Patients with hypertension and heart failure, take note: There has been yet another step in the sweeping federal investigation into suspected contamination of a widely prescribed class of medications.
The U.S. Food and Drug Administration on Wednesday issued a warning letter to a large pharmaceutical manufacturer in China, saying the company is under tight scrutiny after allowing a possible carcinogenic compound to taint the active ingredient used in many generic brands of valsartan.
An estimated 3 million people in the United States are prescribed valsartan to lower blood pressure or manage heart failure. The drug belongs to the family of medications known as angiotensin-2 receptor blockers, or ARBs. The contamination problem first was announced in June, but drugs still were being targeted for recall as recently as Dec. 7.
Not all valsartan brands are subject to the recall, but targeted drugs encompass dozens upon dozens of generics, including a combination form of the drug that contains hydrochlorothiazide, an additive that addresses fluid retention.
Federal officials underscored in their warning that Zhejiang Huahai Pharmaceutical Co. Ltd. engaged in a number of sloppy procedures that caused cross-contamination and raised U.S. concerns about impurities and lack of quality control.
Recalled medications are believed to be tainted with traces of n-nitrosodimethylamine, or NDMA, a byproduct of industrial processes, including pesticide manufacturing. NDMA also is a component of liquid rocket fuel. The U.S. Environmental Protection Agency lists it as a probable human carcinogen.
"We’re continuing to investigate and take action to protect patient health and safety from products in this angiotensin II receptor blocker class that have been found to have dangerous impurities," Dr. Scott Gottlieb, the FDA commissioner, said in a statement Wednesday.
"As part of that investigation, we’ve uncovered serious manufacturing violations at Zhejiang Huahai Pharmaceutical company, which is one of the manufacturing facilities that has been linked to these products," Gottlieb's statement said. "The issues cited in the warning letter are associated with the nitrosamine impurities found in these drugs, and these violations reveal a disturbing lack of oversight."
The FDA's list of valsartan medications subject to the recall runs 10 pages and includes more than 100 drugs, their milligram strength, and expiration dates.
On the Island, Dr. Guy Mintz, director of cardiovascular health for Northwell Health’s Sandra Atlas Bass Heart Hospital in Manhasset, switched the few patients of his who were taking a valsartan generic to other drugs last summer when the voluntary recall first was announced.
One choice is the brand-name drug Diovan, Mintz said, which is made by Novartis and is not contaminated. He added that some patients wind up with generic medications because that is what their insurance carrier will pay for.
The generic drugmakers do not purchase the basic ingredients for their versions of valsartan from the same sources as the brand-name drug, said Mintz, who has researched the global ingredient trade for the medication.
"For the generic, the ingredients may have been purchased in bulk, so they're using cheaper stuff," he said. "There's also manipulation of pricing by insurers."
Last summer, the FDA also had identified a pharmaceutical ingredient company in India as another cheap source for the active ingredient in valsartan.
The warning letter, written by the FDA and made public Wednesday, cited only the company in China for problems with NDMA contamination. The agency earlier named Hetero Drugs — a company in India — as having traces of NDMA in its valsartan ingredients. Hetero’s valsartan is sold in the U.S. as well.
He assured patients that there are multiple other drugs available to control blood pressure and manage heart failure, including other ARBs whose basic ingredients are not sourced in either China or India.
"There are many alternatives available for patients," Mintz said. "There are seven other members of the angiotensin-2 receptor blocker class, including irbesartan, losartan, candesartan, olmesartan, telmisartan, eprosartan, and azilsartan."
Anti-high blood pressure medications outside the ARB family that can be used include diuretics, calcium channel blockers, beta blockers and ACE inhibitors. "These families of medications have been used for decades," Mintz said.
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