Tasigna is a highly-sophisticated chemotherapy medication used to treat a particuarly dogged and nefarious type of cancer known as Philadelphia chromosome-positive Chronic Myeloid Leukemia (Ph+ CML). When Tasigna was approved in 2007, it represented a substantial leap forward in treatment for patients suffering with Ph+ CML, especially over the previous drug entrants by its manufacturer, Novartis. Unfortunately, Tasigna also carries with it risk from serious side effects which some allege have caused stroke or sudden death.
Prescription Name and Overview
Tasigna is the product name for the drug nilotinib. It is available only by prescription and as part of a regimen of chemotherapy for the treatment of Ph+ CML. CML (also known as Chronic Myelogenous Leukemia) typically starts in blood-forming cells of the bone marrow. In CML sufferers, myeloid cells, those responsible for manufacturing: red blood cells; platelets; and white blood cells (except Lymphocytes) change fundamentally due to the modification of a gene called BCR-ABL. These modified cells continue to grow and divide until they spread to other parts of the body. Once in the bloodstream, the modified CML cells can cause other types of cells in the body to follow the same pattern, begin to multiply and cease their normal function. Tasigna works by interfering with the growth and spread of these cancerous cells in the body and is structurally related to the popular chemotheraphy drug imatinib (marketed as Gleevec in the United States). Both medications address ABL kinase site affinity – however, Tasigna has proven to be substantially more effective than Gleevec.
Generic Name and Overview
There is no therapeutically equivalent or generic version of Tasigna available in the United States.
OTC Name and Overview
Manufacturer
Tasigna (Nilotinib)
Novartis AG
Labeled Indications
Tasigna is approved by the Food and Drug Administration (FDA) for the following:
Newly diagnosed Ph+ CML-CP
- Indicated for initial treatment of newly diagnosed Philadelphia chromosome positive (Ph+) chronic phase (CP) chronic myeloid leukemia (CML)
Resistant or intolerant
- Indicated for treatment of CP and accelerated phase (AP) Ph+ CML in patients resistant to or intolerant to prior therapy that included imatinib
Active Ingredients
The active ingredient in Tasigna is nilotinib hydrochloride monohydrate. Nilotinib is a tyrosine kinase inhibitor prescribed as a treatment for CML and is a selective inhibitor of BCR-ABL.
Dosages
Tasigna comes in an oral/pill format in both 150mg and 200mg doses.
What Is It Used For?
Tasigna is used to treat a type of blood cancer called Philadelphia chromosome positive CML and acute lymphoblastic leukemia (ALL) in adults and children who are at least 1 year old. Tasigna is usually given after other medications have been tried without success.
How Does it Work?
Tasigna blocks a tyrosine kinase protein called Bcr-Abl. The protein is made by CML cells that have an abnormal chromosome called the Philadelphia chromosome. Blocking this protein stops the leukaemia cells that have the Philadelphia chromosome growing. Most people with CML have the Philadelphia chromosome. Tasigna binds to and stabilizes the inactive conformation of the kinase domain of Abl protein of the Bcr-Abl fusion protein. It can help to control CML in chronic phase.
What are the Approved Uses?
Tasigna is approved for the treatment of adult patients with newly diagnosed Philadelphia 13 chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase. The effectiveness of Tasigna is based on major molecular response (MMR) and cytogenetic response rates.
Tasigna is also approved for the treatment of chronic phase and accelerated phase Philadelphia chromosome positive chronic myelogenous leukemia (Ph+ CML) in adult patients resistant or intolerant to prior therapy that included imatinib.
Production Anecdotes / History
Tasigna is part of a family of chemotherapy drugs known as tyrosine kinase inhibitors (TKIs) which are targeted treatments for CML. The prototype TKI medication, Gleevec, provided a new tool in the battle against CML, and was useful in the management and treatment of the illness. However, some patients treated with Gleevec either developed a resistance to the drug or were intolerant to its use. Research focused on improving the effectiveness of Gleevec and consequently, drug manufacturer Novartis introduced Tasigna as a “second-generation” TKI as appropriate for use in patients that had developed resistance or were intolerant to Gleevec.
Precautions
QT Prolongation
Tasigna has demonstrated the potential to cause a heart condition known as QT Prolongation. This condition affects the rhythm of the heart and can cause fast or irregular heartbeating as well as other symptoms such as dizziness and fainting. QT Prolongation can also be exacerbated if Tasigna is taken with other drugs that may have a similar impact.
It is recommended to avoid grapefruit and grapefruit juice while taking this medication. Food and grapefruit products may increase nilotinib concentration in the blood. Moreover, it is advised to avoid taking other medicines or supplements with Tasigna that can also lead to QT Prolongation.
Long-Term Use Considerations
Tasigna has been lauded for its high effectiveness as a “first-line” treatment for CML. The cumulative six-year rate for achiving MMR with Tasigna has been documented at 98% with a six-year overall survival rate of 96%. With that in mind, Tasigna has also been linked to “relatively common” cardiovascular toxicity. In studies, the rate of adverse cardiovascular events such as: peripheral arterial obstructive disease; carotid stenosis; agina pectoris and atrial fibrilation were considered “significant”.
Animal studies have revealed that Nilotinib can cause fetal harm when administered to a pregnant woman. Women of reproductive potential should have a pregnancy test prior to starting treatment with Nilotinib. Moreover, it is advised to consult a healthcare provider when a woman becomes pregnant to avoid the risk of embryotoxicity. Additionally, it is not recommended to use this medication during breastfeeding to avoid the risk of its serious adverse reactions in a nursing child.
Drug Interactions
Tasigna is contraindicated with the following drugs/medications:
- arsenic trioxide
- disopyramide
- goserelin
- ibutilide
- indapamide
- leuprolide
- pentamidine
- pimozide
- procainamide
- quinidine
- sotalol
- toremifene
These are the most seriously documented drug interactions with Tasigna. However, this is not a complete list. If you are prescribed Tasigna, please consult your physician and disclose all medications and supplements you take.
Long-Term Side Effects
Tasigna has been documented for its potential to cause serious cardiac side effects known as QT Prolongation. Simply put, QT Prolongation is a cardio-arrhythmatic condition that may cause sudden death in patients suffering with it. Additionally, Tasigna has been linked to cases of increased risk for atherosclerosis and other arterial blockage conditions.
FDA Warnings (History Of)
QT Prolongation
In 2017, the FDA added a “black box” warning to Tasigna’s label. This warning statement on its prescription information advises and warns of its signficiant potential for causing serious cardiac side effects from QT Prolongation.
Atherosclerosis/Arterial Blockage
Atherosclerosis is a disease that occurs in arterial blood vessels (arteries) where the walls of the arteries become thickened and hardened by plaque buildup. As plaque builds up, the arteries narrow and become less flexible. Possible complications from atherosclerosis include heart attacks and strokes.
Beginning in 2013, Candian health officials required safety information about the increased risk of atherosclerosis and atherosclerosis-related conditions from Tasigna on its labeling. Specifically the Canadian warnings refer to: peripheral arterial occlusive disease; femoral artery stenosis; carotid artery stenosis and cerebrovascular incidents. Despite the requirements imposed on Novartis in Canada, the drug manufacturer has declined to include a similar warning for Tasigna in the United States and the FDA has not moved to require Novartis to make similar “black box” warnings on its prescription information.
Other Common Side Effects
Individuals taking Tasigna may experience any of the following:
- Fever
- Cough
- Headache
- Sore throat
- Rash
- Itching
- Pyrexia
- Dyspnea
- Oropharyngeal pain
- Peripheral edema
- Insomnia
- Alopecia
- Tiredness
- Abdominal pain
- Diarrhea
- Night sweats
- Nausea
- Decreased appetite
- Dyspepsia
- Nasopharyngitis
- Myalgia
- Arthralgia
- Asthenia
- Constipation
- Back pain
- Muscle spasms
- Weakness
- Hair loss
- Runny or stuffy nose
- Sneezing
Lawsuits
In 2013, Health Canada required Tasigna’s manufacturer, Novartis, to include warnings about the increased risk of atherosclerosis linked to this drug. Accordingly, Canadian consumers and prescribing physicians are now equipped with this information concerning possible life-threatening complications when planning a chemotherapy strategy. However, in the United States, primarily because the FDA has not required it, Novartis declined to include similar warnings on its prescription lableing for U.S. doctors and patients.
Patients and family members who have been prescribed Tasigna and who have suffered life-altering injuries or death from cardiac conditions stemming from atherosclerosis have started filing lawsuits against Novartis. In these lawsuits, the damaged Plaintiffs have accused Novartis of several alleged wrongful actions. Notably, they allege that Novartis, despite knowing the risks of severe atherosclerosis-related conditions, failed to warn patients and doctors in the United States – and that failure to warn was intentional.
Several individual lawsuits against Novartis have been filed alleging injury from Tasigna, either by the patients themselves or their family members. At this moment, no multidistrict litigation (MDL) or class-action lawsuits have been established.
Lauris v. Novartis, A.G.
Background
In 2016, Kristi Lauris, the wife of Dainis Lauris filed one of the first Tasigna lawsuits against Novartis in federal court in California. Dainis was diagnosed with CML in 2001 and was initially prescribed Gleevec. In 2012, Dainis was switched from Gleevec to Tasigna by his prescribing physician at which time, his condition started to deterioriate from atherosclerotic conditions. After reading an article in a medical journal about Tasigna’s linkage to atherosclerotic conditions, Dainis’ oncologist immediately took him off Tasigna. Despite this measure, Dainis required an angioplasty in his leg due to an occlusion in his femoral artery in 2014. During the procedure, he suffered a major stroke and later died at the age of 49. An autopsy performed on Dainis revealed pervasive blockage in his arteries.
Status
The parties to the Lauris case settled their lawsuit in 2018 for an undisclosed amount.
Dennis McWilliams et al. v. Novartis AG, et al.
Background
Dennis McWilliams was diagnosed with CML in 2007 and was prescribed Gleevec by his oncologist. In June 2011, Dennis was switched to Tasigna and then sufferred a massive stroke in 2013. Dennis and his wife Lori sued Novartis in federal court in South Florida claiming that Tasigna was the primary cause of his stroke and that Novartis failed to warn him and his oncologist of the risk Tasigna posed.
Status
Despite efforts by Novartis to have the McWilliam case thrown out of court through pre-trial motions, the federal judge presiding over the case allowed it to proceed without the possibility for punitive damages being sought against Novartis. The McWilliams and Novartis settled in 2018 and the lawsuit was voluntarily withdrawn with prejudice.
Becker v. Novartis AG et al.
Background
Bruce Becker filed a lawsuit in federal district court in Seattle alleging that he suffered a massive stroke at the age of 66 following his being prescribed Tasigna as part of a chemotherapy regimen treating CML. Bruce had been previously treated with Gleevec, but his oncologist switched him to Tasigna while in MML. Bruce explicity alleged in court documents that he had no atherosclerosis-related conditions prior to taking Tasigna.
Status
At the moment, the Becker case is in its pre-trial phase.
Sources Cited (17)
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Tracy Everhart
Tracy Everhart is the Editor for Drug Law Journal. A highly-trained and certified medical professional, Tracy is also an accomplished medical writer. After spending years on the front lines of the medical profession, Tracy now devotes her expertise and skills to researching and reporting on new drugs and devices that enter the market, as well as their side-effects and the real-life stories involved. Prior to joining Drug Law Journal, Tracy wrote for benchmark online healthcare resources focused on families and, in particular, women’s health issues. Tracy holds post-graduate degrees from both the American College of Healthcare Sciences and the Yale School of Nursing. She is also a graduate of both Hampshire College, where she studied microbiology and the University of South Carolina school of nursing.
