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On October 23, 2024, the FDA announced a Class II recall of 7,107 bottles of duloxetine (Cymbalta; Eli Lilly & Company) because they contained the impurity of the nitrosamine substance N-nitroso-duloxetine. This recall of the drug, which is used to treat mental health conditions such as anxiety and depression, was initiated on October 10th.^1.2 The recalled lot #220128 was described by the FDA as 20 mg extended-release capsules expiring in December 2024.²

People are exposed to trace amounts of nitrosamines, which are found in water, sausage and grilled meat, dairy products and vegetables.^1.3 According to the FDA, nitrosamine impurities may increase the risk of cancer when people are exposed to them for acceptable periods of time and over long periods of time. Additionally, the FDA added that someone who takes a drug containing nitrosamines at or below acceptable daily intake limits every day for 70 years would not be expected to have an increased risk of cancer.^1.3

These nitrosamines can sometimes be contained in drugs or medicines due to the manufacturing process, their chemical structure, or the conditions in which they are stored and packaged. Nitrosamines can also be formed in the body when foods and medications are processed.³ Class II classification means that exposure may cause temporary or medically reversible adverse health effects.^1.3

In an interview, Edwin Gump, PhD, vice president of the small molecule division at the US Pharmacopeia, explained that nitrosamines are “really tricky” because they can be formed through simple chemical processes. Since they occur in nature, they can form very easily.⁴

“Manufacturers have a responsibility to evaluate their processes and products and look for opportunities that could pose a risk for nitrosamines. So if there is a risk, manufacturers need to step in and do more, which may include testing their products.” Confirm that there are no nitrosamines… we're talking real ultra-trace levels here, parts per million, parts per billion, therefore These are not easy analyzes to carry out. They require highly complex analytical equipment and whatever test you need, “I kind of have control over that test,” Gump said in the interview. “People can think of these nitrosamine reference standards as a control standard. These are highly characterized materials that manufacturers can now use in their testing to ensure that when they perform that test, that the test is accurate, that the test is precise, and that they demonstrate evidence of the appropriate values ​​that they needed to control the presence of nitrosamines.”⁴

Gump emphasized the importance of experts doing their part to ensure that nitrosamines or other quality or process-related contaminants are eliminated so that people can rely on their medications. Patients should not have to worry about swallowing harmful substances.⁴

Other medications recalled due to nitrosamines include over 12 million bottles of blood pressure-lowering medications such as valsartan and losartan, which have been withdrawn from the market since 2018. In addition, the same family of contaminants has also triggered recalls of the heartburn drug famotidine (Zantac; Sanofi), the diabetes drug metformin (Fortamet; Ajanta Pharma) and the smoking cessation drug varenicline (Chantix; Pfizer).¹

The FDA recommends that those who may be taking medications with potential nitrosamine to stop taking them. Patients are also encouraged to speak with their healthcare professional about alternative treatment options or any concerns they may have. In addition, healthcare professionals are also encouraged to advise patients of possible nitrosamine contamination when clinically appropriate. Medicines can still be dispensed if they come from a manufacturing batch that has not been recalled.^1.3

REFERENCES

1. USA today. The FDA is recalling more than 7,000 bottles of antidepressants because of a possible cancer-causing chemical. Press release. October 23, 2024. Accessed October 23, 2024. https://www.usatoday.com/story/news/health/2024/10/23/fda-duloxetine-recall-2024/75804668007/

2. US Food and Drug Administration. Enforcement report. Accessed October 23, 2024. https://www.accessdata.fda.gov/scripts/ires/?Product=210449

3. US Food and Drug Administration. Information about nitrosamine impurities in medications. Accessed October 23, 2024. https://www.fda.gov/drugs/drug-safety-and-availability/information-about-nitrosamine-impurities-medications#updates

4. Expert: Nitrosamines “can slip through the manufacturing process,” which is why reference standards to avoid this carcinogen in the drug supply chain are essential. Pharmacy hours. June 29, 2021. Accessed October 23, 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