Keeping Track of Your Ph+ CML Treatment A useful tool to learn how to set goals and track progress.
Please see Important Safety Information for GLEEVEC (imatinib mesylate) and TASIGNA (nilotinib) on pages 30-40, including TASIGNA Boxed WARNING, and enclosed full Prescribing Information and TASIGNA Medication Guide. TASIGNA (nilotinib) Indications TASIGNA is a prescription medicine used to treat adults who have: Newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase. The effectiveness of TASIGNA in these patients is based on a study that measured two types of response to treatment (cytogenetic and molecular) by 1 year. The study is ongoing to find out how TASIGNA works over a longer period of time Ph+ CML in chronic phase and accelerated phase who are no longer benefiting from, or did not tolerate, other treatment including GLEEVEC (imatinib mesylate). The effectiveness of TASIGNA in these patients is based on a study that measured two types of response to treatment (hematologic and cytogenetic) Ph+ CML Glossary definitions for terms are highlighted in light purple and can be found on page 26.
IMPORTANT Hemorrhage SAFETY (abnormal INFORMATION bleeding) ABOUT TASIGNA (nilotinib) Skin blistering Capsules What Low is levels the most of thyroid important hormone information to know about Your prescription doctor will TASIGNA? check you closely for any side effects to stop more serious complications from occurring. Patients with heart disease or risk factors TASIGNA for can heart cause failure QT should prolongation, also be monitored a possible carefully. life-threatening heart problem. QT prolongation causes an irregular heartbeat, GLEEVEC which may is lead sometimes to sudden associated death. Call with your stomach doctor right or intestinal away irritation. GLEEVEC if you feel lightheaded, should be taken faint with or have food an and irregular a large heartbeat glass of water while to minimize this taking problem. TASIGNA. There These have can been symptoms rare reports, of QT including prolongation. deaths, of stomach or intestinal perforation (a small hole or tear). If Your you doctor are experiencing should check any your of the heart above-mentioned with a test side effects, please called an electrocardiogram (ECG): be sure to speak with your doctor immediately. Before starting TASIGNA Common side effects of GLEEVEC 7 days after starting TASIGNA Almost With all patients any dose treated changes with GLEEVEC experience side effects at some Regularly time. Most during side effects TASIGNA are treatment mild to moderate in severity. Some common side effects that you may experience include: Do not take TASIGNA if you have long QTc syndrome Fluid retention (holding water) or low levels of potassium or magnesium in your blood Muscle cramps, pain, or bone pain TASIGNA Abdominal can paininteract with many medicines and supplements. This may increase your chance for serious and Anorexia life-threatening (loss of appetite) side effects. Do not take any other medicine Vomiting while taking TASIGNA unless your doctor tells you it is okay to do so Diarrhea Food Decreased and grapefruit hemoglobin products (decrease increase blood the cells amount which carry oxygen) of TASIGNA in your body. This may increase your Hemorrhage (abnormal bleeding) chance for serious and life-threatening side effects. Take Nausea TASIGNA on an empty stomach. Avoid eating food for at Fatigue least 2 hours before the dose is taken, and avoid eating food for at least 1 hour after the dose is taken. Avoid grapefruit, grapefruit Rash juice, and any supplement containing grapefruit If extract you are while experiencing taking TASIGNA any of the above-mentioned side effects, please be sure to speak with your doctor immediately. The severity of some side effects may be reduced with the help of other medicines and advice from your doctor, while others may require stopping GLEEVEC therapy for a while or changing the dose. However, in some cases, GLEEVEC therapy may need to be discontinued. Ph+ CML 3 39
Ph+ CML WHAT IS Ph+ CML? Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) is a type of cancer of the bone marrow and blood. Leukemia, which means white blood, is caused when your bone marrow makes too many white blood cells. Normal blood cells Blood cells in person with Ph+ CML White blood cell Helps your body fight infection and disease Leukemic cell Diseased white blood cell that grows abnormally Red blood cell Transports oxygen from the lungs to the body Platelet A clear, disk-shaped piece of a cell that forms blood clots and controls bleeding Over time, excess white blood cells crowd out healthy red blood cells and platelets. This has negative health consequences. Note that one of the best ways to know how many leukemic cells are in the body is through a quantitative polymerase chain reaction (PCR) test, which we will review later. Understanding how Ph+ CML works can help you take an active role in treating it.
WHAT ARE THE PHASES OF Ph+ CML? Most adults living with Ph+ CML are diagnosed in the chronic phase, which is the initial phase of the disease. Chronic Phase Accelerated Phase Blast Crisis <10% of blood cells in the bone marrow samples are blast cells 10-19% of blood cells in the bone marrow samples are blast cells >20% of blood cells in the bone marrow samples are blast cells Immature white blood cells, called blast cells, begin to appear in the blood and bone marrow Symptoms are fairly mild, if present at all An increasing number of white blood cells and blast cells are present in the blood and bone marrow, with fewer normal cells present Abnormal platelet count (either very high or very low) May have fever, poor appetite, and weight loss A greater number of blast cells are found in the blood or bone marrow compared with the accelerated phase and begin spreading to other tissues and organs beyond the bone marrow Often associated with fever, poor appetite, and weight loss 5
What is the International Scale (IS)? The International Scale was developed by researchers to better track treatment progress. By providing a standard for reporting PCR results, the International Scale helps assure your progress is measured consistently. Ask your doctor about using a lab that reports PCR results based on the International Scale. Please see Important Safety Information for GLEEVEC (imatinib mesylate) and TASIGNA (nilotinib) on pages 30-40, including TASIGNA Boxed WARNING, and enclosed full Prescribing Information and TASIGNA Medication Guide.
HOW CAN I USE PCR TESTING TO KEEP TRACK OF MY TREATMENT? Help guide your treatment plan by following this easy-to-remember, 3-step formula: UNDERSTAND YOUR NUMBERS SET YOUR GOAL TRACK YOUR PROGRESS Knowledge is important. Understanding your treatment results is an important part of Ph+ CML therapy. The lower the amount of leukemic cells in your body, the better. Therefore, a major goal of Ph+ CML treatment is getting your numbers as low as possible. When this happens, it s called a major molecular response (MMR). Only PCR testing can determine if you ve reached MMR and are staying there. Shoot for MMR as your main treatment goal. But if you don t get there, it may be time to talk to your doctor again about another Ph+ CML treatment. Treatment goals After your baseline measurement, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ) recommend PCR testing following standardization with the International Scale every 3 months, with the goal of reaching MMR at 12 months. 7
UNDERSTANDING TREATMENT MILESTONES There are 3 fundamental treatment milestones for Ph+ CML, each signifying a greater reduction of cancer in your body. Treatment goals Molecular Response Molecular response (most sensitive measure of how much cancer has been destroyed a PCR test can find 1 cancer cell in 1 million normal cells) Uses PCR test (as measured by the International Scale) to determine how many BCR-ABL cells remain in your body A PCR test is a very simple and precise test for measuring how many leukemic cells are in your body A major molecular response (MMR) means that the amount of BCR-ABL found in the bone marrow sample or blood sample is very low An MMR is a high standard of treatment success. While MMR at 12 months is an important goal of treatment for most patients, physicians will also test for lower levels of response along the way.
Cytogenetic response (less sensitive measure than a PCR test of how many leukemic cells have been destroyed can find 1 leukemic cell in up to several hundred normal cells) Cytogenetic Response Uses traditional karyotype or FISH test to determine the amount of cells containing the Ph chromosome left in the bone marrow sample or blood sample Complete cytogenetic response means the test can no longer detect any cells with the Ph chromosome in the bone marrow sample or blood sample A major cytogenetic response means that less than 35% of the cells in the bone marrow sample or blood sample have the Ph chromosome Hematologic response (least sensitive measure of how much cancer has been destroyed) Hematologic Response Uses a complete blood count to determine your blood cell levels Complete hematologic response means your blood cell levels have returned to normal If your doctor hasn t scheduled an IS PCR test for you, ask to have one scheduled during your next visit. 9
Please see Important Safety Information for GLEEVEC (imatinib mesylate) and TASIGNA (nilotinib) on pages 30-40, including TASIGNA Boxed WARNING, and enclosed full Prescribing Information and TASIGNA Medication Guide.
KEEPING TRACK OF YOUR MILESTONES How often do I follow up? The NCCN Guidelines recommend a PCR test upon diagnosis and every 3 months thereafter. At 12 months of treatment, you will be tested to see if you have achieved major molecular response (MMR). MISSING YOUR MILESTONE? Achieving MMR by 12 months is recommended by the NCCN Guidelines. This milestone is measured by a PCR test. If you do not reach this milestone, this may mean your current treatment may not be effective enough, and you may be at risk of resistance. NCCN Guidelines recommend getting an IS PCR test every 3 months. 11
Please see Important Safety Information for GLEEVEC (imatinib mesylate) and TASIGNA (nilotinib) on pages 30-40, including TASIGNA Boxed WARNING, and enclosed full Prescribing Information and TASIGNA Medication Guide.
TASIGNA (nilotinib) YOUR Ph+ CML TREATMENT OPTION TASIGNA is a prescription medicine used to treat adults who have: Newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase. The effectiveness of TASIGNA in these patients is based on a study that measured two types of response to treatment (cytogenetic and molecular) by 1 year. The study is ongoing to find out how TASIGNA works over a longer period of time Ph+ CML in chronic phase and accelerated phase who are no longer benefiting from, or did not tolerate, other treatment including GLEEVEC (imatinib mesylate). The effectiveness of TASIGNA in these patients is based on a study that measured two types of response to treatment (hematologic and cytogenetic) TASIGNA (nilotinib) Please see Important Safety Information for GLEEVEC (imatinib mesylate) and TASIGNA (nilotinib) on pages 30-40, including TASIGNA Boxed WARNING, and enclosed full Prescribing Information and TASIGNA Medication Guide. 13
TASIGNA (nilotinib) Please see Important Safety Information for GLEEVEC (imatinib mesylate) and TASIGNA (nilotinib) on pages 30-40, including TASIGNA Boxed WARNING, and enclosed full Prescribing Information and TASIGNA Medication Guide.
THE GOAL OF TREATMENT WITH TASIGNA (nilotinib) A key goal of treatment is to reduce or eliminate the number of cells that cause Ph+ CML. If you have switched from another medication, like GLEEVEC (imatinib mesylate), to TASIGNA, you may have done so because you were resistant to treatment, and may not have been hitting your treatment milestones. It is important to continue monitoring your numbers to ensure that you maintain your response to therapy and keep the levels of BCR-ABL in your blood and bone marrow low. Only a PCR test is sensitive enough to detect a molecular response, an important treatment response, and determine if you re staying there. 15
HOW TASIGNA (nilotinib) WORKS TASIGNA binds to the BCR-ABL protein May block the signal that leads to the production of leukemic cells Blocking the signal may lead to a reduction of leukemic cells and may help provide room for healthy blood cells to grow TASIGNA TASIGNA binds to the BCR-ABL protein BCR-ABL Protein This process may block the signal that leads to the production of leukemic cells Ph+ CML A reduction of leukemic cells may help provide room for healthy blood cells to grow Make sure you take TASIGNA exactly as prescribed by your physician to help block the signal that may cause your body to produce leukemic cells. Please see Important Safety Information for GLEEVEC (imatinib mesylate) and TASIGNA (nilotinib) on pages 30-40, including TASIGNA Boxed WARNING, and enclosed full Prescribing Information and TASIGNA Medication Guide.
Serious side effects TASIGNA may cause serious side effects, including: Low blood counts. Low blood counts are common with TASIGNA. Your doctor will check your blood counts regularly during treatment with TASIGNA. Symptoms of low blood counts include: Unexplained bleeding or bruising Blood in urine or stool Unexplained weakness QT prolongation. Call your doctor right away if you feel lightheaded, faint or have an irregular heartbeat while taking TASIGNA. These can be symptoms of QT prolongation, a possible life-threatening heart problem Decreased blood flow to the leg, heart, or brain. People who have recently been diagnosed with Ph+ CML and take TASIGNA may develop decreased blood flow to the leg, the heart, or brain. Get medical help right away if you suddenly develop any of the following symptoms: Chest pain or discomfort Numbness or weakness Problems walking or speaking Leg pain Your leg feels cold Change in the skin color of your leg Liver damage. Symptoms include yellow skin and eyes Pancreas inflammation (pancreatitis). Symptoms include sudden stomach area pain with nausea and vomiting Bleeding in the brain. Symptoms include sudden headache, changes in your eyesight, not being aware of what is going on around you and becoming unconscious Tumor Lysis Syndrome (TLS). TLS is caused by a fast breakdown of cancer cells. TLS can cause you to have: kidney failure and the need for dialysis treatment an abnormal heart beat Your doctor may do blood tests to check you for TLS 17
12h 2 2 TAKING TASIGNA (nilotinib) TASIGNA doses should be taken approximately 12 hours apart Take 2 capsules in the morning and 2 capsules in the evening NO FOOD Do not take TASIGNA with food. Do not eat 2 hours before or 1 hour after taking your dose 2x Day 2x2 No Water Food Missed Dose 12h 2 2 NO FOOD TASIGNA doses should be taken approximately 12 hours apart Take 2 capsules in the morning and 2 capsules in the evening Capsules Do not take should be TASIGNA swallowed with food. whole Do not with eat 2 water hours before or 1 hour after taking your dose If a dose is missed, you should not make up the dose but take the next dose as scheduled Water Missed Dose Drug Interactions Capsules should be swallowed whole with water Grapefruit If a dose is missed, you should not make up the dose but take the next dose as scheduled Warfarin Antacids Antacids CYP3A4 is an enzyme that metabolizes many medications, such as TASIGNA. Do not take TASIGNA with CYP3A4 inhibitors or inducers, as it may affect its concentration You should avoid grapefruit products and other foods that are known to inhibit CYP3A4 A single-dose study did not show a drug interaction between TASIGNA and warfarin. Exercise caution when coadministering TASIGNA with substrates for CYP3A4 enzymes that have a narrow therapeutic index If you need to take antacids (medicines to treat heartburn) do not take them at the same time that you take TASIGNA. Take them about 2 hours before or about 2 hours after you take TASIGNA. TASIGNA can interact with many medicines, including prescription and non-prescription vitamins and herbal supplements, and can increase your chance for serious side effects. Know the medicines you take, keep a list of them, and show it to your doctor or pharmacist when you get a new medicine or supplement. Please see Important Safety Information for GLEEVEC (imatinib mesylate) and TASIGNA (nilotinib) on pages 30-40, including TASIGNA Boxed WARNING, and enclosed full Prescribing Information and TASIGNA Medication Guide.
TASIGNA should be taken twice a day, 12 hours apart. Do not eat 2 hours before or 1 hour after taking your dose. EXAMPLE OF DOSING SCHEDULE The following is an example of a typical dosing schedule. By taking your first dose at 8:00 AM, you would wait another 12 hours before taking your next dose at 8:00 PM. To prepare for your dose, you would not eat between 2 hours before and 1 hour after your dose. NO FOOD: FIRST DOSE 8:00AM 6:00-9:00AM SECOND DOSE 8:00PM 6:00-9:00PM Take TASIGNA exactly as your doctor tells you to take it. Do not change your dose or stop taking TASIGNA unless your doctor tells you. TASIGNA is a long-term treatment. Your doctor may change your dose. Your doctor may have you stop TASIGNA for some time or lower your dose if you have side effects with it. Take your dose at the same time every day. You should check with your doctor, nurse, or pharmacist if you have any questions. Review this section in its entirety to be sure you take TASIGNA properly. If you are unable to swallow capsules, the contents of each capsule may be dispersed in 1 teaspoon of applesauce (puréed apple) and the mixture swallowed right away (within 15 minutes). Taking TASIGNA twice a day as prescribed helps to ensure that the medication is always in your system. 19
Please see Important Safety Information for GLEEVEC (imatinib mesylate) and TASIGNA (nilotinib) on pages 30-40, including TASIGNA Boxed WARNING, and enclosed full Prescribing Information and TASIGNA Medication Guide.
Take TASIGNA at the same time every day Set your cell phone or computer to help Use a watch with an alarm to help you take it on an empty stomach Ask a loved one to help you remember Put a check mark on your calendar Get the support you need If you take TASIGNA at the same time every day, it is likely to become part of your daily routine. Set calendar reminders or the alarm clock function on your cell phone or computer to remind you to take your medication. Get a stopwatch or a travel clock to count down the 2 hours since you last ate and the 1 hour until you can eat again. Because food increases the blood level of TASIGNA in your body, patients should not eat 2 hours before taking TASIGNA or 1 hour after taking TASIGNA. Enlist a loved one to help you remember certain restrictions. For example, some foods such as grapefruit juice are known to inhibit CYP3A4, an enzyme that metabolizes many drugs, such as TASIGNA, and change the way TASIGNA is absorbed and should be avoided. Each day, put a check mark on your calendar when you take TASIGNA. Seeing that you re on track can help you stay on track. Join My CML Circle, a free resource to help you stay on top of your treatment. Sign up at www.mycmlcircle.com. 21
TALKING TO YOUR DOCTOR Good communication with your health care provider is important. The following tips can help your next appointment be productive and informative. Bring questions Before your appointment, take a moment to make a list of questions you would like to discuss with your physician. It s common to forget what you wanted to ask when you get into the exam room. Bringing a list can help you make sure you don t leave your physician s office with lingering concerns or questions. Take notes Bring a pen and paper into your appointment so you can write down what your physician says. Not only can this help you remember important information, but writing things down can often spur additional questions that may help clarify your physician s instructions. Take someone with you Sometimes it s easier to talk with your doctor when a spouse, friend, or partner is by your side. This person can also act as the note-taker. Ask questions Don t hesitate to ask questions. Your health care team is there to help you and wants you to have a good understanding of your condition and treatment. If you feel your physician does not have time to answer questions, speak with the nurse. Nurses are a valuable resource and are there to help. Please see Important Safety Information for GLEEVEC (imatinib mesylate) and TASIGNA (nilotinib) on pages 30-40, including TASIGNA Boxed WARNING, and enclosed full Prescribing Information and TASIGNA Medication Guide.
Share information Chances are you are working with several doctors and health care professionals for your treatment or other health conditions. Speak with the nurse at each health care provider s office to make sure that all your providers are sharing important information with each other. For example, make sure your primary doctor is getting test results from your specialist and vice versa. Understand your numbers Be sure to discuss your test results with your physician and that you get a clear understanding of what they mean. Remember your other health needs Most of your energy right now may be going into managing your Ph+ CML, but try not to neglect your other health needs. Be sure to have your blood pressure and cholesterol checked regularly and stay up-to-date on other regular health exams. Managing your disease is important, and so is managing the rest of you. Get your questions prepared for a smarter doctor s visit The My Doctor Dialogue tool provides common questions and answers to many topics you may want to discuss with your doctor. Check it out at www.us.tasigna.com. 23
CO NNECT PLUS CDA-1036847 My Doctor Dialogue Web (9 of 14) Eligibility: Insured Patients ONLY BILL PRIMARY INSURANCE FIRST RxBIN: RxPCN: 601341 OHCP OHXXXXXXX 01 Eligibility: Medicare/Medicaid/Cash BILL DIRECT TO OPUSHEALTH ONLY RxBIN: RxPCN: 601341 OHS OHXXXXXXX 01 Please see accompanying full Prescribing Information, including Boxed WARNING, and the TASIGNA (nilotinib) Medication Guide you received with your prescription. HELPFUL RESOURCES AND SUPPORT Join My CML Circle for free support FOR COMMERCIAL INSURANCE PATIENTS PAY NO MORE THAN $25 OF PRESCRIPTION COST* If you are filling a prescription for commercial insurance patients, use these codes when submitting RxGrp: your claim. RxID: xxxxxxxxxx Suf: CONNECT PLUS CARD FOR MEDICARE/MEDICAID/CASH PATIENTS UP TO 3 MONTHS $0 OUT OF POCKET Eligible patients will pay $0 out of If you are filling a prescription for pocket for up to 3 months. After a patient without insurance or who participates in Medicare, Medicaid, this period, commercial patients or other government-sponsored may pay no more than $25. RxGrp: insurance programs, use these codes RxID: when submitting your claim. xxxxxxxxxx Suf: TASIGNA 150 mg *Limitations apply $0 copay up to a maximum. TASIGNA 200 mg Offer now available for MA commercial patients. My TASIGNA (nilotinib) CONNECT PLUS Card xxxx The TASIGNA CONNECT PLUS Card was created to help you save money on your out-of-pocket costs for TASIGNA prescriptions by providing co-pay assistance. Eligible patients will pay $0 out of pocket for up to 3 months. After this period, commercial patients may pay no more than $25.* *Limitations apply $0 co-pay up to a maximum. Offer now available for MA commercial patients. My CML Circle Support Program Get regular updates from My CML Circle about treatment and follow-up care delivered directly to you with the My CML Circle Support Program. My Doctor Dialogue for a smarter visit This tool will help guide an informed conversation with your doctor. You can pick out your questions from a wide range of topics, review the answers to these questions, and print out the guide to bring to your next visit. Sign up today at www.mycmlcircle.com or call 1-877-890-9741 to join Please see Important Safety Information for GLEEVEC (imatinib mesylate) and TASIGNA (nilotinib) on pages 30-40, including TASIGNA Boxed WARNING, and enclosed full Prescribing Information and TASIGNA Medication Guide.
Take control of monitoring your treatment with IS PCR testing Achieving a major molecular response (MMR) is a critical milestone in your treatment journey. To measure molecular response, your doctor will order a PCR test. The National Comprehensive Cancer Network (NCCN ) recommends that you have a PCR test following standardization with the International Scale upon diagnosis as a baseline measurement. You should then track your progress every 3 months. To help assure your progress is measured consistently, the International Scale was developed to report PCR results. Ask your doctor if their lab uses the International Scale when performing your PCR tests. Free PCR tests Novartis is committed to achieving the highest standard of Ph+ CML care. That s why we re offering free PCR testing through December 31, 2014. Talk to your doctor about access to labs that report PCR results based on the International Scale. Resources & support 25
Ph+ CML GLOSSARY Apoptosis: The programmed death of an abnormal cell. When apoptosis is halted, this may lead to uncontrolled cell growth. BCR-ABL: Refers to both an abnormal gene and a protein that the gene creates. The BCR-ABL gene is formed when 2 specific chromosomes combine. The gene then creates the BCR-ABL protein the underlying cause of Ph+ CML. Blast cell: An immature cell that matures into a blood cell. Bone marrow: The soft, spongy inner part of bones where blood cells are made. Cell proliferation: A rapid growth of new cells. Chromosome: Part of the nucleus of the cell that contains the genes. Complete blood count: A test of the blood that includes red blood cell count, white blood cell count, erythrocyte indices, hematocrit, differential blood count, and sometimes platelet count. Cytogenetic response: A complete cytogenetic response means that, using currently available tests, no cells with the Philadelphia chromosome are found in the bone marrow sample or blood sample. However, this does not mean that your Ph+ CML is cured. Resources & support A major cytogenetic response means that less than 35% of the cells in the bone marrow sample or blood sample have the Philadelphia chromosome. Cytogenetic testing: Tests done on bone marrow cells or white blood cells to see if they contain the Philadelphia chromosome. There are 2 types of cytogenetic testing: karyotyping and FISH (fluorescence in situ hybridization). Please see Important Safety Information for GLEEVEC (imatinib mesylate) and TASIGNA (nilotinib) on pages 30-40, including TASIGNA Boxed WARNING, and enclosed full Prescribing Information and TASIGNA Medication Guide.
DNA: The organic compound inside the nucleus of a cell that carries the genetic instructions for making proteins. Genes are made of DNA. FISH (fluorescence in situ hybridization): A sensitive test done on either blood or bone marrow cells to look for abnormal cells that contain the BCR-ABL gene (which is located on the Philadelphia chromosome). This test can find 1 abnormal cell out of 200 to 500 normal cells. Gene: The basic unit of heredity passed from parent to child. Genes are made of DNA and carry instructions for making proteins. Hematologic response: A complete hematologic response means white blood cell, platelet, and red blood cell counts have returned to a normal range. However, this does not mean that your Ph+ CML is cured. Hematologic testing: A simple blood test to measure levels of white blood cells, red blood cells, and platelets. Karyotyping: A cytogenetic test to identify chromosome abnormalities as the cause of a disease. This test looks at a small number of cells (about 20). Major molecular response: A major molecular response means that the amount of BCR-ABL found in the bone marrow sample or blood sample through an IS PCR test is very low. Molecular testing: The use of PCR (polymerase chain reaction) to find the number of cells expressing BCR-ABL in either blood or bone marrow. 27
Ph+ CML GLOSSARY (cont) Myelocyte: A large cell of the bone marrow that is an immature granulocyte. PCR (polymerase chain reaction): A very sensitive test to count the number of cells containing the BCR-ABL gene (which is located on the Philadelphia chromosome). It can be done on either blood or bone marrow cells and can detect the presence of a single abnormal cell within a sample of 1 million cells. Philadelphia (Ph) chromosome: An abnormal chromosome that is responsible for the constant production of abnormal white blood cells (myeloid cells) that are present in Ph+ CML. Platelet: Type of blood cell that helps blood to clot. Promyelocyte: A cell in bone marrow that is in an intermediate stage of development between a myeloblast and a myelocyte. Protein: An essential component of all living cells that is made up of amino acids. Red blood cell: Type of blood cell that carries oxygen to other cells in the body. Remission: A disappearance of evidence of a disease, usually as a result of treatment. Resistance: A primary resistance means not getting a complete hematologic response within 3 months on treatment, not getting a cytogenetic response within 6 months on treatment, or not getting a major cytogenetic response at 12 months on treatment. A secondary resistance means that a prior hematologic or cytogenetic response that was obtained while on treatment is lost. Please see Important Safety Information for GLEEVEC (imatinib mesylate) and TASIGNA (nilotinib) on pages 30-40, including TASIGNA Boxed WARNING, and enclosed full Prescribing Information and TASIGNA Medication Guide.
Side effects: A side effect, also referred to as an adverse event, is a result of drug therapy that differs from the desired effect. Spleen: An organ that stores and filters blood. Stem cell: An early cell that matures into various types of cells. Stem cell transplant: Procedure used to restore bone marrow after chemotherapy by transplanting blood-forming stem cells into the patient. Translocation: A process in which 2 or more chromosomes break, and the broken parts of the chromosomes switch places. This forms new hybrid chromosomes, often with abnormal functions. Tyrosine kinase: A protein that facilitates the growth of Ph+ CML cells. As a treatment for Ph+ CML, medicines called tyrosine kinase inhibitors target this protein and prevent it from signaling additional cell growth. White blood cell: Type of blood cell that fights infection. 29
INDICATIONS and IMPORTANT SAFETY INFORMATION ABOUT TASIGNA (nilotinib) TASIGNA PATIENT INFORMATION TASIGNA (nilotinib) Indications TASIGNA is a prescription medicine used to treat adults who have: Newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase. The effectiveness of TASIGNA in these patients is based on a study that measured two types of response to treatment (cytogenetic and molecular) by 1 year. The study is ongoing to find out how TASIGNA works over a longer period of time Ph+ CML in chronic phase and accelerated phase who are no longer benefiting from, or did not tolerate, other treatment including GLEEVEC (imatinib mesylate). The effectiveness of TASIGNA in these patients is based on a study that measured two types of response to treatment (hematologic and cytogenetic) Please see enclosed full prescribing information including the Boxed WARNING, and the TASIGNA Medication Guide.
IMPORTANT SAFETY INFORMATION ABOUT TASIGNA (nilotinib) Capsules What is the most important information to know about prescription TASIGNA? TASIGNA can cause QT prolongation, a possible lifethreatening heart problem. QT prolongation causes an irregular heartbeat, which may lead to sudden death. Call your doctor right away if you feel lightheaded, faint or have an irregular heartbeat while taking TASIGNA. These can be symptoms of QT prolongation. Your doctor should check your heart with a test called an electrocardiogram (ECG): Before starting TASIGNA 7 days after starting TASIGNA With any dose changes Regularly during TASIGNA treatment Do not take TASIGNA if you have long QTc syndrome or low levels of potassium or magnesium in your blood TASIGNA can interact with many medicines and supplements. This may increase your chance for serious and life-threatening side effects. Do not take any other medicine while taking TASIGNA unless your doctor tells you it is okay to do so Food and grapefruit products increase the amount of TASIGNA in your body. This may increase your chance for serious and life-threatening side effects. Take TASIGNA on an empty stomach. Avoid eating food for at least 2 hours before the dose is taken, and avoid eating food for at least 1 hour after the dose is taken. Avoid grapefruit, grapefruit juice, and any supplement containing grapefruit extract while taking TASIGNA 31 Important Safety Information
INDICATIONS and IMPORTANT SAFETY INFORMATION ABOUT TASIGNA (nilotinib) (cont) Before taking TASIGNA, tell your doctor about all of your medical conditions, including if you: Have a heart disorder or are taking medication for the heart Have had a stroke or other problems due to decreased blood flow to the brain Have problems with decreased blood flow to your legs Have an irregular heartbeat Have QT prolongation or a family history of it Have liver problems Know that you suffer from low blood levels of electrolytes, such as potassium or magnesium Have had a pancreas disorder known as pancreatitis Have had a surgical procedure involving the removal of the entire stomach (total gastrectomy) Are lactose-intolerant. The TASIGNA capsules contain lactose. Most patients who have mild or moderate lactose intolerance can take TASIGNA Are pregnant or plan to become pregnant. TASIGNA may harm your unborn baby. Women should not become pregnant while taking TASIGNA. Talk to your health care provider right away if you are pregnant or plan to become pregnant Are breastfeeding or plan to breastfeed. It is not known if TASIGNA passes into your breast milk. You and your doctor should decide if you will take TASIGNA or breastfeed. You should not do both It is not known if TASIGNA is safe and effective in children. Important Safety Information Please see enclosed full prescribing information including the Boxed WARNING, and the TASIGNA Medication Guide.
TASIGNA may cause serious side effects, including: Low blood counts: Low blood counts are common with TASIGNA. Your doctor will check your blood counts regularly during treatment with TASIGNA. Symptoms of low blood counts include: Unexplained bleeding or bruising Blood in urine or stool Unexplained weakness QT prolongation: Call your doctor right away if you feel lightheaded, faint or have an irregular heartbeat while taking TASIGNA. These can be symptoms of QT prolongation, a possible life-threatening heart problem Decreased blood flow to the leg, heart, or brain: People who have recently been diagnosed with Ph+ CML and take TASIGNA may develop decreased blood flow to the leg, the heart, or brain. Get medical help right away if you suddenly develop any of the following symptoms: Chest pain or discomfort Numbness or weakness Problems walking or speaking Leg pain Your leg feels cold Change in the skin color of your leg Liver damage: Symptoms include yellow skin and eyes Pancreas inflammation (pancreatitis): Symptoms include sudden stomach area pain with nausea and vomiting 33
INDICATIONS and IMPORTANT SAFETY INFORMATION ABOUT TASIGNA (nilotinib) (cont) Bleeding in the brain: Symptoms include sudden headache, changes in your eyesight, not being aware of what is going on around you and becoming unconscious Tumor Lysis Syndrome (TLS): TLS is caused by a fast breakdown of cancer cells. TLS can cause you to have: kidney failure and the need for dialysis treatment an abnormal heart beat Your doctor may do blood tests to check you for TLS Common side effects Most patients experience side effects at some time. Some common side effects you may experience include: Low blood count Nausea Rash Headache Tiredness Itching Vomiting Diarrhea Cough Constipation Muscle and joint pain Runny or stuffy nose, sneezing, sore throat Fever Night sweats Please see enclosed full prescribing information including the Boxed WARNING, and the TASIGNA Medication Guide.
Tell your doctor if you have any side effect that bothers you or does not go away. These are not all of the possible side effects of TASIGNA. For more information, ask your doctor or pharmacist. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements. Take TASIGNA exactly as your doctor tells you to take it. Do not change your dose or stop taking TASIGNA unless your doctor tells you TASIGNA is a long-term treatment Your doctor may change your dose. Your doctor may have you stop TASIGNA for some time or lower your dose if you have side effects with it If you need to take antacids (medicines to treat heartburn) do not take them at the same time that you take TASIGNA. If you take: A medicine to block the amount of acid produced in the stomach (H2 blocker): Take these medicines about 10 hours before you take TASIGNA, or about 2 hours after you take TASIGNA An antacid that contains aluminum hydroxide, magnesium hydroxide, and simethicone to reduce the amount of acid in the stomach: Take these medicines about 2 hours before or about 2 hours after you take TASIGNA Please see the full prescribing information including the Boxed WARNING, and the TASIGNA Medication Guide. 35
INDICATIONS and IMPORTANT SAFETY INFORMATION ABOUT GLEEVEC (imatinib mesylate) GLEEVEC (imatinib mesylate) is available only by prescription. GLEEVEC Indications GLEEVEC (imatinib mesylate) tablets are indicated for: Newly diagnosed adult and pediatric patients with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in the chronic phase Patients with Ph+ CML in blast crisis (BC), accelerated phase (AP), or in the chronic phase (CP) after failure of interferon-alpha therapy SAFETY: Important product information (Please see accompanying full Prescribing Information.) Who should NOT take GLEEVEC Women who are or could be pregnant. Harm to the unborn child can occur when administered to pregnant women. Therefore, women should not become pregnant and should be advised of the potential risk to the unborn child if GLEEVEC is used during pregnancy Women who are breastfeeding because of the potential for serious adverse reactions in nursing infants Sexually active females should use highly effective birth control while taking GLEEVEC. Be sure to talk to your doctor and/or healthcare professional about these issues before taking GLEEVEC. Warnings and precautions GLEEVEC is often associated with edema (swelling) and serious fluid retention. It is important that patients be weighed and monitored regularly for signs and symptoms of serious fluid retention or unexpected weight gain. Patients experiencing unexpected, rapid weight gain should speak to their doctor about appropriate supportive care treatment. Studies have shown that edema tended to occur more often among patients who are 65 and older or those taking higher doses of GLEEVEC. If you experience severe fluid retention, your doctor may treat you with diuretics and may stop your GLEEVEC treatment until the fluid retention has been managed. Treatment can be returned as appropriate depending on the initial severity of the event Please see enclosed full Prescribing Information.
Cytopenias (reduction or lack of certain cell elements in blood circulation), have occurred. Your doctor will test your blood weekly for the first month, biweekly for the second month, and periodically thereafter. In most cases, your doctor will reduce or interrupt your GLEEVEC therapy; in rare cases, if the cytopenia is severe, your doctor may discontinue treatment Severe congestive heart failure (impaired ability of the heart to pump blood) and left ventricular dysfunction (impaired functioning of the left side of the heart) have been reported, particularly in patients with other health issues and risk factors. Patients with heart disease or risk factors for heart disease or history of renal failure will be monitored and treated for the condition Severe liver problems (hepatotoxicity) may occur. Cases of fatal liver failure and severe liver injury requiring liver transplants have been reported with both short-term and long-term use of GLEEVEC. Your doctor will check your liver function before beginning treatment and continue to monitor liver function as needed. If you experience severe liver problems, your doctor may stop your treatment with GLEEVEC until the liver problem has been managed Bleeding may occur. Severe gastrointestinal (GI) bleeding has been reported in patients with Ph+ CML; therefore, GI symptoms should be monitored at the start of treatment GI perforation (small holes or tears in the wall of the stomach or intestine), in some cases fatal, has been reported In patients with hypereosinophilic syndrome (a condition with increased eosinophils, which are a type of white blood cell) e.g., HES, MDS/MPD, or ASM and heart involvement, cases of heart disease have been associated with the initiation of GLEEVEC therapy. Speak to your doctor regarding appropriate supportive care or discontinuing GLEEVEC Skin reactions, such as fluid-filled blisters, have been reported with the use of GLEEVEC Clinical cases of hypothyroidism (reduction in thyroid hormones) have been reported in patients taking levothyroxine replacement during treatment with GLEEVEC. Your doctor should closely monitor your thyroid hormone levels Long-term use may result in potential liver, kidney, and/or heart toxicities. Immune system suppression may also result from long-term use 37
INDICATIONS and IMPORTANT SAFETY INFORMATION ABOUT GLEEVEC (imatinib mesylate) (cont) GLEEVEC can cause harm to the unborn child when administered to a pregnant woman. Women should be aware of the potential harm to the fetus. Be sure to inform your doctor if you are or think you may be pregnant. You should not breastfeed while taking GLEEVEC Growth retardation (slowing of growth) has been reported in children taking GLEEVEC. The long-term effects of extended treatment with GLEEVEC on growth in children are unknown. Growth retardation may be monitored in children receiving treatment Cases of tumor lysis syndrome (TLS), which refers to an electrolyte disturbance caused by the breakdown of tumor cells, have been reported and can be life threatening in some cases. The patients at risk of TLS are those who have a higher number of tumor cells and whose tumors are fast-growing before beginning therapy. Your doctor should monitor you closely and take appropriate precautions. Correction of clinically significant dehydration and treatment of high uric acid levels are recommended prior to initiation of GLEEVEC Motor vehicle accidents involving patients receiving GLEEVEC have been reported. Patients should be advised that they may experience undesirable effects such as dizziness, blurred vision, or drowsiness during treatment with GLEEVEC. Caution should be recommended when driving a car or operating machinery Additional important safety information The following serious side effects have been reported by patients taking GLEEVEC: Severe fluid retention (holding water), which can cause swelling around the eyes or swelling of the lower legs, lungs, and heart; fatal in rare cases Increased pressure in the heart or brain; fatal in rare cases Low levels of certain blood cells Heart failure Liver problems Please see enclosed full Prescribing Information.
Hemorrhage (abnormal bleeding) Skin blistering Low levels of thyroid hormone Your doctor will check you closely for any side effects to stop more serious complications from occurring. Patients with heart disease or risk factors for heart failure should also be monitored carefully. GLEEVEC is sometimes associated with stomach or intestinal irritation. GLEEVEC should be taken with food and a large glass of water to minimize this problem. There have been rare reports, including deaths, of stomach or intestinal perforation (a small hole or tear). If you are experiencing any of the above-mentioned side effects, please be sure to speak with your doctor immediately. Common side effects of GLEEVEC Almost all patients treated with GLEEVEC experience side effects at some time. Most side effects are mild to moderate in severity. Some common side effects that you may experience include: Fluid retention (holding water) Muscle cramps, pain, or bone pain Abdominal pain Anorexia (loss of appetite) Vomiting Diarrhea Decreased hemoglobin (decrease in blood cells which carry oxygen) Hemorrhage (abnormal bleeding) Nausea Fatigue Rash If you are experiencing any of the above-mentioned side effects, please be sure to speak with your doctor immediately. The severity of some side effects may be reduced with the help of other medicines and advice from your doctor, while others may require stopping GLEEVEC therapy for a while or changing the dose. However, in some cases, GLEEVEC therapy may need to be discontinued. 39
Tell your doctor if you have a history of heart disease or risk factors for heart disease or if you experience side effects, including fever, shortness of breath, blood in your stools, jaundice (yellowing of the skin and/or eyes), sudden weight gain, or symptoms of heart failure during therapy with GLEEVEC. After the approval of GLEEVEC, the following adverse events have been reported in patients treated with GLEEVEC: compression of the heart due to increased fluid, swelling of the brain, GI perforation (holes in the stomach or intestine), and sudden lung failure. These events, including some fatalities, may or may not have been drug related. Take GLEEVEC exactly as prescribed. Do not change your dose or stop taking GLEEVEC unless you are told to do so by your doctor. If you miss a dose, take your dose as soon as possible, unless it is almost time for your next dose. In this case, your missed dose should not be taken. A double dose should not be taken to make up for any missed dose. You should take GLEEVEC with a meal and a large glass of water. Do not take any other medications without talking to your doctor or pharmacist first, including over-the-counter medications such as Tylenol (acetaminophen); herbal products (St. John s wort, Hypericum perforatum); or prescription medications including Coumadin (warfarin sodium); rifampin; erythromycin; metoprolol; ketoconazole; and Dilantin (phenytoin). Taking these with GLEEVEC may affect how they work, or affect how GLEEVEC works. You should also tell your doctor if you are taking or plan to take iron supplements. Patients should also avoid grapefruit juice and other foods that may affect how GLEEVEC works. Tylenol (acetaminophen) is a registered trademark of McNeil Consumer & Specialty Pharmaceuticals, a division of McNeil PPC, Inc. Coumadin (warfarin sodium) is a registered trademark of Bristol-Myers Squibb Company. Dilantin (phenytoin) is a registered trademark of Parke-Davis, a division of Pfizer Inc. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088. Please see accompanying full Prescribing Information. 40
ADDITIONAL RESOURCES Novartis Patient Assistance Program If you are a US resident without prescription drug coverage, you might be eligible for the Novartis Patient Assistance Program. This program helps those in financial need get access to the medications they need for treating Ph+ CML. To find out more about the Novartis Patient Assistance Program, please call 1-800-282-7630 Co-pay Assistance Program Financial support is made available by Independent Charitable Foundations for qualified patients who are unable to afford their co-pay costs. These groups include the Leukemia & Lymphoma Society and Patient Services, Inc. To find out more about co-pay assistance, please call 1-866-MyCML4U (1-866-682-6548) Get more information on these resources at www.tasigna.com Please see Important Safety Information for GLEEVEC (imatinib mesylate) and TASIGNA (nilotinib) on pages 30-40, including TASIGNA Boxed WARNING, and enclosed full Prescribing Information and TASIGNA Medication Guide.
Other resources American Cancer Society www.cancer.org 800-ACS-2345 (800-227-2345) CancerCare www.cancercare.org 800-813-HOPE (800-813-4673) Leukemia & Lymphoma Society www.lls.org 800-955-4572 National Cancer Institute (NCI) www.cancer.gov NCI s Cancer Information Service www.cancer.gov/aboutnci/cis 800-4-CANCER (800-422-6237) National Patient Advocate Foundation www.npaf.org 202-347-8009 The organizations and websites listed under additional resources are maintained by third parties over whom Novartis Pharmaceuticals Corporation has no control. As such, Novartis Pharmaceuticals Corporation makes no representation as to the accuracy or any other aspect of the information supplied by these organizations or contained in these websites. Please see Important Safety Information for GLEEVEC (imatinib mesylate) and TASIGNA (nilotinib) on pages 30-40, including TASIGNA Boxed WARNING, and enclosed full Prescribing Information and TASIGNA Medication Guide. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088. Novartis Pharmaceuticals Corporation East Hanover, NJ 07936-1080 2014 Novartis Printed in USA 4/14 AM7-1080793 Printed on Recycled Paper