Infectious Diseases and Therapy (Jan 2024)
Safety and Effectiveness of Molnupiravir in Japanese Patients with COVID-19: Final Report of Post-marketing Surveillance in Japan
Abstract
Abstract Introduction Molnupiravir is an orally available prodrug of N-hydroxycytidine that received special approval for emergency treatment of coronavirus disease 2019 (COVID-19) in Japan in December 2021 and full approval in April 2023. To assess the real-world safety and effectiveness of molnupiravir in Japanese patients with COVID-19, we conducted nationwide post-marketing surveillance to collect data at registered institutions in Japan. Methods The surveillance data were collected from December 27, 2021, to May 2, 2023. All reported adverse events were collected for safety analysis. Adverse drug reactions (ADRs) were assessed by the treating physicians. Effectiveness was assessed by the composite of hospitalization or all-cause death in outpatients and the composite of oxygen/mechanical ventilation initiation or all-cause death in inpatients. The observation period was from molnupiravir initiation through day 29. Results Of 3214 patients enrolled in the survey, 3179 were analyzed for safety. At baseline, 52.31% (1663/3179) of patients were male, the median (range) age was 69.0 (18–107) years, 82.38% (2619/3179) received COVID-19 vaccines, and 95.72% (3043/3179) had risk factors for severe COVID-19 illness. COVID-19 severity at baseline was mild in 86.44% (2748/3179) and moderate I in 10.22% (325/3179). A total of 205 ADRs occurred in 5.50% (175/3179) of patients; ADRs that occurred in > 0.5% of patients were diarrhea (1.86% [59/3179]) and rash (0.69% [22/3179]). Seven serious ADRs were reported in seven patients. In the effectiveness analysis population, the incidence of all-cause death through day 29 was 1.14% (34/2988), and the incidence of death through day 29 related to COVID-19 was 0.40% (12/2988). The cumulative incidence of the composite endpoint was 2.34% (47/2006) in outpatients and 4.60% (38/826) in inpatients. Conclusions This large-scale survey showed that molnupiravir was safe and effective in real-world settings in highly vaccinated Japanese patients with COVID-19, including older patients and those with comorbidities.
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