Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's NMIMS, V.L. Mehta Road, Vile Parle (W), Mumbai 400056, India.
J Med Chem. 2021 Mar 25;64(6):2923-2936. doi: 10.1021/acs.jmedchem.0c02120. Epub 2021 Mar 11.
A product recall is the outcome of a careful pharmacovigilance; and it is an integral part of drug regulation. Among various reasons for product recall, the detection of unacceptable levels of carcinogenic impurities is one of the most serious concerns. The genotoxic and carcinogenic potential of -nitrosamines raises a serious safety concern, and in September 2020, the FDA issued guidance for the pharmaceutical industry regarding the control of nitrosamines in drug products. The FDA database shows that >1400 product lots have been recalled from the market due to the presence of carcinogenic -nitrosamine impurities at levels beyond the acceptable intake limit of 26.5 ng/day. The drugs that were present in recalled products include valsartan, irbesartan, losartan, metformin, ranitidine, and nizatidine. This perspective provides a critical account of these product recalls with an emphasis on the source and mechanism for the formation of -nitrosamines in these products.
产品召回是谨慎的药物警戒的结果；它是药品监管的一个组成部分。在产品召回的各种原因中，检测到不可接受水平的致癌杂质是最严重的问题之一。-亚硝胺的遗传毒性和致癌潜能引起了严重的安全关注，因此，2020 年 9 月，FDA 发布了针对制药行业的关于控制药品中亚硝胺的指南。FDA 数据库显示，由于存在致癌-亚硝胺杂质，超过可接受的 26.5ng/天的摄入量限制，超过 1400 批产品已从市场上召回。召回产品中包含的药物有缬沙坦、厄贝沙坦、氯沙坦、二甲双胍、雷尼替丁和尼扎替丁。本文从这些产品中-亚硝胺的来源和形成机制出发，对这些产品召回事件进行了批判性的分析。
