Pharmacoepidemiol Risk Manage.  2024 Mar;16(1):65-78. 10.56142/perm.24.0006.

Safety Monitoring of Oral Antiviral COVID-19 Treatment Using Korea Adverse Event Reporting System (KAERS) Database

• Choe Y
• Park SJ
• Kim JH
• Yoon D
• Kang DY
• Jung JH
• Shin JY

• KMID: 2556394
• DOI: http://doi.org/10.56142/perm.24.0006

Abstract

Objective
This study aimed to evaluate the association between nirmatrelvir/ritonavir, molnupiravir and adverse events and identify safety signals not previously known.
Methods
To identify major adverse events and safety signals associated with nirmatrelvir/ritonavir and molnupiravir, we conducted pharmacovigilance study using drug-related adverse events reported to KIDS KAERS DB (2305A0011). Disproportionality analysis were performed using reporting odds ratio (ROR) and information component (IC) method to detected new safety signals not listed in drug label.
Results
Adverse events related to nirmatrelvir/ritonavir and molnupiravir were frequently reported in women and person aged ≥ 65, and mostly reported as not serious. Following nirmatrelvir/ritonavir administration, ‘sensory abnormalities’ (20.18%), ‘diarrhoea’ (13.76%), and ‘nausea and vomiting symptoms’ (9.87%) were most commonly reported, while for molnupiravir, ‘nausea and vomiting symptoms’ (15.92%), ‘neurological signs and symptoms’ (15.92%), ‘urticarias’ (10.45%) were predominantly reported. Disproportionality analysis revealed a significant association of nirmatrelvir/ritonavir with ‘sensory abnormalities’ (ROR [95% CI] = 223.74 [207.24–241.55]), ‘interactions’ (ROR [95% CI] = 37.35 [15.10–92.35]), ‘faecal abnormalities’ (ROR [95% CI] = 32.33 [18.68–56.36]). Adverse events not listed on drug label included ‘olfactory nerve disorders’, ‘appitite disorder’, ‘hallucinations’ and urinary adverse events. For molnupiravir, strong association were observed with cardiovascular adverse events such as ‘heart rate and pulse investigations’ (ROR [95% CI] = 58.60 [18.96–181.16]) and ‘vascular tests’ (ROR [95% CI] = 10.97 [4.09–29.47]), which were not included in drug label.
Conclusion
Adverse events following the use of nirmatrelvir/ritonavir and molnupiravir were generally not serious, but some safety signals not listed on drug label were newly detected and warranted attention. We expected this study to provide basic data of safety for oral antivirals of COVID-19 and may contribute to the development of future drug safety guidelines.

Keyword

Nirmatrelvir and ritonavir drug combination; Molnupiravir; Drug-related side effects and adverse reactions; Pharmacovigilance