FDA Recalls 233,000 Bottles of Duloxetine Over Risk of Cancerous Chemical

The FDA recalled over 233,000 bottles of duloxetine (Cymbalta; Eli Lilly & Company), citing concerns over severe levels of nitrosamine drug substance impurity, N-nitroso-duloxetine, a known carcinogenic chemical. This follows the recall in October 2024, which pulled approximately 7000 bottles from pharmacy shelves.^1,2

Use of duloxetine yes, no questionnaire | Image Credit: © Richelle - stock.adobe.com

Duloxetine is a common, widely used antidepressant approved in 2004 that is used to treat anxiety, depression, and other mental health disorders. On December 5, 2024, the FDA classified the medication as a class II risk, the second most severe classification level that indicates risk temporary or medically reversible adverse health consequences. This is due to the presence of nitrosamine, which can increase cancer risk when exposed above acceptable levels.^1-4

Trace amounts of nitrosamines are commonly found in food, namely water, cured and grilled meats, dairy products, and vegetables. In some cases, nitrosamines can be present in medications due to the manufacturing process, its chemical structure, or the conditions in which it is stored and packed. Other medications have been recalled due to presence of nitrosamines including over 12 million bottles of blood pressure-lowering drugs, such as valsartan and losartan, which have been removed from the market since 2018.2

Additionally, the same family of contaminants have been found in the heartburn drug famotidine (Zantac; Sanofi), the diabetes drug metformin (Fortamet; Ajanta Pharma), and the smoking cessation medication varenicline (Chantix; Pfizer), leading to their respective recalls.²

“These are compounds that have been studied for a number of years. There’s at least a number of compounds in this class that are known mutagenic carcinogens. So, they're basically fairly nasty cancer-causing actives,” Edwin Gump, PhD, vice president of the Small Molecules Department at US Pharmacopeia, said in an interview with Pharmacy Times®. “One of the things that makes nitrosamines really tricky is that they actually can be formed very simply through really simple chemistries. The building blocks that you need to create nitrosamines are all around us in nature, and so they can form very easily.”⁵

The recall in October 2024 included 20-mg delayed-release capsules from lot #220128, and the recall in December included delayed-release capsules 30 count, 90 count and 1000 count. According to a statement from the FDA, "a person taking a drug that contains nitrosamines at-or-below the acceptable daily intake limits every day for 70 years is not expected to have an increased risk of cancer." However, the agency recommends patients discontinue use of medications with potential nitrosamine to stop taking them. Patients should consult their health care providers or pharmacists regarding concerns and treatment adjustments.^1,2

REFERENCES

1. FDA recalls more than 233,000 bottles of antidepressant over possible cancerous chemical. USA Today. December 12, 2024. Accessed December 19, 2024. https://www.usatoday.com/story/news/health/2024/12/12/duloxetine-recall-fda-risk/76948609007/

2. FDA recalls over 7000 bottles of duloxetine because of chemical presence. Pharmacy Times. October 24, 2024. Accessed December 19, 2024. https://www.pharmacytimes.com/view/fda-recalls-over-7000-bottles-of-duloxetine-because-of-chemical-presence

3. Drug approval package. FDA. August 3, 2004. Accessed December 19, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/021427_s000_Cymbalta.cfm#:~:text=Approval%20Date%3A%208%2F03%2F2004

4. Recalls, corrections and removals (devices). FDA. Accessed December 19, 2024. https://www.fda.gov/medical-devices/postmarket-requirements-devices/recalls-corrections-and-removals-devices#:~:text=Class%20II%20%2D%20a%20situation%20in,adverse%20health%20consequences%20is%20remote

5. Expert: nitrosamines ‘can slip through the manufacturing process,’ making reference standards essential to avoid this carcinogen in the drug supply chain. Pharmacy Times. June 29, 2021. Accessed December 19, 2024. https://www.pharmacytimes.com/view/expert-nitrosamines-can-slip-through-the-manufacturing-process-making-reference-standards-essential-to-avoid-this-carcinogen-in-the-drug-supply-chain