Frequently prescribed for type 2 diabetes treatment, metformin hydrochloride is designed to lower blood glucose levels and has also been used off-label for polycystic ovary syndrome and investigated from a growing number of indications. Following a recall of metformin 500 mg tablets this past summer, the United States Food and Drug Administration (FDA) announced an extended recall notice for additional manufacturers, forms, and dosages on October 8, 2020. The list of recalled drug combinations continues to grow as investigators discover additional contaminated compounds, now totaling 175 different formulations.
The commonly used drug has been recalled due to high levels of a carcinogen contaminant called N-Nitrosodimethylamine (NDMA), which led to the recall of Zantac tablets earlier this year. NDMA is a common contaminant found in water and grilled or cured meats, however, it can also enter drugs during manufacturing processes.
Risks associated with nitrosamines remains unclear although the FDA believes that short-term exposure to NDMA at high levels is likely not dangerous. Long-term exposure, on the other hand, is believed to lead to jaundice, nausea, fever, and liver damage as well as an increased risk of cancer.
Widespread Metformin Recall
Both Marksans Pharma Limited, a pharmaceutical company based in India, and Sun Pharmaceutical Industries have recently recalled metformin hydrochloride extended-release tablets as a result of high NDMA levels as part of the 175 different drug combinations affected. However, it appears that immediate release tablets have not been contaminated.
The recall applies to tablets between 500 mg and 750 mg sold under the brand name Time-Cap Labs, Inc.; a complete list of products identified by their National Drug Code numbers can be found here.
“We recalled one lot of metformin hydrochloride extended-release tablets, after the U.S. FDA tested it and showed results for N-Nitrosodimethylamine (NDMA) levels in excess of the Acceptable Daily Intake Limit (ADI),” Jordan Berman, Apotex Vice President, Global Corporate Affairs, Transformation & Strategy, told SingleCare in an interview. “Out of an abundance of caution, we extended the recall to all lots of metformin hydrochloride extended-release tablets in the US. Apotex stopped selling this product in the U.S. in February 2019, and there remains only limited product on the market. To date, we have not received any reports of adverse events related to use of the product.”
For patients currently taking metformin extended release tablets, transitioning to a replacement medication is recommended; they should not abruptly stop taking the medication as this can lead to adverse effects. Alternatives include immediate-release formulas, which are also the most commonly prescribed forms of metformin and are equally effective and often more affordable.
Coupled with the prior recall of the same product this summer, the current recall adds to a growing list of metformin products contaminated with NDMA discovered in the past year. Currently, the Food and Drug Administration is investigating the source of the carcinogen contaminants found in the medication tablets and potential other formulations that may have been affected.