Recalls of the diabetes drug metformin continue, with the Food and Drug Administration announcing two additional voluntary recalls of extended-release formulations last week.
Drugmakers Marksans Pharma and Sun Pharmaceutical Industries are both pulling select lots of metformin that may contain the impurity NDMA (N-nitrosodimethylamine). NDMA is a chemical with the potential to cause cancer when consumed in unsafe amounts over long periods of time.
This year, a total of 11 pharmaceutical companies and drug distributors have withdrawn specific extended-release lots of metformin, leaving countless patients searching for alternatives.
Metformin is widely used to control type 2 diabetes, in combination with diet and exercise. It is sold under various brand names, including Glucophage, Glucophage XR, Glumetza, Riomet and Fortamet.
What diabetes patients taking metformin need to know
The latest recall applies to one lot of extended-release oral metformin (500 mg per 5 mL) by Sun Pharmaceutical Industries. The drug is sold under the name Riomet ER. Marksans Pharma has also expanded its previous recall to now include 76 lots of metformin extended-release tablets (500 mg and 750mg). The drug is labeled as Time-Cap Labs.
The FDA hasn’t found evidence of possible NDMA contamination in immediate-release metformin products.
Patients taking extended-release metformin can search the FDA website by brand and lot number to see if their medication has been recalled. The agency encourages patients taking recalled metformin to continue taking the drug until their provider or pharmacist prescribes a replacement or offers a treatment alternative.
Those experiencing side effects can report their health issue through MedWatch, the FDA’s adverse-event reporting system.
NDMA and cancer
NDMA is classified as “probably carcinogenic to humans” by the International Agency for Research on Cancer, an arm of the World Health Organization. Similarly, the FDA considers
NDMA a substance that could cause cancer in humans based on results from laboratory tests. Short-term exposure to NDMA at unsafe levels, however, according to the FDA, is not anticipated to increase cancer risk.
NDMA can occur in low levels in water and some foods, including dairy products, meat and vegetables. A human-made contaminant, NDMA is released into the environment as a byproduct of some industrial processes and is also found as a contaminant in several pesticides. The origin of NDMA in metformin is currently under investigation by the FDA.
NDMA investigations
Early this year, the FDA began investigating whether metformin was possibly tainted with unsafe levels of NDMA. But concerns about possible NDMA contamination extend beyond metformin.
In April, fearing NDMA contamination, the FDA asked drugmakers to voluntarily and immediately recall all over-the-counter and prescription ranitidine drug products. Ranitidine is the active ingredient in the popular heartburn medication Zantac and its generic formulations.
More recently, the FDA issued new guidance for pharmaceutical companies on limiting drug impurities to ensure patient safety. The guidance followed a slate of recalls of common medications — including Zantac, Axid and angiotensin II receptor blockers — related to unacceptable levels of NDMA and other nitrosamine impurities.
The FDA guidance set an acceptable nitrosamine intake limit of 96 nanograms per day. The agency also encouraged drugmakers to perform risk assessments, work closely with third-party manufacturers and regularly test medications for NDMA and other forms of nitrosamine impurities.