Due to Impurity FDA Recalls Valsartan – Heart Drug Over Cancer Concerns
The FDA has announced a voluntary recall of several drugsthat contain the heart drug valsartan because a possible carcinogen was found in the recalled products.
VALSARTAN – Uses, Side Effects, Contraindications & Mechanism of action
Valsartan is used to treat high blood pressure, congestive heart failure, and to reduce death for people with left ventricular dysfunction after having had a heart attack.
There is contradictory evidence with regard to treating people with heart failure with a combination of an angiotensin receptor blocker like valsartan and an angiotensin-converting enzyme inhibitor, with two major clinical trials (CHARM-additive and ValHeFt) showing a reduction in death, and two others (VALIANT and ONTARGET) showing no benefits, and more adverse effects including heart attacks.
In people with type II diabetes and high blood pressure or albumin in the urine, valsartan is used to slow the worsening and the development of end-stage renal disease.
The packaging for valsartan includes a warning stating the drug should not be used with the renin inhibitor aliskiren in people with diabetes mellitus. It also states the drug should not be used in people with kidney disease.
Valsartan falls in FDA pregnancy category D and includes a black box warning for fetal toxicity. Discontinuation of these agents is recommended immediately after detection of pregnancy and an alternative medication should be started. The US labeling makes no recommendation regarding continuation or discontinuation of valsartan for breast-feeding mothers. The Canadian labeling does not recommend use by nursing women.
Rates of side effects depends on the reason the medication is used.
Rates of adverse effects are based on a comparison versus placebo in people with heart failure. Most common side effects include dizziness (17% vs 9% ), low blood pressure (7% vs 2%), and diarrhea (5% vs 4%). Less common side effects include joint pain, fatigue, and back pain (all 3% vs 2%).
Clinical trials for valsartan treatment for hypertension versus placebo demonstrate side effects like viral infection (3% vs 2%), fatigue (2% vs 1%) and abdominal pain (2% vs 1%). Minor side effects that occurred at >1% but were similar to rates from the placebo group include:
- upper respiratory infection
Valsartan blocks the actions of angiotensin II, which include constricting blood vessels and activating aldosterone, to reduce blood pressure. The drug binds to angiotensin type I receptors (AT1), working as an antagonist. This mechanism of action is different than that of the ACE inhibitor drugs, which block the conversion of angiotensin I to angiotensin II. As valsartan acts at the receptor, it can provide more complete angiotensin II antagonism since angiotensin II is generated by other enzymes as well as ACE. Also, valsartan does not affect the metabolism of bradykinin like ACE inhibitors do.
NDMA, which was found in the valsartan products, could cause cancer, according to lab tests. “The presence of NDMA was unexpected and is thought to be related to changes in the way the active substance was manufactured,” the FDA said in a statement.
Valsartan is used to treat hypertension and heart failure. The following valsartan products are being recalled:
Valsartan Major Pharmaceuticals
Valsartan Solco Healthcare
Valsartan Teva Pharmaceuticals
Valsartan/Hydrochlorothiazide (HCTZ) Solco Healthcare
Valsartan/Hydrochlorothiazide (HCTZ) Teva Pharmaceuticals
All of the companies say the possibly contaminated valsartan was supplied by one outside company. But not all of their valsartan drugs feature material from that company, which the FDA did not name. The supplier has stopped distributing its product, known as the valsartan active pharmaceutical ingredient, and the FDA is working with the affected companies to lessen or remove it from future products.
The FDA is investigating how much NDMA is in the recalled products and is trying to find out the possible effects on patients who have been taking them.
“We have carefully assessed the valsartan-containing medications sold in the United States, and we’ve found that the valsartan sold by these specific companies does not meet our safety standards. This is why we’ve asked these companies to take immediate action to protect patients,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research, in a statement.
The recall, like the one announced earlier by the European Medicines Agency, is because the API in those drugs was unexpectedly tainted with N-nitrosodimethylamine (NDMA), a substance that could cause cancer.
The recalled finished products in the U.S. include all non-expired generic valsartan sold by Major Pharmaceuticals, Teva and Huahai’s U.S. subsidiary, Solco Healthcare, as well as valsartan/hydrochlorothiazide (HCTZ) made by Teva and Solco. Valsartan’s original developer Novartis previously told FiercePharma none of its valsartan products marketed in the U.S.—branded or generic— are affected
“The FDA is committed to maintaining our gold standard for safety and efficacy. That includes our efforts to ensure the quality of drugs and the safe manner in which they’re manufactured,” FDA Commissioner Scott Gottlieb, MD, said in the statement.
Because valsartan is used to treat serious medical conditions, patients taking the recalled products should continue taking their medicine until they have a replacement product, the FDA advises.
Patients should contact their doctor or pharmacist if their medication is part of the recall.
Earlier this month, European authorities recalled drugs that had valsartan that were supplied by a Chinese drugmaker over concerns they may contain NDMA, as reported by Medscape Medical News.
News Source: webmd.com, fiercepharma.com, newsweek.com