Metformin Recall: NDMA Contamination in Blood Sugar Medication

In January 2022, the Food and Drug Administration announced a voluntary recall of metformin. People with type 2 diabetes use metformin to control their blood sugar alongside a healthy diet and exercise. Concerns over higher-than-acceptable levels of the probable cancer-causing contaminant N-nitrosodimethylamine (NDMA) prompted the recall. 

The recall came when Nostrum Laboratories, Inc. announced that it voluntarily recalled one lot of its metformin HCl extended-release tablets. The affected product was packaged in 100-tablet bottles, has the NDC of 29033-056-01, a lot number of MET200501, and an expiration date of July 2022. 

As of January 2023, Nostrum Laboratories, Inc. hasn't received any reports of adverse events related to the recall.

The January 2022 incident wasn't the first time metformin has been recalled over NDMA concerns. In fact, per the Food and Drug Administration, metformin recalls span back to early 2020. 

If you use metformin or have a loved one taking the medication, it's more than understandable to be concerned. Here's what you need to know about NDMA, how it ends up in metformin, and what your next steps should be if there's another recall.

What Is NDMA?

NDMA is a semi-volatile organic chemical that forms in industrial and natural processes. Per the Environmental Protection Agency, NDMA is a yellow liquid with no distinct odor and is a member of N-nitrosamines, a family of potent carcinogens. Carcinogens are cancer-causing substances.

The Environmental Protection Agency lists NDMA as a "priority pollutant." In other words, NDMA is a pollutant that the agency regulates and can practically use. But exposure to high levels of NDMA can cause symptoms like:

• Headache
• Fever
• Nausea and vomiting
• Jaundice, or yellowing of the skin
• Stomach cramps
• Enlarged liver
• Reduced function of the liver, kidneys, and lungs
• Dizziness

How Can NDMA End Up in Medication?

Manufacturers have previously used NDMA to produce rocket fuel, antioxidants, and softeners for objects like nitrile rubber. But as of 2023, people only use NDMA for research purposes.

Still, NDMA can be an accidental byproduct of the chlorination of wastewater at treatment plants. Also, industrial sources may unintentionally produce and release NDMA as a byproduct of chemical reactions. For example, alkylamines with nitrogen oxides, nitrous acid, or nitrite salts may produce NDMA.

So, when it comes to metformin, NDMA can be a result of the manufacturing process, Karl Nadolsky, DO, an endocrinologist at Spectrum Health Medical Group, told Health. Or NDMA may be a contaminant that ends up in the medication.

Also, the medication's structure may affect the byproducts and produce NDMA, Jamie Alan, PhD, an associate professor of pharmacology and toxicology at Michigan State University, told Health.

However, "in the case of metformin, this is probably a contaminant," noted Alan.

According to the Food and Drug Administration, levels of nitrosamine impurities should not be higher than 96 nanograms per day. Recalls over nitrosamine impurities exceeding that limit occurred before the January 2022 incident.

For example, on December 28, 2021, Viona Pharmaceuticals, Inc. issued a voluntary recall of 33 lots of its metformin HCl extended-release tablets after detecting NDMA.

So, why do those recalls happen so many times? Well, many companies buy the raw powder to make those medications from the same supplier, Bruce Ruck, PharmD, managing director of the NJ Poison Control Center at Rutgers New Jersey Medical School, told Health.

"Even though my tablet may be from company A and your tablet may be from company B, the raw powder is probably from the same company way up on the chain," explained Ruck. "If that powder is contaminated, it will end up in multiple brands."

What Should You Do if You’re Taking Recalled Metformin?

Before the January 2022 recall, the Food and Drug Administration advised people taking metformin to continue taking it until a healthcare provider replaced their prescription. Or a healthcare provider could provide a different treatment option. 

Per the Food and Drug Administration, if people with type 2 diabetes stop taking metformin, they may have dangerous side effects. So, if a recall affects your prescription, consulting a healthcare provider before making any changes is important. 

Also, as of January 2023, the agency has not found NDMA in immediate-release tablets. And those tablets are some of the most commonly prescribed types of metformin.

Taking a medication contaminated with a potentially cancer-causing ingredient may seem odd. Still, panicking over any recalls may not be necessary, urged Dr. Nadolsky.

Instead, reach out to a healthcare provider or pharmacist as soon as possible to ask about alternatives, recommended Dr. Nadolsky.

"This is weighing the benefits versus the risk," said Alan. "If the patient's blood sugar gets too high, this can be life-threatening." 

Symptoms of high blood sugar, or hyperglycemia, include:

• Excessive thirst
• Dry mouth
• Blurry vision
• Dry skin
• Fatigue
• Frequent urination
  

In the case of NDMA, "you have to be exposed to a certain amount over your lifetime," added Alan. "Meanwhile, high blood sugars can be extremely dangerous in the short term."

A Quick Review

Learning that a common medication contains a possible carcinogen can be scary. Still, if you have type 2 diabetes, stopping metformin may cause adverse side effects. 

So, if a recall affects you or a loved one, reach out to a healthcare provider or pharmacist. They can advise you on what to do and guide you on the next steps.