Mylan and Teva Pharmaceutical Industries have issued a voluntary recall to the consumer level of select lots of valsartan-containing products due to detected trace amounts of an impurity, N-nitrosodiethylamine (NDEA) contained in the active pharmaceutical ingredient (API) valsartan. Mylan announced its recall November 20, 2018 after NDEA was found in its valsartan manufactured at one of its plants in India. Teva announced its recall one week later when it detected NDEA in the valsartan supply it received from Mylan’s India plant. NDEA is a substance that occurs naturally in certain foods, drinking water, air pollution, and industrial processes, and has been classified as a probable human carcinogen according to the International Agency for Research on Cancer.

For Mylan, the recall included six lots of amlodipine and valsartan tablets (USP 5 mg/160 mg, 10 mg/160 mg, and 10 mg/320 mg strengths), seven lots of valsartan tablets (USP 40-mg, 80-mg, 160-mg, and 320- mg strengths), and two lots of valsartan and hydrochlorothiazide tablets (USP 320 mg/25 mg).

Teva’s recall included all lots (49) of its amlodipine/valsartan combination tablets and amlodipine/valsartan/ hydrochlorothiazide combination tablets. As of November 27, 2018, Teva had not received any reports of adverse events signaling a potential link or exposure to valsartan.

The recalls follow several other recalls of “sartan” APIs in the US and European Union. Most recently, in November 2018, Sandoz, the generics arm of Novartis, voluntarily recalled in the US one lot of losartan potassium hydrochlorothiazide tablets (USP 100 mg/25 mg) due to a trace amount of NDEA found in the API. The API was manufactured by Zhejiang Huahai Pharmaceuticals (ZHP), a Linhai, China-based pharmaceutical company.

Earlier this year, the FDA and EMA began their initial investigation into the “sartans” after the EMA learned that Zhejiang Huahai Pharmaceuticals had detected N-nitrosodimethylamine (NDMA) and NDEA, two probable human carcinogens, in several batches of its valsartan API. The FDA’s investigation began when a manufacturer of valsartan products detected NDMA in its API supplied from Zhejiang Huahai Pharmaceuticals, which followed with other companies recalling valsartan products, including Teva. The EU’s detection of the two impurities led to an EU-wide review of all valsartan medicines marketed in the EU. The review was subsequently extended to other “sartan” medicines when very low levels of NDEA were found in losartan made by Hetero Labs, a Hyderabad, India-headquartered pharmaceutical company. In October 2018, the EMA updated that it was evaluating the APIs, candesartan, irbesartan, losartan, and olmesartan, marketed in the EU in addition to its investigation into valsartan products. After low levels of NDEA were found in irbesartan, supplied to a US pharmaceutical company by Aurobindo Pharma, a Hyderabad, India-headquartered generics and API manufacturer, the FDA expanded its investigation to include both valsartan and irbesartan. An investigation of losartan followed in November.

Source: Teva Pharmaceutical Industries and Mylan