FDA probes tainted blood pressure drug valsartan; might still be in use

Hypertension patients may still be taking a popular medication that is part of a wide-ranging federal investigation into the drug’s possible contamination with trace amounts of a compound linked to cancer.

A recall of the medication known as valsartan was first announced in July and then expanded in August to include valsartan medications that also contain hydrochlorothiazide, an additive that addresses fluid retention. The U.S. Food and Drug Administration this month confirmed its investigation is continuing with no set date for completion.  

The recalled medications are tainted with n-nitrosodimethylamine, or NDMA, a byproduct of some industrial processes, including pesticide manufacturing. It’s also a component of liquid rocket fuel. NDMA has been known to taint drinking water and can be a food contaminant. The Environmental Protection Agency lists it as a probable human carcinogen.

“There are probably patients and physicians who don’t know about the recall,” said Mintz, director of cardiovascular health for Northwell Health’s Sandra Atlas Bass Heart Hospital in Manhasset.

“I emphasize to my patients and any lay people who call me that they have to meet with their doctors and be switched to another medication,” Mintz said. “The onus should not be on the patients to track down their own lot numbers.”

Valsartan is prescribed to an estimated 3 million people in the United States, but the contamination, which stems from a manufacturing problem in China, also has led to recalls in 22 other countries.

Drugs on the recall list include those made by A-S Medication Solutions; AvKARE; Prinston Pharmaceuticals  Inc.; ReadyRepack, Inc.; Teva Pharmaceuticals and Teva USA. Recalled medications involve unexpired lots dated through 2019 and dosages that range from a low of 30 milligrams to a high of 320 milligrams. 

It’s because expiration dates stretch into next year and some patients may have a pill supply lasting months. Mintz is also concerned about electronic medical record systems: They’re not yet sophisticated enough to search patients by name, medical condition and specific brand and lot-number data.

“These systems don’t have a button to press and valsartan and its derivatives just pop up,” he said.

There is additional concern, Mintz said, because the tainted medications have likely been in the U.S. marketplace since at least 2012, even though the contamination was discovered only recently, he said.            

At St. Francis Hospital in Flower Hill, Dr. Richard Shlofmitz  has taken his patients — and himself — off the recalled medications.

“Valsartan is a great drug. It’s what I have been taking because I have hypertension,” said Shlofmitz, chairman of cardiology at the hospital. “It’s what a majority of my patients have been on for years.”

Shlofmitz described valsartan’s drug family as an ARB, which stands for angiotensin-2 receptor blocker.  

Angiotensin-2 is a powerful hormone in the blood that causes constriction of muscles surrounding blood vessels, causing them to narrow.

Narrowing increases pressure within vessels as blood courses through them —  high blood pressure. The medications work by blocking the activity of angiotensin-2, preventing it from latching onto docking points — receptors — in muscles surrounding vessels.

There are eight drugs in the ARB family. Valsartan is widely sold under the brand name, Diavan. Not all valsartan products are part of the recall; only those with links to source ingredients from certain companies abroad.

How NDMA wound up in some brands of valsartan highlights a largely unknown but growing global trade in the raw ingredients used in the production of prescription drugs. These chemical components are sold and repackaged around the world.

Trace amounts of NDMA were detected in valsartan’s active ingredients during tests in June by laboratory experts at Prinston Pharmaceuticals Inc. in New Jersey. Prinston’s source of the active ingredients was Zhejiang Huahai Pharmaceutical Co. in Linhai, China.

Although amounts of NDMA detected by Prinston were minute, the FDA opened its investigation because NDMA is a probable carcinogen.

The contamination problem broadened in recent weeks because the FDA found that a pharmaceutical company in India — Hetero Drugs —  also had traces of NDMA in its valsartan ingredients. Hetero’s valsartan is sold in the U.S. as well.

Agency investigators concluded that Hetero used production methods similar to that of Zhejiang Huahai.

FDA scientists have tried to put NDMA’s cancer risk into perspective.

“We estimated that if 8,000 people took the highest valsartan dose [320 mg] from NDMA-affected medicines daily for four years (the amount of time we believed the affected products had been on the U.S. market), there may be one additional case of cancer over the lifetimes of these 8,000 people beyond the average cancer rate among Americans,” according to the FDA statement.

For Mintz, the NDMA issue raises concerns about possible future recalls.

“No one can say how it got there,” Mintz said of NDMA tainting valsartan’s active ingredients in China. “There are many different companies that are repackaging valsartan under different names. Manufacturers sell their active ingredients; the buyers manufacture the drugs.”