目的:Nirmatrelvir作为一种新的3CL蛋白酶抑制剂用于治疗COVID-19的抗病毒药物,潜在的副作用尚未得到充分研究。这项研究的目的是通过基于最大的全球公开药物警戒数据库分析上市后安全性数据来识别Nirmatrelvir的潜在安全性信号。
方法:我们在2022年根据FDA不良事件报告系统数据库分析了Nirmatrelvir不良事件,以识别和表征相关安全性信号。病例/非病例方法用于估计报告比值比(ROR)和信息分量(IC),并具有相关置信区间(95%CI),用于≥4个计数的不良事件(AE)。
结果:共纳入26846例。疾病复发[ROR(95CI)=413.2(395.6-431.59)],消化不良[ROR(95CI)=110.84(106.04-115.85)],嗅觉缺失[ROR(95CI)=15.21(12.76-18.11)],主要的安全信号是急性发作[ROR(95CI)=9.80(8.50-11.3)]和荨麻疹[ROR(95CI)=1.91(1.69-2.17)]。此外,上腹痛和皮肤毒性是Nirmatrelvir的两个特定安全性信号。在怀孕的人群中,危及生命的ROR显著增加[ROR(95CI)=8.00(1.77-36.20)].
结论:我们的研究确定Nirmatrelvir的主要和特定的安全信号是疾病复发,熟食症,上腹痛和皮肤毒性。临床医生和药剂师应该警惕这些不良事件,尽管区分COVID-19症状和AE可能具有挑战性。值得注意的是,Nirmatrelvir的潜在安全问题应该是一个警告,基于怀孕人群中的少量事件.然而,现有数据不足,需要进一步持续的药物警戒和监测才能充分理解这一问题。
Nirmatrelvir 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.
We 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.
A 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]).
Our 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.