Valsartan, Losartan & Irbesartan Recalled Due to Cancer Risk

The U.S. Food and Drug Administration (FDA) is recalling a number of high blood pressure medications over potential cancer risks. Name brand medications like Diovan, Valturna, Exforge, Byvalson, Entresto, Cozaar, and Avapro were taken off the market after high levels of potentially cancer-causing contaminants were found in batches of drugs. These brand name medications contain the active ingredients valsartan, losartan, or irbesartan, and are used to treat high blood pressure in millions of Americans.

The FDA initiated what would become its largest class I drug recall to date in July 2018 and has since expanded the number of contaminated products involved. Over 2 million Americans received notices in the mail alerting them of the recall and their potential exposure to a probable carcinogen. Similar warnings have also been issued the World Health Organization (WHO), Health Canada, the European Medical Association (EMA), and the Hong Kong Department of Health.

Largest Class I Recall Means Millions of Americans Possibly Exposed to Cancer-Causing Chemical

The recall of dozens of lots of valsartan-, losartan-, and irbesartan-containing drugs has become the FDA’s largest class I recalls in its history. These generic chemicals are used in a number of brand-name angiotensin II receptor blockers (ARBs), popular high blood pressure medications that millions of Americans rely on every day to treat their condition.

In a March 1 press release issued by the FDA, Commissioner Dr. Scott Gottlieb said the agency is “deeply concerned” about the presence of potential cancer-causing contaminants in these drugs. Since the agency’s initial recall announcement in July 2018, the FDA has found three different types of contaminants in popular ARBs. The recall has been expanded to include dozens of lots of different ARBs. The FDA is continuously updating its lists of recalled products and urges patients to check frequently to see if their specific ARB is involved in the market withdrawal. The lists of valsartan, losartan, and irbesartan drugs can be found at the following links:

• List of recalled valsartan drugs
• List of recalled losartan drugs
• List of recalled irbesartan products

More than 100 million adults in the United States have hypertension, or high blood pressure, and more than 2 million use ARBs to treat their condition. This means millions of Americans were potentially exposed to cancer-causing impurities in their medications, increasing their risk of cancers such as:

• liver cancer
• stomach cancer
• colorectal cancer
• bowel cancer
• kidney cancer

To determine if your prescription is part of the recall, patients should look at the drug name and company name on the label of their prescription bottle. If the information is not on the bottle, they should contact the pharmacy that dispensed the medicine.

If a patient’s medicine is included in the recall, the FDA says to follow the instructions provided by the specific company. This information can be found on the FDA’s website. Patients should also contact their healthcare provider, including the pharmacist that dispensed the medication and the doctor who prescribed it, to see if another valsartan product should be used instead or if there is an alternative treatment option.

Manufacturers Taking Contaminated Products off the Market

There are number of manufacturers recalling lots of tainted valsartan, losartan, and irbesartan ARBs, and that number could continue to grow. The first drug companies involved in the recall were manufacturers of valsartan-containing products. These companies included:

• Major Pharmaceuticals – Valsartan
• Solco Healthcare – Valsartan
• Teva Pharmaceuticals Industries Ltd. – Valsartan
• Solco Healthcare – Valsartan/Hydrochlorothiazide (HCTZ)
• Teva Pharmaceuticals Industries Ltd. – Valsartan/Hydrochlorothiazide (HCTZ)

Since the recall was first announced in July 2018, a number of additional companies that manufacture or repackage losartan- and irbesartan-containing ARBs were included in the recall. These additional companies include:

• Torrent Pharmaceuticals
• Prinston Pharmaceutical Inc.
• Actavis
• A-S Medication Solutions
• AvKARE
• NuCare Pharmaceuticals Inc.
• Bryant Ranch Prepack Inc.
• Northwind Pharmaceuticals
• RemedyRepack
• Camber Pharmaceuticals Inc.
• Aurobindo Pharma
• Macleods Pharmaceuticals
• Mylan Pharmaceuticals
• Sandoz
• ScieGen Pharmaceuticals
• H. J. Harkins Company Inc.
• Lake Erie Medical, doing business as Quality Care Products LLC
• Proficient Rx
• Hetero Labs Inc.
• Preferred Pharmaceuticals

As the FDA’s investigation into the contaminated products continues, the agency is constantly updating its lists of affected drugs and their manufacturers. Check back often to see if your ARB drug is included in the recall. The lists to recalled ARB products can be found at the following links:

• List of recalled valsartan drugs
• List of recalled losartan drugs
• List of recalled irbesartan products

Zhejiang Huahai Pharmaceuticals, located in Linhai, China, may be responsible for manufacturing the contaminated APIs and selling them to various pharmaceutical companies to use in their ARBs. ZHP has since been placed on an import alert—meaning none of its APIs can legally be imported into the United States—and the FDA issued a warning to the company after uncovering “serious manufacturing violations” while inspecting its facilities in China.  

The companies listed below are recalling all lots of non-expired products that contain the ingredient valsartan supplied to them by Zhejiang Huahai Pharmaceuticals, Linhai, China. Not all valsartan-containing medicines distributed in the United States have valsartan active pharmaceutical ingredient (API) supplied by this specific company. Zhejiang Huahai has stopped distributing its valsartan API and the FDA is working with the affected companies to reduce or eliminate the valsartan API impurity from future products.

Why Are Certain ARBs Being Recalled?

In July 2018, the FDA warned consumers and healthcare professionals that certain blood pressure medications were contaminated with an impurity called N-nitrosodimethylamine, or NDMA. NDMA is a possible carcinogen, and exposure at high levels can lead to significant risk of cancer. NDMA has been linked to liver cancer and liver failure, stomach cancer, colorectal cancer, bowel cancer, and kidney cancer.

NDMA is an organic chemical that can be produced unintentionally through certain chemical reactions. It has been used to make rocket fuel, softeners and lubricants, and exposure in high levels may cause liver damage in humans, according to a CNN report.

As the FDA continued its investigation into valsartan-containing ARBs, it found similar impurities in drugs manufactured with losartan and irbesartan. These drugs were found to contain the impurities N-Nitrosodiethylamine, or NDEA, and N-Nitroso-N-methyl-4-aminobutyric acid, or NMBA. These impurities are potential human carcinogens and are known to cause cancer in animals.

The FDA believes these impurities may be caused when specific chemicals and reaction conditions are present in the manufacturing process of the drug’s API, or active pharmaceutical ingredient. In other words, when the drug’s active ingredient—valsartan, losartan, or irbesartan—is combined with other chemicals during the drug-making process, these unwanted and dangerous impurities are created as byproducts. These impurities are known collectively as nitrosamines.

The FDA said the nitrosamines might also form when certain materials such as solvents are reused by manufacturing companies. Reusing materials is a way to cut costs for these pharmaceutical companies, but at what cost to patients? Reducing costs should not come at the expense of patient health.

FDA’s response to largest class I recall

Since it made its first announcement in July 2018, the FDA has issued more than 30 updates to what is now the largest class I recall in the agency’s history. Over the course of its still-ongoing investigation, the FDA found three types of impurities in certain ARBs and has called on manufacturers to do their due diligence when it comes to proper manufacturing procedures.

In a March 1 update, FDA Commissioner Gottlieb remarked on the third impurity found in ARB drugs by the regulatory agency.

“We are deeply concerned about the presence of a third nitrosamine impurity in certain ARB medications, but it’s important to underscore that, based on the FDA’s initial evaluation, the increased risk of cancer to patients with NMBA exposure appears to be the same for NDMA exposure but less than the risk from NDEA exposure. That said, any presence of such impurities in drug products is not acceptable. Over the past few months, the FDA has conducted a major investigation and has worked with drug companies to address the presence of impurities in these products,” said Gottlieb.

Because there is a potential for discovering other nitrosamine impurities, the FDA is working to develop new methods of detecting such impurities, and will share these new methods with international regulators, industry and the public.

“We are making important strides at understanding how these impurities form and we are continuing to examine if nitrosamine impurities may also arise during the manufacture of other ARB drug products,” said Gottlieb. “The FDA is committed to implementing measures to prevent the formation of these impurities during drug manufacturing processes in the future.”

As the FDA continues to test ARBs for potential contaminants, the agency said it will “work with companies to swiftly remove affected products from the market.”

Alternatives to Valsartan, Losartan, and Irbesartan

There are some alternatives to valsartan, losartan, and irbesartan that patients with high blood pressure may consider switching to. Patients should continue taking their medication, even if it has been recalled, until they speak with their doctor and determine the next course of action. Their healthcare provider may recommend switching to a product that was not affected by the recall, or they may recommend a different treatment option altogether.

There are other ARB drugs on the market today that have not been affected by the recall that patients can speak with their doctors about to see if they are viable alternatives for them.

Other ARBs currently on the market include:

• Eprosartan (generic name) – Teveten (brand name)
• Olmesartan (generic name) – Benicar (brand name)
• Telmisartan (generic name) – Micardis (brand name)
• Candesartan (generic name) – Atacand (brand name)
• Azilsartan medoxomil (generic name) – Edarbi (brand name)

At least one of these ARB medications has been linked to other health problems in patients. Benicar has been associated with an increased risk for developing a life-threatening gastrointestinal disorder called sprue-like enteropathy. The disorder mimics celiac disease and put sufferers in the hospital due to rapid weight loss and severe dehydration. A settlement in the Benicar litigation was reached in 2017 for $300 million to be paid out to those who experienced intestinal issues after using the drug.

In addition to ARBs, there are medications in other drug classes that can be used to control blood pressure. Patients should speak with their healthcare provider to see which option is best for them.

FDA Action Timeline

The FDA first alerted patient and healthcare providers about the recall of certain valsartan-containing ARBs in July 2018. Since then, the recall has been expanded to include losartan- and irbesartan-containing products and additional manufacturers. For the full information on these updates, visit the FDA’s Drug Safety website.

FDA Action Timeline:

July 13, 2018 – FDA first announces recall of valsartan-containing ARBs due to impurities

July 18, 2018 – list of recalled valsartan product manufacturers published

July 24, 2018 – list of valsartan-containing products not part of the recall published

July 27, 2018 – levels of NDMA found in contaminated products announced; product information for contaminated valsartan products updated

Aug. 2, 2018 – FDA reminds manufacturers to evaluate processes, updates product information for contaminated valsartan products

Aug. 9, 2018 – list of recalled valsartan products expanded as additional manufacturers recall contaminated drugs

Aug. 20, 2018 – Torrent Pharmaceuticals Limited recalls valsartan products due to NDMA

Aug. 22, 2018 – Torrent expands list of recalled valsartan products

Aug. 24, 2018 – Torrent expands list of recalled valsartan products again

Sept. 24, 2018 – list of valsartan products not under recall updated

Sept. 28, 2018 – Zhejiang Huahai Pharmaceuticals placed on import alert

Oct. 5, 2018 – lab analyses of NDMA levels in recalled valsartan products posted; FDA says it is testing for NDEA impurities as well

Oct. 11, 2018 – FDA releases new method for detection and quantification of NDMA and NDEA

Oct. 16,  2018 – additional detection method for NDMA and NDEA released

Oct. 24, 2018 – list of recalled valsartan products expanded

Oct. 30, 2018 – ScieGen recalls irbesartan drugs due to NDEA

Nov. 9, 2018 – Sandoz recalls losartan drugs due to NDEA

Nov. 21, 2018 – Mylan recalls valsartan products due to NDEA

Nov. 27, 2018 – Teva recalls valsartan products due to NDEA

Dec. 6, 2018 – Mylan expands its recall of contaminated valsartan products

Dec. 12, 2018 – FDA posts warning letter to Zhejiang Huahai Pharmaceuticals; updates NDMA and NDEA detection methods

Dec. 19, 2018 – FDA publishes interim acceptable levels of nitrosamine impurities that humans can safely ingest

Dec. 20, 2018 – Torrent recalls losartan products due to NDEA

Jan. 2, 2019 – Aurobindo recalls valsartan products due to NDEA

Jan. 3, 2019 – Torrent expands recall of losartan products

Jan. 18, 2019 – Solco Healthcare recalls irbesartan products due to NDEA

Jan. 23, 2019 – Torrent expands recall of losartan products again

Feb. 25, 2019 – Macleods Pharmaceuticals recalls losartan products due to NDEA

Feb. 28, 2019 – FDA updates interim limits for nitrosamine impurities in ARBs

March 1, 2019 – FDA issues press release updating public about contaminated ARB drugs; Aurobindo expands recall of valsartan-containing products; Torrent and Hetero expand recalls of losartan products

Valsartan, Losartan, and Irbesartan Cancer Lawsuits

While the FDA continues its investigation into contaminated products, patients who were exposed to the potentially cancer-causing chemicals NDMA, NDEA, and NMBA can take legal action against the manufacturers. Valsartan, Losartan, and Irbesartan lawsuits accuse the drug makers of manufacturing a defective products and failing to warn about their risks.

Patients who took valsartan have already begun filing lawsuits against the various manufacturers and asking to centralize their claims in the U.S. District Court of New Jersey. U.S. District Court Judge Freda Wolfson is the plaintiffs’ preferred judge. Judge Wolfson is currently overseeing the multidistrict litigation involving talcum powder claimants.

If you or a loved one took a valsartan, losartan, or irbesartan product that was recalled due to contamination, you may be entitled to financial compensation. Call Schmidt National Law Group today at 1-800-631-5656 to see if you qualify for a lawsuit, or visit nationalinjuryadvocates.com to file a claim now.

Sources

FDA news release. “FDA announces voluntary recall of several medicines containing valsartan following detection of an impurity.” Published July 2018. Access March 2019: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm613532.htm

FDA. “Losartan products under recall.” Updated March 2019. Accessed March 2019: https://www.fda.gov/downloads/Drugs/DrugSafety/UCM628993.pdf

FDA. “Irbesartan products under recall.” Updated February 2019. Accessed March 2019: https://www.fda.gov/downloads/Drugs/DrugSafety/UCM629626.pdf

FDA. “Valsartan products under recall.” Updated March 2019. Accessed March 2019:https://www.fda.gov/downloads/Drugs/DrugSafety/UCM615703.pdf

FDA news release. “FDA provides update on its ongoing investigation into ARB drug products; reports on finding of a new nitrosamine impurity in certain lots of losartan and product recall.” Published March 2019. Accessed March 2019:https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm632425.htm?utm_campaign=030119_PR_FDA%20update%20on%20investigation%20into%20ARB%20drugs%3B%20new%20losartan%20recall&utm_medium=email&utm_source=Eloqua

FDA news release. “FDA updates on angiotensin II receptor blocker (ARB) recalls including valsartan, losartan and irbesartan.” Updated March 2019. Accessed March 2019:https://www.fda.gov/Drugs/DrugSafety/ucm613916.htm

CNN. “Valsartan recall: 4 things patients should know.” By Jacqueline Howard. Published November 2018. Accessed March 2019:
https://www.cnn.com/2018/07/19/health/valsartan-recall-explainer/index.html

FDA news release. “FDA warns API manufacturer involved in valsartan recall, provides information for patients taking these medications.” Published December 2018. Accessed March 2019: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm628189.htm