Nitrosamine Impurities Continue to Plague Pharmaceutical Industry

In the last several years, millions of bottles of blood pressure medications and other drugs have been recalled over concerns that they may be contaminated with cancer-causing chemicals known as nitrosamines. Most recently, several lots of quinapril have been recalled over nitrosamine contamination concerns.

Other recalls conducted since 2018 have included ARB blood pressure medications valsartan, losartan and irbesartan, heartburn remedies Zantac, Axid, ranitidine and nizatidine, diabetes drugs metformin and sitagliptin, anti-smoking medication Chantix and others. All of these medications were recalled due to potential contamination with nitrosamines.

Nitrosamines are a group of cancer-causing compounds that may be found at low levels in foods, tobacco, water, and many other places, often developing in fermenting or preservation processes. Drugs can also be contaminated with nitrosamines, sometimes at much higher levels than other products.

Nitrosamines recently found in pharmaceutical products include N-Nitrosodimethylamine (NDMA), N-Nitrosodiethylamine (NDEA), and N-Nitroso-N-methyl-4-aminobutyric acid (NMBA). All of these compounds have been shown to be carcinogenic.

Formation of Nitrosamines in Drug Manufacturing

Unlike other contamination events, nitrosamines are not generally linked to unsanitary conditions. They are instead formed during manufacturing processes when solvents, raw materials and other agents combine and are not properly handled. In many cases, it appears that nitrosamines found in medications were formed during the manufacturing of the active ingredient.

Most of the U.S. drug supply is manufactured using active ingredients formulated outside of the country. Up to 75% of raw ingredients for the pharmaceutical industry is now estimated to come from China. Chemicals, including drugs manufactured outside of the U.S. may not be subject to standards required by regulations inside of the country.

Some experts have suggested that the nitrosamine contamination issue has become more problematic as manufacturers continue to cut corners, placing profit over safety. In addition, consumers continue to demand lower prices and ongoing supply chain issues mean drug supplies continue to tighten. These issues may prevent resolution of contamination problems and could potentially expand the issue to encompass more drugs.

Manufacturers Facing Nitrosamine Contamination Lawsuits

Multiple drug manufacturers continue to face thousands of lawsuits filed by people and loved ones of those who may have developed cancer after using nitrosamine-contaminated products. Notable lawsuits include those filed for nitrosamine contamination of Diovan (valsartan), Zantac (ranitidine), and Axid (nizatidine). More recently, recalls have involved certain lots of Chantix (varenicline), metformin, and Accupril (quinapril). The U.S. Food and Drug Administration has allowed sales of certain critical medications including antiviral Rifampin and diabetes drug sitagliptin to remain on the market on a case-by-case basis to reduce the severity of drug shortages but has established a “safe” level of nitrosamine impurities for most drugs.