Valsartan Lawsuit News and Updates

Valsartan Lawsuit Update: The Science Behind the Claims

March 20, 2024

The valsartan lawsuits regarding cancer that was caused by the consumption of contaminated drugs are going strong! Judge Kugler, who presides over the national valsartan lawsuits had initially scheduled the first valsartan trial to begin now (the third week of March, 2024). However, last week the first valsartan trial was postponed due to an illness within the court. At this time, it is unknown when the first valsartan lawsuit will actually go to trial. The first valsartan trial could still happen in a few weeks, or this could be a several month delay on the first valsartan trial. Regardless, our valsartan attorneys are fully prepared for trial and continue to refine their valsartan trial strategy!

   First Valsartan Trial   

The valsartan MDL 2875 is composed of many different types of valsartan lawsuits. The valsartan lawsuits within MDL 2875 include individual personal injury claims for those who were injured by consuming contaminated valsartan and subsequently developing cancer, a class action for the individuals who paid for contaminated valsartan and want their money back, and a third-party payor (TPP) claim for insurance companies that paid for contaminated valsartan.

The judge over the valsartan lawsuits decided that the first valsartan lawsuit to go to trial would be the class action for third-party payor (TPP) claim for insurance companies that paid for the contaminated valsartan. There can be numerous benefits to the litigation as a whole by having the first valsartan lawsuit trial be for the money that insurance companies paid for the contaminated valsartan. For instance, specific causation that would have to be proven in a valsartan personal injury case (that the consumption of contaminated valsartan caused a specific person's cancer) does not have to be proven in a third-party payor valsartan lawsuit, which is just about getting money back for paying for contaminated drugs. Furthermore, many rulings in the third-party payor valsartan trial will apply to future trials, such as the cancer personal injury valsartan cases. The rulings that will apply to future valsartan trials include decisions regarding valsartan expert admissibility and potentially even issue preclusion on key aspects of the case, such as was the valsartan sold "adulterated".

April 28, 2023
Author: Daniel Gala
Despite nearly five years having passed since the first valsartan recalls were announced in July 2018, there continues to be much controversy over the severity of the danger posed by the contaminated blood-pressure medication. Have individuals been exposed on a daily basis to a powerful carcinogen in concentrations sufficient to cause their risk of cancer to skyrocket? Or has their exposure merely been the equivalent of, say, eating a single slice of bacon at breakfast each morning? The outcome of hundreds of valsartan-related lawsuits—and the course of thousands if not millions of lives—hinges on the answer to these questions.   

In this article, we will take a step back from the legal proceedings involving the valsartan lawsuits and the related drugs losartan and irbesartan to take a closer look at the science behind the litigation.     

The Valsartan Recalls   

In July 2018, the United States Food and Drug Administration (FDA) announced a recall of generic valsartan, a widely used medication for high blood pressure and heart failure. At the time, the FDA explained that the recall was “due to an impurity…which was found in the recalled products.”   

That impurity—nitrosodimethylamine, or NDMA—is, the FDA explained in its news release, “classified as a probable human carcinogen (a substance that could cause cancer).”   

Complicating the matter further was the essential nature of the medication being recalled. “Because valsartan is used in medicines that treat serious medical conditions, patients taking the recalled valsartan-containing medicines should continue taking their medicine until they have a replacement product,” the FDA advised at the time, forcing patients to make the impossible choice between taking a medicine they knew to be unsafe or facing the health consequences of not taking it.     

FDA Downplays the Risk   

In the weeks and months that followed, the scope of the recalls would expand greatly as NDMA and other carcinogenic contaminants were detected in additional batches of valsartan and the related drugs losartan and irbesartan. Even as the scale of the crisis broadened, the FDA sought to downplay the severity of the situation, noting in a July 27, 2018 update that the associations between NDMA and cancer were based on “animal studies” that “were done using amounts of NDMA much higher than the impurity levels in recalled valsartan batches.” Further, the FDA emphasized that “NDMA is found in some water supplies and some foods,” implying that a certain level of exposure is unavoidable and even normal.   

Despite the July 27, 2018 update being titled, “Analysis of [NDMA] Levels in Recalled Valsartan in the US,” it is not until deep in the third paragraph that the FDA drops the bombshell news that “FDA scientists estimate that if 8,000 people took the highest valsartan dose (320 mg) from the recalled batches daily for the full four years [during which the contamination was thought to have taken place], there may be one additional case of cancer over the lifetimes of those 8,000 people.” While the July 27 FDA update did not reveal the exact levels of NDMA detected in the recalled valsartan, it did offer this point of comparison: Consuming up to 96 nanograms of NDMA per day is considered safe for human health. At these levels, NDMA exposure is estimated to result in one case of cancer per 100,000 people.   

While the FDA’s figures, and those presented by other health agencies around the globe, were meant to minimize the perceived cancer risk, the impact becomes more significant when one considers the many millions of people taking valsartan and the other recalled angiotensin II receptor blockers (ARBs), losartan and irbesartan. According to Chemical & Engineering News, in 2017, approximately 1.8 million people took valsartan globally. At one case of cancer per 8,000 people, this would mean 225 additional cancer cases due to NDMA contamination of valsartan alone. Add into this the global figures for losartan (10 million) and irbesartan (2.3 million), and that number jumps to 1,762 cases of cancer that would not have existed but for the contamination of approved medications.   

The FDA’s pattern of normalizing the carcinogenic contamination continued in the months following the initial recalls. On August 20, 2018, the agency issued the bizarrely titled update, “FDA updates valsartan-containing product information and presents NDMA levels in some foods.” As the name suggests, in addition to announcing the recall of additional lots of tainted valsartan, the update includes a list of the “Estimated Range of Daily NDMA Consumption for certain foods” including cured meat (0.004-0.23 micrograms), smoked meat (0.004-1.02 micrograms), grilled meat (0.006-0.13 micrograms), and bacon (0.07-0.09 micrograms), adding that “[i]n more ordinary terms, for example, one pound of bacon may contain 0.304-0.354 micrograms of NDMA.” However, without knowing the exact levels of NDMA contained in contaminated doses of valsartan, it is impossible to accurately compare apples to apples or, as the case may be, bacon to ARBs.   

Thankfully, Chemistry & Engineering News has provided the missing link for us, reporting based on the FDA’s own data that the highest levels of NDMA detected in a single dose of valsartan was 20.19 micrograms, a shocking 210 times the recommended daily limit of 0.096 micrograms. Put in the FDA’s terms, this means that a single dose of tainted valsartan contained as much as 5,000 times the NDMA found in the recommended daily intake of cured or smoked meat; 3,365 times the NDMA in grilled meat; and 66 times the amount of NDMA found in an entire pound of bacon.   

C. Michael White, Chair of the Department of Pharmacy Practice at the University of Connecticut School of Pharmacy, called attention to the problematic nature of the FDA’s culinary comparisons in a November 2019 editorial for the Annals of Pharmacotherapy titled, “Understanding and Preventing (N-Nitrosodimethylamine) NDMA Contamination of Medications.” White, C. Michael. (First published online 26 November 2019). Understanding and Preventing (N-Nitrosodimethylamine) NDMA Contamination of Medications. Annals of Pharmacotherapy.Referring to ranitidine (Zantac), another drug recalled for being tainted with NDMA, White wrote:   

“In a recent FDA statement, they write that the amount of NDMA found in ranitidine is in line with eating a large steak. Although I know they are trying to avoid panic, they should not be so dismissive of the nature of this issue either. A 1-kg steak has ~700 ng of NDMA, but few people eat that much steak and not on a chronic basis. The chronic use of ranitidine, with NDMA dosages of 560 to 860 ng/tablet, on top of other NDMA-contaminated medications and added to the basal NDMA exposure from food and water, does not seem to pose inconsequential risk, and if it did, the FDA would not be supporting product recalls.”     

  The Truth about NDMA   

In downplaying the potential risk posed by NDMA contamination, the FDA itself cites a technical fact sheet issued by the US Environmental Protection Agency (EPA) in November 2017. However, this fact sheet clearly offers a more grim portrayal of the risks of NDMA than is presented by the FDA, noting that NDMA was “[f]ormerly used in the production of rocket fuel, antioxidants, and softeners for copolymers” but is “[c]urrently used only for research purposes.”   

“NDMA is a drinking water contaminant of concern because of its miscibility [ability to mix] with water, as well as its carcinogenicity and toxicity,” the EPA fact sheet warns (italics added).   

In fact, the carcinogenic qualities of NDMA are well-established, with the EPA having classified the nitrosamine as “a B2 (probable human) carcinogen” and the US Department of Health and Human Services (DHHS) declaring that NDMA “is reasonably anticipated to be a human carcinogen.” Further, the International Agency for Research on Cancer (IARC), part of the World Health Organization, has classified NDMA as a Group 2A probable carcinogen. According to the April 2020 article in Chemical & Engineering News, “This means that there isn’t any direct evidence that the compound causes cancer in humans, but it’s likely that it does because it has caused cancer in animals.”   

Despite the lack of direct evidence that NDMA causes cancer in humans, largely due to the lack of research in this area, the evidence that NDMA produces cancer in animals is extremely well established. As the EPA fact sheet notes, “DHHS states that NDMA caused tumors in the numerous species of experimental animals, at several different tissues sites, and by several different routes of exposure. Tumors occurred primarily of the liver, respiratory tract, kidney and blood vessels.”   

A toxicological profile of NDMA prepared by the Agency for Toxic Substances and Disease Registry (ATSDR) goes even further, identifying a correlation between exposure to NDMA and cancer in humans.   

“In a study of occupational exposure to NDMA, associations between NDMA exposure and a number of cancer types (including gastric, liver, bladder, and prostate cancers, as well as leukemia and multiple myeloma) were reported,” the ATSDR’s profile says. “Epidemiological studies of general population exposure showed associations between dietary intake and cancers of the gastrointestinal tract, especially the stomach…and colon/rectum.”     

Despite the large amount of evidence showing a connection between NDMA and various forms of cancer in humans, there remains a pressing need for further study. For example, according to the ATSDR, “[n]o human studies examining the association between oral exposure to NDMA and liver cancer (the primary tumor type seen in laboratory animals exposed to NDMA) were located in the literature reviewed” for its toxicological profile.   

Despite the need for further research in humans, the ATSDR’s conclusion is unequivocal: “NDMA’s carcinogenicity is widely recognized,” citing such authorities as the International Agency for Research on Cancer (IARC), EPA, and DHSS.   

A great deal of scientific evidence also exists for the non-cancer health risks posed by NDMA exposure. These include documented cases of severe liver damage in humans and of developmental effects on unborn fetuses, including fetal or neonatal mortality, in animals.     

Perhaps most frustratingly, the dangers of NDMA have been well known for decades. “NDMA was initially recognized as a contaminant in foods, beverages, and rubber products more than 40 years ago,” the ATSDR says. “Since that time, producers and manufacturers have modified their processes and techniques to substantially reduce nitrosamine formation. Elimination of NDMA from these products has, however, proved difficult due [to] the abundance of NDMA precursors and the ease with which it is formed.”   

  Where Does NDMA Come From?   

Despite NDMA posing a variety of health risks to humans and animals and no longer having any productive uses, it unfortunately remains relatively widespread in our environment. This is because NDMA is the byproduct of a number of common chemical reactions, some of which have commercial applications. “Thus,” the ATSDR explains, “potential exists for release into the environment from industries such as tanneries, pesticide manufacturing plants, rubber and tire manufacture/use sites, fish processing industries, foundries and dye manufacturers.”   

Additionally, NDMA can be formed in low levels during chlorination of drinking water at water treatment facilities. This happens because NDMA “is readily formed when alkylamines (mainly di- and trimethylamine) come in contact and react with nitrogen oxides, nitrous acid, or nitrite salts.” For the same reason, NDMA can form in our body when we consume nitrites, such as can be found in some preserved and/or processed meats.   

  The Growing Prevalence of NDMA Contamination   

Valsartan was hardly the last medication found to be tainted with NDMA or other nitrosamines. On April 1, 2020, the FDA made the shocking announcement that it was requesting the removal of all Zantac and generic ranitidine from the US market after NDMA was detected in the blockbuster heartburn medication. Unlike the valsartan contamination, which was discovered to have resulted from faulty manufacturing practices, the NDMA in Zantac and generic ranitidine was determined to be caused by chemical changes to the drug itself. The ingredients in Zantac and generic ranitidine, under certain conditions, can undergo a chemical transformation that results in the formation of NDMA. This chemical reaction is more likely to take place when the medication is stored in conditions of high heat and humidity, and it also can occur as the drug is digested in the human stomach.   

In addition to valsartan (July 2018), irbesartan (September 2018), losartan (October 2018), and Zantac/ranitidine (April 2020), other drugs recalled over the presence of NDMA have included Nizatidine, another heartburn medication, which was recalled by its manufacturer Mylan in January 2020. Further, NDMA also has been detected in the diabetes medication metformin, a drug that is taken by nearly 16 million people globally.   

And that’s not all. In March 2022, drugmaker Sandoz, Inc. announced a nationwide recall of 13 lots of Orphenadrine Citrate—a medication used “for the relief of discomfort associated with acute painful musculoskeletal conditions”—citing nitrosamine contamination. That same month, Pfizer recalled several shipments of its own blood-pressure drug Accuretic along with some authorized generic versions, also over NDMA concerns.   

Experts point to multiple sources of NDMA contamination, “including side reactions from drug syntheses, the breakdown of unstable drug compounds, and contamination from recycled solvents used in manufacturing,” according to Chemical & Engineering News.   

Whether NDMA contamination is on the rise or whether expanded testing is revealing what always has been there is as yet unclear. What is certain is that something must be done to better ensure the safety of medications worldwide. The discovery of carcinogenic contaminants in drugs that were allowed to enter the US market has raised serious concerns about the FDA’s ability to properly oversee and regulate an increasingly global pharmaceutical supply chain. Such contamination not only exposes those taking the affected medications to serious health risks, the resulting recalls also can severely impact the availability and affordability of life-saving drugs.     

“The recalls have caused disruptions, especially for doctors and the tens of millions of people in the world who take the drugs to treat chronic illnesses,” reported Chemical & Engineering News (CEN), which further noted that losartan appears on the World Health Organization Model List of Essential Medicines.   

“These are patients that were stable on their medications,” Erin Michos, director of women’s cardiovascular health and associate professor of medicine at Johns Hopkins University, told CEN, referring to individuals who had been taking medications that were subsequently subject to recall due to NDMA contamination. “Suddenly, you’re switching their meds around, and now they have to kind of start over with trying to find the right dose.”   

The result can extend well beyond a single medication, with patients losing faith in the healthcare industry as a whole. “With this loss of trust between patients and their doctors and trust in the drug supply, it’s even harder to convince patients to take medications they need,” Michos added.     

Conclusion: What Can Be Done to Prevent NDMA Contamination?   

Regulators, drugmakers, distributors, pharmacies, and researchers all are working to determine what can be done to eliminate or at least severely reduce the amount of NDMA contamination being detected in medications around the world. C. Michael White—author of the 2019 editorial in the Annals of Pharmacotherapy—offers a few suggestions, most of which involve increased testing. First, White applauds pharmacy groups that have taken it upon themselves to test the purity of the drugs they sell “because it is clearly not being adequately assessed by manufacturers,” adding that “[s]uch testing should continue or even intensify.” Similarly, White says that manufacturers of finished drug products who obtain their active pharmaceutical ingredients (API) from a separate manufacturer should test that API prior to making it into capsules or tablets. Even drugs that already have reached the market should be routinely tested until they have reached their expiration date. Any batch found to have NDMA levels exceeding acceptable limits should be subject to recall.   

Further, White urges the FDA to be more aggressive in its approach, writing, “The FDA needs to move beyond reactively waiting until they are alerted to NDMA issues from outside groups and proactively alert manufacturers of ingredients, such as ranitidine, that have chemical structures prone to the creation of NDMA.” Along the same lines, White argues that more research should be conducted into the conditions under which such medications are more or less likely to form NDMA, looking particularly at factors such as temperature, exposure to light, and time since manufacture.   

One potential solution that White does not mention includes using the legal system to hold those who manufacture, distribute, and sell tainted medications accountable for the harms they cause. Unless they face a realistic threat of severe consequences, unscrupulous actors will continue to cut corners in order to save money, compromising patient safety to maximize profits. Using the courts to financially punish these individuals and companies for their negligence and/or wrongdoing acts as a strong disincentive for those who might consider engaging in similar practices, so long as the penalties are severe enough to counteract any fiscal gains to be made from noncompliance.       

  Sources:   

United States Food and Drug Administration (FDA). (13 July 2018). FDA announces voluntary recall of several medicines containing valsartan following detection of an impurity. FDA News Release.   

United States Food and Drug Administration (FDA). (20 August 2018). UPDATE – FDA updates recalled valsartan-containing product information and presents NDMA levels in some foods. FDA Updates and Press Announcements on Angiotensin II Receptor Blocker (ARB) Recalls (Valsartan, Losartan, and Irbesartan).   

United States Food and Drug Administration (FDA). (20 August 2018). UPDATE – FDA updates recalled valsartan-containing product information and presents NDMA levels in some foods. FDA Updates and Press Announcements on Angiotensin II Receptor Blocker (ARB) Recalls (Valsartan, Losartan, and Irbesartan).   

United States Environmental Protection Agency (EPA). (November 2017). Technical Fact Sheet – NDMA.   

Agency for Toxic Substances and Disease Registry (ATSDR). (January 2022). Toxicological Profile for N-Nitrosodimethylamine (NDMA).   

United States Food and Drug Administration (FDA). (1 April 2020). FDA Requests Removal of All Ranitidine Products (Zantac) from the Market. FDA News Release.   

Boerner, Leigh Krietsch. (20 April 2020). NDMA, a contaminant found in multiple drugs, has industry seeking sources and solutions. Chemical & Engineering News.   

Pfizer. (21 March 2022). Pfizer Voluntary Nationwide Recall of Lots of ACCURETIC (quinapril HCI/hydrochlorothiazide), quinapril and hydrochlorothiazide Tablets, and quinapril HCI/hydrochlorothiazide Tablets Due to N-Nitroso-Quinapril Content. Pfizer Newsroom.   

White, C. Michael. (First published online 26 November 2019). Understanding and Preventing (N-Nitrosodimethylamine) NDMA Contamination of Medications. Annals of Pharmacotherapy.