This week, two more blood pressure medications containing the ingredient valsartan were recalled by the manufacturer because of NDEA contamination.
On November 27, Israel-based Teva Pharmaceuticals announced the recall of all lots of Amlodine and Amlodine/Hydrochlorothiazide because the active ingredient, valsartan, was found to contain high levels of an industrial chemical known to cause cancer.
The contaminated valsartan was a product of Mylan Pharmaceutical’s India-based operation. It is not the first time Mylan has had problems with NDEA contamination. Only days earlier, the global pharmaceutical giant issued a recall for 15 lots of anti-hypertensive and heart medications containing valsartan due to trace amounts of NDEA. On November 19, the European Medicines Agency (EMA) issued an order that effectively prohibits the use of valsartan from Mylan India in medications sold and used in the EU.
Other sartan blood pressure medications that have been affected include losartan, a product of Novartis subsidiary Sandoz, and irbesartan, sold as a generic by Sciegen Pharmaceuticals. In August, Torrent Pharmaceuticals issued a voluntary recall for three valsartan containing products. Both the EMA and the FDA are testing all such medications for the presence of NDEA.
NDEA, or N-nitroso-diethylamine, is a substance used in jet fuel and industrial lubricants. According to the website PubChem, NDEA is a “synthetic light-sensitive, volatile, clear yellow oil that is soluble in water, lipids, and other organic solvents” that emits “toxic fumes” at high temperatures. Scientists use NDEA to induce liver cancer in laboratory rats. It is “reasonably anticipated to be a human carcinogen” as well.
While NDEA levels found in sartan drugs are extremely low, the New Jersey State Department of Health points out that “scientists believe that there is no safe level of exposure to a carcinogen.” This suggests that while one-time exposure to NDEA may not necessarily lead to cancer, long-term exposure over several months or years could increase the risks substantially.
The contaminated valsartan has been traced back to a drug manufacturer in China, known as Zhejiang Huahai Pharmaceuticals (ZHP). It is not known how the NDEA contamination occurred. Some investigations indicate that it may be related to some changes in the manufacturing process that ZHP instituted in 2012 that was intended to make it more efficient.
The scientific explanation is complex. The simple explanation is a chemical change that came about because of the manufacturing changes. According to one auditor who inspected the ZHP operation, the improvements that were made resulted in a chemical reaction between the various substances used to synthesize valsartan. These reactions resulted in the unintentional production of NDEA.
For patients taking sartan drugs and are concerned about NDEA exposure, the FDA keeps a regularly-updated list of sartan drugs found to be contaminated. Patients who take such medications are advised not to discontinue their regimen without consulting with their physicians. If they find their prescription is included in a recall or listing of NDEA-contaminated products, they can ask to be switched to a different prescription.