More on Carcinogenic Nitrosamines in Drugs (Part 2)

Is your medication on the list?

Part 1 - (posted last week) - Cymbalta In The News...Again, Does your medication contain the NDMA contaminant? can be found here.

Nitrosamines are a group of compounds that can damage DNA. Long-term exposure can increase the risk of developing cancer. The first nitrosamine was identified in July 2018 in blood pressure medicines known as ‘sartans’, which are classified as angiotensin II receptor blockers. It was determined that the nitrosamine contaminant came from an active ingredient sourced from an overseas manufacturer, Zhejiang Huahai Pharmaceutical Co. (ZHP), which had changed its manufacturing process. The FDA report on how this contaminant was found and the steps that were taken at this link.

The contaminant detected was N-nitrosodimethylamine (NDMA), which is a genotoxic and carcinogenic agent in animals and is classified as “probably carcinogenic to humans” (a Class 2A carcinogen by the WHO’s International Agency for Research on Cancer (IARC)). This led to a voluntary recall of several drugs under the generic names of valsartan, losartan, and irbesartan, medications for high blood pressure and heart failure.

The generic name is the drug's standard scientific name that manufacturers universally recognize. Each generic drug is also sold under multiple trade names depending on the manufacturer and region. The trade name is the name a pharmaceutical company chooses to market the drug under, and it is usually the name you recognize and is on your prescription bottle.

For the “sartan” drugs, here is a list of drugs more readily recognized. Some of these medications had more than one type of nitrosamine in the final product:

• Trade names for losartan : Cozaar, Angizaar, Losatc

• Trade names for valsartan: Diovan, Prexxartan, Valcacor

• Trade names for olmesartan: Benicar, Olmetec

• Trade names for candesartan: Atacand, Blopress

• Trade names for irbesartan: Avapro, Irbegen

• Trade names for telmisartan: Micardis, Pritor

• Trade names for eprosartan: Teventen

• Trade names for azilsartan: Edarbi

In addition to the “sartan” family of medications, the FDA has also found nitroamine impurities in other drugs; some contain more than one type:

• histamine-2 blockers -

  • rantidine - Zantac, withdrawn, remade, and now marketed as Zantac -360

  • nizatidine - Axid - pulled from the US market, but still sold internationally

• diabetic medications

  • metformin - Glucophage, Riomet, Fortamet - extended-release formulas recalled due to NDMA and NMEA

  • sitagliptin - Januvia - contains NDMA but in “accepted levels” and not removed from the market

• varenicline - Chantrix - used for smoking cessation, Pfizer halted distribution temporarily then re-released it in the U.S. in 2022 with lower NDMA levels that comply with safety standards.

In 2021, the FDA used a guidance document for the industry, which was updated in 2024 for pharmaceutical quality and manufacturing standards (CGMP), saying,

The unexpected finding of nitrosamine impurities, which are probable or possible human carcinogens, in certain drug products has made clear the need for a risk assessment strategy for the potential presence of nitrosamines in any drug product.

Nitrosamines in drugs: how do they get there?

The chemistry that leads to the formation of a nitrosamine contaminant is complex. For example, the solvents used to create a reaction can lead to the toxic by-product, vendor-sourced raw materials can add nitrosamines or its precursors to the mix, nitrous acid can come in contact with the drug’s active ingredient, spinning off nitrosamine by-products or the packaging materials can leach out nitrosamine impurities when stored.

Besides NDMA (N-nitroso-dimethylamine), other types of nitrosamine impurities that have been found in pharmaceutical products include:

• NDEA (N-nitroso-diethylamine)

• NMBA (N-nitroso-morpholine)

• NDBA (N-nitroso-dibutylamine)

• NDCA (N-nitroso-dicyclohexylamine)

• NDIPA (N-nitroso-diisopropylamine)

• NDYR (N-nitroso-pyrrolidine)

• NDPA (N-nitroso-dipropylamine)

• NCHA (N-nitroso-cyclohexylamine)

• NMOR (N-nitroso-morpholine)

• NMEA (N-nitroso-methyl-ethanolamine)

• NNT (N-nitroso-1,4-dimethyl-pentylamine)

• NBA (N-nitroso-butylamine)

• NMA (N-nitroso-methylamine)

This list covers some of the more common nitrosamine impurities found in pharmaceuticals. These nitrosamines, like NDMA, are classified as probable human carcinogens and are typically formed during the manufacturing process or due to the degradation of certain chemicals, especially those used in drugs. While the first three on this list are the most commonly found and have led to recalls, manufacturers are now testing for all of these by-products and are required to report the levels found to be greater than 96 ng/ml.

The 46-page regulatory document gives a long list of actions drug companies are RECOMMENDED to take to eliminate or at least minimize nitrosamine contaminants in their products (drugs). FDA RECOMMENDS that manufacturers and applicants should “take appropriate actions to ensure that their drug products are safe.”

Isn’t that a given expectation? Don’t manufacturers routinely test the pills they make for known carcinogens?

…And these guidelines are only recommended, not required. in fact, the Guidance paper begins with a Black Box label that says the following:

This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. To discuss an alternative approach, contact the FDA staff responsible for this guidance, as listed on the title page.

…and then at the top of every page of the Guideline document says, “Contains Nonbinding Recommendations.” Apparently, FDA findings are something the drug manufacturers can “take under advisement.” Does the FDA make rules that must be followed? Apparently not.

What about nitrosamines in foods?

Nitrosamines can also be found in food, particularly in products containing nitrates or nitrites, commonly used as preservatives or color fixatives. These compounds form when nitrites react with amines (organic compounds) under acidic or high-temperature conditions. Processed meats, such as bacon, sausages, hot dogs, salami, pepperoni, and deli meats, are among the most common sources of nitrosamines. When these meats are cooked at high temperatures—like grilling, frying, or barbecuing—nitrosamines can form.

Similarly, smoked foods, including smoked meats and fish, can also contain nitrosamines due to the nitrates used in the smoking process. Certain alcoholic beverages, particularly beer, may contain nitrosamines if they are produced with nitrate-containing ingredients. Vegetables like spinach, lettuce, and celery, which naturally contain nitrates, can convert into nitrosamines in the digestive tract, particularly in highly acidic conditions. Processed cheeses can also be a source, as they may contain nitrites or nitrate preservatives that can form nitrosamines.

The primary health concern surrounding nitrosamines in food is the same as the risk in medication: their carcinogenic nature. Studies have linked these compounds to an increased risk of cancers, especially gastric and esophageal cancers.

To reduce the risk of nitrosamine exposure and its potential health risks, here are some practical health tips:

1. Limit Processed Meats: Minimize consumption of processed meats like bacon, sausages, hot dogs, and deli meats. Opt for fresh, unprocessed meats whenever possible.

2. Choose Nitrate-Free Products: Look for nitrate-free or nitrite-free processed meat alternatives. Many brands now offer products without these additives.

3. Avoid High-Temperature Cooking: High-temperature cooking methods such as grilling, frying, or charbroiling can promote the formation of nitrosamines. Instead, choose gentler cooking methods like baking, steaming, or slow cooking.

4. Increase Antioxidants: Foods rich in antioxidants, such as vitamin C and vitamin E, can help neutralize the formation of nitrosamines. Include more fruits, vegetables, nuts, seeds, and whole grains in your diet.

5. Avoid Smoked Foods: Since smoking can lead to the formation of nitrosamines, limit consumption of smoked meats and smoked fish. Opt for fresh or baked options instead.

6. Drink Clean Alcoholic Beverages: Choose alcohol that is minimally processed and avoid beers or wines that may contain nitrosamines from additives used during production.

7. Detox your body: Use Touchstone PBX Zeolite spray with Vital Cleanse to eliminate daily toxicities from drugs, food, and the environment.

Let the buyer beware when it comes to prescription medications. Do your best to lose weight, get healthy, and avoid as many toxic petrochemical products as possible. In the best case, eliminate and/or avoid them all. When it comes to food, make these simple adjustments to your diet and cooking habits to reduce your exposure to nitrosamines and better protect your health.