Aurobindo Pharma USA, Inc. has issued a voluntary recall of three of its sartan-based prescription medications after discovering trace amounts of a carcinogenic substance known as N-nitrosodiethylamine (NDEA). The recall, which the FDA announced on Dec. 31st, affects a total of 80 lots of Valsartan, Amlodipine Valsartan, and Valsartan HCTZ pills with expiration dates between May 2019 and March 2021.
The Aurobindo products are the latest to join a long list of sartan-based blood pressure medications that have been found to be tainted with the industrial chemical. Pharmaceutical companies that have recalled NDEA-contaminated sartan drugs this past year include A-S Medication Solutions (Socol Healthcare), Bryan Ranch Prepack, H.J. Harlins Co., Northern Pharmaceuticals, Teva Pharmaceuticals and its distributors, Mylan, Novartis and subsidiary Sandoz, and Hetero Labs.
The contamination has been traced to the Zhejiang Huahai Pharmaceuticals plant located in Linhai, China. While it is not known for certain how the contamination occurred, investigators have found evidence indicating that a change designed to optimize the manufacturing process made six years ago may be responsible. Those changes involved the replacement of one chemical with another that led to a much better yield of the final product. However, it also resulted in an unforeseen chemical reaction that led to the formation of nitrosamines.
Before the changes, Zhejiang Huahai had no issues with quality control. Phillipe Andre, an auditor who inspected the plant earlier in 2018, told PharmTech that company management was generally excellent. He noted that the company had fulfilled all legal obligations and provided all required documentation. He added that both U.S. and European regulators had been aware of the changes and had approved them. However, he also said that they “...may have missed the potential formation of some genotoxic impurities.”
In addition to industrial applications, nitrosamines such as NDMA can occur naturally in some smoked meats and as a result of high-temperature frying. Physicians have attempted to reassure the public by pointing out that “...it would take 8000 patients taking the maximum daily dose of the drug (320 milligrams) every day for four years” before a single case of cancer would appear. However, the dose-response (the amount required to cause malignant tumors to start forming) is extremely minimal. The liver is particularly vulnerable to nitrosamines.
NDEA and NDMA contamination of these hypertension medications may have been an accident. What is not accidental are allegations that pharmaceutical companies concealed this information from physicians and their patients for months – and possibly years. What is also troubling is that the FDA only began issuing recall notices after 22 other countries had taken sartan medications off of pharmacy shelves.
Patients currently taking ACE inhibitors such as valsartan, losartan, olmesartan or irbesartan are advised not to stop their medications until they have discussed the issue with their primary care doctor and look into getting a replacement, such as an ARB, as it can be dangerous to simply stop taking a prescription.