In a recent study published in JAMA Network is openIn this study, the authors examined the prevalence of contraindications to nermatrilvir-ritonavir (Paxlovid) in hospitalized novel coronavirus disease 2019 (COVID-19) patients.
The US-Food and Drug Administration (US-FDA) has listed several medical contraindications for nermatrilvir ritonavir. A recent study suggested that these may be more prevalent in COVID-19 patients who are at high risk of progression to severe disease.
Clinical trials have shown that Paxlovid treatment reduces the risk of hospitalization and death in most high-risk patients due to its elevation. effectiveness versus placebo. It is also preferred because it provides convenience in oral dosing.
However, in certain circumstances, Paxlovid should be avoided due to the effects of ritonavir. In some patients, ritonavir raises concentrations of drugs that are more dependent on cytochrome P450 metabolism, family 3, and the CYP3A subfamily A (CYP3A), for example, in patients with severe renal and hepatic insufficiency.
In this study, the researchers enrolled a large cohort of patients (63,656 inpatients) with confirmed COVID-19 by positive reverse transcription-polymerase chain reaction (RT-PCR) test from 36 Université Grande Paris hospitals between January 24, 2020, to January 30. November 2021. None of these patients received Paxlovid treatment.
However, because these patients sought hospitalization for complications related to COVID-19, the researchers hypothesized that the rate of contraindications would be high in these patients.
The primary study outcome was the number of patients with contraindications to nermatrivir-ritonavir. Next, the researchers determined the proportion of individuals who died within 28 days of hospitalization. These patients may require other treatment (not Paxlovid) in an emergency setting.
Furthermore, the team divided the study analysis by gender, age (less than or greater than 65 years of age), and comorbidities among these patients.
The study followed the guidelines for the Enhancement of Reporting of Observational Studies in Epidemiology (STROBE) guidelines and received approval from the Institutional Review Board (IRB) for the Clinical Data Repository of Assistance Publique – Hôpitaux de Paris.
Only 62,525 COVID-19 patients met study criteria, of which 9,136 (14.6%) had medical contraindications to nirmatrelvir-ritonavir. The study population consisted of 31,561 women [50.5%]The average age of the participants was 52.8 years. The researchers noted that the rates of medical contraindications for nirmatrelvir-ritonavir were higher in men than in women (18% vs. 11.3%). Similarly, these rates were higher in older patients than in younger patients (26.9% vs 8.8%) and people with comorbidities. face to face Those without comorbidities (>37% vs 3.9%).
Notably, about 50% (2463 of 4861) of the patients who died of COVID-19 also had contraindications to nermatilvir-ritonavir. In these patients, rates were similar in men and women, and older and younger patients, but higher in patients with comorbidities versus those without. In particular, the most common contraindications in the study group were severe renal impairment and the use of drugs that depend on the CYP3A filtering gene.
The results of the current study raise concerns that medical contraindications to nirmatrelvir-ritonavir may have confounded the results of observational studies. Such studies may have overestimated the efficacy of baxlovid treatment, especially if they did not exclude patients with contraindications to this treatment. In fact, some contraindicated medications should be suspended (temporarily) in the course of Paxlovid use.
However, in agreement with previous studies, the current study also found medical inconsistencies with nermatrilvir-ritonavir in hospitalized individuals with COVID-19.