We originally published a safety advisory on 16 September 2022 regarding our investigation of potential contamination of sitagliptin medicines with very low levels of a nitrosamine impurity, known as NTTP.
We determine acceptable intake (AI) limits for nitrosamines in medicines to ensure that these impurities do not pose a safety concern for patients. We originally set an AI limit for NTTP of 37 nanograms (ng) per day.
To prevent a shortage of sitagliptin, on 6 December 2023, we published an extension to the transition period to allow supply of sitagliptin medicines containing NTTP that exceeded the AI limit at levels NTTP of up to 246 ng per day until 30 June 2024. This was on the basis that the short term exposure posed no additional health concern compared with the risks for patients that cannot access their sitagliptin medicines.
As this issue evolves, we continue to align our approach with other international regulators. Based on the available information we are revising the AI limit for NTTP to 100 nanograms (ng) per day. The revised AI limit has been set according to the Carcinogenic Potency Categorisation Approach (CPCA), consistent with the approaches taken by other regulators such as the European Medicines Agency (EMA) and Health Canada.
Sitagliptin medicines remain available, and consumers are advised to continue to take their sitagliptin medicines as prescribed.
NTTP
NTTP is a type of nitrosamine that is present as an impurity with the name 7-Nitroso-3-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo-[4,3- a]pyrazine. 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 NTTP being detected in sitagliptin 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 duloxetine and fluoxetine products in 2023.
What consumers should do
There is no immediate health risk from this issue as the risks are associated with long-term use.
If you take sitagliptin, do not stop your treatment without first consulting a doctor or pharmacist. It is very important to keep diabetes under control. Stopping your diabetes medicines poses a greater and more immediate risk to health than potential low-level contamination with NTTP.
If you have any other questions or concerns about this issue, you should speak to your health professional.
What health professionals should do
The impurity NTTP may be present at very low levels in sitagliptin products supplied in Australia. However, there is no reason to stop prescribing sitagliptin as the benefits continue to far outweigh the risk posed by the impurity.
You may wish to remind patients of the importance managing their diabetes and to continue taking their medicines as prescribed. Patients should be reassured that that the risks posed by NTTP at the trace levels observed in products supplied in Australia and overseas are considered very low.
What we are doing
We have reviewed results reported by Australian sponsors of sitagliptin 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 sitagliptin medicine sponsors to respond to this issue.
We recognise thethe importance of sitagliptin in managing diabetes in Australia. Consistent with international regulatory approaches, including in Europe, Canada and the United States, we are temporarily allowing sponsors to supply sitagliptin products with trace amounts of NTTP above the AI level to ensure that patients have continued access to this essential medicine.
We have determined that the risk of exposure to NTTP poses a lower risk when compared to the risks of not taking sitagliptin as prescribed.
We are requiring sponsors to investigate this issue. Sponsors are expected to monitor and report to the TGA the levels of NTTP in their sitagliptin medicines, while they address the presence of the impurity. We are working with sponsors to oversee the implementation of improved manufacturing and testing processes that will ensure that sitagliptin medicines supplied in Australia meet appropriate high standards for quality.
After the transition period, the AI of 100 ng per day will apply to all sitagliptin medicines. Any regulatory action will take into consideration the need to ensure continued availability of sitagliptin in the interest of public health.
Reporting problems
Consumers and health professionals can report problems with medicines or vaccines. The reports will contribute to our 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.