Is Metformin Safe? Global Health Agencies Investigating Link to NDMA

Over the past year, world regulatory agencies such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have uncovered, investigated, and recalled medications due to nitrosamine impurities such as NDMA. In 2018, many of the blood pressure ‘sartan’ medications (angiotensin II receptor blockers known as ARBs), including Valsartan and Losartan, were recalled due to NDMA contamination. In 2019 and 2020, various companies have issued voluntary recalls of popular heartburn medication Zantac and other ranitidine products after uncovering NDMA contamination.

In December 2019, the global investigations of NDMA impurities extended to the type-2 diabetes drug Metformin after the public health agency of Singapore recalled three out of the 46 locally marketed Metformin medications due to the presence of NDMA.

Singapore Metformin Recalls

Singapore’s Health Sciences Authority (HSA) tested all 46 locally distributed Metformin medicines and three were found to have trace amounts of NDMA which were “above the internationally accepted level.”

As a result, on December 4, 2019 the HSA recalled the three medicines as a “precautionary measure” but also announced that the other 43 Metformin medications were not contaminated.

Which Metformin Medications were Recalled in Singapore?

  • One batch of Glucient XR Tablet 500mg—supplied by Glorious Dexa Singapore
  • All batches of Meijumet Prolonged Release Tablet in 750mg and 1000mg –supplied by Pharmazen Medical

Singapore’s HSA claims that the risk to patients who have been taking the affected medications is “very low” because the potential risks of nitrosamine contamination is associated with long-term use of the affected drugs, and the recalled medicines have only been sold in Singapore since 2018.

Have Any Other Government Health Agencies Recalled Metformin?type-2-diabetes-pills

Currently, only Singapore’s HSA has issued recalls for Metformin medications. However, as a result of the recalls, worldwide regulatory agencies such as the U.S. FDA, Health Canada, European Medicines Agency (EMA), and the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) have opened investigations into possible NDMA contamination in their Metformin medications.

In statements from the FDA, EMA, Health Canada, and MHRA, the agencies claim that there is no evidence that any Metformin medications distributed in their respective territories are affected and have advised patients to continue taking their medications.

U.S. FDA’s Metformin Investigation

The FDA reacted to Singapore’s Metformin recalls by announcing an investigation into potential NDMA impurities in Metformin available in the United States. Currently, no Metformin recalls have been issued by the FDA and no NDMA contamination has been found in lots sold in the United States.

Pertaining to the affected samples outside of the United States, the FDA claims that “based on the information we have available, the levels of NDMA seen outside the U.S. are within the range that is naturally occurring in some foods and in water.”

The investigation will determine whether there is NDMA in Metformin, and if so whether that amount is above the United States’ acceptable daily intake limit of 96 nanograms. The FDA “will recommend recalls as appropriate if high levels of NDMA are found,” according to a statement from Dr. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research.

Dr. Woodcock recommends that U.S. patients should continue taking Metformin while the investigation continues to keep their diabetes under control because “there are no alternative medications that treat this condition in the same way.”

European Medicine Agency’s Metformin Investigation

The EMA—the drug advising department for the European Union—has partnered with companies manufacturing and distributing Metformin within the EU to test the medication for NDMA. The results have thus far found no data indicating that EU Metformin medicines have been affected and recommends that patients in the EU should continue taking Metformin as prescribed.

The EMA is aware of trace amounts of NDMA found in a small number of Metformin medications outside of the EU; however, the organization claims that the levels of NDMA found in affected non-EU Metformin medicines are very low and appear to be within or even below the range people can be exposed to from other sources including water and certain foods.

Health Canada’s Metformin Investigation

Health Canada has asked drug manufacturers and distributors of Metformin to “test their own Metformin products” and will be “collecting samples from those companies to conducts its own testing.”

After the investigation, Health Canada announced that it is not aware of any Metformin products available in Canada that contain NDMA above the acceptable limits; however, it is working closely with international regulatory agencies to continually assess the concerns.

What is Metformin?

Metformin is a prescription medication available in both generic and brand name forms that helps those suffering from type 2 Diabetes by lowering blood sugar levels. The immediate-release form of the medication is Glucophage and the extended-release forms of the medication are Glucophage XR, Fortamet, and Glumetza.

How Does It Work?

In patients suffering from type 2 Diabetes, insulin (the hormone that helps the body remove extra sugar from the blood) naturally produced by the pancreas is unable to get sugar into the body’s cells where it can be properly converted into energy. Metformin, which belongs to a class of drugs known as biguanides, works by reducing the amount of glucose (sugar) made by the liver, decreasing the amount of glucose absorbed by the body, and increasing the impact of naturally produced insulin within the body.

What is NDMA Contamination?

N-nitrosodimethylamine (NDMA) is classified as a probable human carcinogen—meaning that the substance can cause cancer and belongs to class of impurities known as nitrosamines.

NDMA is commonly found in drinking water, some processed foods (pickled vegetables, salted fish, and processed meat products such as bacon and sausages), and as a result of air pollution.

NDMA was once used to make rocket fuel. However, after high levels of NDMA were uncovered in the air, soil, and water samples near manufacturing plants, NDMA use was discontinued. However, NDMA contamination occurs today through unintentional chemical reactions at industrial sites or in the manufacturing process of drugs.

Low levels of NDMA exposure are not dangerous. However, if more than 96 nanograms of NDMA are ingested daily, there is an increased risk of cancer.

Overexposure to NDMA can lead to:

  • Jaundice
  • Fever
  • Vomiting
  • Abdominal cramps
  • Dizziness

Prolonged Exposure to NDMA Contamination can lead to tumors and cancer of the:

  • Liver
  • Stomach
  • Colon & Intestines
  • Esophagus
  • Kidneys
  • Pancreas
  • Bladder

How GoldenbergLaw Can Help You

If you or a loved one contracted cancer after taking a drug recalled due to NDMA contamination, contact the dangerous drug attorneys at GoldenbergLaw. We are committed to promoting safety through accountability and providing you with the gold standard of advocacy.

What You Should Know About The FDA Recall of Zantac

The Food and Drug Administration (FDA) continues to announce recalls of the popular heartburn medication Zantac and its generic formulation ranitidine due to contamination with the known carcinogen N-Nitrosodimethylamine (NDMA). The latest announcements of five additional Zantac and ranitidine recalls come a month after the agency announced initial recalls by Sandoz and Apotex and alerted the public that NDMA had been found in samples of ranitidine. These recalls include both prescription and over-the-counter Zantac.

Do I Have A Case?

Zantac has been on the market for over thirty years and millions of people have taken these medications. For anyone currently taking these drugs, you should immediately contact your doctor to discuss your options.

Zantac Recall Summary

Appco Pharma Ranitidine Recall

On January 8, 2020, Appco Pharma LLC announced a voluntary recall of all lots of its Ranitidine Hydrochloride capsules due to potential NDMA contamination. The recall includes all prescription Ranitidine Hydrochloride capsules in strengths of 150 mg and 300 mg manufactured and distributed by Appco and its marketing partner, ANI Pharmaceuticals.

Northwinds Pharmaceuticals Ranitidine Recall

On January 8, 2020, Denton Pharma, an affiliate of Northwind Pharmaceuticals LLC, voluntarily recalled all lots of prescription Ranitidine 150 mg and 300 mg tablets it had repackaged and distributed at the consumer level.  The recall in is response to the manufacturer’s recall of these medications, which had since been repackaged by Denton Pharma, due to concerns of potential NDMA contamination.

Glenmark Pharmaceuticals Ranitidine Recall

On December 17, 2019, Glenmark Pharmaceuticals Inc. issued a voluntary recall of its unexpired Ranitidine tablet products and halted product distribution due to worries over potential NDMA contamination. In total, 928 lots of Ranitidine 150mg and 300 mg tablets are affected in the recall.

Precision Dose Ranitidine Recall

On November 19, 2019, repackaging company Precision Dose Inc. voluntarily recalled 5 lots of Ranitidine Oral Solution–USP 150mg/ 10mL from the market. The ranitidine product is being recalled due to potential NDMA presence above the standards approved by the Food and Drug Administration.

The recall was initiated after manufacturer Amneal Pharmaceuticals, LLC) issued a voluntary recall which included lots repackaged by Precision Dose Inc.

Golden State Ranitidine Recall

On November 15, 2019, repackaging company Golden State Medical Supply, Incorporated (GSMS, Inc.) voluntarily recalled all quantities and lots of Ranitidine HCl 150mg and 300mg capsules due to the potential presence of NDMA above levels approved by the Food and Drug Administration.

The voluntary recall comes after GSMS, Inc received a recall notice from manufacturer Novitium on October 25, 2019 and initially recalled 7 lots of Ranitidine HCl 150mg and 12 lots of Ranitidine HCl 300mg capsules on November 6, 2019.

American Health Ranitidine Recall

On November 8, 2019, American Health Packaging voluntarily recalled 8 lots of Ranitidine Syrup (Ranitidine Oral Solution USP) 150mg/10mL Liquid Unit Dose Cups from the consumer market due to an “unexpected impurity” of NDMA detected in the finished products at levels deemed unsafe by the Food and Drug Administration.

The recall comes in response to manufacturer Lannett Company, Inc.’s voluntary recall of ranitidine products which included affected lots that were repackaged by American Health Packaging.

Amneal Ranitidine Recall

On November 8, 2019, Amneal Pharmaceuticals, LLC voluntarily recalled Ranitidine Tablets, 150mg and 300mg, and Ranitidine Syrup (Ranitidine Oral Solution, USP), 15mg/mL that were distributed directly to wholesalers, distributors, retailers, and re-packagers due to potential NDMA levels deemed unacceptable by Food and Drug Administration standards.

Lannett Ranitidine Recall

On October 28, 2019 the FDA announced that Lannett Company, Inc. recalled all lots of its prescription ranitidine syrup. The recall includes Lannett’s ranitidine oral solution prescribed in 15mg/mL doses due to the confirmed presence of NDMA.

Novitium Pharma Ranitidine Recall

On October 25, 2019, the FDA confirmed that Novitium Pharma LLC recalled all lots of its over-the-counter Ranitidine Hydrochloride capsules in the United States. Novitium’s ranitidine recall includes all lots of 150 mg and 300 mg dosages sold in 30, 60, 100, and 500 count bottles. The FDA announcement states that the recall was due to potential unsafe levels of NDMA found in the capsules.

Perrigo Ranitidine Recall

On October 23, 2019, the FDA announced that Perrigo Company plc issued a worldwide recall of all lots of its over-the-counter ranitidine products. The announcement states that Perrigo halted shipments of its ranitidine products on October 8 due to the possible presence of NDMA. The Perrigo recall includes many popular ranitidine products, including the Publix over-the-counter store brand.

Dr. Reddy’s Ranitidine Recall

On October 23, 2019, the FDA announced that Dr. Reddy’s Laboratories, LTD. issued a voluntary recall of all lots of its ranitidine products – both prescription and over-the-counter – sold in the United States on October 1. This recall includes lots of ranitidine sold under store brand names at Walgreens, Target, Walmart, Kroger, and CVS. The ranitidine recall was initiated after product testing confirmed unsafe levels of NDMA. For a full list of products recalled under the Dr. Reddy’s ranitidine recall, visit the FDA recall page.

zantac-pill-containersSanofi Zantac OTC Recall

The FDA also confirmed on October 23, 2019 that Sanofi recalled all lots of its Zantac OTC (over-the-counter) medications sold in the United States and Canada on October 18. The company cited “inconsistencies in preliminary test results of the active ingredient used in the U.S. and Canadian products” as the reason for the recall. The Sanofi Zantac OTC recall includes all lots of Zantac 150, Zantac 150 Cool Mint, and Zantac 75.

Apotex Ranitidine Recall

On September 25, 2019, the FDA announced that Apotex Corp. voluntarily recalled its over-the-counter Ranitidine Hydrochloride tablets on a precautionary basis due to concerns of NDMA contamination. The Apotex ranitidine recall applied to 75 mg and 150 mg tablets sold under store brand names at Rite Aid, Walmart, and Walgreens pharmacies.

Sandoz Ranitidine Recall

On September 23, 2019, the FDA announced that Sandoz Inc. recalled all lots of its Ranitidine Hydrochloride capsules sold over-the-counter in the United States due to confirmed NDMA contamination. Sandoz is a subsidiary of the Swiss pharmaceutical conglomerate Novartis. The Sandoz ranitidine recall applies to 14 lots of Ranitidine 150 mg and 300 mg capsules sold in 30, 60, and 500 count bottles.

What Is Zantac?

Zantac is a medication that limits the production of stomach acid and belongs to a class of medications known as H2 blockers. It is sold as a generic under the name of its active ingredient, ranitidine. Zantac is sold over-the-counter to treat heartburn and acid indigestion, and prescribed for the treatment of duodenal and gastric ulcers, gastroesophageal reflux disease, and certain stomach and esophagus conditions.

What Is NDMA?

NDMA is classified as a probable human carcinogen that can form as a byproduct of industrial processes or, as in Zantac, from a reaction with the body. The chemical can be found in small quantities in drinking water but in levels that are considered generally harmless. The NDMA found in the recalled Zantac and ranitidine products is above levels considered safe by the FDA. NDMA had previously been found in the blood pressure medication Valsartan, which prompted a string of product recalls starting in July 2018.

NDMA exposure in Zantac and ranitidine has been linked to digestive system cancers such as:

  • Stomach cancer
  • Intestinal cancer (both of the small and large intestines)
  • Esophageal cancer
  • Prostate cancer
  • Pancreatic cancer
  • Leukemia
  • Non-Hodgkin’s Lymphoma
  • Multiple Myeloma
  • Bladder cancer
  • Stomach cancer
  • Colorectal Cancer
  • Liver Cancer
  • Kidney Cancer

Additionally, in babies born to mothers who took Zantac consistently throughout their pregnancies, NDMA has been linked to cancers, including brain cancers, in young children.

How We Can Help

GoldenbergLaw is currently investigating cases where an individual has taken Zantac or ranitidine and been diagnosed with one of the cancers listed above. Contact our Minnesota cancer attorneys today for a free consultation or call 612-436-5026. We have over 30 years of experience fighting negligent drug companies and have national leadership in NDMA contamination cases, let us deliver the Gold standard you deserve.

Does Heat Produce the Carcinogen Found in Zantac? New Study Says Yes

New testing from a California pharmacy has found elevated levels of the probable human carcinogen NDMA in Zantac when the drug is exposed to heat. As a result of its troubling findings, Emery Pharma has filed a Citizen Petition with the Food and Drug Administration (FDA) requesting the agency pull all products containing ranitidine, Zantac’s active ingredient, from the market immediately. The FDA began announcing individual Zantac and ranitidine recalls in September 2019, but there has yet to be a universal recall of the drug.

Does Heat Produce NDMA?

Emery tested multiple samples of ranitidine stored in different conditions over different periods of time. Samples stored for five days at 158 degrees Fahrenheit were found to contain 142 nanograms of NDMA, well over the FDA’s acceptable limit of 96 nanograms. Equally concerning, samples stored at temperatures as low as 77 degrees Fahrenheit showed a steady increase of NDMA production up to 25 nanograms after 12 days. The latter finding falls under the FDA’s threshold for acceptable levels of NDMA intake, however it raises the possibility that levels could continue to raise over longer periods of time at that temperature.

The results were troubling enough for Emery’s CEO to suggest that even something as simple as leaving the drug in a hot car could lead to NDMA production. “The more you heat it, the more NDMA you generate,” Emery CEO Ron Najafi told Bloomberg News. “I am worried that if it just sits at home at room temperature, it could gradually generate NDMA.”

Why Is This Important?

The most concerning element to Emery’s findings is that NDMA can be produced in ranitidine products after passing through testing done by the manufacturer. Since September 2019, the FDAzantac-bottle has been asking pharmaceutical companies to test Zantac and ranitidine products for NDMA contamination prior to putting them on the market. As of January 2020, twelve different manufacturers and repackaging companies have recalled some or all lots of the Zantac and ranitidine products they produce due to NDMA contamination.

Emery’s findings suggest that Zantac and ranitidine products that have been deemed safe for consumption could still produce enough NDMA to be dangerous if exposed to certain conditions.

Why Is NDMA Dangerous?

 According to the World Health Organization, NDMA is a probable human carcinogen, or a substance that causes cancer, that can be found in drinking water in generally harmless levels through the degradation of dimethylhydrazine (component of rocket fuel). NDMA can also be found in tanneries, pesticide manufacturing plants, and rubber and tire manufacturing facilities.

NDMA exposure in Zantac and ranitidine has been linked to cancers such as:

  • Bladder Cancer
  • Stomach Cancer
  • Intestinal Cancer
  • Colon/Colorectal Cancer
  • Liver Cancer
  • Kidney Cancer
  • Prostate Cancer
  • Esophageal Cancer
  • Pancreatic Cancer
  • Leukemia
  • Non-Hodgkin’s Lymphoma
  • Multiple Myeloma

Who Is Emery Pharma?

Emery Pharma is an independent laboratory based out of Alameda, California. Emery was hired to conduct these tests by the online pharmacy Valisure, LLC, which had originally petitioned the FDA to recall Zantac and ranitidine products in September 2019. Valisure is an online pharmacy company that launched in 2018 as a pharmacy, lab, and wholesaler. Valisure is licensed in 38 states and regularly analyzes the safety of 2,000 different pharmaceutical products in order to increase individual quality control to the pharmaceutical testing industry.

How Was NDMA Discovered in Zantac?

Once the FDA discovered NDMA and other carcinogens in Angiotensin II Receptor Blocker (ARB) drugs such as Valsartan, Losartan, and Irbesartan, Valisure added more product tests for carcinogens to its testing panels, and one of the first compounds it tested was ranitidine. Valisure’s analysis turned up “extremely concerning results” of 3 milligrams of NDMA, far exceeding the acceptable limits of 96 nanograms per day, in a single 150-mg tablet of ranitidine.

Valisure’s testing found that Zantac is not necessary “contaminated” with NDMA; rather, the carcinogen is produced by the breakdown of the ranitidine molecule during digestion. Valisure CEO David Light explains that “the fundamental problem is that it’s an unstable molecule. The drug itself can directly degrade and form, with very high efficiency, NDMA.” Therefore, Zantac’s NDMA contamination is not specific to a certain manufacturer or batch; it can occur within any ranitidine molecule when exposed to the right conditions.

What Is The FDA Saying?

The FDA has yet to issue an official comment on Emery’s petition, other saying it will review its findings and respond to Emery directly. The agency has been investigating NDMA contamination of Zantac and ranitidine products since Valisure’s petition in September 2019. Upon analyzing Valisure’s initial findings, the FDA opened an investigation and challenged Valisure’s high-heat testing method that involves heating the compound to 266 degrees Fahrenheit. Instead, the FDA used a lower-heat testing method known as the Liquid Chromatography- High Resolution Mass Spectrometry Method (LC-HRMS) when evaluating ranitidine. Despite using the LC-HRMS, international agencies including the FDA have still found unacceptably high levels of NDMA in ranitidine products.

Countries such as Canada, Germany, France, Italy, Switzerland, and Austria have already recalled ranitidine drugs. In addition, major U.S. drug retailers such as CVS, Walmart, Walgreens, Kroger, and Rite-Aid have removed all ranitidine medications, including name brand Zantac, from their stores.

How We Can Help

GoldenbergLaw is currently investigating cases where an individual has taken Zantac or ranitidine and been diagnosed with one of the digestive cancers listed above. Contact our Minnesota cancer attorneys today for a free consultation or call 612-436-5026. We have over 30 years of experience fighting negligent drug companies and have national leadership in NDMA contamination cases, let us deliver the Gold standard you deserve.