Concerns that metformin products may contain a carcinogenic N-nitroso impurity have yet to be confirmed and patients should be strongly advised not to stop taking the medication, the TGA says.
Following a recent recall of ranitidine products due to contamination with the chemical N-nitrosodimethylamine (NDMA), international regulators are now investigating whether metformin products have also been affected by the manufacturing impurity issue.
In an advisory statement, the TGA said it was aware that some overseas regulators had detected low levels of NDMA in a small number of metformin products, but stressed the reports had yet to be clarified.
“It has not yet been confirmed that NDMA is present in any metformin products supplied in Australia. The TGA is working with other international regulators and medicine sponsors to further investigate this issue and determine what actions may be required,” the agency said.
The TGA statement noted that N-nitroso compounds are commonly found in low levels in foods such as smoked and cured meats. Animal studies have suggested that long-term exposure, over many years, may increase an individual’s risk of developing cancer, but the risk of the trace levels detected in metformin is considered to be very low.
Detection of NDMA in ranitidine and angiotensin II receptor blockers (‘sartans’) has led to some product recalls, but there was no case for such action yet with metformin, the TGA concluded.
“There is no reason to stop prescribing metformin. It has not yet been confirmed that NDMA is present in any metformin products supplied in Australia,” its statement said.
“You may wish to remind patients of the importance of keeping diabetes under control and reassure them that that the risks posed by NDMA at the trace levels observed overseas are considered very low.”
In December 2019 the European Medicines Agency announced that trace amounts of NDMA had been found in a small number of metformin diabetes medicines manufactured outside the EU.
It said that EU medicines were currently being tested for impurities, but there was no cause for stopping prescribing or discontinuing metformin.
“The risk from not having adequate diabetes treatment far outweighs possible effects of the low levels of NDMA seen in tests. Healthcare professionals should remind patients of the importance of keeping their diabetes under control,” it said.