Abstract：
OBJECTIVE: Nirmatrelvir in association with ritonavir (PAXLOVID™, Pfizer) is an antiviral agent targeting the 3-chymotrypsin-like cysteine protease enzyme (3C-like protease or Mpro) which is a key enzyme of the viral cycle of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This combination with a well-known pharmacokinetic enhancer leads to a high risk for drug-drug interactions in a polymedicated elected population for treatment. The aim of this work was to provide recommendations on behalf of the national French society of pharmacology (French Society of Pharmacology and Therapeutics; SFPT), by suggesting optimal and pragmatic therapeutic strategies if nirmatrelvir/ritonavir is to be given together with drugs commonly used, in order to ensure secured physicians\' prescription.
METHODS: Six clinical pharmacologists search the scientific literature to provide a first draft of recommendations. Thereafter, twelve other clinical pharmacologists verified the recommendations and proposed modifications. The final draft was then validated by all 18 participants.
RESULTS: Five distinct recommendations were issued: i) contra-indications, ii) \"PAXLOVID™ not recommended with the comedication\", iii) \"PAXLOVID™ possible whether the comedication is discontinued\", iv) \"PAXLOVID™ possible only after an expert advice\" and v) \"PAXLOVID™ possible without modification of the associated treatment\". The final document comprises recommendations for 171 drugs/therapeutic classes aiming to secure prescription. In complex situations, clinicians are advised to contact their pharmacology department to obtain specific recommendations on the management of drug-drug interactions with nirmatrelvir/ritonavir.
CONCLUSIONS: These recommendations intend to be a help for clinicians willing to prescribe nirmatrelvir/ritonavir and to prevent drug-drug interactions leading to adverse drug reactions or loss of efficacy. They constitute a guideline for primary care situations. Of course, some complex situations may require expert advices and here, again, clinical pharmacologists are at the forefront in providing therapeutic advice.
METHODS: Six clinical pharmacologists search the scientific literature to provide a first draft of recommendations. Thereafter, twelve other clinical pharmacologists verified the recommendations and proposed modifications. The final draft was then validated by all 18 participants.
RESULTS: Five distinct recommendations were issued: i) contra-indications, ii) \"PAXLOVID™ not recommended with the comedication\", iii) \"PAXLOVID™ possible whether the comedication is discontinued\", iv) \"PAXLOVID™ possible only after an expert advice\" and v) \"PAXLOVID™ possible without modification of the associated treatment\". The final document comprises recommendations for 171 drugs/therapeutic classes aiming to secure prescription. In complex situations, clinicians are advised to contact their pharmacology department to obtain specific recommendations on the management of drug-drug interactions with nirmatrelvir/ritonavir.
CONCLUSIONS: These recommendations intend to be a help for clinicians willing to prescribe nirmatrelvir/ritonavir and to prevent drug-drug interactions leading to adverse drug reactions or loss of efficacy. They constitute a guideline for primary care situations. Of course, some complex situations may require expert advices and here, again, clinical pharmacologists are at the forefront in providing therapeutic advice.
摘要：
目标：Nirmatrelvir与利托那韦（PAXLOVID™，Pfizer）是一种针对3-胰凝乳蛋白酶样半胱氨酸蛋白酶（3C样蛋白酶或Mpro）的抗病毒剂，该酶是严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的病毒循环的关键酶。这种与众所周知的药代动力学增强剂的组合导致用于治疗的多药物选择群体中药物-药物相互作用的高风险。这项工作的目的是代表国家法国药理学会（法国药理学和治疗学学会；SFPT）提供建议，通过建议最佳和实用的治疗策略，如果尼马特雷韦/利托那韦与常用药物一起使用，为了确保安全的医生处方。
方法：六位临床药理学家搜索科学文献以提供建议初稿。此后,其他12名临床药理学家验证了这些建议并提出了修改建议.最终草案随后由所有18名参与者验证。
结果：发布了五项不同的建议：i）禁忌症，ii)\“PAXLOVID™不推荐与妥协\”，iii）\“PAXLOVID™可能是否停止了奉献\”，iv)\"PAXLOVID™仅在获得专家建议后才能使用\"和v)\"PAXLOVID™在不修改相关治疗的情况下可能使用\"。最终文件包括旨在确保处方的171种药物/治疗类别的建议。在复杂的情况下,我们建议临床医生联系他们的药理学部门,获得关于尼马特雷韦/利托那韦药物相互作用管理的具体建议.
结论：这些建议旨在帮助愿意开尼马特雷韦/利托那韦的临床医生，并防止药物相互作用导致药物不良反应或疗效丧失。它们构成了初级保健情况的指导方针。当然,一些复杂的情况可能需要专家的建议，在这里，再次，临床药理学家在提供治疗建议方面处于最前沿。
方法：六位临床药理学家搜索科学文献以提供建议初稿。此后,其他12名临床药理学家验证了这些建议并提出了修改建议.最终草案随后由所有18名参与者验证。
结果：发布了五项不同的建议：i）禁忌症，ii)\“PAXLOVID™不推荐与妥协\”，iii）\“PAXLOVID™可能是否停止了奉献\”，iv)\"PAXLOVID™仅在获得专家建议后才能使用\"和v)\"PAXLOVID™在不修改相关治疗的情况下可能使用\"。最终文件包括旨在确保处方的171种药物/治疗类别的建议。在复杂的情况下,我们建议临床医生联系他们的药理学部门,获得关于尼马特雷韦/利托那韦药物相互作用管理的具体建议.
结论：这些建议旨在帮助愿意开尼马特雷韦/利托那韦的临床医生，并防止药物相互作用导致药物不良反应或疗效丧失。它们构成了初级保健情况的指导方针。当然,一些复杂的情况可能需要专家的建议，在这里，再次，临床药理学家在提供治疗建议方面处于最前沿。
