Last year’s discovery of toxic substances in certain lots of Valsartan has triggered the largest prescription drug recall in years. The list of manufacturers with tainted medications continues to grow by the week. There is confusion at pharmacies for patients who can’t get what they need, and worry for those who don’t know if their stock of Valsartan is safe.
Along with Valsartan (Diovan), two other similar medications have been recalled: Losartan (Cozaar) and Irbesartan (Avapro). These drugs are classified as angiotensin II receptor blockers, or ARBs, and they help a person’s blood pressure from rising. More than 60 million Americans, not including veterans, take 1 of these 3 medications every day.
FDA Investigation Likely to Uncover More Lots of Tainted Pills
Although the source of the impurity has been identified, a second toxic substance, NDEA, was discovered, as well as a second contamination site.
“The investigation isn't concluded,” said Dr. Janet Woodcock, the director at the Food and Drug Administration (FDA) responsible for the response. Woodcock told CNN that she believes there are more tainted pills to find.
The toxic substance discovered in Valsartan that triggered the recalls is called N-nitrosodimethylamine, or NDMA. The World Health Organization (WHO) lists NDMA as a possible carcinogen for humans. This makes sense because NDMA is primarily used in oncology research to induce tumors in experimental animals.
The FDA has said that the risk posed by the impurities is low — 1 person in 8000 will develop cancer from taking contaminated medication for 4 years — but it is impossible to rest easy given the massive number of people who depend on ARBs.
What Are Angiotensin II Receptor Blockers?
Valsartan and similar blood pressure medications reduce blood pressure by blocking the actions of a hormone known as angiotensin II. Part of the system in the body that regulates blood pressure, angiotensin II causes blood vessels to narrow. This increases blood pressure. By blocking this hormone, ARBs reduce blood pressure.
Having high blood pressure (hypertension) can damage the heart, brain, and kidneys. Valsartan is supposed to help people live longer after they have suffered a heart attack. ARBs are very safe and have few side effects. In short, they are important drugs that improve a person’s chance of living a healthy life.
How Were the Drugs Contaminated?
The source of the contamination has been traced to at least 2 foreign drug manufacturing facilities: Zhejiang Huahai Pharmaceuticals (ZHP) in China, and Hetero Labs in India. Based on the information they have so far, the FDA believes that chemical reactions during the manufacturing process inadvertently generated NDMA.
The FDA is confident they have identified the changes that ZHP made to its manufacturer process that caused the impurity. In an FDA statement from Woodcock and Gottlieb, they explained how the impurity went undetected:
“Before we undertook this analysis, neither regulators nor industry fully understood how NDMA or NDEA could form during this particular manufacturing process. This is troubling to us and we know it’s troubling to the public.”
In retrospect, it is easy to understand how ZHP did not detect the contamination. Yet prior FDA investigations of the company’s facilities had revealed, “systemic problems of supervision that could have created the conditions for quality issues to arise.” The FDA has placed ZHP on import alert, which means that none of its products may enter the U.S. legally.
Valsartan Recall Raises Questions About FDA’s Ability to Monitor Generic Drug Production
With low manufacturing costs, Asia has quickly become a key part of the supply chain for generic drug production. In the wake of the Valsartan recall, critics are worried that the FDA is not equipped to monitor the overseas production of generic prescription drugs.
In a letter to FDA Commissioner Scott Gottlieb, the U.S. House of Representatives Committee on Energy and Commerce requested a briefing on the impact of the ARB recalls and the FDA’s protocols for conducting foreign inspections. Committee members noted that roughly 400 foreign facilities that produce drugs for the U.S. market have never been inspected.
The problem with questionable generic drugs is by no means limited to foreign companies. A Bloomberg investigation revealed shocking lapses in oversight at pharmaceutical manufacturing facility in West Virginia operated by Mylan. Along with a number of safety violations, inspectors found bins full of shredded quality control records.
For Patients Who Are Taking Valsartan
Up-to-date information on the specific lots of Valsartan, Losartan, and Irbesartan that are affected can be found on the recall list maintained by the FDA.
The FDA stresses that people who are on Valsartan should continue to take their medication as directed. Patients are encouraged to talk with their doctor or pharmacist to determine the best course of action.
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