Blood Pressure Medication Recall 2019

Even more recalls for blood pressure medications.

Updated June 27, 2019, with new recall lots.

An online pharmacy told U.S. regulators it found another cancer-causing chemical in widely prescribed blood-pressure pills, raising new questions about a complex global web of companies that produces medicine for millions of people.

A solvent called dimethylformamide was discovered in the drug valsartan made by several companies, including Swiss pharmaceutical giant Novartis, according to a filing last week to the Food and Drug Administration by New Haven, Connecticut-based Valisure.

DMF, as the solvent is known, is classified by the World Health Organization as a probable carcinogen.

Dozens of forms of generic valsartan have been recalled since July 2018, when the carcinogenic chemical N-Nitrosodimethylamine, or NDMA, was detected in a version of the drug made by a Chinese company. Valsartan is a decades-old treatment for hypertension that is frequently combined with other medicines into a single pill.

In late June, Macleods Pharmaceuticals Limited announced a new recall because of trace amounts of NMBA, N-Nitroso-N-methyl-4-aminobutyric acid, which carries a risk of cancer.

List of medications under recall below.

When drugs are made, the initial raw materials may need to change form before they go into a pill. To break them down, a solvent like DMF may be used, but it's supposed to largely vanish by the time a pill is put into a bottle for sale. DMF is cheaper than some other solvents, making it appealing for companies coping with the bruising economics of the generic-drug business.

The FDA allows drugs to contain the equivalent of about 8.8 million nanograms of daily exposure to DMF. The agency last revised its allowable solvent levels in 2017; the WHO classified DMF as a probable carcinogen in 2018.

Valisure found DMF in valsartan made by five of the six drugmakers it tested, including Novartis, which makes the brand-name version called Diovan. That drug was first approved in the U.S. in 1996. Diovan's DMF levels were among the lowest that tested positive.

Novartis doesn't use DMF in making Diovan and documents provided by suppliers it purchases ingredients from indicate that they don't, either, said spokesman Althoff. But companies that its suppliers buy from could.

Those suppliers provide components including inactive ingredients, of which Diovan has about eight. The FDA regulates those less stringently than the active ingredients that fight disease. The focus surrounding valsartan has been on the active ingredient, largely supplied to the companies under recall by Zhejiang Huahai Pharmaceutical Co. in China and Hetero Labs in India.

Lawyers for plaintiffs, including 34 people and insurers that paid for contaminated drugs, filed a class-action complaint Monday claiming that Zhejiang Huahai's actions constitute "an explicit effort to conceal and destroy evidence and to willfully and recklessly introduce adulterated and/or misbranded" valsartan into the market. A Bloomberg News investigation this year detailed efforts at the company to manipulate data and ignore warning signs that their drugs didn't meet U.S. standards.

Plaintiffs' attorneys also filed a separate class-action complaint on behalf of patients who took contaminated valsartan and are seeking payment for medical monitoring for everyone who took the tainted drugs.

NDMA cancer risk

For every 8,000 people who took the highest dose of valsartan contaminated with NDMA, there would be one additional case of cancer, the FDA has estimated. In standalone and combined forms, valsartan has been a go-to therapy for cardiovascular issues for a generation.

Some of the valsartan that was positive for DMF was on a list of medicines the FDA had earlier deemed safe to use amid the recalls, including drugs manufactured by Alembic Pharmaceuticals Ltd. and Macleods Pharmaceuticals Ltd., both based in India.

Alembic doesn't use DMF in its manufacturing process, according to spokesman Ajay Desai, who said the contamination likely occurred during analysis. A representative for Macleods couldn't be reached for comment.

According to the assessments that it has posted online, the FDA hasn't yet screened valsartan that Valisure tested from Aurobindo Pharma Ltd., Lupin Ltd. and Novartis.

Representatives for Aurobindo and Lupin didn't respond to requests for comment.

See below for recalled medications.

Keep reading to find information about the earlier Teva recall and voluntary recalls by many other companies that make blood pressure medications.

On April 24, 2019, Legacy expanded its recall.

Legacy Pharmaceutical Packaging, LLC is recalling 40 repackaged lots of Losartan Tablets USP 25mg, 50mg, and 100mg to the consumer level. This recall was prompted due to Camber Pharmaceuticals, Inc. issuing a Voluntary Nationwide Recall of Losartan Tablets, USP, due to the detection of trace amounts of N-Nitroso N-Methyl 4-amino butyric acid (NMBA) a possible process impurity or contaminant in an active pharmaceutical ingredient, manufactured by Hetero Labs Limited, (API manufacturer).

They were distributed nationwide.

As of March 19, 2019, the Legacy Pharmaceutical Packaging recall was expanded, affecting 40 lots. According to fda.gov:

NMBA is a potential human carcinogen. To date, Legacy has not received any reports of adverse events related to this recall.

An expansion of the recall was announced March 19, 2019, on fda.gov:

NMBA is a potential human carcinogen. To date, Legacy has not received any reports of adverse events related to this recall.

As of March 15, 2019, according to fda.gov:

Legacy Pharmaceutical Packaging, LLC is recalling 3 repackaged lots of Losartan Tablets USP 50mg to the consumer level. This recall was prompted due to Torrent Pharmaceuticals LTD issuing a Voluntary Nationwide Recall of Losartan Tablets, USP, due to the detection of trace amounts of N-Nitroso N-Methyl 4-amino butyric acid (NMBA) a possible process impurity or contaminant in an active pharmaceutical ingredient, manufactured by Hetero Labs Limited, (API manufacturer).

NMBA is a potential human carcinogen. To date, Legacy has not received any reports of adverse events related to this recall.

American Health Packaging

American Health Packaging added to the list of recalls on March 7, 2019.

Valsartan Tablets USP 160 mg, 100 count Unit Dose Blisters
Carton NDC#: 60687-139-01
(Individual Dose NDC: 60687-139-11)

Camber said in a statement on Thursday that it was recalling 87 lots of losartan tablets due to the discovery. The company said it hadn't received any reports of patients being harmed related to the recall. Kirk Hessels, a spokesman for Camber, didn't immediately respond to requests for comment on Friday.

Problems with potential cancer-causing agents in blood-pressure medications first cropped up in July, when an ARB called valsartan was recalled by Chinese drugmaker Zhejiang Huahai Pharmaceutical Co.

A Bloomberg investigation found that an FDA inspector had raised concerns at the factory that made the valsartan in May 2017. The official had recommended Zhejiang Huahai, one of China's largest exporters of pharmaceuticals, receive a warning from the agency, but was overruled by higher-ups at the FDA. Zhejiang Huahai has said it has been in close contact with the FDA since the recall began.

The FDA has said it thinks the potential carcinogens, known as nitrosamine impurities, are a result of the manufacturing processes the companies used. The agency said that the risk of a patient who took a recalled ARB getting cancer is low.

-- Bloomberg News

AurobindoPharma USA Inc.

As of March 1, 2019, AurobindoPharmaUSA expanded its voluntary recall.

Camber Pharmaceuticals Inc.

According to fda.gov:

Camber Pharmaceuticals, Inc. is recalling 87 lots of Losartan Tablets USP 25 mg, 50 mg, and 100 mg to consumer level. This recall was prompted due to the detection of trace amounts of N-Nitroso N-Methyl 4-amino butyric acid (NMBA) a possible process impurity or contaminant in an active pharmaceutical ingredient, manufactured by Hetero Labs Limited, Unit – I (API manufacturer).

NMBA is a potential human carcinogen. To date, Camber has not received any reports of adverse events related to this recall.

Macleods Pharmaceuticals Limited

According to fda.gov, as of Feb. 22, 2019:

Macleods Pharmaceuticals Limited is voluntarily recalling one lot of Losartan Potassium/Hydrochlorothiazide combination tablets 100mg/25mg to the consumer level due to the detection of trace amounts of an unexpected impurity (NDEA) found in finished product manufactured with active pharmaceutical ingredient made by Hetero Labs Limited.

Torrent Pharmaceuticals Limited

On Jan. 22, 2019, Torrent Pharmaceuticals Limited expanded its voluntary recall to include 6 lots of Losartan potassium and hydrochlorothiazide tablets, USP. See below for previous Torrent recalls of other blood pressure medications.

An FDA statement Friday disclosed that the contaminants, called N-Nitrosodimethylamine and N-Nitrosodiethylamine, are created when "specific chemicals and reaction conditions are present . . . and may also result from the reuse of materials, such as solvents." The agency said those byproducts would not have been detected in routine inspections because the process depends on scientists knowing which chemical intruders are likely to be accidentally created during the process, knowledge that they said regulators and companies lacked until recently.

The agency has downplayed the public health risks of the contamination, pointing out that if 8,000 people took the highest dose of one drug, valsartan, for four years, there could be one additional case of cancer. The carcinogens are found in smoked and grilled meats. But the official limit considered "safe" for human consumption brings a much lower risk than the possible exposure from tainted drugs - causing less than one additional case of cancer in 100,000 people over a lifetime.

-- The Washington Post

Valsartan has been in shortage since August, and the agency warned in its statement that "other types of products may fall into shortage soon," without offering any specifics. The agency is urging patients to continue taking their medications until a pharmacist or doctor provides another option because they need to balance the risks of out-of-control blood pressure against that of a tiny elevated risk of cancer.

An FDA spokeswoman said the investigation continues and it is impossible to predict how many more recalls there might be. She said that drug manufacturers will continue to test their products and recall pills that contain impurities over an interim limit the FDA established to make sure patients can continue to have access to the medications in the short term.

-- The Washington Post

Torrent Pharmaceuticals Limited

On Jan. 3, 2019, Torrent Pharmaceuticals Limited expanded its voluntary recall from 2 lots of Losartan potassium tablets USP to a total of 10 lots, according to fda.gov. Here are the 10 lots.

Prinston Pharmaceutical Inc., dba Solco Healthcare LLC

On Jan. 18, 2019, Prinston Pharmaceutical Inc., dba Solco Healthcare LLC., initiated a voluntary recall of one (1) lot of Irbesartan and seven (7) lots of Irbesartan HCTZ Tablets used to treat blood pressure. Fda.gov said the recall was due to t to the detection of trace amount of an unexpected impurity.

Aurobindo Pharma USA, Inc

According to fda.gov:

Aurobindo Pharma USA, Inc. is conducting a voluntary recall of 80 lots of Amlodipine Valsartan Tablets USP, Valsartan HCTZ Tablets, USP and Valsartan Tablets USP to the consumer level due to the detection of trace amounts of an unexpected impurity found in the finished drug product. The impurity detected in the finished drug product is N-nitrosodiethylamine, which is has been classified as a probable human carcinogen.

The government site also says the risks of going off the medication may be greater than the risk of taking it so patients should not stop but should contact their health care provider or pharmacist for guidance.

Torrent Pharmaceuticals Limited

Torrent Pharmaceuticals Limited recalled two lots of Losartan potassium tablets, USP because of trace amounts of N-nitrosodiethylamine (NDEA), which is a probable human carcinogen. See above for additional recalls by Torrent.

A week after two more blood pressure drugs were recalled because they have a possible cancer-causing ingredient, the U.S. based Mylan Pharmaceuticals expanded its consumer-level voluntary nationwide recall to include all lots of Valsartan-containing products within dates of expiration.

Some of the batches aren't due to expire until August 2020.

—The 104 additional lots include 26 lots of Amlodipine and Valsartan tablets, USP (including the 5mg/160mg, 10mg/160mg, 5mg/320mg and 10mg/320mg strengths).

—Also: 51 lots of Valsartan tablets, USP (including 40 mg, 80 mg, 160 mg and 320 mg strengths), and 27 lots of Valsartan and Hydrochlorothiazide tablets, USP (80mg/12.5mg, 160mg/12.5mg, 160mg/25mg, 320mg/12.5mg and 320mg/25mg strengths).

"Out of an abundance of caution, these products are being recalled due to detected trace amounts of an impurity, N-nitrosodiethylamine (NDEA) contained in the API Valsartan, USP, manufactured by Mylan Laboratories Limited," the Food and Drug Administration posted Tuesday.

According to the Food and Drug Administration, NDEA is a substance that occurs naturally in certain foods, drinking water, air pollution, and industrial processes. NDEA has been classified as a "probable human carcinogen" according to the International Agency for Research on Cancer.

The finished products are manufactured by Mylan Pharmaceuticals Inc. and Mylan Laboratories Limited. These batches were distributed domestically between March 2017 and November 2018.

The full list of expanded recalled batches can be viewed at https://www.fda.gov/Safety/Recalls/ucm627647.htm.

Late last month, Teva Pharmaceuticals pulled all lots of Amlodipine/Valsartan and Amlodipine/Valsartan/Hydrochlorothiazide combination tablets for the same reason: too much NDEA in its Valsartan, the active ingredient made by Mylan India.

In November, Mylan also recalled 15 heart attack and blood pressure medications and Sandoz recalled Losartan blood pressure meds.

In July, five medications of Valsartan/Hyrdrochlorothiazide blood pressure drugs manufactured by Major Pharmaceuticals, Teva Pharmaceuticals and Solco Healthcare were recalled.

According to the FDA, Valsartan is used for the treatment of high blood pressure and for the treatment of heart failure, and to reduce cardiovascular mortality following myocardial infarction.

Valsartan in combination with Amlodipine or Hydrochlorothiazide is used for the treatment of high blood pressure.

The recall suggests that patients who use these medications should contact their pharmacist or physician for advice on alternative treatment before returning their medication.

The voluntary recall was expanded in December by Mylan to all unexpired lots.

At the top of this list is the newly recalled lots. Following that is earlier Mylan recalls.

Lower in the list are the Teva Pharmaceuticals lots under voluntary recall, as posted at fda.gov.

-- Tribune Content Agency