We are investigating the presence of low levels of a nitrosamine impurity known as N-nitroso-duloxetine (NDLX) in medicines containing duloxetine.
Duloxetine is a prescription medicine commonly used to treat major depression, pain, and anxiety disorders. It is marketed in Australia under multiple trade names.
N-Nitrosamine compounds (nitrosamines) are commonly found in water and food. We are all exposed to nitrosamines at differing levels. However, nitrosamine impurities may increase the risk of developing cancer, with the risk dependent on the level and length of exposure: higher levels over a short period of time can have an equivalent risk to lower levels for a longer period of time.
We determine acceptable intake (AI) limits for nitrosamines in medicines to ensure that these impurities do not pose a safety concern for patients. We have set an AI limit for NDLX over a lifetime exposure (i.e. long-term exposure). Some Australian sponsors of duloxetine products have reported that their products currently contain levels of NDLX that are higher than this limit. We have determined that there are no health concerns associated with the short-term use of these medicines. Nitrosamine impurities also affect duloxetine products supplied overseas, and our approach is similar to other regulators such as the European Medicines Agency (EMA).
Duloxetine medicines remain available and consumers are advised to continue to take their medicine as prescribed.
What is NDLX?
NDLX is a type of nitrosamine that is present as an impurity. Nitrosamines are a group of compounds which can damage DNA. They are commonly found in low levels in a variety of foods, including smoked and cured meats, dairy products, vegetables, in some drinking water, and in air pollution. Long-term exposure, over years, can increase an individual's risk of developing cancer.
The additional risk that would be posed by the trace levels of NDLX being detected in duloxetine is likely to be very low. However, the presence of nitrosamine impurities is generally considered unacceptable for a medicine. The actual health risk depends on the medicine and dose taken and will vary from person to person.
Nitrosamine impurities have also been found in other medicines. They were first identified in ’sartan‘ medicines in 2018. Medicines affected by nitrosamine impurities in Australia include ’sartan’ blood pressure medicines in 2018, metformin and ranitidine products in 2019, varenicline products and rifampicin products in 2021, quinapril and sitagliptin products in 2022, and in fluoxetine products in 2023.
What should consumers do?
There is no immediate health risk from this issue as the risks are associated with long-term use.
If you take duloxetine, do not stop your treatment without first consulting your doctor. It is very important to treat your condition. Stopping your medicine abruptly poses a greater and more immediate risk to health than potential low-level contamination with NDLX.
If you have any other questions or concerns about this issue, you should speak to your doctor or pharmacist.
What should health professionals do?
The impurity NDLX may be present at very low levels in duloxetine products supplied in Australia. However, there is no reason to stop prescribing duloxetine as the benefits continue to far outweigh the risk posed by the impurity.
You may wish to remind patients of the importance of managing their condition and continuing taking their medicines in line with the instructions in the Product Information. Patients should be reassured that that the risks posed by NDLX at the trace levels observed in products supplied in Australia and overseas are considered very low.
What action we are taking
We have reviewed results reported by Australian sponsors of duloxetine medicines on the Australian Register of Therapeutic Goods (ARTG) that are available on the market. We continue to work with our international regulatory partners and duloxetine medicine sponsors to respond to this issue.
We recognise the importance of duloxetine in managing major depressive, pain, and anxiety disorders in Australia. Consistent with international regulatory approaches, including in Europe, we are temporarily allowing sponsors to supply duloxetine products with trace amounts of NDLX above the AI level to ensure that patients have continued access to these medicines.
We have determined that the risk of exposure to NDLX poses a lower risk when compared to the risks of not taking duloxetine as prescribed.
We are working with sponsors to oversee the implementation of improved manufacturing and testing processes that will ensure that duloxetine medicines supplied in Australia meet appropriate high standards for quality.
Any regulatory action will take into consideration the need to ensure continued availability of duloxetine in the interest of public health.
Reporting problems
Consumers and health professionals can report problems with medicines or vaccines. The reports will contribute to product monitoring.
We cannot give advice about an individual's medical condition. Consumers are strongly encouraged to talk with a health professional if they are concerned about a possible adverse event associated with a medicine or vaccine.
Related links
Nitrosamine impurities in medicines - Information for sponsors and manufacturers