新型冠状病毒感染主要治疗药物超说明书应用专家共识

Expert consensus on off-label administration of drugs in COVID-19

新型冠状病毒感染(COVID-19)救治过程中存在对免疫治疗药物不熟悉、特殊人群(如吞咽困难、严重肾功能不全的患者等)用药以及药物的可及性等问题,部分药物存在超说明书用药的现象。为此,"新型冠状病毒感染主要治疗药物超说明书应用专家共识"编写组组织多学科专家,基于循证医学证据,参照Micromedex的Thomson有效性等级、推荐等级及证据强度分类,通过共识会议最终形成10条超说明书用药推荐意见,其中超说明书改变剂型给药3条,超适应证给药5条,超适用人群给药2条,旨在为临床医生提供合理用药依据并为药学部门管理提供参考。

Challenges to the clinical management of coronavirus disease 2019(COVID-19)include the unfamiliarity of immunomodulator prescription,the difficulty of drug administration in special patient populations(e.g.,patients with dysphagia or severe renal insufficiency),and limited medication accessibility.Off-label administration of some medications for COVID-19 has been documented.Here,we highlighted several issues relevant to the clinical application of COVID-19 medications by soliciting multidisciplinary experts.We summarised the drug specifications from and outside the mainland of China,the guidelines for the clinical management of COVID-19 and the evidence from high-quality research.Recommendations were formed through teleconference with the consensus conference method,taking into account the level of effectiveness and recommendation,and the strength of evidence from the Thomson Micromedex.We made 10 recommendations for off-label drug administration,including three recommendations for off-label modification of drug dosage form for oral or gastric tube feeding administration(dissolution of nirmatrelvir-ritonavir tablets into suspension,solution preparation for monulpiravir capsules,and solution of dispersed baricitinib tablets),five recommendations for off-indication use(intravenous injection of tocilizumab or baricitinib for severely or critically ill patients with COVID-19,subcutaneous injection of tocilizumab for severely or critically ill patients with COVID-19 if intravenous tocilizumab or baricitinib tablets were inaccessible,substitution with tofacitinib 10 mg twice daily if tocilizumab and baricitinib were inaccessible;methylprednisolone or prednisone for severely or critically ill patients with COVID-19 to reduce all-cause mortality)and two recommendations for off-label use among the targeted populations(no titration of tocilizumab doses for COVID-19 patients with severe renal insufficiency,baricitinib 2 mg once every other day or 1 mg daily for severely or critically ill patients with severe renal insufficiency and eGFR 15-30 ml·min^(-1)·1.73 m^(-2)).This consensus document aimed to provide a reference for the rational use of medicines by clinicians and for pharmacovigilance monitoring.