Post‐marketing safety concerns with nirmatrelvir: A disproportionality analysis of spontaneous reports submitted to the FDA Adverse Event Reporting System

Abstract

AimsNirmatrelvir is an antiviral drug with a novel mechanism of action, targeting the 3‐CL protease, and is used in the treatment of COVID‐19. However, the potential side effects have not yet been fully studied. The aim of this study was to identify potential safety signals of nirmatrelvir by analysing post‐marketing safety data based on the largest publicly available worldwide pharmacovigilance database.MethodsWe analysed nirmatrelvir adverse events to identify and characterize relevant safety signals based on the FDA Adverse Event Reporting System database in 2022. The case/non‐case approach was used to estimate the reporting odds ratio (ROR) and information component (IC) with relevant confidence intervals (95% CI) for adverse events (AEs) that numbered 4 or more.ResultsA total of 26 846 cases were included. Disease recurrence (ROR [95% CI] = 413.2 [395.6–431.59]), dysgeusia (ROR [95% CI] = 110.84 [106.04–115.85]), anosmia (ROR [95% CI] = 15.21 [12.76–18.11]), ageusia (ROR [95% CI] = 9.80 [8.50–11.3]) and urticaria (ROR [95% CI] = 1.91 [1.69–2.17]) were the main safety signals. In addition, abdominal pain upper and skin toxicity were two specific safety signals of nirmatrelvir. In the pregnant population, there was a significant increased ROR for life‐threatening conditions (ROR [95% CI] = 8.00 [1.77–36.20]).ConclusionsOur study identified that the main and specific safety signals of nirmatrelvir were disease recurrence, dysgeusia, abdominal pain upper and skin toxicity. Clinicians and pharmacists should be vigilant of these AEs, although differentiating between COVID‐19 symptoms and AEs can be challenging. Notably, a potential safety concern of nirmatrelvir should be a warning based on a small number of events in the pregnant population. However, the available data are insufficient, and further continued pharmacovigilance and surveillance is needed to fully understand this issue.