Sun Pharma, a wholly owned subsidiary of Sun Pharmaceutical Industries, a Mumbai, India-based pharmaceutical company, is the latest company recalling a metformin extended-release product due to a nitrosamine impurity, N-ntrosodimethylamine (NDMA), found to be above the allowable acceptable daily intake limit established by the US Food and Drug Administration (FDA). NDMA is classified as a probable human carcinogen.

The company is voluntarily recalling one lot of Riomet ER (metformin hydrochloride for extended-release oral suspension), 500 mg per 5 mL, to the consumer level. To date (September 23, 2020), Sun Pharma reports it has not received any reports of adverse events related to this recall. Riomet ER is a prescription oral medication indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with Type 2 diabetes mellitu

In June (June 2020), five companies—Teva Pharmaceuticals USA, Lupin, Apotex, Anmeal Pharmaceuticals and Marksans Pharma—voluntarily recalled in the US select lots of metformin extended-release formulations due to elevated levels of NDMA.

Those recalls followed an announcement by the FDA in May (May 2020) that its laboratory testing had revealed elevated levels of NDMA above the agency’s acceptable intake limit in several lots of products. The FDA said at the time that it was in contact with five firms to recommend to them to voluntarily recall select lots.

The FDA began its investigation into nitrosamine impurities in metformin in late 2019, when it reported it had become aware of NDMA in some metformin products in other countries. The agency began testing to determine whether the metformin in the US supply was at risk as part of its ongoing investigation into nitrosamine impurities across medication types. By February 2020, the agency had identified very low levels of NDMA in some samples, but at that time, no FDA-tested sample of metformin exceeded the acceptable intake limit for NDMA. The FDA’s acceptable intake limit for NDMA in drug formulations is 96 nanograms per day.

The FDA’s investigation into potential nitrosamine impurities in metformin is part of ongoing investigations and company recalls due to nitrosamine impurities in other active pharmaceutical ingredients. 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.

Source: US Food and Drug Administration