抗新型冠状病毒小分子药物在妊娠期和哺乳期的安全性  

Safety of Small Molecule Anti-SARS-CoV-2 Drugs During Pregnancy and Lactation

作　　者：申潜 郑金琪 张水仙[2] 白梦如 SHEN Qian;ZHENG Jinqi;ZHANG Shuixian;BAI Mengru(Zhejiang Research Center for API Security,Zhejiang Institute for Food and Drug Control,Hangzhou 310052,China;Hangzhou First People′s Hospital,Hangzhou 310006,China)

机构地区：[1]浙江省食品药品检验研究院,浙江省原料药安全研究中心,杭州310052 [2]杭州市第一人民医院,杭州310006

出　　处：《中国药学杂志》2024年第18期1757-1763,共7页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金项目资助(82003838);浙江省自然科学基金项目资助(LY22H310006);浙江省卫生健康科技计划项目资助(2021RC021);浙江省药品监督管理局科技计划项目资助(2022001)。

摘　　要：目的孕产妇是新冠感染重型/危重型高危人群,一旦感染对母婴均造成严重危害,迫切需要安全有效的防治措施。奥密克戎系列变异株JN.1的免疫逃逸能力强,疫苗和抗体药物的疗效大幅下降,小分子抗病毒药物的优势凸显。但其在孕产妇中的安全性尚不明确。方法通过检索国内外文献及数据库,对已上市的7种抗新冠病毒小分子药物在妊娠期和哺乳期使用的安全性数据和经验,分别从遗传毒性、动物与人类生殖毒性、胎盘转运、乳汁分泌等方面进行阐述。结果未发现明显生殖毒性及母婴不良后果,但瑞德西韦我国尚未上市。结论权衡利弊后妊娠期可慎重使用奈玛特韦/利托那韦,待药物清除后再哺乳。OBJECTIVE Pregnant women are at a high risk of severe/critical SARS-CoV-2 infection,which can cause serious harm to both mothers and fetuses.Therefore,safe and effective medications are urgently needed.The current circulating strain Omicron variant JN.1 has been observed to elicit immune escape,leading to a decline in the efficacy of vaccines and neutralizing antibody drugs.As a result,the importance of small molecule antiviral drugs has become increasingly apparent,but their safety in pregnant and lactating women are not clear.METHODS Through searching domestic and international literature and databases,this paper reviews the safety data and experience of the approved small molecule anti-SARS-CoV-2 drugs(including remdesivir,molnupiravir,azvudine,renmindevir,nirmatrelvir/ritonavir,simnotrelvir/ritonavir,and leritrelvir)during pregnancy and lactation.The paper also presents information on genetic toxicity,animal and human reproductive toxicity,placental transport,and milk secretion.RESULTS Among them,the research data on remdesivir and nirmatrelvir/ritonavir are relatively sufficient.Animal studies have not found obvious reproductive toxicity,and the use of these drugs during human pregnancy has not shown serious adverse effects on mothers and fetuses.However,remdesivir is not yet listed in our country.CONCLUSION Nirmatrelvir/ritonavir may be an option for anti-SARS-CoV-2 treatment during pregnancy,and breast-feeding should be done after the drug is cleared.

关 键 词：奈玛特韦/利托那韦 瑞德西韦 新型冠状病毒 妊娠期 哺乳期 

分 类 号：R978.7[医药卫生—药品]