More Lots of Antidepressant Drug Recalled Due to N-Nitrosoduloxetine

Breckenridge Pharmaceutical Inc. has announced the recall of over 360,000 bottles of Duloxetine Delayed-Release Capsules across various strengths in the U.S., citing the detection of Nitrosamine Drug Substance-Related Impurity (NDSRI) above FDA acceptable limits. The drug product is manufactured by Towa Pharmaceutical Europe. This is the 13th in a series of recalls of Duloxetine drug products by Breckenridge and Towa Pharma. There has been a series of recalls of Duloxetine drug products by different generic players including major recalls by Breckenridge / Iowa(13 recalls), Rising Pharma / Aurobindo (8 recalls), Ameri Source / Aurobindo (6 recalls). Since April 2024 over 2.5 million bottles of the drug has been recalled by different Firms across more than 30 recall events.

Duloxetine is indicated for the treatment of Major Depressive Disorder (MDD), Generalized Anxiety Disorder (GAD), and Neuropathic pain. Duloxetine API is a secondary amine molecule with five alpha hydrogen atoms around the amine functional group making it highly susceptible to nitrosation reactions in the presence of nitrites and nitrosating agents. The synthetic route for Duloxetine API does not involve nitrosating reagents, making the formation of NDSRI impurities during synthesis highly unlikely. However nitrites impurities from pharmaceutical excipients used in the manufacture of the drug product can cause the formation of the NDSRI. To mitigate nitrosamine risk it is critical for drug product manufacturers to comprehensively assess the risk of nitrosating agents from excipients and implement control strategies. A robust risk assessment and control strategy should include supplier qualification program, monitoring and control of APIs, excipients, and process water for nitrosating agents, nitrites, and amines, changing excipients / excipient sources where risk of nitrosamines is high, reformulation of the product to reduce and prevent nitrosamine generation in the product if necessary.

Also Read:

• Major Recall of Aurobindo’s Anti-Depressant Drug for Nitrosamine NDSRI, N-Nitroso-duloxetine
• USFDA Enforcement Report / Recall of Duloxetine Delayed-Release Capsules by Breckenridge Pharmaceutical Inc (April 2025)