Hendrick Victoria, Pohorylo Erast, Merchant Lubna, Gerhart Jackie, Arham Iqra Naz, Draica Florin, Quercia Romina, Ayoub Ayman, Mehta Reema
Worldwide Medical and Safety, Pfizer Research and Development, Sandwich, Kent, UK.
Worldwide Medical and Safety, Pfizer Research and Development, Collegeville, PA, USA.
Infect Dis Ther. 2024 Dec;13(12):2545-2561. doi: 10.1007/s40121-024-01050-w. Epub 2024 Oct 26.
Nirmatrelvir/ritonavir (NMV/r) is approved in the United States (US) and more than 70 other countries for the treatment of mild to moderate COVID-19 in nonhospitalized adults at high risk for severe disease. Because ritonavir inhibits several drug metabolizing enzymes, potential drug-drug interactions (DDIs) between ritonavir and concomitant medications are an important consideration for prescribers. Here, we conducted a real-world analysis of data from Pfizer's global safety database regarding adverse events (AEs) reported during use of NMV/r concomitantly with potentially interacting drugs.
Data were extracted regarding DDI cases occurring from the start of NMV/r authorization through October 31, 2023. Results regarding concomitant treatment, specific AEs, and clinical outcomes are summarized. Overall NMV/r exposure was estimated based on packs of medication dispensed and was used to calculate reporting rates.
Among 19,617,670 patients exposed globally to NMV/r, 966 cases of potential DDIs were reported. Of these, 594 occurred in the US against an estimated US exposure of 14,646,990 patients, representing a reporting rate of 0.004%. Globally and in the United States, 66.8% and 77.3% of cases, respectively, were nonserious. Simvastatin and tacrolimus were the most frequently reported drugs associated with potential DDIs, and the most frequently reported AE regarding a specific event or symptom was dysgeusia (altered sense of taste), an AE known to be associated with NMV/r.
Low reporting rates of DDIs support the potential for NMV/r treatment to be safely managed with careful use of available drug interaction resources to aid in risk mitigation.
奈玛特韦/利托那韦（NMV/r）在美国及其他70多个国家被批准用于治疗有重症风险的非住院成年患者的轻至中度新冠肺炎。由于利托那韦会抑制多种药物代谢酶，因此利托那韦与同时使用的其他药物之间潜在的药物相互作用（DDIs）是处方医生需要重点考虑的问题。在此，我们对辉瑞全球安全数据库中有关NMV/r与潜在相互作用药物联合使用期间报告的不良事件（AE）的数据进行了真实世界分析。
提取了从NMV/r获批开始至2023年10月31日期间发生的药物相互作用病例的数据。总结了联合治疗、特定不良事件和临床结局的结果。根据发放的药包估算了NMV/r的总体暴露量，并用于计算报告率。
在全球19,617,670例暴露于NMV/r的患者中，报告了966例潜在药物相互作用病例。其中，594例发生在美国，估计美国有14,646,990例患者暴露，报告率为0.004%。在全球和美国，分别有66.8%和77.3%的病例为非严重病例。辛伐他汀和他克莫司是报告中与潜在药物相互作用最常相关的药物，关于特定事件或症状最常报告的不良事件是味觉障碍（味觉改变），这是一种已知与NMV/r相关的不良事件。
药物相互作用的低报告率表明，通过谨慎使用可用的药物相互作用资源来降低风险，NMV/r治疗有望得到安全管理。
