With blood pressure patients on edge after numerous recalls of valsartan, losartan and irbesartan for too much NDEA, FDA commissioner Scott Gottlieb and Center for Drug Evaluation and Research Director Janet Woodcock issued a lengthy joint statement last week.
Impurities in NDEA (N-Nitrosodiethylamine) and NDMA (N-Nitrosodimethylamine) have been classified as “probable human carcinogens,” meaning they cause cancer. While both substances are found in water and food, the FDA declares “their presence in drug products is not acceptable.”
Here are some of the highlights of the joint statement:
▪ There is now a shortage of valsartan and “other types of products may fall into shortage soon.” The FDA is considering changing the acceptable amount of NDEA in angiotensin II receptor blocker (ARB) medicines.
▪ The actual danger from NDEA is small. The statement reiterated the FDA estimate that “that if 8,000 people took the highest daily valsartan dose (320 mg) that contained NDMA, for four years (the time we think the affected products had been on the U.S. market), there may be one additional case of cancer beyond the average cancer rate among those 8,000 Americans.”
▪ As far as what causes the NDEA in these products, the leading theory is “the impurities may be generated when specific chemicals and reaction conditions are present in the manufacturing process of the drug’s API (active pharmaceutical ingredient), and may also result from the reuse of materials, such as solvents.”
▪ The statement says this examination of the blood pressure drugs started when the FDA found that the active pharmaceutical ingredient made by the Chinese company, Zhejiang Huahai Pharmaceitucal (ZHP), for generic valsartan had NDMA.
“Since then, the FDA and additional manufacturers of other ARB medicines have identified more cases of NDMA impurities, as well as NDEA impurities,” the statement read. “We’ve placed a ZHP facility on import alert to stop all its API and finished drugs made using ZHP’s API from legally entering the U.S. We also issued them a warning letter outlining several manufacturing violations, including impurity control, change control and cross contamination from one manufacturing process line to another.”