Nirmatrelvir-ritonavir (Paxlovid) reduces COVID-related morbidity and mortality. Hospitalized patients may have contraindications to its use. Ritonavir may elevate drug concentrations if dependent on hepatic cytochrome P-450-3A (CYP3A) metabolism. Coadministration with CYP3A inducers can significantly reduce nirmatrelvir concentrations with loss of drug response. Severe kidney and liver disease patients were excluded from clinical trials. In 36 Parisian University Hospitals, the authors studied records from January 24, 2020 to November 30, 2021, a period before patients received nirmatrelvir-ritonavir. Of 62,500 PCR-proven patients; 9,136 (14.6%) had a medical contraindication (men 18%, women 11%; older (>65)- 27%; co-morbidities-37%). Among 4,861 patients who died, 50.7% had a contraindication. The authors conclude that published nirmatrelvir-ritonavir hospital studies may overestimate treatment efficacy by avoiding patients with contraindications. A large unmet need remains for effective COVID treatments.

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2798450