Diabetes med metformin has been in the FDA’s crosshairs since the agency found high levels of a probable carcinogen, NDMA, that had already triggered global recalls for Zantac and a commonly used class of blood pressure drugs. Now, an Indian drugmaker will expand its own metformin recall after confirming the FDA’s testing.Lupin Pharmaceuticals has pulled all lots of metformin after discovering unacceptably high levels of a probable carcinogen, N-Nitrosodimethylamine (NDMA), in tested samples, the drugmaker said Tuesday.
The recall includes the 500- and 1,000-milligram versions of extended-release metformin sold in 60-, 90- and 100-count bottles distributed between early November and late May, Lupin said.So far, Lupin hasn’t received any reports of serious side effects. The Indian company previously recalled just one lot of its 500-mg version of the drug back in early June.Monday, the FDA said Virginia-based Granules Pharmaceuticals would also pull its own version of extended-release metformin off shelves based on the same NDMA contamination concerns.
Granules noted that it had found unacceptably high levels of NDMA in just one of 12 tested batches that reached distribution. The recall, however, covered all 12 batches “out of an abundance of caution” and includes the 750-mg formulation in 100- and 500-count bottles.Granules was the only drugmaker outside of a group of five companies previously targeted by the FDA for voluntary recalls of their extended-release metformin products.In late May, the FDA asked the manufacturers to pull their extended-release metformin products after pushing recalls of heartburn med Zantac and “sartan” blood pressure drugs for the same contamination.
The FDA said it would work with the companies to determine whether the recommended recalls would cause a shortage in the U.S. The move didn’t apply to metformin’s immediate-release formulation, and the FDA specified that “there are additional manufacturers of the metformin ER formulation that supply a significant portion of the U.S. market, and their products are not being recalled.”The other drugmakers included Apotex, Teva, Amneal and Marksans, all of which launched their own recalls in early June.
The FDA’s about-face in May came months after the agency said it found low levels of NDMA in sampled metformin lots and didn’t recommend sweeping recalls despite earlier crises over branded and generic Zantac and the sartan drugs.
In March, independent testing laboratory Valisure disputed the FDA’s earlier findings, saying it had discovered NDMA contamination at unacceptable levels in 42% of the batches it checked.In a Public Citizen petition (PDF), Valisure asked for an immediate recall of the contaminated products it had identified and contended the situation was likely to get worse as COVID-19 wreaks havoc on supply chains.
Valisure said it had tested 38 batches of metformin from 22 companies and found 16 batches from 11 companies had NDMA exceeding the FDA’s acceptable daily level of 96 ng. The laboratory found several batches that contained levels 10 times the daily acceptable intake limit.
It also found “significant variability from batch to batch, even within a single company,” which it says in its petition underscores the need for expanded testing of some drugs at the batch level. It asked another testing lab, Emery Pharma, to check its findings and Emery came to the same conclusions, Valisure said.