We are investigating the presence of low levels of the nitrosamine impurity known as N‑nitrosofluoxetine in medicines containing fluoxetine.
Fluoxetine is a prescription medicine used to treat major depression, obsessive-compulsive disorder, and premenstrual dysphoric disorder. 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 N-nitrosofluoxetine over a lifetime exposure (i.e. long-term exposure). Some Australian sponsors of fluoxetine products have reported that their products currently contain levels of N-nitrosofluoxetine 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 fluoxetine products supplied overseas, and our approach is similar to other regulators such as the European Medicines Agency (EMA).
Alphapharm Pty Ltd, the sponsor that supplies Zactin Tabs (fluoxetine 20 mg dispersible tablets (AUST R 90913), has provided information to us that this product contains levels of N-nitrosofluoxetine above the temporary higher limit. As a precautionary measure, Alphapharm has paused distribution of the product and recalled stock from wholesalers while this issue is investigated. We recognise the importance of Zactin Tabs to patients and up to date information about what we are doing to manage the resulting shortage is available on the About the shortage of Zactin Tabs webpage. Details of the recall can be found in our System for Australian Recall Actions database.
Fluoxetine capsule products remain available.
What is N-nitrosofluoxetine?
N-Nitrosofluoxetine 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 N-nitrosofluoxetine being detected in fluoxetine 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 duloxetine 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 fluoxetine, do not stop your treatment without consulting your doctor or pharmacist. 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 N-nitrosofluoxetine.
Your doctor is best placed to advise about ongoing treatment options. You should speak to your doctor or pharmacist if you are unable to access your medicine due to the current medicine shortage of fluoxetine dispersible tablets. Advice about the management of the shortage of fluoxetine dispersible tablets is on the About the shortage of Zactin Tabs webpage.
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 N-nitrosofluoxetine may be present at very low levels in fluoxetine capsule products supplied in Australia. However, there is no reason to stop prescribing fluoxetine capsules as the benefits continue to far outweigh the risk posed by the impurity. Advice on the management of the shortage of Zactin Tabs fluoxetine dispersible tablets is available at the About the shortage of Zactin Tabs webpage.
What action we are taking
We have reviewed results reported by Australian sponsors of fluoxetine 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 fluoxetine medicine sponsors to respond to this issue.
We recognise the importance of fluoxetine in managing major depressive, obsessive compulsive, and premenstrual dysphoric disorders in Australia. Consistent with international regulatory approaches, including in Europe, we are temporarily allowing sponsors to supply fluoxetine products with trace amounts of N‑nitrosofluoxetine above the AI level to ensure that patients have continued access to these medicines.
We have determined that the risk of exposure to N-nitrosofluoxetine poses a lower risk when compared to the risks of not taking fluoxetine as prescribed.
We are working with sponsors to oversee the implementation of improved manufacturing and testing processes that will ensure that fluoxetine medicines supplied in Australia meet appropriate high standards for quality.
Any further regulatory action will take into consideration the need to ensure continued availability of fluoxetine in the interest of public health.
Advice on the management of the shortage of Zactin Tabs fluoxetine dispersible tablets is available on the About the shortage of Zactin Tabs webpage.
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
Medicine shortage reports database