In the last three months, several drugs have faced recalls due to unacceptable levels of nitrosamines, human carcinogens. The tainted drugs have included medicine for stomach issues, drugs for high blood pressure and diabetes, and a treatment to help people stop smoking cigarettes.
Nitrosamines have been linked to causing several cancers, including lung, brain, liver, kidney, bladder, stomach and esophageal cancer. We are exposed to small amounts of nitrosamines in daily life – in our drinking water (through the process of purification) and in the foods we eat (including some cured and grilled meat). Although, when it comes to certain amounts of nitrosamines in medicine, the Food and Drug Administration (FDA) has urged people to stop taking specific drugs and speak to their doctor to find a substitute for the drug as quickly as possible.
According to an article by Bloomberg, after nitrosamines forced recalls of several blood pressure medications in 2018, a task force of FDA chemists, toxicologists and analytical lab staff began meeting to determine how widespread the nitrosamines issue was and how to move forward. Although ideally, the agency would like the toxins eliminated from the country’s drugs, this has not yet been possible. There is an assortment of challenges as well as never-ending, complicated manufacturing processes and a complex global supply chain for pharmaceutical ingredients.
Drug Recalls for Nitrosamines
Here is a look at recalls in the last 36 months and what caused the nitrosamine in the drugs:
- Valsartan/Angiotensin II receptors (ARBs): In late 2018 and into 2019, the FDA submitted a string of recalls on ARBs which are used to treat high blood pressure and heart failure. The nitrosamines in the drugs were most likely caused in manufacturing when the solvent used to break down ingredients was not properly eliminated, yielding a reaction that formed the toxin.
- Zantac (ranitidine): In April of 2020, the FDA told all manufacturers to withdraw the popular medicine used for ulcers and stomach acid, stating, “…the agency has determined that the impurity in some ranitidine products increases over time and when stored at higher than room temperatures and may result in consumer exposure to unacceptable levels of this impurity.”
- Metformin: In May 2020, the FDA asked five companies to recall some types of metformin, a widely used drug used to help control high blood sugar in type-2 diabetes. The FDA said it found the impurity in certain extended-release versions of the drug. The contamination, scientists believe, took place during manufacturing.
- Chantix: In September 2021, the anti-smoking aid was recalled after Valisir, an online pharmacy, discovered a nitrosamine could be formed from a chemical reaction involving the drug’s active ingredient, varenicline.
The FDA has determined in many instances how the nitrosamine developed within the drugs, whether through a chemical reaction while manufacturing, an instance where a solvent does not break down ingredients properly, or a storage problem. The FDA also has noted that a “certain’’ level of nitrosamines is “acceptable.’’
However, the recent events show us that there is still much that is unknown. According to Bloomberg, Deborah Johnson, a chemist for the FDA, admitted to the taskforce earlier this year her concerns when she said she doesn’t think “we have a complete understanding of all the possible ways the impurities could form.”
Learning How to Eliminate Nitrosamines
While recent efforts by scientists have not found a definitive way to keep the impurities from our drugs completely, about 40 years ago, scientists in Germany found such success in another surprising industry – beer brewing.
It was then that cancer researchers discovered certain beers contained nitrosamines, encouraging scientists to study the brewing process. They were formed when malt, the source of sugar in beer, was dried in high-heat kilns and browned. The natural nitrous oxide in the hot air formed the reaction that created the nitrosamines.
By changing to indirect heat, the carcinogen was eliminated, and the new batches of beer were free of the carcinogens.
Improved Technology Helps Detect Nitrosamines
When a consumer learns of continuing recalls of medicines due to carcinogens like nitrosamines, they can grow fearful of taking medicine, even when doctors have stressed the need. On its website, the FDA acknowledges this and stresses that they have better testing methods than ever before. The FDA explained that improved technology “… has helped detect even trace amounts of impurities in drug products and may be the reason why more products have been found to have low levels of nitrosamines.”
The statement also leaves room for future recalls.
“As our investigations and testing continues, along with the investigations done by other drug regulatory agencies, we may find low levels of nitrosamines in additional drugs,’’ it said.
Visit the FDA recalls web page to keep up with news on further recalls of drugs related to nitrosamines.