Food and Drug Administration (FDA) announces additional impurity in valsartan (Diovan®) recall

By: Karen Chen, PharmD Candidate c/o 2019

On July 13^th, 2018, the U.S. Food and Drug Administration (FDA) announced a voluntary recall of several different national drug codes (NDCs) of medications containing the active ingredient valsartan (Diovan®) after the discovery of an impurity called N-nitrosodimethylamine (NDMA). The reason for the recall was because the impurity is classified as a probable human carcinogen based on results from laboratory tests and such results do not meet the FDA’s safety standards.¹ Valsartan is an angiotensin II receptor blocker (ARB) indicated for the treatment of high blood pressure and heart failure. Many healthcare providers have since switched their patients to an alternative medication within the drug class in order to avoid discontinuation of therapy.^1,2

NDMA was discovered in medications with the active pharmaceutical ingredient valsartan by Prinston Pharmaceuticals Inc., who contacted the FDA‘s Center for Drug Evaluation and Research (CDER), notifying the agency that their manufacturer, Zhejiang Huahai Pharmaceutical Co. (ZHP), had discontinued manufacturing valsartan after discovering an impurity in its products.³ The levels of NDMA in ZHP’s valsartan products were in trace amounts which are considered to be a low risk to patients taking the affected products. Despite this, the impurity was considered unacceptable by the FDA.² Only certain lots of the contaminated valsartan NDCs were removed from the market.

Sudden withdrawal of such a large volume of affected valsartan lot numbers from the market combined with a lack of unaffected lots of valsartan available for distribution and dispensing resulted in a drug shortage for uncontaminated generic valsartan. Upon discovery of the impurity, the FDA took swift action to alert the public and healthcare professionals to remove generic valsartan medications containing NDMA from the market and alleviate the drug shortage resulting from this recall.¹ The FDA is hoping to increase production of uncontaminated valsartan from other manufacturers to fulfill the needs of the public. ²

On September 13^th, 2018, the FDA updated the public about their ongoing investigation surrounding the recall of valsartan containing medication contaminated with NDMA, and announced a second impurity discovered in a batch of medications containing valsartan known as N-Nitrosodiethylamine (NDEA). NDEA is similar to NDMA in that it is a known animal carcinogen, and a probable human carcinogen.³ The batch of medications containing NDEA-contaminated valsartan was found in three lots of Torrent Pharmaceuticals’ recalled valsartan drug products. It was determined that the batches containing NDEA impurity came from Zhejiang Huahai Pharmaceuticals (ZHP). The FDA took action to remove these drug products from the market, however, not all products made using ZHP manufacturing contained the NDEA impurity.³ Both the NDMA and NDEA impurities were believed to have formed as a result of errors made in valsartan manufacturing .^1,3

Patients are encouraged to double check and examine their bottle of valsartan to ensure that they are not taking valsartan from a recalled lot, and pharmacists should check to ensure that they are not carrying an affected lot in their inventory. Pharmacists also play an important role in reaching out to prescribers to obtain an alternative ARB for patients that have been affected by the recall to avoid abrupt discontinuation of therapy. Pharmacists have the responsibility to ensure the continuation and high quality of care for all patients. Not all valsartan products contain NDMA or NDEA, so pharmacists may reach out to patients and recommend a drug product not affected by the recall. Pharmacists play an important role as the most accessible healthcare provider for most patients and have the responsibility to educate patients about the impact of the recall.

SOURCES:

1. U.S. Food and Drug Administration. FDA announces voluntary recall of several medicines containing valsartan following detection of an impurity. Updated 08/07/2018. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm613532.htm. Accessed 09/25/2018.
2. U.S. Food and Drug Administration. FDA provides update on its ongoing investigation into valsartan products; and reports on the finding of an additional impurity identified in one firm’s already recalled products. Updated 08/30/2018. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm619024.htm. Accessed 09/25/2018.
3. U.S. Food and Drug Administration. FDA provides update on its ongoing investigation into valsartan products; and reports on the finding of an additional impurity identified in one firm’s already recalled products. Updated 09/13/2018. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm620499.htm. Accessed 09/25/2018.