virologic response.1 The Canadian product monograph for Paxlovid includes a long list of drugs that are contraindicated for concomitant use with Paxlovid.2 Patients with severe kidney impairment and severe liver impairment were excluded from nirmatrelvir–ritonavir clinical trials.1 The Canadian product monograph does not recommend Paxlovid use in patients with severe renal impairment (eGFR < 30 mL/min) or severe hepatic impairment.2 Investigators in France recently explored the prevalence of these contraindications to nirmatrelvir–ritonavir in 62,525 patients hospitalized with COVID-19, in 36 Paris University hospitals. They examined the proportion of patients with contraindications to nirmatrelvir–ritonavir, who therefore would have needed therapy other than nirmatrelvir–ritonavir in the ambulatory setting.1 Results showed the following: Of the 62,525 patients in the analysis, 9,136 (14.6%) had a medical contraindication to nirmatrelvir–ritonavir. The rate of contraindications was higher in men (5,568 [18.0%]) than in women (3,577 [11.3%]). The rate of contraindications was higher in patients older than 65 years (5,398 of 20,064 [26.9%]) compared to younger patients (3,738 of 42,461 [8.8%]). The rate of contraindications was higher in patients with comorbidities (> 37.0% for most comorbidities) than in those without comorbidities (1,475 of 37,748 [3.9%]). Among the 4,861 patients who died, 2,463 (50.7%) had a contraindication to nirmatrelvir–ritonavir, with similar rates in men and women, as well as older and younger patients, but higher rates in patients with comorbidities versus those without. The most prevalent contraindications were severe kidney impairment and use of medications dependent on CYP3A for clearance.1 The authors conclude that in this study, 14.6% of individuals hospitalized with COVID-19 had a contradiction to nirmatrelvir–ritonavir therapy. These findings support the need for alternate treatments for a significant number of ambulatory patients and for continued research to develop new and less expensive treatment options. The authors acknowledge that some contraindications to the use of nirmatrelvir–ritonavir are not absolute, as some contraindicated medications can be temporarily held, allowing use of nirmatrelvir–ritonavir therapy.1 References 1. Hoertel N, Boulware DR, Sánchez-Rico M, et al. Prevalence of contraindications to nirmatrelvir-ritonavir among hospitalized patients with COVID-19 at risk for progression to severe disease. JAMA Netw Open 2022;5(11):e2242140. (accessed November 15, 2022). 2. Pfizer Canada ULC. Paxlovid (nirmatrelvir tablets; ritonavir tablets) product monograph. Kirkland, QC; June 13, 2022. (accessed November 15, 2022).

Prevalence of contraindications to Paxlovid in hospitalized patients with COVID-19

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