FDA Updates Investigation of Nitrosamine Impurities in Metformin

As part of an investigation of potential nitrosamine impurities in metformin, the active pharmaceutical ingredient (API) in diabetes medications, the US Food and Drug Administration (FDA) reported that the levels of nitrosodimethylamine (NDMA), a probable human carcinogen, tested in metformin products ranged from not detectable to low levels. The FDA reported in December 2019 that it was conducting an investigation following the recall of certain products by regulatory agencies outside the US, including Singapore’s Health Sciences Authority, which recalled three out of 46 locally marketed metformin medicines after determining they contained NDMA above internationally acceptable levels.

The FDA’s investigation into potential nitrosamine impurities in metformin is part of ongoing investigations and company recalls due to nitrosamine impurities in other APIs. In 2018, the FDA and the European Medicines Agency initiated investigations of nitrosamine impurities in certain “sartan”-containing APIs, used in anti-hypertensive and cardiovascular drugs, such as valsartan candesartan, irbesartan, losartan, and olmesartan. They later broadened those investigations into prescription and over-the-counter forms of ranitidine, a H2 (histamine-2) blocker used to decrease the amount of acid created by the stomach.

With regard to its investigation into NDMA impurities into metformin, the FDA reported (as of February 3, 2020), that no sample of metformin that the FDA tested exceeded the acceptable daily intake for NDMA of 96 nanograms.  The FDA has not recommended metformin recalls in the US. The FDA posted its laboratory results showing the levels of NDMA in the US metformin products tested.   

The agency said it will also work with companies to test samples of metformin sold in the US and will recommend recalls as appropriate if high levels of NDMA are found.

The agency said it plans to post the methods used in laboratory testing of metformin in the near future. The FDA is also collaborating with international regulators to share testing results for metformin, along with testing results for other drugs. The FDA said it will continue to monitor NDMA in metformin, along with other drugs products, and will provide updates of new developments, including product recalls.

Source: US Food and Drug Administration




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