PDF(Pubmed)
Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：Nirmatrelvir/ritonavir（Paxlovid®）目前是针对非需氧性成年患者的2019年冠状病毒病（COVID-19）治愈性治疗的少数治疗选择之一，这些患者有很高的发展为严重疾病的风险。这种最近批准的加强抗病毒治疗存在药物-药物相互作用（DDI）的显着风险。作为法国COVID-19药物和疫苗强化监测计划的一部分，查询了法国国家药物警戒数据库（BNPV[基本国家药物警戒]），以便更好地表征药物安全性，特别关注DDI。该研究的目的是描述通过BNPV报告的药物不良反应。
方法：所有nirmatrelvir/ritonavir报告在法国首次授权的BNPV中验证（1月，20th2022)toDecember,考虑了第3届2022年（查询日期）。还进行了对科学文献(PubMed®)和来自WHO药物警戒数据库(Vigibase)的分析。
结果：在此期间（11个月），228例报告（占严重报告的40％）登记，性别比为1.9女性/1男性，平均年龄为66岁。DDI报告占报告的13％以上（n=30），主要与免疫抑制药物过度接触有关（n=16）。在复杂的临床环境中报告了总共10/228例致命结局的报告。报告的主要意外药物不良反应（ADR）是高血压（n=7），混乱（n=5），急性肾损伤（AKI，n=7）和各种皮肤反应（n=22）。除了疾病复发的情况(在本分析中没有发现)，Pubmed®和Vigibase的数据也报告了上述感兴趣的事件。
结论：总体而言，该分析表明,尼马特雷韦/利托那韦的安全性符合当前的产品特征总结(SmPC).主要关注的是DDI的风险。因此,在开始这种抗病毒之前，应系统地咨询SmPC和专家建议，这特别适用于多重用药患者。在这些复杂的情况下，需要包括临床药理学家在内的逐案多学科方法。血压升高,混乱,皮肤反应和AKIs是值得关注的主要意外不良反应，但随着时间的推移和新的报告，需要用定性的方法来确认。
方法：所有nirmatrelvir/ritonavir报告在法国首次授权的BNPV中验证（1月，20th2022)toDecember,考虑了第3届2022年（查询日期）。还进行了对科学文献(PubMed®)和来自WHO药物警戒数据库(Vigibase)的分析。
结果：在此期间（11个月），228例报告（占严重报告的40％）登记，性别比为1.9女性/1男性，平均年龄为66岁。DDI报告占报告的13％以上（n=30），主要与免疫抑制药物过度接触有关（n=16）。在复杂的临床环境中报告了总共10/228例致命结局的报告。报告的主要意外药物不良反应（ADR）是高血压（n=7），混乱（n=5），急性肾损伤（AKI，n=7）和各种皮肤反应（n=22）。除了疾病复发的情况(在本分析中没有发现)，Pubmed®和Vigibase的数据也报告了上述感兴趣的事件。
结论：总体而言，该分析表明,尼马特雷韦/利托那韦的安全性符合当前的产品特征总结(SmPC).主要关注的是DDI的风险。因此,在开始这种抗病毒之前，应系统地咨询SmPC和专家建议，这特别适用于多重用药患者。在这些复杂的情况下，需要包括临床药理学家在内的逐案多学科方法。血压升高,混乱,皮肤反应和AKIs是值得关注的主要意外不良反应，但随着时间的推移和新的报告，需要用定性的方法来确认。
