Current Status of Angiotensin Receptor Blocker Recalls

Abstract

Losartan was the ninth most prescribed drug in the United States in 2016, and several other angiotensin-II receptor blockers (ARBs) are widely prescribed. Since July 2018, >2 dozen specific ARB products have been recalled owing to the presence of potentially carcinogenic nitrosamine impurities in selected lots. As is the case with all U.S. drug recalls, the ARB recalls have been voluntary on the part of the companies involved. In April 2019, the Food and Drug Administration categorized marketed ARB products with respect to nitrosamine impurities: (1) not present, (2) to be determined with no prior lots removed from the market (TBD), or (3) to be determined in the context of prior lots having been removed from the market (TBD*). The data were structured as hundreds of rows of products. Owing to the complexity of these data, more than a year into the recalls, it remains difficult for clinicians to understand which ARB products are free of impurities.

Figure 1.

Percent of ARB-containing products (at the level analysis of each manufacturer’s dosage forms [dosage strengths], total n=1,111) in three categories assessed by the US Food and Drug Administration. Not present (green) indicates that the FDA has completed a comprehensive assessment. TBD (yellow) indicates that “one or more parts of FDA’s assessment remain incomplete.” TBD* (red) indicates that “certain lots of the product did have impurity levels above interim acceptable limits, however they have already been removed from the market.”

Figure 2.

The structures of the US-marketed ARB molecules, with tetrazole ring circled when present. Panel A shows molecules containing a tetrazole ring and for which selected lot of some products have been removed from the market via publicly announced recalls (valsartan, irbesartan, losartan) or through an unspecified mechanism (olmesartan). Panel B shows the structure of candesartan, an ARB molecule containing a tetrazole ring; no recalls related to nitrosamine impurities have affected candesartan products as of now. Panel C shows US-marketed ARB molecules that do not contain a tetrazole ring, none of which has been affected by recalls.