Abstract

As global health services respond to the coronavirus pandemic, many prescribers are turning to experimental drugs. This review aims to assess the risk of drug–drug interactions in the severely ill COVID-19 patient. Experimental therapies were identified by searching ClinicalTrials.gov for ‘COVID-19’, ‘2019-nCoV’, ‘2019 novel coronavirus’ and ‘SARS-CoV-2’. The last search was performed on 30 June 2020. Herbal medicines, blood-derived products and in vitro studies were excluded. We identified comorbidities by searching PubMed for the MeSH terms ‘COVID-19’, ‘Comorbidity’ and ‘Epidemiological Factors’. Potential drug–drug interactions were evaluated according to known pharmacokinetics, overlapping toxicities and QT risk. Drug–drug interactions were graded GREEN and YELLOW: no clinically significant interaction; AMBER: caution; RED: serious risk. A total of 2378 records were retrieved from ClinicalTrials.gov, which yielded 249 drugs that met inclusion criteria. Thirteen primary compounds were screened against 512 comedications. A full database of these interactions is available at www.covid19-druginteractions.org. Experimental therapies for COVID-19 present a risk of drug–drug interactions, with lopinavir/ritonavir (10% RED, 41% AMBER; mainly a perpetrator of pharmacokinetic interactions but also risk of QT prolongation particularly when given with concomitant drugs that can prolong QT), chloroquine and hydroxychloroquine (both 7% RED and 27% AMBER, victims of some interactions due to metabolic profile but also perpetrators of QT prolongation) posing the greatest risk. With management, these risks can be mitigated. We have published a drug–drug interaction resource to facilitate medication review for the critically ill patient.

中文翻译：

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药物相互作用：对实验性 COVID-19 疗法中未见危险的回顾。

 抽象的

随着全球卫生服务机构应对冠状病毒大流行，许多处方医生开始转向实验药物。本综述旨在评估重症 COVID-19 患者中药物相互作用的风险。通过在 ClinicalTrials.gov 中搜索“COVID-19”、“2019-nCoV”、“2019 新型冠状病毒”和“SARS-CoV-2”来确定实验疗法。最后一次检索于 2020 年 6 月 30 日进行。草药、血液制品和体外研究被排除在外。我们通过在 PubMed 中搜索 MeSH 术语“COVID-19”、“合并症”和“流行病学因素”来识别合并症。根据已知的药代动力学、重叠毒性和 QT 风险评估潜在的药物相互作用。药物间相互作用分为绿色和黄色：没有临床显着的相互作用；琥珀色：谨慎；红色：严重风险。从 ClinicalTrials.gov 中总共检索到 2378 条记录，其中产生了 249 种符合纳入标准的药物。针对 512 种药物筛选了 13 种主要化合物。有关这些相互作用的完整数据库，请访问 www.covid19-druginteractions.org。 COVID-19 的实验性疗法存在药物相互作用的风险，洛匹那韦/利托那韦（10% 红色，41% 琥珀色；主要是药代动力学相互作用的肇事者，但也存在 QT 延长的风险，特别是与可延长 QT 的合并药物一起使用时）、氯喹和羟氯喹（均为 7% 红色和 27% 琥珀色，由于代谢特征而成为某些相互作用的受害者，但也是 QT 延长的肇事者）构成最大的风险。通过管理，可以减轻这些风险。我们发布了药物相互作用资源，以方便危重患者的药物审查。