Real-world safety of nirmatrelvir plus ritonavir in patients with COVID-19 in Japan: A post-marketing surveillance study

This large-scale post-marketing surveillance study (163 sites; February 2022-May 2023) evaluated the real-world safety and effectiveness of a newly initiated nirmatrelvir plus ritonavir combination for patients with COVID-19 in Japan. The current study reports the safety evaluation. The observation period was 28 days after the last day of administration. The safety analysis set comprised 2829 patients (mean [standard deviation] age, 63.1 [18.0] years; mild COVID-19, 80.8%; ≥1 risk factor for progression to severe COVID-19, 97.3%). The most common reason for discontinuing follow-up was symptom improvement (17.1%). Adverse drug reactions (ADRs) were observed in 423 (15.0%) patients (incidence [%]): dysgeusia (6.7%), diarrhea (2.6%), taste disturbance (1.5%), nausea (1.2%), vomiting (0.5%), decreased appetite (0.5%), and rash (0.5%). The median times to onset and recovery of these ADRs were 1-2 days and 2-6 days, respectively. Serious ADRs were observed in 6 patients (0.2%). No new safety signals were observed. The study showed that nirmatrelvir plus ritonavir was well tolerated in Japanese patients with COVID-19 in a real-world clinical setting. ClinicalTrials.gov number: NCT05263908.