(012) Safety of using nirmatrelvir/ritonavir and cardiovascular medications with potential drug-drug interactions: Comparative safety analysis using WHO international database

Publication Number: 1008

Background: COVID-19 pandemic led to an urgent need for effective treatment options. Among the therapeutic interventions, oral antiviral medications have gained significant attention due to their potential to provide convenient and accessible treatment options for infected individuals. However, the safety profile of these oral antiviral drugs and their potential adverse events have not been comprehensively explored.

Objectives: To explore adverse events of nirmatrelvir/ritonavir(NMV/r) and molnupiravir using the WHO pharmacovigilance database, VigiBase.

Methods: We conducted a case-non-case study using the spontaneous adverse event reports on NMV/r or molnupiravir in VigiBase between December 2021 and March 2023. Cases were reports with NMV/r or molnupiravir. Non-cases were all other reports with the drugs of interest. The signal for adverse event with the use of NMV/r or molnupiravir were defined using reporting odds ratio (ROR) with 95% confidence interval (CI).

Results: Of 4,651,859 individual reports after Emergency use authorization of NMV/r and molnupiravir, 28,227 reports listed NMV/r and 2,003 reports listed molnupiravir. The most frequently reported events were disease recurrence (49.2%), followed by dysgeusia (15.8%), and 87.6% of outcomes were non-serious for NMV/r. For molnupiravir, diarrhea (9.4%) and nausea (7.1%) were the most frequently reported, and 80.1% of outcomes were non-serious. In disproportionality analysis, NMV/r was associated with events of nausea (ROR: 1.21, 95% CI: 1.15-1.26) and taste disorder such as ageusia (4.80, 4.22-5.46), anosmia (4.39, 3.73-5.16) and dysgeusia (120.98, 118.15-123.87). Molnupiravir was associated with events of rash (ROR 3.55, 95% CI: 3.07-4.09), diarrhea (8.36, 7.48-9.34) and taste disorder such as dysgeusia (4.03, 2.81-5.78) and dyspepsia (3.04, 1.91-4.83).

Conclusions: : It was noteworthy that both medications were generally associated with non-serious adverse events, indicating a low risk of serious adverse events with use of NMV/r or molnupiravir. However, as their association with nausea, diarrhea and taste disorder might be due to disease recurrence or COVID-19 itself, further investigation should be conducted.