Marksans Pharma Recalls 76 Lots of Metformin ER Tablets

By Miranda Greenberg -

October 8, 2020

Marksans Pharma, a Mumbai, India-based pharmaceutical company, is voluntarily recalling 76 lots of metformin hydrochloride extended-release (ER) tablets (USP 500 mg and 750 mg) to the consumer level in the US due to some lots exceeding acceptable daily intake limit levels of a nitrosamine impurity, N-Nitrosodimethylamine (NDMA), a probable human carcinogen. Metformin ER is indicated as an adjunct to diet and exercise to improve blood glucose control in adults with Type 2 diabetes.

This most recent recall is in addition to Marksans’ earlier recall of select lots of metformin ER tablets in the US in June (June 2020) due to NDMA impurities. Marksans was one of five companies in June (June 2020) that had recalled metformin ER products in the US due to NDMA impurities. The others were: Teva Pharmaceuticals USA, Lupin, Apotex, and Anmeal Pharmaceuticals. Late last month (September 2020), Sun Pharma recalled one lot in the US of Riomet ER (metformin hydrochloride for extended-release oral suspension), 500 mg per 5 mL, to the consumer level.

These recalls are part of an ongoing investigation by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) into nitrosamine impurities in certain active pharmaceutical ingredients (APIs), with metformin extended-release products being the latest product of inquiry. In May (May 2020), the FDA reported that its laboratory testing had revealed elevated levels of NDMA above the agency’s acceptable intake limit in several lots of products. 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 ER products is part of ongoing investigations and company recalls due to nitrosamine impurities in APIs. In 2018, the FDA and the EMA 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