Department of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, Heidelberg, Germany; Cooperation Unit Clinical Pharmacy, Department of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, Heidelberg, Germany; Drug Commission of German Pharmacists (AMK), Berlin, Germany; Institute of Pharmacy, Freie Universität Berlin, Berlin, Germany.
Dtsch Arztebl Int. 2022 Apr 15;119(15):263-269. doi: 10.3238/arztebl.m2022.0152.
Five-day oral therapies against early COVID-19 infection have recently been conditionally approved in Europe. In the drug combination nirmatrelvir + ritonavir (nirmatrelvir/r), the active agent, nirmatrelvir, is made bioavailable in clinically adequate amounts by the additional administration of a potent inhibitor of its first-pass metabolism by way of cytochrome P450 [CYP] 3A in the gut and liver. In view of the central role of CYP3A in the clearance of many different kinds of drugs, and the fact that many patients with COVID-19 are taking multiple drugs to treat other conditions, it is important to assess the potential for drug interactions when nirmatrelvir/r is given, and to minimize the risks associated with such interactions.
We defined the interaction profile of ritonavir on the basis of information derived from two databases (Medline, GoogleScholar), three standard electronic texts on drug interactions, and manufacturer-supplied drug information. We compiled a list of drugs and their potentially relevant interactions, developed a risk min - imization algorithm, and applied it to the substances in question. We also compiled a list of commonly prescribed drugs for which there is no risk of interaction with nirmatrelvir/r.
Out of 190 drugs and drug combinations, 57 do not need any special measures when given in combination with brief, low-dose ritonavir treatment, while 15 require dose modification or a therapeutic alternative, 8 can be temporarily discontinued, 9 contraindicate ritonavir use, and 102 should preferably be combined with a different treatment.
We have proposed measures that are simple to carry out for the main types of drug that can interact with ritonavir. These measures can be implemented under quarantine conditions before starting a 5-day treatment with nirmatrelvir/r.
针对早期 COVID-19 感染的 5 天口服疗法最近在欧洲有条件批准。在奈玛特韦/利托那韦（nirmatrelvir/r）药物组合中，通过肠道和肝脏中细胞色素 P450 [CYP] 3A 对其首过代谢的强效抑制剂，使奈玛特韦以临床足够的量生物利用。鉴于 CYP3A 在清除许多不同种类药物中的核心作用，以及许多 COVID-19 患者正在服用多种药物来治疗其他疾病的事实，评估奈玛特韦/r 给药时的药物相互作用潜力并将与这些相互作用相关的风险最小化非常重要。
我们根据来自两个数据库（Medline、GoogleScholar）、三本关于药物相互作用的标准电子文本和制造商提供的药物信息的信息，定义了利托那韦的相互作用特征。我们编制了一份药物及其潜在相关相互作用的清单，制定了风险最小化算法，并将其应用于所讨论的物质。我们还编制了一份常见处方药物清单，这些药物与奈玛特韦/r 没有相互作用的风险。
在 190 种药物和药物组合中，有 57 种在与短期、低剂量利托那韦联合使用时不需要采取特殊措施，而 15 种需要剂量调整或替代治疗，8 种可以暂时停药，9 种药物与利托那韦相互作用禁忌，102 种药物最好与其他治疗方法联合使用。
我们提出了在开始 5 天奈玛特韦/r 治疗之前在隔离条件下易于实施的主要类型药物相互作用的措施。
