How some drugs can become a cancer-causing chemical in the body
Drug companies recalled metformin, a type II diabetes drug, after high levels of impurities of NDMA, a known carcinogen, were found in the tablets. Scott Olson via Getty Images When consumers obtain a prescription drug at the pharmacy, they assume that it has been tested and is safe to use. But what if a drug changes in harmful ways when it is stored on the shelf or in the body? A dangerous result has been the creation of N-nitrosodimethylamine (NDMA), a probable carcinogen, in certain drugs. NDMA is found in chlorinated water, food, and medicine in small amounts. To minimize exposure, the Food and Drug Administration has set an acceptable level of NDMA in each pill of less than 96 nanograms. But in recent years, the FDA has found excessive amounts of NDMA in various medications for hypertension, diabetes, and heartburn. As a result, the agency has initiated recalls to protect the public. These products were contaminated with NDMA during the manufacturing process. The FDA recommended best practices for manufacturers to minimize this risk in the future. Unfortunately for the buying public, emerging evidence suggests that NDMA can also be created when some pills are left on the store shelf or in the medicine cabinet, or even after the patient ingests them. Therefore, there is no way to verify its presence at the factory. I am a distinguished pharmacist and professor who has written extensively on FDA oversight and manufacturing issues associated with drugs and dietary supplements in the past, including the topic of NDMA contamination. In a new article, I look at how NDMA can end up on a patient’s medication if it wasn’t put there during its manufacture. Zantac, the heartburn drug, was pulled from the shelf, along with its generic versions, after the FDA found low levels of NDMA in the drug. Yichuan Cao / NurPhoto via Getty Images NDMA levels rise after manufacture Ranitidine (Zantac) was a commonly used over-the-counter and prescription heartburn and ulcer drug for decades before the FDA pulled it from the market on 1 April 2020. Be the canary in the coal mine for NDMA post-fabrication creation. In one study, researchers found that ranitidine contained only 18 nanograms of NDMA after it was manufactured. However, when stored at 158 ° F for 12 days, as if the drug had been left in a hot car, the NDMA doses rose above 140 ng. This is only slightly above the 96 ng limit that the FDA has deemed safe, but this was only 12 days later. In another study, storing ranitidine where it was exposed to higher temperatures or high humidity improved NDMA creation over time. This suggests that some medications can leave the factory with a safe amount of NDMA, but if kept for too long at home or on store shelves, they may exceed known acceptable limits for when patients use them. In a new study at JAMA Network Open, researchers simulated the stomach environment and found that when ranitidine is exposed to an acidic environment with a nitrite source, these chemicals can create more than 10,000 ng of NDMA. These results support a clinical study in which urine samples were collected from 10 adults before and after using ranitidine. After people ingested ranitidine, urinary doses of NDMA increased from about 100 ng to more than 40,000 ng over the next day. A doctor explains why Zantac was called. Other Medications Need More Detailed Investigation In another study, researchers added chloramine, a disinfectant that is routinely added to sterilize drinking water, to water samples that contained one of several medications that are structurally similar to ranitidine. They found that several commonly used medications, including antihistamines (doxylamine and chlorpheniramine), a migraine medication (sumatriptan), another heartburn medication (nizatidine), and a blood pressure medication (diltiazem) generated NDMA. It is not clear if the amount of NDMA created by these drugs when stored in hot and humid environments or after a patient ingests them is dangerous, as is the case with ranitidine. I think more studies are needed immediately to find out. Prevention is always better than cure, especially when it comes to a possible carcinogen. [Deep knowledge, daily. Sign up for The Conversation’s newsletter.]This article is republished on The Conversation, a non-profit news site dedicated to sharing ideas from academic experts. It was written by: C. Michael White, University of Connecticut. Read more: Drug Safety: Health Canada Must Act Faster When Approved Drugs Show Risks Explanation: How Clinical Trials Test COVID-19 Vaccines No, CBD is not a miracle molecule that can cure coronavirus, just like it will not cure many other illnesses claimed by its advocates C. Michael White does not work for, consult, own stock, or receive funding from any company or organization that benefits from this article, and has disclosed no relevant affiliations beyond his academic position.