Details
In 2018, North American and European drug regulatory agencies notified the public about recalls of valsartan and certain other angiotensin II receptor blocker (ARB) products after discovering the presence of potentially carcinogenic nitrosamine impurities, N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA), in the products. There was insufficient data available on how the recall notices impacted valsartan and other ARB utilization in the U.S. and Europe.
The U.S. Food and Drug Administration (FDA) initiated this study to estimate the number of patients affected by these drug recalls and compare the impact of country-specific recalls on valsartan and non-valsartan ARB utilization in the U.S., Canada, the U.K., and Denmark using the FDA’s Sentinel System and international data sources.
Despite the availability of valsartan products without nitrosamine impurities at the time of the recall, results from the U.S., Canada and Denmark revealed a substantial decline in valsartan use following the first recall notices in 2018. Switching from valsartan to the most commonly dispensed ARB in each country appeared to be responsible for the decline. In the U.S., these were most commonly losartan, irbesartan, and olmesartan. Increased switching also was observed around the time of subsequent recalls (after the first notice on valsartan in July 2018) of other affected ARBs, losartan and irbesartan; however, overall usage trends remained unchanged.
Results also demonstrated that despite the widespread use of recalled generic valsartan between 2012 and 2018, individuals’ duration of use was relatively short and likely did not pose an elevated risk of nitrosamine-induced cancer.
These findings provided reassurance that exposure to nitrosamine impurities in valsartan products in the U.S. was limited, and therefore, FDA determined further studies on cancer risk were not necessary.