After traces of carcinogenic industrial chemicals have been found in the common blood pressure medication valsartan, the antidepressant alprazolam (Xanax) and the antacid ranitidine (Zantac), regulators are turning their sights on metformin – an otherwise relatively innocuous and safe prescription drug used by type-2 diabetics to control blood sugar levels.
Metformin is a derivative of the French lilac plant, a folk remedy used for centuries for what was once known as “sweetwater disease.” Part of a class of medications known as biguanides, metformin is sold in generic form under a number of brand names, including Glucophage, Fortamet, and Riomet. It is also used as combination therapy with SGLT2 inhibitors and other diabetic prescription meds. It works by reducing production of glucose in the liver. It is quite inexpensive (a 30-day supply runs approximately $8), well-tolerated, and serious side effects are rare.
The current FDA investigation was sparked by a recall by the Singaporean Health Sciences Authority of 3 versions of metformin sold in that country, which were found to have levels of NDMA in excess of the “internationally acceptable amount.” NDMA, which has also been discovered in sartan-based medications as well as ranitidine, is part of a class of industrial chemicals known as nitrosamines, which are known to cause cancer.
The European Medicines Agency (EMA) has also begun its own investigation. Thus far, their scientists have not found “unsafe levels” in samples that have been tested. The EMA has also requested pharmaceutical companies to test their metformin for contamination. In a statement, the EMA said, “Although the risk from NDMA seen so far has been very low, impurities such as NDMA should be avoided in medicines. If NDMA is found above a certain level, authorities will take necessary action.”
Here at home, the FDA is still “in the beginning stages” of its investigation into NDMA contamination in metformin. So far, they have not discovered levels of NDMA above the “acceptable daily intake”, which under U.S. regulations is no more than 96 nanograms. FDA press officer Jeremy Kahn says, “These investigations take time. The FDA will communicate further information when we understand more of the situation and of what, if any, actions health care professionals and patients should take.”
The current scares over chemical adulteration of pharmaceutical products appears to be directly related to “outsourcing” by U.S. and European drugmakers to countries such as India and China, where safety regulations (and therefore, production costs) are less stringent. It is not known with certainty how these medications wind up with NDMA contamination, but inspections at one Chinese plant discovered that changes in the production process had inadvertently caused a chemical reaction, resulting in the formation of NDMA. Another source of NDMA contamination was traced to a factory in Hyderabad, India, which received a warning letter from the FDA over its failure to maintain and clean its equipment and follow good manufacturing practice.