Understanding the molecular–pharmaceutical basis of sartan recalls focusing on valsartan

Abstract

Angiotensin receptor blockers (ARBs) or the ‘sartans’ are widely used for the management of hypertension and heart failure. There have been a series of recent incidents where drug formulations containing different ARBs as active pharmaceutical ingredients have been recalled by various pharmaceutical firms. This article addresses valsartan as well as other sartan recalls besides discussing the recent recalls of ranitidine and metformin, giving insights  into the molecular-pharmaceutical basis of the recalls. A thorough literature search of PubMed/Medline and Google Scholar databases was performed to identify all relevant articles and information published up to 29th April 2020 using Medical Subject Headings (MeSH terms) and Boolean operators. We also searched for relevant information on the web using web-browsers and reference lists from original research papers and review articles. The main impurity found was N-nitrosodimethylamine (NDMA) which was thought to be formed due to a change in the manufacturing process of valsartan. Besides, other impurities such N- nitrosodiethylamine (NDEA) and N-nitroso-N-methyl-4-aminobutyric acid (NMBA) were found in batches of other sartans, such as losartan and irbesartan. All of these are carcinogens and harmful if consumed at a level beyond a certain acceptable daily limit. Ranitidine, and more recent metformin recalls, have also been linked with valsartan in view of the presence of NDMA, the same impurity. Safety of ARBs is a major concern among healthcare professionals after the recalls of valsartan in the recent years. Periodic quality assessment of the manufacturing process and the drugs is key to ensure safe, effective and high-quality drugs for the global population. Additionally, practising physicians need to be vigilant in reporting adverse events in their patients receiving treatments.