(104) Impact of Angiotensin-Receptor-Blocker (ARB) Recalls Due to Nitrosamine Contamination on ARB Utilization in Germany: A Multinational Study with a Common Protocol Led by FDA

Publication Number: 435

Background: Nitrosamine formation during manufacturing was detected at a site that supplied valsartan products. International regulatory agencies immediately recalled contaminated valsartan batches exceeding accepted exposure limits for potential carcinogens in July 2018. Further contaminated batches were identified later including also other angiotensin receptor blockers (ARBs). In Germany, batch recalls were issued July 2018 - March 2019 for valsartan, losartan and irbesartan.

Objectives: To examine ARB utilization trends and switching patterns in Germany before and after July 2018.

Methods: ARB prescribing trends were studied in general practices using the electronic health records database IMS® Disease Analyzer Germany from January 2014 to June 2020 via a multinational protocol led by the US Food and Drug Administration (FDA). The monthly proportion of all ARB prescriptions was determined for each individual ARB. In addition, the quarterly proportion of ARB users that switched to an alternative ARB or an ACE inhibitor was determined, based on longitudinal follow-up of ARB users that had at least one year observability at the time of the first ARB prescription and ≥2 ARB prescriptions. Changes were assessed by reviewing graphical outputs visually.

Results: A total of 5.74 million ARB prescriptions were identified in 552,512 patients during the study period (329,472 patients were followed up for switches). Valsartan and candesartan were the most commonly prescribed ARBs. After July 2018 a significant decline in the monthly proportion of valsartan prescriptions was observed, reaching its lowest level in June 2019. The proportion for valsartan out of all ARB prescriptions decreased from 35.2% in June 2018 to 17.8% in June 2019 (19.3% at end of study). The decrease for valsartan was matched by a corresponding increase for candesartan, from 39.5% in June 2018 to 56.9% in June 2019 (58.0% at end of study). Smaller changes were observed for other ARBs. In line with the decreased monthly proportion for valsartan, increased switching was observed in valsartan users, mainly to use of candesartan, between the third quarter (Q3) 2018 and Q3 2019. There was also evidence of increased switching from irbesartan between Q4 2019 and Q1 2020, 6-12 months after the last batch recall, but no evidence of increased switching from losartan. There was no evidence of increased switching from ARBs to ACE inhibitors.

Conclusions: Batch recalls for valsartan resulted in an immediate decline in use of valsartan and switching mainly to candesartan in Germany. For irbesartan there was evidence of increased switching 6-12 months after the last batch recall.