Receiving a cancer diagnosis is extremely difficult and often life-changing. Patients must put their faith in their doctors and the treatments they recommend. Unfortunately, some patients taking Tasigna have discovered that the treatments can sometimes cause additional health problems.
Tasigna (nilotinib) is prescribed to treat chronic myelogenous leukemia (CML), a cancer that affects the blood cells and bone marrow. Recent studies have linked it to an increased risk of atherosclerosis, or artery disease, caused by a buildup of fats and cholesterol, commonly referred to as “plaques”, on the artery walls. This causes the arteries to become thickened and hardened and to restrict blood flow.
Atherosclerosis a leading causes of heart attacks and strokes. In 2013, Health Canada and drug manufacturer Novartis released a public safety alert warning that Tasigna had been linked to cases of atherosclerosis-related conditions during clinical trials and post-marketing patient experience after the drug was released on the market. Manufacturer Novartis has never warned about this potential side effect in the U.S. in their product or marketing materials.
Patients prescribed Tasigna for CML should watch for symptoms of atherosclerosis, including:
- high blood pressure,
- peripheral artery disease or other artery problems,
- angina-related chest pain,
- muscle weakness in the legs,
- and kidney problems.
Those who took the drug and then developed artery narrowing may be eligible to file a Tasigna lawsuit to recover damages.
What is Chronic Myelogenous Leukemia (CML)?
CML is a rare type of blood cell cancer that affects the white blood cells. Also called the “leukocytes” and “immunity cells,” white blood cells protect the body from infectious agents and fight off bacterial, viral, and other foreign invaders to keep you from getting sick.
As they flow through the bloodstream they identify, destroy, and remove pathogen, damaged cells, cancerous cells, and foreign matter from the body. You can think of them as your body’s defense system.
The bone marrow is responsible for making most types of white blood cells. (Certain types of white blood cells are also produced in the lymph nodes, spleen, and thymus gland).
White blood cells don’t live very long—some for only a few days—so the bone marrow consistently has to make more. Once they’re produced, the body stores them in the blood and lymphatic tissues until they’re needed.
As explained by the Merck Manual “[w]ithin the bone marrow, all blood cells originate from a single type of unspecialized cell called a stem cell. When a stem cell divides, it first becomes an immature red blood cell, white blood cell, or platelet-producing cell. The immature cell then divides, matures further, and ultimately becomes a mature red blood cell, white blood cell, or platelet.”
In a person with CML, the process goes wrong for some reason.
According to the American Cancer Society (ACS), a genetic mutation called the “Philadelphia chromosome” occurs while the cells are still developing. Each human cell contains 23 pairs of chromosomes, which contain molecules of DNA which carries our genes and instructs our cells how to function.
“Most cases of CML start when a ‘swapping’ of chromosomal material (DNA) occurs between chromosomes 9 and 22 during cell division. Part of chromosome 9 goes to 22 and part of 22 goes to 9”, the ACS explains.
This new abnormal Philadelphia chromosome then leads to the formation of a new abnormal gene (or protein) called “BCR-ABL.” This protein—a type of tyrosine kinase protein—then tells the cells to grow abnormally, which causes CML cells to grow and reproduce out of control.
CML is a slow-building cancer that gets worse with time. The cancer cells continue to grow and divide, and they don’t die off like normal cells do, so eventually they crowd out the other healthy white blood cells. As a result, there aren’t enough white blood cells to fight off bacterial, viral, and other foreign invaders. The overabundance of CML cells can also cause a shortage of red blood cells and platelets, which can lead to anemia and excessive bleeding or bruising.
Soon, the abnormal cells migrate from the bone marrow to other parts of the body, including the spleen. For a long time, a patient may not notice symptoms or may experience symptoms like weight loss or a general feeling of sickness without knowing why.
Over time, however, the patient may develop symptoms, including fever, skin changes, night sweats, easy bruising, and pain below the ribs on the left side.
Scientists don’t know what causes CML, though most people who have it do have the Philadelphia chromosome. Doctors diagnose the disease through a blood test, bone marrow tests, or specialized tests that analyze blood or bone marrow samples for the presence of the Philadelphia chromosome or BCR-ABL protein.
What is Tasigna?
Tasigna (nilotinib) is a prescription drug used to treat adult patients with CML. It belongs to a class of drugs known as “tyrosine kinase inhibitors,” which interferes with the production of the abnormal BCR-ABL tyrosine kinase protein. By inhibiting the production of this protein, it helps slow down the accelerated growth rate in abnormal cancer cells. These abnormal cells then die.
The FDA first approved Tasigna in 2007 for the treatment of patients with Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) resistant or intolerant to prior therapy that included imatinib (Gleevec), another similar drug also manufactured by Novartis. In fact, Novartis first began developing Tasigna to eventually replace Gleevec. The patent for Gleevec ran out in 2015, after which generic companies began manufacturing the drug.
The FDA also approved Tasigna in 2010 for the treatment of patients with newly diagnosed CML in its chronic phase. They noted that the drug’s safety and efficacy was demonstrated in a single randomized clinical trial involving only 846 patients.
What’s Wrong with Tasigna?
Tasigna, like any prescription drug, has some side effects. Many of these are listed in the literature accompanying the product, and include things like nausea and diarrhea, headache, fatigue, constipation, vomiting, night sweats, joint pain, and fever. But one very serious potential side effect is not included anywhere in the prescribing information: atherosclerosis.
Atherosclerosis is a disease of the arteries that causes them to become narrowed and stiff. It results from the buildup of fats, cholesterol, and other substances in the artery walls. (Interestingly, in the clinical trial used for the 2010 Tasigna approval, commonly reported adverse effects from the drug included hypercholesterolemia, or high cholesterol.)
Over time, these components form a hard plaque on the inner lining of the arteries, which makes them less flexible. It is then harder for the heart to pump blood through them, which can result in high blood pressure and heart disease. If the arteries become too narrowed, or if part of the plaque breaks off, this may cause a blood clot to develop, which in turn can cause a heart attack or stroke.
Any arteries in the body may be affected, including those around the heart, in the legs, and leading to the brain.
A number of studies have reported that patients taking Tasigna may be at a higher risk of atherosclerosis.
Studies Show that Tasigna Can Increase Risk of Atherosclerosis
The first study to link Tasigna with atherosclerosis came out in 2011. Since then, other studies have reported similar findings, spurring Mayo Clinic Doctor Ayalew Tefferi to recommend that doctors stick with imatinib whenever possible: “[t]herefore, in the absence of evidence for survival advantage, it is hard to justify the risk of treatment with SG-TKIs [second-general tyrosine kinase inhibitors], in the context of frontline therapy for CP-CML.”
Researchers examined 24 patients treated with Tasigna and found that three of them developed a “rapidly progressive” peripheral artery occlusive disease (PAOD) during treatment. In all three cases, the patients required repeated angioplasty and/or multiple surgeries within a few months. None of them had PAOD before they started using the drug.
According to the researches, patients who are started on the drug should be screened for pre-existing PAOD and for vascular risk factors such as diabetes mellitus before starting Tasigna and in the follow up during Tasigna-therapy.
In another 2011 letter, published in the American Journal of Hematology, researchers reported on a case in which a female patient taking Tasigna developed “severe and unrelenting” peripheral artery disease and coronary artery disease after taking the drug for about three years of treatment. A second patient died suddenly after receiving the drug for three weeks. Neither of the patients had a history of cardiovascular disease or tobacco use.
In a retrospective study, researchers evaluated patients with CML taking either imatinib alone or Tasigna as a first or second-line treatment (after imatinib didn’t work) for about 24 months. Results showed that 4 out of 27 developed PAOD or other vascular occlusive events, including one heart attack. They also looked at a subset of patients taking only imatinib or only Tasigna, and found that the 10-year probability of remaining PAOD-free was 100 percent in the imatinib group, and 67 percent in the Tasigna group.
Researchers screened CML patients for peripheral artery occlusive disease (PAOD) and found that it was more common in patients taking Tasigna than in those taking imatinib. A second 2013 study found similar results—Tasigna was associated with higher rates of PAOD versus imatinib.
A described the case of one woman who developed Tasigna-associated PAD, and was then diagnosed with coronary artery disease three years later. Thereafter, she had a stroke. During the course of her Tasigna treatment, she was also diagnosed with both high blood pressure and high blood cholesterol.
Finally, Mayo Clinic Doctor Tefferi published a letter to the editor in Leukemia, entitled, “Nilotinib [Tasigna] treatment-associated accelerated atherosclerosis: when is the risk justified?” He referred to the other studies linking Tasigna to artery disease, noting that in one 2011 study, researchers stated that treatment with Tasigna “may be associated with an increased risk of vascular adverse events, including PAOD development. In a subgroup of patients, these events are severe or even life-threatening.”
Health Canada Warns of Tasigna Dangers
On April 12, 2013, Health Canada warned doctors and patients that Tasigna could increase the risk of atherosclerosis-related conditions. They noted that side effects related to atherosclerosis had been reported during clinical trials, and in patients prescribed the drug once it was on the market. They added that a review of the Novartis global safety database between January 1, 2005, and January 1, 2013, identified a total of 277 cases of atherosclerosis, 14 of which were Canadian cases.
Novartis worked with Health Canada to include new safety information regarding atherosclerosis-related conditions in the Canadian Product Monograph—the document that physicians use when prescribing a drug in Canada—and in the Consumer Information Leaflet.
No such warning has been released in the U.S. as of this writing (February 2018). The product is still sold in the U.S. without any warning about an increased risk of atherosclerosis-related conditions.
Types of Injuries Associated with Tasigna
Individuals taking Tasigna may be at risk for the following serious side effects:
- Peripheral artery disease
- Coronary artery disease
- Femoral artery stenosis (hardening and narrowing of the arteries in the upper thigh)
- Coronary artery stenosis (narrowing and hardening of the arteries supplying the heart)
- Carotid artery stenosis (narrowing and hardening of the carotid artery in the neck)
- Angina (chest pain)
- Heart attack
Novartis Pays $390 Million for Illegal Kickbacks
In November 2015, Novartis agreed to a $390 million settlement with the federal government and more than 40 states over charges that it “paid specialty pharmacies illegal kickbacks in exchange for inducing patients to refill certain medications,” according to Reuters.
The U.S. Attorney for the Southern District of New York brought the False Claims Act lawsuit case, which involved six drugs, including Tasigna. The pharmacies were paid kickbacks so they would recommend the medications to doctors and patients, which is illegal. A former Novartis employee sales manager brought the issue to the government’s attention while still employed by the company, but he later resigned.
In March 2016, a new Tasigna lawsuit was filed in the Eastern District of California. The plaintiffs were the family members of a man who had taken the drug for CML, starting in 2012. According to the Daily Hornet, he was diagnosed with peripheral artery disease in September 2013, with 90-100 percent blockages in the arteries in his legs. His doctor switched him to another leukemia medication, but the man died from atherosclerosis in March 2014.
The plaintiffs claimed that Novartis failed to provide adequate warnings about the side effects associated with Tasigna, and that they downplayed the risks when promoting the drug.
If you or a loved one took Tasigna and then experienced serious side effects such as atherosclerosis and those listed above, you may be eligible to file a Tasigna lawsuit to recover damages. Chaffin Luhana is now investigating these cases and invites you to call us today at 1-888-316-2311.