The Therapeutic Goods Administration (TGA) is investigating potential contamination of sitagliptin medicines with very low levels of a nitrosamine impurity, known as NTTP.
Sitagliptin is a prescription medicine used to treat type 2 diabetes. It is marketed in Australia under multiple trade names.
The TGA has set an acceptable intake (AI) limit for NTTP of 37 nanograms (ng) per day, detailed in our information for sponsors and manufacturers. Australian sponsors of sitagliptin products have reported that some sitagliptin products in the Australian market contain levels of NTTP that are higher than this limit. This issue also affects sitagliptin products supplied overseas.
To prevent a shortage of sitagliptin, the TGA is temporarily allowing supply of sitagliptin medicines containing NTTP that exceed the AI limit. The TGA has assessed that an intake of up to 246 ng NTTP per day does not pose a health concern based on short-term exposure compared with the risks for patients that cannot access their sitagliptin medicines. The risks of not taking sitagliptin as prescribed, is greater that the risk associated with this impurity.
Consumers are advised to continue to take their sitagliptin medicines as prescribed. Patients should not stop taking their sitagliptin medicines unless instructed to by their health professional.
What is 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, and quinapril products in 2022.
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 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.
Complications associated with uncontrolled diabetes include heart disease, nerve problems, kidney damage, eye problems and damage to the foot that can lead to amputations.
If you have any other questions or concerns about this issue, you should speak to your health professional.
What should health professionals do?
Please be aware that 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 this impurity.
You may wish to remind patients of the importance of keeping diabetes under control and to continue taking their medicines in line with the instructions in the Product Information. Patients should be reassured that that the risks posed by NTTP at the trace levels observed overseas are considered very low.
What is the TGA doing?
The TGA has reviewed results reported by Australian sponsors of sitagliptin medicines on the 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 and will determine whether other actions are required.
The TGA recognises the important role of sitagliptin in managing diabetes in Australia. Consistent with international regulatory approaches, including in Europe and the United States, the TGA is temporarily allowing sponsors to supply sitagliptin products with trace amounts of NTTP above the AI level to the Australian market to ensure that patients have continued access to this essential medicine.
The TGA has evaluated the risk of exposure to NTTP at an intake level of up to 246 ng per day until 31 May 2023. The assessment determined that short term exposure poses a minimal additional cancer risk when compared to a lifetime of exposure to NTTP at the AI 37 ng per day level.
The TGA is 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 also 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 37 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 the TGA's product monitoring.
The TGA 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.