Duloxetine (Cymbalta): Recalled by FDA Due to Nitrosamine Impurities

Duloxetine (Cymbalta) – a medication used to treat depression, anxiety, and chronic pain, is being recalled by the U.S. Food and Drug Administration (FDA) due to the presence of N-nitroso-duloxetine, an impurity with potential cancer-causing risks.

1. Reasons Behind the Duloxetine Recall

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The recall of duloxetine (brand name Cymbalta) due to contamination with N-nitroso-duloxetine—a nitrosamine impurity with potential carcinogenic risks—highlights the critical role of quality control in the manufacturing and distribution of pharmaceuticals. The affected batch, labeled 220128, has an expiration date of December 2024 and was manufactured by Towa Pharmaceutical Europe. While this represents only a small fraction of the duloxetine products on the market, the incident has raised alarms about the presence of nitrosamines in pharmaceuticals and their potential health impacts on users.

2. Duloxetine and N-nitroso-duloxetine Impurities:

Duloxetine, a selective serotonin and norepinephrine reuptake inhibitor (SNRI), is widely used for treating depression, anxiety, and chronic pain. N-nitroso-duloxetine, a specific nitrosamine impurity associated with the active ingredient, has been detected in certain duloxetine batches. The occurrence of this impurity may arise from several factors:

Manufacturing Process: Nitrosation reactions during the synthesis of duloxetine may unintentionally generate N-nitroso-duloxetine.
Chemical Structure: The chemical structure of duloxetine contains amine groups that react with nitrosating agents to form nitrosamine impurities.
Storage and Packaging Conditions: Environmental factors, including temperature, humidity, light, and exposure to other substances during storage and packaging, can contribute to nitrosamine formation.

The FDA is actively collaborating with manufacturers to investigate the origins of N-nitroso-duloxetine impurities and will provide public updates. Additionally, the FDA is working to enhance controls and mitigate the risk of nitrosamine contamination in pharmaceuticals through stricter guidelines and regulations.

3. What Are Nitrosamine Impurities?

Nitrosamines are a group of chemical compounds with potential carcinogenic properties. They are commonly found in various sources such as food, drinking water, cosmetics, and tobacco products. Chemically, nitrosamines consist of a bond between an amine group and a nitroso group. As such, they can be formed through reactions between secondary or tertiary amines and nitrosating agents.

Nitrosamines are known to interact with DNA, potentially causing mutations that elevate cancer risk. Key considerations include:

Pharmaceuticals are not the sole source of nitrosamine exposure. These impurities can also be present in food, water, air, and other drugs, contributing minimally to an individual’s overall exposure.
The global baseline cancer risk is approximately 33%.
Current data suggest that nitrosamine exposure from pharmaceuticals increases cancer risk by only 0.001% to 0.01%.
The acceptable daily intake limits for nitrosamines in medications are set lower than exposure levels from other sources, indicating a negligible increase in cancer risk (below 0.001%).
In some cases, drug recalls are triggered by nitrosamine levels exceeding permissible limits. However, in many instances, the detected levels only slightly surpass the regulatory thresholds.

While not all nitrosamines are harmful, certain types can pose serious risks when present in high concentrations or over prolonged exposure periods.

Acceptable Limits for Nitrosamine Impurities

Nitrosamine Impurity Analysis - Emery Pharma

FDA Guidance for Cymbalta Patients

The FDA advises patients currently using Cymbalta not to stop taking the medication abruptly, as this could lead to a relapse of depression symptoms. Patients should consult their healthcare providers to discuss alternative treatment options.