FDA News

Valsartan recalls continue as new impurity detected

The FDA announced that more recalls of several drug products containing the active ingredient valsartan, commonly used to treat high BP and HF, are taking place, and that a second impurity was found in some products.

The initial recalls were due to an impurity, N-nitrosodimethylamine (NDMA), which was found in the products being recalled. NDMA is classified as a probable human carcinogen based on laboratory test results. The presence of NDMA was unexpected and is believed to be related to changes in the way the active substance was manufactured, according to the FDA press release.

In September, the FDA announced a second impurity, N-Nitrosodiethylamine, was found in two companies’ valsartan products. 

The FDA issued an update on Sept. 13 on the agency’s investigation of the drugs in the recall and reported that three lots of recalled products by Torrent Pharmaceuticals have an additional impurity, N-Nitrosodiethylamine, which is a suspected human carcinogen. Some valsartan products by Zhejiang Huahai Pharmaceuticals also have the newfound impurity, although not all of their products contain it, according to the agency.

“As we continue to investigate the root cause of the impurities found in products that contain valsartan, our scientists are testing these products to better understand these impurities and to ensure they’re not present in other products,” FDA Commissioner Scott Gottlieb, MD, said in an email from the agency. “We’re also taking steps to make sure we’re providing stringent oversight of manufacturing processes to reduce the likelihood that impurities could be introduced into other products.”

The FDA continues to test all products for N-Nitrosodiethylamine and related impurities, and plans to work with companies that produce products with the impurities to ensure that the products are removed from the market, according to the Sept. 13 update.

In an FDA update on July 27, the agency notes that amounts of NDMA found in recalled batches of valsartan exceed acceptable levels. According to estimates from FDA scientists, if 8,000 people took the highest valsartan dose (320 mg) from the recalled batches daily for 4 years, there may be one additional case of cancer over the lifetimes of these 8,000 people. This assessment led to the FDA’s decision to recall batches.

Since the initial recall announcement on July 13, the recall has expanded to include five manufacturers and other companies that repackage these products under a different name. The FDA states that more products may need to be recalled.

The following are under recall, as of  Nov. 27:

  • ·valsartan products by Teva Pharmaceuticals labeled as Major Pharmaceuticals;
  • ·valsartan products by Prinston Pharmaceutical Inc. labeled as Solco Healthcare LLC;
  • ·valsartan products by Teva Pharmaceuticals USA labeled as Actavis;
  • ·vasartan products by AvKARE (Teva/Actavis);
  • ·valsartan products by RemedyRepack Inc. (Prinston/Solco);
  • ·valsartan products by A-S Medication Solutions LLC (Teva/Actavis and Prinston/Solco);
  • ·valsartan products by Bryant Ranch Prepack Inc. (Teva/Actavis);
  • ·valsartan products by H J Harkins Company Inc. dba Pharma Pac (Prinston/Solco);
  • ·valsartan products by Northwind Pharmaceuticals (Teva/Actavis);
  • ·valsartan products by Hetero Labs, Inc labeled as Camber Pharmaceuticals Inc.;
  • ·valsartan products by NuCare Pharmaceuticals Inc. (Prinston/Solco);
  • ·valsartan products by RemedyRepack Inc. (Hetero/Camber);
  • ·valsartan products by AvKARE (Hetero/Camber);
  • ·valsartan products by Preferred Pharmaceuticals Inc. (Hetero/Camber);
  • ·valsartan products by Torrent Pharmaceuticals Limited;
  • ·valsartan products by RemedyRePack Inc. (Torrent); 
  • ·valsartan, amlodipine/valsartan and hydrochlorothiazide/valsartan products by Mylan Pharmaceuticals; and
  • ·amlodipine/valsartan and amlodipine/valsartan/hydrochlorothiazide products by Teva Pharmaceuticals.
  • valsartan, amlodipine/valsartan and hydrochlorothiazide/valsartan products by Aurobindo Pharma USA Inc.
  • valsartan products by American Health Packaging

The companies above are recalling all lots of nonexpired products containing the ingredient valsartan supplied by a third party. The supplier has stopped distributing its valsartan active pharmaceutical ingredient, according to the release. Specific product information, lot numbers and expiration dates can be found on the FDA website.

However, the FDA notes that not all products containing valsartan are affected by the recall.

The review is ongoing and the FDA is investigating levels of NDMA in the recalled products, possible effects on patients who have taken this medicines and measures to reduce or eliminate the impurity from future batches produced by the company.

To determine whether a specific product has been recalled, the FDA advises that patients look at the drug name and company on the label of their prescription bottle or contact the pharmacy that dispensed the medicine. Additionally, the FDA notes that patients taking the recalled valsartan-containing medicines should continue to take their medicine until they have a replacement product. Patients should also contact their health care professional who dispensed or prescribed the medication to discuss their treatment options, if affected by the recall.

“The FDA is working to make certain that patients have access to the treatment they need. Currently, more than half of all valsartan products on the market are being recalled. But prescribers can find a similar replacement product within the same class to substitute for patients who require this medication,” according to the statement.

On Aug. 30, the FDA issued a statement from Gottlieb and Janet Woodcock, MD, director of the Center for Drug Evaluation and Research, on its ongoing investigation into the impurities and recalls.

“The FDA currently has a major operation underway to investigate and address this troubling finding,” Gottlieb and Woodcock said in the statement. “This investigation is led by a dedicated task force of experts focused solely on this important work. Their mandate is to oversee the investigation and track new developments and information coming in from valsartan manufacturers. This multidisciplinary team of chemists, toxicologists, medical doctors, pharmacists, investigators, communication specialists and analytical lab staff coordinates across the FDA and acts on the newest available information.”

Mylan N.V. announced on Nov. 20 that Mylan Pharmaceuticals will be conducting a voluntary nationwide recall on select lots of products that contain valsartan, as they may have trace amounts of N-Nitrosodiethylamine:

  • Six lots of amlodipine and valsartan tablets, which include doses of 5 mg/160 mg, 10 mg/16 0mg and 10 mg/320 mg
  • Seven lots of valsartan tablets, which include 40 mg, 80 mg, 160 mg and 320 mg strengths
  • Two lots of valsartan and hydrochlorothiazide tablets, at the 320mg/25mg strength.

These batches were distributed in the U.S. between March 2017 and November 2018, according to an announcement from the company. Mylan has sent a letter to distributors and customers to arrange a return of the recalled products.

On Dec. 4, Mylan announced that its recall expanded to include all lots of products containing valsartan within expiry, for a total of 104 additional lots. The products include amlodipine/valsartan and hydrochlorothiazide/valsartan combinations.

On Nov. 27, Teva Pharmaceuticals announced that it has initiated a voluntary recall of all amlodipine/valsartan combination tablets and amlodipine/valsartan/hydrochlorothiazide combination tablets, as they may contain the impurity N-nitroso-diethylamine that was found in medications produced by Mylan India. The company has not received any reports of adverse events that are associated with valsartan, according to an announcement from the company.

The company has notified its customers and distributers by certified mail and is currently organizing a return/reimbursement of recalled products that are returned. Retailers and distributors who possess the recalled product are advised to stop distribution immediately and return the recalled product to the company. Affected lots, product descriptions and expiration dates can be found on the FDA website.

On Dec. 31, 2018, Aurobindo Pharma USA announced that it has voluntarily recalled 80 lots of the following tablets due to trace amounts of NDEA: Valsartan/hydrochlorothiazide tablets, amlodipine/valsartan tablets and valsartan tablets.

The company has not received any reports of adverse events related to the impurity, according to an alert from the FDA. Patients taking any of the affected tablets are recommended to continue taking the medication, as the risk for harm may be higher if the therapy is stopped immediately. The company advises patients to contact their physician or pharmacist to discuss alternative treatment options. Affected product descriptions, lots and expiration dates can be found on the FDA website.

On March 1, 2019, the voluntary recall by Aurobindo Pharma USA was expanded to 38 additional lots of valsartan and amlodipine tablets and valsartan tablets. Information on the affected products can be found on the FDA website.

On March 7, 2019, American Health Packaging voluntarily recalled one lot of 160 mg tablets of valsartan due to trace amounts of NDA. This recall is in response to a recall by the manufacturer, Aurobindo Pharma USA, according to an alert from the FDA.

The recalled lot (No. 179791, NDC: 60687-139-11) was a 100-count unit dose blisters of valsartan tablets that expire on March 31, 2020. No adverse events or injury have been reported, but patients should continue their treatment and contact their physician or pharmacist for options for alternative treatment, according to the alert.

American Health Packaging sent a recall letter on March 6, 2019 to instruct their distributors to stop distributing the affect lot immediately and inform their subaccounts. All recalled lots should be returned to Genco Pharmaceutical Services, as instructed in the letter.

Disclosures: Gottlieb is FDA Commissioner. Woodcock is an employee of the FDA.

Editor’s note: This article was updated on Aug. 31, 2018 to incorporate a statement from the FDA on the agency’s ongoing investigation into valsartan impurities; on Sept. 14, 2018 to add an update about the additional impurity; on Nov. 21, 2018 to add information from Mylan Pharmaceuticals; on Nov. 27, 2018 to add information from Teva Pharmaceuticals; and again on Dec. 7, 2018 to add additional information from Mylan Pharmaceuticals; on Jan. 2, 2019 and March 1, 2019 to add information from Aurobindo Pharma USA; and again on March 11, 2019 to add information from American Health Packaging.

The FDA announced that more recalls of several drug products containing the active ingredient valsartan, commonly used to treat high BP and HF, are taking place, and that a second impurity was found in some products.

The initial recalls were due to an impurity, N-nitrosodimethylamine (NDMA), which was found in the products being recalled. NDMA is classified as a probable human carcinogen based on laboratory test results. The presence of NDMA was unexpected and is believed to be related to changes in the way the active substance was manufactured, according to the FDA press release.

In September, the FDA announced a second impurity, N-Nitrosodiethylamine, was found in two companies’ valsartan products. 

The FDA issued an update on Sept. 13 on the agency’s investigation of the drugs in the recall and reported that three lots of recalled products by Torrent Pharmaceuticals have an additional impurity, N-Nitrosodiethylamine, which is a suspected human carcinogen. Some valsartan products by Zhejiang Huahai Pharmaceuticals also have the newfound impurity, although not all of their products contain it, according to the agency.

“As we continue to investigate the root cause of the impurities found in products that contain valsartan, our scientists are testing these products to better understand these impurities and to ensure they’re not present in other products,” FDA Commissioner Scott Gottlieb, MD, said in an email from the agency. “We’re also taking steps to make sure we’re providing stringent oversight of manufacturing processes to reduce the likelihood that impurities could be introduced into other products.”

The FDA continues to test all products for N-Nitrosodiethylamine and related impurities, and plans to work with companies that produce products with the impurities to ensure that the products are removed from the market, according to the Sept. 13 update.

In an FDA update on July 27, the agency notes that amounts of NDMA found in recalled batches of valsartan exceed acceptable levels. According to estimates from FDA scientists, if 8,000 people took the highest valsartan dose (320 mg) from the recalled batches daily for 4 years, there may be one additional case of cancer over the lifetimes of these 8,000 people. This assessment led to the FDA’s decision to recall batches.

Since the initial recall announcement on July 13, the recall has expanded to include five manufacturers and other companies that repackage these products under a different name. The FDA states that more products may need to be recalled.

The following are under recall, as of  Nov. 27:

  • ·valsartan products by Teva Pharmaceuticals labeled as Major Pharmaceuticals;
  • ·valsartan products by Prinston Pharmaceutical Inc. labeled as Solco Healthcare LLC;
  • ·valsartan products by Teva Pharmaceuticals USA labeled as Actavis;
  • ·vasartan products by AvKARE (Teva/Actavis);
  • ·valsartan products by RemedyRepack Inc. (Prinston/Solco);
  • ·valsartan products by A-S Medication Solutions LLC (Teva/Actavis and Prinston/Solco);
  • ·valsartan products by Bryant Ranch Prepack Inc. (Teva/Actavis);
  • ·valsartan products by H J Harkins Company Inc. dba Pharma Pac (Prinston/Solco);
  • ·valsartan products by Northwind Pharmaceuticals (Teva/Actavis);
  • ·valsartan products by Hetero Labs, Inc labeled as Camber Pharmaceuticals Inc.;
  • ·valsartan products by NuCare Pharmaceuticals Inc. (Prinston/Solco);
  • ·valsartan products by RemedyRepack Inc. (Hetero/Camber);
  • ·valsartan products by AvKARE (Hetero/Camber);
  • ·valsartan products by Preferred Pharmaceuticals Inc. (Hetero/Camber);
  • ·valsartan products by Torrent Pharmaceuticals Limited;
  • ·valsartan products by RemedyRePack Inc. (Torrent); 
  • ·valsartan, amlodipine/valsartan and hydrochlorothiazide/valsartan products by Mylan Pharmaceuticals; and
  • ·amlodipine/valsartan and amlodipine/valsartan/hydrochlorothiazide products by Teva Pharmaceuticals.
  • valsartan, amlodipine/valsartan and hydrochlorothiazide/valsartan products by Aurobindo Pharma USA Inc.
  • valsartan products by American Health Packaging

The companies above are recalling all lots of nonexpired products containing the ingredient valsartan supplied by a third party. The supplier has stopped distributing its valsartan active pharmaceutical ingredient, according to the release. Specific product information, lot numbers and expiration dates can be found on the FDA website.

However, the FDA notes that not all products containing valsartan are affected by the recall.

The review is ongoing and the FDA is investigating levels of NDMA in the recalled products, possible effects on patients who have taken this medicines and measures to reduce or eliminate the impurity from future batches produced by the company.

To determine whether a specific product has been recalled, the FDA advises that patients look at the drug name and company on the label of their prescription bottle or contact the pharmacy that dispensed the medicine. Additionally, the FDA notes that patients taking the recalled valsartan-containing medicines should continue to take their medicine until they have a replacement product. Patients should also contact their health care professional who dispensed or prescribed the medication to discuss their treatment options, if affected by the recall.

“The FDA is working to make certain that patients have access to the treatment they need. Currently, more than half of all valsartan products on the market are being recalled. But prescribers can find a similar replacement product within the same class to substitute for patients who require this medication,” according to the statement.

On Aug. 30, the FDA issued a statement from Gottlieb and Janet Woodcock, MD, director of the Center for Drug Evaluation and Research, on its ongoing investigation into the impurities and recalls.

“The FDA currently has a major operation underway to investigate and address this troubling finding,” Gottlieb and Woodcock said in the statement. “This investigation is led by a dedicated task force of experts focused solely on this important work. Their mandate is to oversee the investigation and track new developments and information coming in from valsartan manufacturers. This multidisciplinary team of chemists, toxicologists, medical doctors, pharmacists, investigators, communication specialists and analytical lab staff coordinates across the FDA and acts on the newest available information.”

Mylan N.V. announced on Nov. 20 that Mylan Pharmaceuticals will be conducting a voluntary nationwide recall on select lots of products that contain valsartan, as they may have trace amounts of N-Nitrosodiethylamine:

  • Six lots of amlodipine and valsartan tablets, which include doses of 5 mg/160 mg, 10 mg/16 0mg and 10 mg/320 mg
  • Seven lots of valsartan tablets, which include 40 mg, 80 mg, 160 mg and 320 mg strengths
  • Two lots of valsartan and hydrochlorothiazide tablets, at the 320mg/25mg strength.

These batches were distributed in the U.S. between March 2017 and November 2018, according to an announcement from the company. Mylan has sent a letter to distributors and customers to arrange a return of the recalled products.

On Dec. 4, Mylan announced that its recall expanded to include all lots of products containing valsartan within expiry, for a total of 104 additional lots. The products include amlodipine/valsartan and hydrochlorothiazide/valsartan combinations.

On Nov. 27, Teva Pharmaceuticals announced that it has initiated a voluntary recall of all amlodipine/valsartan combination tablets and amlodipine/valsartan/hydrochlorothiazide combination tablets, as they may contain the impurity N-nitroso-diethylamine that was found in medications produced by Mylan India. The company has not received any reports of adverse events that are associated with valsartan, according to an announcement from the company.

The company has notified its customers and distributers by certified mail and is currently organizing a return/reimbursement of recalled products that are returned. Retailers and distributors who possess the recalled product are advised to stop distribution immediately and return the recalled product to the company. Affected lots, product descriptions and expiration dates can be found on the FDA website.

On Dec. 31, 2018, Aurobindo Pharma USA announced that it has voluntarily recalled 80 lots of the following tablets due to trace amounts of NDEA: Valsartan/hydrochlorothiazide tablets, amlodipine/valsartan tablets and valsartan tablets.

The company has not received any reports of adverse events related to the impurity, according to an alert from the FDA. Patients taking any of the affected tablets are recommended to continue taking the medication, as the risk for harm may be higher if the therapy is stopped immediately. The company advises patients to contact their physician or pharmacist to discuss alternative treatment options. Affected product descriptions, lots and expiration dates can be found on the FDA website.

On March 1, 2019, the voluntary recall by Aurobindo Pharma USA was expanded to 38 additional lots of valsartan and amlodipine tablets and valsartan tablets. Information on the affected products can be found on the FDA website.

On March 7, 2019, American Health Packaging voluntarily recalled one lot of 160 mg tablets of valsartan due to trace amounts of NDA. This recall is in response to a recall by the manufacturer, Aurobindo Pharma USA, according to an alert from the FDA.

The recalled lot (No. 179791, NDC: 60687-139-11) was a 100-count unit dose blisters of valsartan tablets that expire on March 31, 2020. No adverse events or injury have been reported, but patients should continue their treatment and contact their physician or pharmacist for options for alternative treatment, according to the alert.

American Health Packaging sent a recall letter on March 6, 2019 to instruct their distributors to stop distributing the affect lot immediately and inform their subaccounts. All recalled lots should be returned to Genco Pharmaceutical Services, as instructed in the letter.

Disclosures: Gottlieb is FDA Commissioner. Woodcock is an employee of the FDA.

Editor’s note: This article was updated on Aug. 31, 2018 to incorporate a statement from the FDA on the agency’s ongoing investigation into valsartan impurities; on Sept. 14, 2018 to add an update about the additional impurity; on Nov. 21, 2018 to add information from Mylan Pharmaceuticals; on Nov. 27, 2018 to add information from Teva Pharmaceuticals; and again on Dec. 7, 2018 to add additional information from Mylan Pharmaceuticals; on Jan. 2, 2019 and March 1, 2019 to add information from Aurobindo Pharma USA; and again on March 11, 2019 to add information from American Health Packaging.