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

TL;DR

This study examines the real-world effectiveness and safety of molnupiravir in high-risk COVID-19 outpatients, finding no deaths or hospitalizations and common side effects like nausea and dizziness.

Contribution

The study provides real-world evidence of molnupiravir's effectiveness and safety in high-risk patients ineligible for first-line therapy.

Findings

No deaths or hospitalizations were reported among high-risk patients treated with molnupiravir.

Common adverse events included nausea, dizziness, bitter taste, and headache, with older and overweight individuals more affected.

Molnupiravir showed potential as an alternative treatment for patients ineligible for first-line therapies.

Abstract

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 Although it was withdrawn from the market after the present study was conducted, understanding its long-term effects remains pertinent.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.

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.

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.

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.

The online version contains supplementary material available at 10.1007/s43440-025-00729-2.

• Our study suggests that molnupiravir is safe and effective, offering an alternative treatment option for high-risk COVID-19 outpatients who are ineligible for first-line therapy.

• Molnupiravir was associated with no instances of all-cause mortality or hospitalisation among high-risk COVID-19 patients, highlighting its effectiveness in preventing severe disease progression.

• The most frequently reported AE were nausea, dizziness, bitter taste, and headache, with nausea appearing as early as one day post-treatment, persisting for up to three months, and being notably serious in one-fourth of these instances.

• AE with attributed causality were more frequently described in older or overweight individuals, suggesting these factors might influence the occurrence of AE with molnupiravir.

• Despite recent molnupiravir’s market withdrawal, continued research on its long-term effects is crucial to repurposing it for other viral infections and advancing medical knowledge based on the experiences of treated patients.

The online version contains supplementary material available at 10.1007/s43440-025-00729-2.

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