Post-marketing surveillance study on the effectiveness and safety of molnupiravir in high-risk COVID-19 outpatients: a prospective case series study

BACKGROUND: Molnupiravir, approved for treating mild to moderate COVID-19 in adults, aims to reduce hospitalisation and mortality rates. Although it was withdrawn from the market after the present study was conducted, understanding its long-term effects remains pertinent. We aimed to assess the real-world effectiveness and safety of molnupiravir in high-risk COVID-19 outpatients. METHODS: This prospective, multicenter, noninterventional, postmarketing cohort study enrolled high-risk COVID-19 outpatients with mild to moderate COVID-19, eligible under national prescribing criteria, who initiated molnupiravir within five days of symptom onset and were ineligible for first-line antiviral therapy. Patients were consecutively enrolled from eight Portuguese study sites and monitored for three months. Effectiveness was assessed by all-cause mortality and hospitalisation through day 29. Safety was evaluated by the incidence, severity, and causality of adverse events (AE), coded using MedDRA terminology and assessed via the WHO-UMC system. Data were collected through structured patient questionnaires and electronic health records. Statistical analysis was descriptive; proportions were reported with 95% confidence intervals (CI), and comparisons between groups were performed using appropriate statistical tests. RESULTS: By day 29 post-treatment initiation, no deaths were reported (n = 0; 0%; 95%CI = [0,26]), and all patients were either at home or institutionalised, with favourable outcomes. Out of the 12 patients enrolled, eight (67%; 95%CI = [35,90]) reported at least one AE, with the median time to the first AE being five days (range 5-7 days). Half of the patients (n = 6; 95%CI = [21,79]) reported AE deemed possibly or probably related to molnupiravir, involving nausea (25%), dizziness (17%), bitter taste (17%), and headache (17%). These AE were more commonly observed in older individuals and those overweight, indicating a potential influence of these factors on AE occurrence. CONCLUSIONS: Molnupiravir appears to show good safety and effectiveness, offering an alternative for high-risk COVID-19 outpatients ineligible for first-line therapy. Despite its market withdrawal, ongoing research into its long-term effects is crucial to potentially repurpose it for other viral infections.