Bihan Kevin, Lipszyc Lorène, Lemaitre Florian, Dautriche Anne, Fédrizzi Sophie, Atzenhoffer Marina, Vitores Aurélie, Page Annabelle, Lebrun-Vignes Bénédicte
Département de pharmacologie, centre régional de pharmacovigilance Pitié-Saint Antoine, GH Pitié-Salpêtrière, AP-HP, 75000 Paris, France.
Centre régional de pharmacovigilance, GH Henri-Mondor, AP-HP, 94000 Créteil, France.
Therapie. 2023 Sep-Oct;78(5):531-547. doi: 10.1016/j.therap.2023.03.001. Epub 2023 Mar 7.
Nirmatrelvir/ritonavir (Paxlovid®) is currently one of the few therapeutic options for coronavirus disease 2019 (COVID-19) curative treatment in non-oxygen-requiring adult patients at-high risk of progressing to severe disease. This recently approved boosted antiviral therapy presents a significant risk of drug-drug interactions (DDI). As part of the enhanced surveillance program in France for COVID-19 drugs and vaccines, the French national pharmacovigilance database (BNPV [base nationale de pharmacovigilance]) was queried in order to better characterize the drug safety profile, with a special focus on DDI. The aim of the study was to describe the adverse drug reactions reported through the BNPV.
All nirmatrelvir/ritonavir reports validated in the BNPV from the first authorization in France (January, 20th 2022) to December, 3rd 2022 (date of the query) were considered. An analysis of the scientific literature (PubMed®) and from the WHO pharmacovigilance database (Vigibase) was also performed.
Over this period (11 months), 228 reports (40% of serious reports) were registered with a sex ratio of 1.9 female/1 male and a mean age of 66 years old. DDI reports account for more than 13% of reports (n=30) and were mainly related to immunosuppressive drugs overexposure (n=16). A total of 10/228 reports with fatal outcomes were reported in complex clinical settings. The main reported unexpected adverse drug reaction (ADRs) were high blood pressure (n=7), confusion (n=5), acute kidney injuries (AKI, n=7) and various skin reactions (n=22). Apart from situations of disease recurrence (not found in this analysis), data from Pubmed® and Vigibase also reported the above-mentioned events of interest.
Overall, this analysis shows that nirmatrelvir/ritonavir safety profile was conform to current summary of product characteristics (SmPC). The main concern was the risk of DDI. Therefore, SmPC and expert recommendations should be systematically consulted before initiation of this antiviral, which is particularly indicated in polypharmacy patients. A case-by-case multidisciplinary approach including a clinical pharmacologist is required in these complex situations. Blood pressure elevation, confusion, cutaneous reactions and AKIs were the main unexpected ADRs of interest to follow, but need to be confirmed with a qualitative approach over time and new reports.
奈玛特韦/利托那韦（Paxlovid®）是目前少数可用于治疗2019冠状病毒病（COVID-19）的疗法之一，适用于有进展为重症疾病高风险、无需吸氧的成年患者。这种最近获批的强化抗病毒疗法存在显著的药物相互作用（DDI）风险。作为法国加强对COVID-19药物和疫苗监测计划的一部分，查询了法国国家药物警戒数据库（BNPV [base nationale de pharmacovigilance]），以便更好地描述该药物的安全性概况，特别关注药物相互作用。本研究的目的是描述通过BNPV报告的药物不良反应。
考虑所有在法国首次获批（2022年1月20日）至2022年12月3日（查询日期）期间在BNPV中验证的奈玛特韦/利托那韦报告。还对科学文献（PubMed®）和世界卫生组织药物警戒数据库（Vigibase）进行了分析。
在此期间（11个月），共登记了228份报告（占严重报告的40%），男女比例为1.9:1，平均年龄为66岁。药物相互作用报告占报告总数的13%以上（n = 30），主要与免疫抑制药物暴露过量有关（n = 16）。在复杂的临床环境中，共报告了10/228份有致命结局的报告。报告的主要意外药物不良反应（ADR）为高血压（n = 7）、意识模糊（n = 5）、急性肾损伤（AKI，n = 7）和各种皮肤反应（n = 22）。除了疾病复发情况（本分析未发现）外，来自PubMed®和Vigibase的数据也报告了上述相关事件。
总体而言，该分析表明奈玛特韦/利托那韦的安全性概况符合当前的产品特性摘要（SmPC）。主要关注点是药物相互作用的风险。因此，在开始使用这种抗病毒药物之前，应系统查阅SmPC和专家建议，这在联合用药患者中尤为适用。在这些复杂情况下，需要采用包括临床药理学家在内的逐案多学科方法。血压升高、意识模糊、皮肤反应和急性肾损伤是后续主要关注的意外药物不良反应，但需要随着时间推移和新报告采用定性方法加以确认。
