(86) Impact of Angiotensin-Receptor-Blocker (ARB) Recalls Due to Nitrosamine Contamination on ARB Utilization in The U.S., Canada, and Denmark

Publication Number: 417

Background: In July 2018, some marketed angiotensin-receptor-blockers (ARBs) were found to be contaminated with nitrosamines at levels exceeding regulated exposure limits. Immediately, international regulatory agencies began systematic withdrawals of affected ARB products as the nitrosamine contamination in each product was confirmed.

Objectives: To examine the trends of ARB utilization and switching patterns in the U.S., Canada, and Denmark, before and after July 2018, when the first ARB (valsartan) was recalled.

Methods: As part of FDA’s international collaboration efforts, healthcare data from four Canadian provinces and Denmark were converted to Sentinel’s standardized common data model. We conducted a retrospective study between 2014 and 2020 to determine the monthly proportion of utilization of each ARB relative to all ARB use, and the quarterly proportions of ARB users who switched to other ARBs or antihypertensives before and after the recall notices.

Results: We identified 10,590,009, 790,356 and 492,229 ARB users in the U.S., Canada, and Denmark, respectively. Losartan had the largest market share in the U.S. and Denmark (≥60%), while candesartan and valsartan dominated the ARB market equally in Canada. In July 2018, we observed an immediate steep decline in the proportion of valsartan use in the U.S. and Canada that did not return to the pre-recall levels. In Denmark, where valsartan contributed only 1% to the ARB market, valsartan trend changes were negligible. With the decline in valsartan use from July 2018, we observed significant increase in switching from valsartan to other ARBs in the third quarter, 2018 (Q3-2018) in the U.S. and Canada. Increased switching was not sustained after Q4-2018. There was a small increase in switching to angiotensin-converting-enzyme inhibitors relative to the valsartan-to-other-ARBs switch. We also observed increased switching from olmesartan, irbesartan, and losartan to other ARBs in Q1-2019, in U.S. and Canada. In the U.S., more valsartan users switched to losartan than to other ARB. Losartan users switched more to olmesartan, irbesartan to losartan and olmesartan to losartan. In Canada, more valsartan, losartan, irbesartan and olmesartan users switched to candesartan than to other ARB.

Conclusions: Changes in ARB utilization matched the timing of ARB recalls. A rapid decline in valsartan use occurred immediately after the July 2018 recalls. Losartan, olmesartan and irbesartan switching to other ARBs occurred in the first quarter of 2019 matching the recall period for these ARBs.