What you need to know about SPRYCEL

Transcription

1 What you need to know about SPRYCEL (dasatinib). All individuals depicted are models used for illustrative purposes only, unless otherwise indicated.

2 Table of Contents Information on CML 4 What happens in CML (and how it is treated) About SPRYCEL (dasatinib) 5 How SPRYCEL works SPRYCEL for adults 6 Clinical trials in adults 9 Patient stories 10 Side effects 13 How to take SPRYCEL SPRYCEL for children 14 Important facts about childhood CML and SPRYCEL 15 Clinical trials in children 17 Side effects 18 How children should take SPRYCEL Resources 19 SPRYCEL Assist 20 Advocacy groups 21 Important Facts About SPRYCEL 25 Glossary What is SPRYCEL? SPRYCEL is a prescription medicine used to treat: Adults with newly diagnosed Philadelphia chromosome positive () chronic myeloid leukemia (CML) in chronic phase (CP) Children with CML in chronic phase IMPORTANT FACTS ABOUT SPRYCEL (dasatinib) What should I discuss with my healthcare provider before starting SPRYCEL? Talk to your healthcare provider about all of your medical conditions, including if you have any of these medical conditions: problems with your immune system heart problems, including a condition called congenital long QT syndrome low potassium or low magnesium levels in your blood lactose (milk sugar) intolerance Please read pages for Important Facts about SPRYCEL. 2

3 Is CML a treatable disease? Philadelphia chromosome-positive () chronic myeloid leukemia (CML) in chronic phase (CP) may be a disease you ve never heard of, but remember: you are not alone. You may want to know more about the disease and what you can do about it. There are medications to help treat CML. You can also count on the healthcare providers who are treating you. Did you know? About 70,000 people in the United States are living with CML. What kind of help and support are available? The best resource to answer any of your CML-related questions is a specialized healthcare team. The oncologist and other team members can help you. They will talk about the disease and its treatment, and set a schedule for regular follow-ups. And we re here too. You can find helpful facts in this brochure, including suggestions for additional resources and support. IMPORTANT FACTS ABOUT SPRYCEL (dasatinib) Tell your healthcare provider if you are: Pregnant or plan to become pregnant. SPRYCEL can harm your unborn baby. If you are able to become pregnant, you should use effective birth control during treatment and for 30 days after your final dose of SPRYCEL. If you become pregnant during treatment with SPRYCEL, talk to your healthcare provider right away. Breastfeeding or plan to breastfeed. It is not known if SPRYCEL passes into your breast milk. You should not breastfeed during treatment and for 2 weeks after your final dose of SPRYCEL. Females who are pregnant should not handle crushed or broken SPRYCEL tablets. During treatment with SPRYCEL, make sure you also talk to your healthcare provider before you begin to take anything new. Your healthcare provider can help identify any potential interactions and help find alternatives. Please read pages for Important Facts about SPRYCEL. 3

4 Information on CML What happens in CML? What do I need to know about blood cells? Blood cells are made in the bone marrow (the soft spongy center of the bone). Bone marrow makes a certain number called a count of 3 types of cells and each type has a job to do. CML is a kind of leukemia or cancer of the blood. It causes the white blood cells to behave differently. When you have CML, the bone marrow produces too many immature or damaged white blood cells. These damaged white blood cells do not work properly and crowd out normal white blood cells, red blood cells, and platelets. Normal Blood Cells in Blood Vessel Blood Cells With CML Red blood cells carry oxygen White blood cells fight infection An abnormal protein that triggers overproduction of damaged white blood cells BCR-ABL Blood vessel Platelets help control bleeding Excessive damaged white blood cells Normal cells are crowded out The decrease in normal white blood cells, red blood cells, and platelets may lead to many of the signs and symptoms of CML. Did you know? The Philadelphia chromosome is an abnormal chromosome that contains the BCR-ABL gene which can lead to the overproduction of white blood cells. How is CML treated? Not too long ago, people with CML had few treatment options. Then, a whole new kind of therapy was introduced in the early 2000s. It s called tyrosine kinase inhibitors (TKIs). TKIs work by blocking the abnormal BCR-ABL protein from producing more abnormal white blood cells. TKIs have helped many people manage their disease. Please read pages for Important Facts about SPRYCEL. 4

5 About SPRYCEL How does SPRYCEL (dasatinib) work? When you have CML, the bone marrow produces too many immature or damaged white blood cells. SPRYCEL is a TKI and works by helping to reduce the number of damaged white blood cells in your body. This reduction may allow for more normal blood cells to be produced. SPRYCEL may cause low red blood cell counts (anemia), low white blood cell counts (neutropenia), and low platelet counts (thrombocytopenia). Blood Cells With CML An abnormal protein that triggers overproduction of damaged white blood cells Blood Cells With CML SPRYCEL may help inhibit BCR-ABL BCR-ABL BCR-ABL Overproduction of damaged white blood cells This is for illustrative purposes only to show how SPRYCEL is thought to work. White blood cells fight infection Red blood cells carry oxygen Platelets help control bleeding IMPORTANT FACTS ABOUT SPRYCEL SPRYCEL may cause serious side effects, including low blood cell counts, bleeding problems, fluid retention, heart problems, pulmonary arterial hypertension, severe skin reactions, tumor lysis syndrome, and slowing of growth and development in children. Side effects of SPRYCEL which are considered common in adults include: diarrhea, headache, skin rash, shortness of breath, tiredness, nausea, and muscle pain. The most common side effects of SPRYCEL in children include: headache, nausea, pain in hands or feet (extremities), diarrhea, skin rash, and stomach (abdomen) pain. SPRYCEL may cause fertility problems in males and females. This is not a complete list of all side effects with SPRYCEL. Tell your healthcare provider if you have any side effects while taking SPRYCEL. Please read pages for Important Facts about SPRYCEL. 5

6 SPRYCEL for Adults Why has my doctor prescribed SPRYCEL (dasatinib) for me? Your doctor has chosen SPRYCEL because he or she believes it is the right treatment for you. SPRYCEL is approved for use in newly diagnosed adult patients with CML in chronic phase based on a head to head clinical trial compared to imatinib. How many patients have been treated with SPRYCEL? Since its introduction in 2006, more than 20,000 adult patients have been treated with SPRYCEL.* * SPRYCEL received initial approval in June 2006 for treatment of adults with chronic phase, accelerated phase, or myeloid or lymphoid blast phase CML with resistance or intolerance to prior therapy, including imatinib; the effectiveness of SPRYCEL was based on treatment response that was seen in both the blood and bone marrow. SPRYCEL also received approval at that time for adults with Philadelphia chromosome-positive acute lymphoblastic leukemia with resistance or intolerance to prior therapy. How was SPRYCEL studied? SPRYCEL was studied in people who were newly diagnosed with CML in chronic phase in direct comparison with another TKI called imatinib. PATIENTS ON SPRYCEL mg once a day 519 ADULTS IN THE TRIAL 260 PATIENTS ON imatinib 400 mg once a day The study was open-label, meaning both the researchers and the participants knew which treatment was given. The main goal of the trial was to see the effect of SPRYCEL and imatinib on cccyr by one year. Another goal of the study was to measure MMR. Confirmed Complete Cytogenetic Response (cccyr) A cytogenetic response occurs in the bone marrow, not just the blood. A confirmed Complete Cytogenetic Response means that there were no signs of bad cells in 2 bone marrow tests Major Molecular Response (MMR) This is a very sensitive test that can detect other bad cells in the bone marrow. A Major Molecular Response means that the amount of BCR-ABL protein is very low. IMPORTANT FACTS ABOUT SPRYCEL What are the possible side effects of SPRYCEL? Serious side effects Low blood cell counts: Low blood cell counts are common with SPRYCEL and can be severe, including low red blood cell counts (anemia), low white blood cell counts (neutropenia), and low platelet counts (thrombocytopenia). Your healthcare provider will do blood tests to check your blood cell counts regularly during your treatment with SPRYCEL. Call your healthcare provider right away if you have any of these symptoms during treatment with SPRYCEL: fever any signs of infection Please read pages for Important Facts about SPRYCEL. 6

7 SPRYCEL for Adults What were the results? At Year 1: More people who took SPRYCEL (dasatinib) achieved both a confirmed CCyR and MMR than people who took imatinib. Read below for more details. At Year 5: Results showed that more people who took SPRYCEL were able to achieve a confirmed CCyR and MMR at the end of the 5-year study. 200 patients on SPRYCEL (Total: 259) 172 patients on imatinib (Total: 260) at1 YEAR cccyr * by 1 Year 77% 66% 220 patients on SPRYCEL (Total: 259) 206 patients on imatinib (Total: 260) YEAR 5 cccyr * by Year 5 83% 79% 135 patients on SPRYCEL (Total: 259) 89 patients on imatinib (Total: 260) MMR at 1 Year 52% 34% 197 patients on SPRYCEL (Total: 259) 91 patients on imatinib (Total: 260) MMR at Year 5 76% 64% *A confirmed Complete Cytogenetic Response (cccyr) means that there were no signs of bad cells in 2 bone marrow tests. A Major Molecular Response (MMR) means that the amount of BCR-ABL protein is very low. IMPORTANT FACTS ABOUT SPRYCEL What are the possible side effects of SPRYCEL? (cont d) Serious side effects Bleeding problems: Bleeding problems are common with SPRYCEL. Sometimes these bleeding problems can be serious and lead to death. Call your healthcare provider right away if you have: unusual bleeding or bruising of your skin bright red or dark tar-like stools decreased alertness, headache, or change in speech Please read pages for Important Facts about SPRYCEL. 7

8 SPRYCEL for Adults Did SPRYCEL (dasatinib) help patients achieve cccyr earlier than 1 year? The main goal of the study was to achieve cccyr by 1 year. Patients were followed up after 5 years. For those patients who achieved a cccyr, the median time to cccyr was 3.1 months for those who took SPRYCEL, and 5.8 months for those who took imatinib. SPRYCEL imatinib 3.1months in 215 of 259 treated people 5.8 months in 204 of 260 treated people Median means the middle of the different times to this response. IMPORTANT FACTS ABOUT SPRYCEL What are the possible side effects of SPRYCEL? (cont d) Serious side effects Your body may hold too much fluid (fluid retention): Fluid retention is common with SPRYCEL and can sometimes be severe. In severe cases, fluid may build up in the lining of your lungs, the sac around your heart, or your stomach cavity. Call your healthcare provider right away if you have any of these symptoms during treatment with SPRYCEL: swelling all over your body weight gain chest pain when taking a deep breath Heart problems: SPRYCEL may cause an abnormal heart rate, heart problems, or a heart attack. Your healthcare provider will monitor the potassium and magnesium levels in your blood, and your heart function. Pulmonary Arterial Hypertension (PAH): SPRYCEL may cause high blood pressure in the vessels of your lungs. PAH may happen at any time during your treatment with SPRYCEL. Your healthcare provider should check your heart and lungs before and during your treatment with SPRYCEL. Call your healthcare provider right away if you have any of these symptoms: shortness of breath tiredness shortness of breath, especially if this happens with low levels of physical activity or at rest dry cough swelling all over your body (fluid retention) Please read pages for Important Facts about SPRYCEL. 8

9 SPRYCEL for Adults Where can I hear from other people who take SPRYCEL (dasatinib)? There are many patients out there like you who have gone on with their lives. You can hear some of their inspiring stories at sprycel.com. You ll find that people with CML may be able to live productive and satisfying lives. I can remember the day the world stopped to find out that there was a medication, a pill that I could take every morning that was a great comfort. Lee Devastating is the best word I was singularly focused on trying to find the right treatment for me once I found that, I was able to sit back a little bit. Tom Your experience and results may vary. These patient experiences were provided by actual patients with CML in chronic phase who are taking SPRYCEL. They have received payment for contributing to SPRYCEL educational and informational materials. IMPORTANT FACTS ABOUT SPRYCEL What should I discuss with my healthcare provider before starting SPRYCEL? Talk to your healthcare provider about all of your medical conditions, including if you have any of these medical conditions: problems with your immune system heart problems, including a condition called congenital long QT syndrome low potassium or low magnesium levels in your blood lactose (milk sugar) intolerance Please read pages for Important Facts about SPRYCEL. 9

10 SPRYCEL for Adults What are the side effects? Medications like SPRYCEL (dasatinib) can cause side effects, or undesired effects that people may experience. For instance, people may experience diarrhea, cramping, or fatigue it can vary from person to person. Be sure to tell your doctor if you think you re having a side effect with SPRYCEL. Try to talk to your doctor soon, even if the side effect is minor. Your doctor may be able to help. Side effects reported in at least 10% of newly-diagnosed adult patients taking SPRYCEL or imatinib Side Effect * A side effect of special interest that was reported in less than 10% of patients SPRYCEL (259 patients) imatinib (260 patients) Buildup of fluid in the body 38% 45% Excess fluid around the lungs 28% 1% Swelling caused by fluid buildup in a specific part of the body High blood pressure in the arteries of the lungs Swelling caused by fluid buildup throughout the body 14% 38% 5% <1% 4% 7% Fluid around the heart 4% 1% Congestive heart failure/cardiac dysfunction 2% 1% Fluid buildup in the lungs 1% 0% Diarrhea 22% 23% Musculoskeletal pain 14% 17% Rash 14% 18% Headache 14% 11% Stomach pain 11% 8% Fatigue 11% 12% Nausea 10% 25% Muscle pain 7% 12% Joint pain 7% 10% Bleeding* 8% 8% Within stomach and/or intestines 2% 2% Other bleeding 6% 6% Brain or spine area <1% <1% Vomiting 5% 12% Muscle spasms 5% 21% Please read pages for Important Facts about SPRYCEL. 10

11 SPRYCEL for Adults What are the side effects? (cont d) Your doctor will perform routine blood tests to see how you are doing while on SPRYCEL (dasatinib). This is a chart of serious abnormal test results from this trial of adult patients. Serious abnormal test results Side Effect SPRYCEL (259 patients) imatinib (260 patients) Low white blood cell counts 29% 24% Low platelet counts 22% 14% Low red blood cell counts 13% 9% Low phosphate levels in the bloodstream 7% 31% Low potassium in the bloodstream 0% 3% Low calcium in the bloodstream 4% 3% Higher liver enzyme levels in the bloodstream (elevated SGPT) Higher liver enzyme levels in the bloodstream (elevated SGOT) High levels of a substance caused by the breakdown of red blood cells High levels of a protein that estimates kidney damage <1% 2% <1% 1% 1% 0% 1% 1% Talk to your doctor if you have any side effects. Don t wait until your symptoms get worse. IMPORTANT FACTS ABOUT SPRYCEL Most common side effects Side effects of SPRYCEL that are considered common in adults include: diarrhea headache skin rash shortness of breath tiredness nausea muscle pain These are not all of the possible side effects of SPRYCEL. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. You may report side effects to the FDA by calling FDA Please read pages for Important Facts about SPRYCEL. 11

12 SPRYCEL for Adults What are the side effects? (cont d) Talk to your doctor if you have any side effects. Don t wait until your symptoms get worse. Here are some examples of the kinds of things your doctor may suggest if appropriate for you*: For nausea: For diarrhea: For fatigue: Eat soft, bland foods such as crackers, toast, yogurt, chicken noodle soup, cottage cheese, or sherbet Drink water, unsweetened juice, ginger ale, or sports drinks Stay away from greasy, fried, or fatty foods. Avoid tobacco, alcohol, and foods with a strong odor such as coffee, onions, and garlic Sip fluids or nibble on ice chips or popsicles so that you don t get dehydrated Eat small meals and snacks throughout the day Avoid greasy food, raw fruits and vegetables, hot or spicy food, alcohol, caffeine, and tomato or citrus juice Decide which things are most important to do, and try to take care of those first Don t force yourself to do more than you can manage Ask friends and family members to help with tasks such as cooking, housework, or errands *Tips drawn from CancerCenter.com and the American Cancer Society. Speak to your healthcare provider before taking any new prescription, over-the-counter medicines, vitamins, antacids, and herbal supplements. If an antacid is needed, it should be taken 2 hours before or 2 hours after your dose of SPRYCEL (dasatinib). IMPORTANT FACTS ABOUT SPRYCEL What are the possible side effects of SPRYCEL? (cont d) Serious side effects Severe skin reactions: SPRYCEL may cause skin reactions that can sometimes be severe. Get medical help right away if you have any of these symptoms: skin reaction with fever sore mouth or throat blistering or peeling of your skin or in the mouth Tumor Lysis Syndrome (TLS): TLS is caused by a fast breakdown of cancer cells. TLS can cause kidney failure and an abnormal heartbeat. Kidney failure may require the need for dialysis treatment. Your healthcare provider may do blood tests to check you for TLS. Slowing of growth and development in children: Effects on bone growth and development in children with chronic phase CML have happened with SPRYCEL and can sometimes be severe. Please read pages for Important Facts about SPRYCEL. 12

13 SPRYCEL for Adults How do I take SPRYCEL (dasatinib)? SPRYCEL is taken once daily, with or without food no fasting is required. Be sure to take it exactly as prescribed by your doctor. If you have CML in chronic phase, the usual dose is 100 mg once daily. Your healthcare provider may change your dose or temporarily stop treatment with SPRYCEL. Do not change or stop treatment without first talking to your healthcare provider. It s important to take your medicine exactly as your doctor prescribed. One Pill Once Daily With or Without Food Quick tip: Make SPRYCEL part of your daily routine. Pick a time or activity you do every day so that taking your medication is easy for you to remember and maintain. For instance, you could take it right after getting up or at breakfast or dinner. Follow these steps when taking SPRYCEL DO DO take SPRYCEL with or without food, either in the morning or evening once a day DO swallow SPRYCEL tablets whole DO tell your pharmacist you re taking SPRYCEL so he or she can ensure that it does not conflict with any other medicines you take DO tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, antacids, and herbal supplements like St. John s wort. Talk to your doctor about how these medicines or other products may interact with SPRYCEL DO tell your healthcare provider if you are not feeling well or running even a low fever DON T DON T cut, crush, or chew the tablets DON T drink grapefruit juice during your treatment with SPRYCEL DON T take St. John s wort during your treatment with SPRYCEL DON T change your dose or stop taking SPRYCEL without first talking to your healthcare provider DON T self-medicate if you are not feeling well DON T ignore any change in your health and how you feel If you take an antacid medicine, take it 2 hours before or 2 hours after your dose of SPRYCEL. What if I miss a dose of SPRYCEL? If you miss a dose of SPRYCEL, take your next scheduled dose at your regular time. Do not take two doses at the same time. Call your healthcare provider or your pharmacist if you are not sure what to do. What if I take too much SPRYCEL? Call your healthcare provider or go to the nearest hospital emergency room right away. Please read pages for Important Facts about SPRYCEL. 13

14 SPRYCEL for Children What are some important facts about CML in children? CML is a form of leukemia, or cancer of the blood, that can affect children CML is a chronic form of leukemia, meaning it is slower growing than other leukemias Out of all the childhood leukemias, CML accounts for less than 3% of the total number of cases Did you know? Researchers discovered that the cause of CML is connected to the Philadelphia chromosome. This is an abnormal chromosome that contains the BCR-ABL gene, which can lead to the overproduction of white blood cells. These white blood cells are often damaged and can crowd out healthy blood cells. This chromosome is found in almost everyone who has CML. Read more about what happens in CML on page 4 of this brochure. What is SPRYCEL (dasatinib)? SPRYCEL is a prescription medication used to treat children with CML in chronic phase. What can we expect from treatment? Your child s doctor will discuss the treatment goals with you. He or she will see your child for follow-up appointments to check if your child is reaching those goals. The doctor will let you know how often your child should come for appointments, and what tests to expect. Quick tip: Keep all of your child s doctor appointments to make sure he or she is on track. What is SPRYCEL? SPRYCEL is a prescription medicine used to treat: Children with CML in chronic phase IMPORTANT FACTS ABOUT SPRYCEL What should I discuss with my healthcare provider before starting SPRYCEL? Talk to your healthcare provider about all of your medical conditions, including if you have any of these medical conditions: problems with your immune system heart problems, including a condition called congenital long QT syndrome low potassium or low magnesium levels in your blood lactose (milk sugar) intolerance Please read pages for Important Facts about SPRYCEL. 14

15 SPRYCEL for Children Have there been any clinical trials with SPRYCEL (dasatinib) in children? SPRYCEL has been studied in children with CML in chronic phase. The information shown here is from a combined analysis of two clinical trials that included 51 newly diagnosed and 46 previously treated children for a total of NEWLY DIAGNOSED CHILDREN with CML in chronic phase 46 PREVIOUSLY TREATED with imatinib They had been resistant to or intolerant of imatinib (meaning imatinib had not worked or had caused side effects that led to discontinuing treatment) What were the main goals of the trials? The main goals were to find out the effects of SPRYCEL on: Complete Cytogenetic Response (CCyR) Occurs in the bone marrow, not just the blood. A Complete Cytogenetic Response means that there were no signs of bad cells. Major Cytogenetic Response (MCyR) Measures a decrease in the amount of bad cells in the bone marrow. Major Molecular Response (MMR) Means that the amount of BCR-ABL protein is very low. IMPORTANT FACTS ABOUT SPRYCEL What are the possible side effects of SPRYCEL? (cont d) Serious side effects Bleeding problems: Bleeding problems are common with SPRYCEL. Sometimes these bleeding problems can be serious and lead to death. Call your healthcare provider right away if you have: unusual bleeding or bruising of your skin bright red or dark tar-like stools decreased alertness, headache, or change in speech Please read pages for Important Facts about SPRYCEL. 15

16 SPRYCEL for Children What were the results with SPRYCEL (dasatinib)? These charts show the percentage of pediatric patients that achieved a response for CCyR, MCyR, and MMR at specific timepoints. CCyR results Newly diagnosed children (n=51) 3 months 6 months 12 months 24 months 43 % 67 % 96 % 96% Resistant to/intolerant of imatinib (n=46) 46 % 72 % 78 % 83% MCyR results Newly diagnosed children (n=51) 3 months 6 months 12 months 24 months 61 % 90 % 98 % 98% Resistant to/intolerant of imatinib (n=46) 61 % 83 % 89 % 89% MMR results Newly diagnosed children (n=51) 3 months 6 months 12 months 24 months 8 % 31 % 57 % 75% Resistant to/intolerant of imatinib (n=46) 15 % 26 % 39 % 52% IMPORTANT FACTS ABOUT SPRYCEL What are the possible side effects of SPRYCEL? (cont d) Serious side effects Your body may hold too much fluid (fluid retention): Fluid retention is common with SPRYCEL and can sometimes be severe. In severe cases, fluid may build up in the lining of your lungs, the sac around your heart, or your stomach cavity. Call your healthcare provider right away if you have any of these symptoms during treatment with SPRYCEL: swelling all over your body weight gain chest pain when taking a deep breath shortness of breath, especially if this happens with low levels of physical activity or at rest dry cough Heart problems: SPRYCEL may cause an abnormal heart rate, heart problems, or a heart attack. Your healthcare provider will monitor the potassium and magnesium levels in your blood, and your heart function. Please read pages for Important Facts about SPRYCEL. 16

17 SPRYCEL for Children What were the side effects seen in the clinical trials in children? Adverse Reactions reported in 10% of SPRYCEL-treated pediatric patients (n=97) Side Effect ALL GRADES GRADE 3/4 Headache 28% 3% Nausea 20% 0% Diarrhea 21% 0% Skin rash 19% 0% Vomiting 13% 0% Pain in extremity 19% 1% Abdominal pain 16% 0% Fatigue 10% 0% Arthralgia 10% 1% 97 children were included in total in the studies that looked at the safety profile of SPRYCEL. One of the children (1%) stopped taking treatment because of side effects. How should I store my child s SPRYCEL (dasatinib)? Store SPRYCEL tablets at room temperature between 68ºF to 77ºF (20ºC to 25ºC) Wear latex or nitrile gloves when handling tablets that have accidently been crushed or broken Keep SPRYCEL and all medicines out of reach of children Ask your healthcare provider or pharmacist about the right way to throw away outdated or unused SPRYCEL Women who are pregnant should not handle crushed or broken SPRYCEL tablets IMPORTANT FACTS ABOUT SPRYCEL What are the possible side effects of SPRYCEL? (cont d) Serious side effects Pulmonary Arterial Hypertension (PAH): SPRYCEL may cause high blood pressure in the vessels of your lungs. PAH may happen at any time during your treatment with SPRYCEL. Your healthcare provider should check your heart and lungs before and during your treatment with SPRYCEL. Call your healthcare provider right away if you have any of these symptoms: shortness of breath tiredness swelling all over your body (fluid retention) Please read pages for Important Facts about SPRYCEL. 17

18 How should my child take SPRYCEL (dasatinib)? SPRYCEL for Children The doctor will decide on the appropriate dosage based on your child s weight. Follow your doctor s advice when your child is taking SPRYCEL. It s important that your child take SPRYCEL exactly as prescribed. One Pill Once Daily With or Without Food Quick tip: Establish a daily routine so your child is familiar with taking SPRYCEL every day. It s a good idea to make sure your child understands the importance of taking their medication as prescribed by the doctor. Be sure to keep SPRYCEL, and all medications out of the reach of children. Follow these steps when taking SPRYCEL DO DO give your child their SPRYCEL with or without food, either in the morning or evening once a day DO make sure your child takes SPRYCEL exactly as your healthcare provider says DO ask your pharmacist to make sure SPRYCEL doesn t conflict with other medicines your child may take DO tell your healthcare provider about other medicines your child may be taking including prescription and over the counter medicines, vitamins, antacids, and herbal supplements. If your child takes an antacid medicine have them take it 2 hours before or 2 hours after their dose of SPRYCEL DO make sure your child swallows the SPRYCEL tablet whole DO call your healthcare provider, or go to the nearest hospital emergency room if your child takes too much SPRYCEL DON T DON T cut, crush, or chew the tablets DON T let your child drink grapefruit juice during treatment with SPRYCEL DON T let your child take St. John s wort during treatment with SPRYCEL DON T change your child s dose or have them stop taking SPRYCEL without talking to your healthcare provider DON T let your child miss a dose. If you do, wait until your child s next scheduled dose at the regular time DON T give two doses of SPRYCEL at the same time DON T ignore any change in your child s health and how they feel Please read pages for Important Facts about SPRYCEL. 18

19 Resources What kind of support may be available for people who take SPRYCEL (dasatinib)? SPRYCEL Assist is a helpful resource for people who take SPRYCEL. It offers you practical help and information about your condition and your treatment. $ $0 co-pay offer for eligible commercially insured patients* Subject to an annual maximum benefit of $32,000 One Card $0 Co-Pay Offer* For eligible commercially insured patients 1-Month Free Trial* For new eligible Medicare/Medicaid/Cash patients 1-month free trial for new, eligible Medicare, Medicaid, or cash patients* Dedicated patient support coordinators ACTIVATION REQUIRED Call SPRYCEL ( ) or visit to activate your card. *RESTRICTIONS APPLY. SEE ELIGIBILITY TERMS AND CONDITIONS. THIS CARD IS NOT INSURANCE Information, support, and resources every step of the way *Please see page 26 for the SPRYCEL One Card full Eligibility Terms and Conditions, or visit You can also take advantage of educational resources that can help you learn more about your disease and treatment. You can get live support and assistance at SPRYCEL ( ) Monday to Friday, 8:00 am to 8:00 pm EST. If you don t have a SPRYCEL One Card, ask your doctor or call SPRYCEL ( ). Did you know? The SPRYCEL Assist program has been developed to help along your journey. Be sure to speak with your doctor s office staff or one of our support coordinators to get the details. IMPORTANT FACTS ABOUT SPRYCEL What are the possible side effects of SPRYCEL? (cont d) Serious side effects Severe skin reactions: SPRYCEL may cause skin reactions that can sometimes be severe. Get medical help right away if you have any of these symptoms: skin reaction with fever sore mouth or throat Please read pages for Important Facts about SPRYCEL. blistering or peeling of your skin or in the mouth 19

20 Resources Are there CML groups that can provide additional support? There are many organizations that may be able to help you on your CML journey. See the list of national organizations below. Your doctor s office can let you know about groups in your area. This list of resources is provided as a convenience. Bristol-Myers Squibb does not endorse and is not responsible for information provided by third-party organizations. The Leukemia & Lymphoma Society (LLS) lls.org The LLS offers weekly online chats that provide a friendly forum for discussing the stresses and triumphs of those living with CML. These chats are moderated by an oncology social worker. Cancer Support Community cancersupportcommunity.org CSC offers a menu of personalized services and education for all people affected by cancer. These services are available through a network of professionally led community-based centers, hospitals, community oncology practices, and online. The National CML Society nationalcmlsociety.org The National CML Society organizes group meetings for CML patients, family members, and caregivers around the United States. CancerCare cancercare.org HOPE CancerCare provides free, professional support and information to help people manage the emotional, practical, and financial challenges of cancer. Services include counseling and support groups over the phone, online and in-person, educational workshops, publications, and financial assistance. IMPORTANT FACTS ABOUT SPRYCEL What are the possible side effects of SPRYCEL? (cont d) Serious side effects Tumor Lysis Syndrome (TLS): TLS is caused by a fast breakdown of cancer cells. TLS can cause kidney failure and an abnormal heartbeat. Kidney failure may require the need for dialysis treatment. Your healthcare provider may do blood tests to check you for TLS. Slowing of growth and development in children: Effects on bone growth and development in children with chronic phase CML have happened with SPRYCEL and can sometimes be severe. Please read pages for Important Facts about SPRYCEL. 20

21 Important Facts About SPRYCEL (dasatinib) This is a summary of important information that you need to know about SPRYCEL. Your healthcare team can work with you to help answer any questions you may have about SPRYCEL. Keep this document in a safe place, so you can refer to it before and during your treatment. Look out for the following icons as you read: Talk to your healthcare provider Call a healthcare provider right away Helpful information to remember What is SPRYCEL? SPRYCEL is a prescription medicine used to treat adults who have Newly diagnosed Philadelphia chromosome positive () chronic myeloid leukemia (CML) in chronic phase (CP) Children with CML in chronic phase Example SPRYCEL tablet. Tablet is not actual size. Tablets are white to off-white, with BMS appearing on one side. These letters may be followed by a number indicating the strength of the tablet, in milligrams. In addition, an identification number will be marked on the other side. Size and shape may vary by dose. Tablets are taken by mouth. What should I discuss with my healthcare provider before starting SPRYCEL? Talk to your healthcare provider about all of your medical conditions, including if you have any of these medical conditions: problems with your immune system heart problems, including a condition called congenital long QT syndrome Tell your healthcare provider if you are: low potassium or low magnesium levels in your blood lactose (milk sugar) intolerance Pregnant or plan to become pregnant. SPRYCEL can harm your unborn baby. If you are able to become pregnant, you should use effective birth control during treatment and for 30 days after your final dose of SPRYCEL. If you become pregnant during treatment with SPRYCEL, talk to your healthcare provider right away. (Continued on next page) 21

22 Important Facts About SPRYCEL (dasatinib) (cont d) Breastfeeding or plan to breastfeed. It is not known if SPRYCEL passes into your breast milk. You should not breastfeed during treatment and for 2 weeks after your final dose of SPRYCEL. Females who are pregnant should not handle crushed or broken SPRYCEL tablets. Tell your healthcare provider about all the medicines you take, including: prescription and over-the-counter medicines vitamins antacids herbal supplements If you take an antacid medicine, take it 2 hours before or 2 hours after your dose of SPRYCEL. SPRYCEL may interact with other medicines you are taking. This can change the relative effectiveness of SPRYCEL, or cause unwanted side effects. During treatment with SPRYCEL, make sure you also talk to your healthcare provider before you begin to take anything new. Your healthcare provider can help identify any potential interactions and help find alternatives. How should I take SPRYCEL? Take SPRYCEL exactly as your healthcare provider tells you to take it. Your healthcare provider may change your dose of SPRYCEL or temporarily stop treatment with SPRYCEL. Do not change your dose or stop taking SPRYCEL without first talking to your healthcare provider. Do: Take SPRYCEL one (1) time a day Take SPRYCEL with or without food, either in the morning or in the evening, at the same time each day* Swallow SPRYCEL tablets whole with water *Setting an alarm clock or calendar notification is a great way to remember to take medication. Do not: DO NOT cut, crush, or chew the tablets DO NOT drink grapefruit juice during treatment with SPRYCEL DO NOT take St. John s wort during treatment with SPRYCEL What if I miss a dose of SPRYCEL? If you miss a dose of SPRYCEL, take your next scheduled dose at your regular time. Do not take two doses at the same time. Call your healthcare provider or your pharmacist if you are not sure what to do. What if I take too much SPRYCEL? Call your healthcare provider or go to the nearest hospital emergency room right away. (Continued on next page) 22

23 Important Facts About SPRYCEL (dasatinib) (cont d) What are the possible side effects of SPRYCEL? Serious side effects SPRYCEL may cause serious side effects, including those listed below. Call your healthcare provider right away if you have any symptoms of the side effects below, or any other concerns about these side effects: Low blood cell counts: Low blood cell counts are common with SPRYCEL and can be severe, including low red blood cell counts (anemia), low white blood cell counts (neutropenia), and low platelet counts (thrombocytopenia). Your healthcare provider will do blood tests to check your blood cell counts regularly during your treatment with SPRYCEL. Call your healthcare provider right away if you have any of these symptoms during treatment with SPRYCEL: fever any signs of infection Bleeding problems: Bleeding problems are common with SPRYCEL. Sometimes these bleeding problems can be serious and lead to death. Call your healthcare provider right away if you have: unusual bleeding or bruising of your skin bright red or dark tar-like stools Your body may hold too much fluid (fluid retention): Fluid retention is common with SPRYCEL and can sometimes be severe. In severe cases, fluid may build up in the lining of your lungs, the sac around your heart, or your stomach cavity. Call your healthcare provider right away if you have any of these symptoms during treatment with SPRYCEL: swelling all over your body weight gain chest pain when taking a deep breath Heart problems: SPRYCEL may cause an abnormal heart rate, heart problems, or a heart attack. Your healthcare provider will monitor the potassium and magnesium levels in your blood, and your heart function. Pulmonary Arterial Hypertension (PAH): SPRYCEL may cause high blood pressure in the vessels of your lungs. PAH may happen at any time during your treatment with SPRYCEL. Your healthcare provider should check your heart and lungs before and during your treatment with SPRYCEL. Call your healthcare provider right away if you have any of these symptoms: shortness of breath tiredness decreased alertness, headache, or change in speech Severe skin reactions: SPRYCEL may cause skin reactions that can sometimes be severe. Get medical help right away if you have any of these symptoms: skin reaction with fever sore mouth or throat shortness of breath, especially if this happens with low levels of physical activity or at rest dry cough swelling all over your body (fluid retention) blistering or peeling of your skin or in the mouth Tumor Lysis Syndrome (TLS): TLS is caused by a fast breakdown of cancer cells. TLS can cause kidney failure and an abnormal heartbeat. Kidney failure may require the need for dialysis treatment. Your healthcare provider may do blood tests to check you for TLS. Slowing of growth and development in children: Effects on bone growth and development in children with chronic phase CML have happened with SPRYCEL and can sometimes be severe. (Continued on next page) 23

24 Important Facts About SPRYCEL (dasatinib) (cont d) Most common side effects The most common side effects of SPRYCEL in adults include: diarrhea headache skin rash The most common side effects of SPRYCEL in children include: headache nausea shortness of breath tiredness pain in hands or feet (extremities) diarrhea nausea muscle pain skin rash stomach (abdomen) pain SPRYCEL may cause fertility problems in males and females. Talk to your healthcare provider if this is a concern for you. These are not all of the possible side effects of SPRYCEL. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. Call your healthcare provider for medical advice about side effects. You may report side effects to the FDA by calling FDA How do I store SPRYCEL? SPRYCEL tablets should be stored at room temperature between 68 F to 77 F (20 C to 25 C). Ask your healthcare provider or pharmacist about the right way to throw away outdated or unused SPRYCEL. Wear latex or nitrile gloves when handling tablets that have accidentally been crushed or broken. Females who are pregnant should not handle crushed or broken SPRYCEL tablets. Keep SPRYCEL and all medicines out of the reach of children. This document has summarized the most important safety information for SPRYCEL. For more in-depth safety information, please read the Patient Information in the full Prescribing Information in the pages that follow. SPRYCEL and the Sprycel logo are trademarks of Bristol-Myers Squibb Company. All other brands listed are the trademarks of their respective owners. 24

25 Glossary BCR-ABL: an abnormal protein that triggers overproduction of damaged white blood cells, causing leukemia. Bone marrow: the soft tissue inside bones that produces blood cells. Chronic myeloid leukemia (CML): a slow-developing cancer of the blood in which the body produces uncontrolled numbers of abnormal cells. Chronic-phase CML: the first phase of CML; it can last for months or years; most people are diagnosed with CML during this phase. Complete cytogenetic response (CCyR): occurs in the bone marrow, not just the blood. A Complete Cytogenetic Response means that there were no signs of bad cells. Confirmed complete cytogenetic response (cccyr): means that there were no signs of bad cells in 2 bone marrow tests. Major cytogenetic response (MCyR): means a decrease in the amount of bad cells in the bone marrow. Major molecular response (MMR): means that the amount of BCR-ABL protein is very low. Myelosuppression: a condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets being produced. Philadelphia chromosome (Ph chromosome): the chromosome abnormality that causes CML; when present, it can lead to the overproduction of white blood cells. Platelets: blood cells that help control bleeding; when platelet levels are lower than normal, it is called thrombocytopenia. Pleural effusion: buildup of fluid in the area between the layers of tissue that line the lungs and the chest cavity. Red blood cells: blood cells that carry oxygen to all parts of the body; when red blood cell levels are lower than normal, it is called anemia. Side effects: the undesired effects of a drug. Tyrosine kinase inhibitors (TKIs): a class of medications that block the production of abnormal proteins. Tumor Lysis Syndrome (TLS): a metabolic disorder caused by a fast breakdown of cancer cells; can cause kidney failure and an abnormal heartbeat. White blood cells: blood cells that help fight infections; when the level of a certain type of white blood cell is lower than normal, it is called neutropenia. To Learn More About SPRYCEL (dasatinib), visit Bristol-Myers Squibb may be able to provide information and support for your SPRYCEL prescription. Call SPRYCEL ( ). SPRYCEL and the Sprycel logo are trademarks of Bristol-Myers Squibb Company. All other trademarks are property of their respective owner Bristol-Myers Squibb Company. All rights reserved. 729US /17 Printed in USA

26 TERMS AND CONDITIONS FOR SPRYCEL (dasatinib) ONE CARD Co-pay Assistance Eligibility, Terms, and Conditions Patients must have commercial (private) insurance, but their coverage does not cover the full cost of the prescription. Co-pay assistance is not valid where the entire cost of the prescription is reimbursed by insurance Patients are not eligible if they have prescription insurance coverage through a state or federal healthcare program, including but not limited to Medicare, Medicaid, MediGap, CHAMPUS, TRICARE, Veterans Affairs (VA), or Department of Defense (DoD) programs; patients who move from commercial to state or federal healthcare program insurance will no longer be eligible Cash-paying patients are not eligible for co-pay assistance Patients who purchase their prescription drug insurance through a Health Insurance Exchange (also known as a Health Insurance Marketplace) or Small Business Health Options Program (SHOP) Marketplace are currently eligible for co-pay assistance Patients must be currently receiving treatment with SPRYCEL for one of its FDA-approved indications Patients or their guardian must be 18 years of age or older The Program will pay an eligible patient s monthly co-pay, excluding certain dispensing costs, up to a maximum annual benefit of $32,000 1-Month Free Trial Eligibility, Terms, and Conditions Patients must be new to SPRYCEL and have not previously filled a prescription for SPRYCEL Patients must have a valid 30-day prescription for SPRYCEL. The Free Trial may not be redeemed on prescriptions written for longer than 30 days The Free Trial is not available to patients who have commercial insurance that pays for all or part of their medication or to patients who purchase their prescription drug insurance through a Health Insurance Exchange or SHOP Marketplace Patients must be currently receiving treatment with SPRYCEL for one of its FDA-approved indications Patients or their guardian must be 18 years of age or older Patients eligible for the Free Trial may not count the Free Trial as an expense incurred for purposes of determining out-of-pocket costs for any plan, including true out-of-pocket costs ( TrOOP ), for purposes of calculating the out-of-pocket threshold for Medicare Part D plans One Card Program Timing Activation and first use of the One Card must take place by December 31, The One Card expires on December 31, Absent a change in Massachusetts law, for Massachusetts residents only, this offer will expire on June 30, 2019 Additional Terms & Conditions Patients, pharmacists, and prescribers may not seek reimbursement from health insurance, health savings or flexible spending accounts, or any third party, for any part of the benefit (either the Free Trial or co-pay assistance) received by the patient through this offer If the patient has prescription drug insurance, the assistance offered by the card must be consistent with the patient s insurance and patient must report the value received as may be required by his/her insurance provider Offer valid only in the United States and Puerto Rico. Void where prohibited by law, taxed, or restricted The One Card Program is not insurance One Card is not transferable and is limited to 1 per patient. This offer cannot be combined with any other offer, rebate, coupon, or free trial This offer is not conditioned on any past, present, or future purchase, including refills No membership fees Bristol-Myers Squibb reserves the right to rescind, revoke, or amend this offer without notice BY USING THIS CARD, YOU AND YOUR PHARMACIST UNDERSTAND AND AGREE TO COMPLY WITH THESE ELIGIBILITY REQUIREMENTS AND TERMS OF USE Bristol-Myers Squibb Company. All rights reserved. SPRYCEL is a trademark of Bristol-Myers Squibb Company. 729US /17

27 HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use SPRYCEL safely and effectively. See full prescribing information for SPRYCEL. SPRYCEL (dasatinib) tablets, for oral use Initial U.S. Approval: RECENT MAJOR CHANGES Indications and Usage (1) 11/2017 Dosage and Administration (2) 11/2017 Warnings and Precautions (5) 11/ INDICATIONS AND USAGE SPRYCEL is a kinase inhibitor indicated for the treatment of newly diagnosed adults with Philadelphia chromosome-positive () chronic myeloid leukemia (CML) in chronic phase. (1, 14) adults with chronic, accelerated, or myeloid or lymphoid blast phase CML with resistance or intolerance to prior therapy including imatinib. (1, 14) adults with Philadelphia chromosome-positive acute lymphoblastic leukemia ( ALL) with resistance or intolerance to prior therapy. (1, 14) pediatric patients with CML in chronic phase (1, 14) DOSAGE AND ADMINISTRATION Chronic phase CML in adults: 100 mg once daily. (2) Accelerated phase CML, myeloid or lymphoid blast phase CML, or ALL in adults: 140 mg once daily. (2) Chronic phase CML in pediatrics: starting dose based on body weight. (2) Administer orally, with or without a meal. Do not crush, cut, or chew tablets. (2) DOSAGE FORMS AND STRENGTHS Tablets: 20 mg, 50 mg, 70 mg, 80 mg, 100 mg, and 140 mg. (3, 16) CONTRAINDICATIONS None. (4) WARNINGS AND PRECAUTIONS Myelosuppression and Bleeding Events: Severe thrombocytopenia, neutropenia, and anemia may occur. Use caution if used concomitantly with medications that inhibit platelet function or anticoagulants. Monitor complete blood counts regularly. Transfuse and interrupt SPRYCEL when indicated. (2.5, 5.1, 5.2, 6.1) Fluid Retention: Fluid retention, sometimes severe, including pleural effusions. Manage with supportive care measures and/or dose modification. (2.5, 5.3, 6.1) Cardiac Dysfunction: Monitor patients for signs or symptoms and treat appropriately. (5.4, 6.1) Pulmonary Arterial Hypertension (PAH): SPRYCEL (dasatinib) may increase the risk of developing PAH which may be reversible on discontinuation. Consider baseline risk and evaluate patients for signs and symptoms of PAH during treatment. Stop SPRYCEL if PAH is confirmed. (5.5) QT Prolongation: Use SPRYCEL with caution in patients who have or may develop prolongation of the QT interval. (5.6) Severe Dermatologic Reactions: Individual cases of severe mucocutaneous dermatologic reactions have been reported. (5.7, 6.3) Tumor Lysis Syndrome: Tumor lysis syndrome has been reported. Maintain adequate hydration and correct uric acid levels prior to initiating therapy with SPRYCEL. (5.8) Embryo-Fetal Toxicity: Can cause fetal harm. Advise of potential risk to fetus and avoid pregnancy. (5.9, 8.1, 8.3) Effects on Growth and Development in Pediatric Patients: epiphyses delayed fusion, osteopenia, growth retardation, and gynecomastia have been reported. Monitor bone growth and development in pediatric patients. (5.10, 6.3) ADVERSE REACTIONS Most common adverse reactions ( 15%) in patients included myelosuppression, fluid retention events, diarrhea, headache, skin rash, hemorrhage, dyspnea, fatigue, nausea, and musculoskeletal pain. (6) To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb at or FDA at FDA-1088 or DRUG INTERACTIONS Strong CYP3A4 Inhibitors: Dose reduction may be necessary. (2.3, 7.1) Strong CYP3A4 Inducers: Dose increase may be necessary. (2.3, 7.1) Antacids: Avoid simultaneous administration. (7.1) H 2 Antagonists and Proton Pump Inhibitors: Avoid coadministration. (7.1) USE IN SPECIFIC POPULATIONS Lactation: Not recommended (8.2) See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling. Revised: 11/2017 FULL PRESCRIBING INFORMATION: CONTENTS* 1 INDICATIONS AND USAGE 2 DOSAGE AND ADMINISTRATION 2.1 Dosage of SPRYCEL in Adult Patients 2.2 Dosage of SPRYCEL in Pediatric Patients 2.3 Dose Modification 2.4 Dose Escalation 2.5 Dose Adjustment for Adverse Reactions 2.6 Duration of Treatment 3 DOSAGE FORMS AND STRENGTHS 4 CONTRAINDICATIONS 5 WARNINGS AND PRECAUTIONS 5.1 Myelosuppression 5.2 Bleeding-Related Events 5.3 Fluid Retention 5.4 Cardiovascular Events 5.5 Pulmonary Arterial Hypertension 5.6 QT Prolongation 5.7 Severe Dermatologic Reactions 5.8 Tumor Lysis Syndrome 5.9 Embryo-Fetal Toxicity 5.10 Effects on Growth and Development in Pediatric Patients 6 ADVERSE REACTIONS 6.1 Clinical Trials Experience 6.2 Additional Pooled Data from Clinical Trials 6.3 Postmarketing Experience 7 DRUG INTERACTIONS 7.1 Effect of Other Drugs on Dasatinib 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy 8.2 Lactation 8.3 Females and Males of Reproductive Potential 8.4 Pediatric Use 8.5 Geriatric Use 10 OVERDOSAGE 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 12.2 Pharmacodynamics 12.3 Pharmacokinetics 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 14 CLINICAL STUDIES 14.1 Newly Diagnosed Chronic Phase CML in Adults 14.2 Imatinib-Resistant or -Intolerant CML or ALL in Adults 14.3 CML in Pediatric Patients 15 REFERENCES 16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied 16.2 Storage 16.3 Handling and Disposal 17 PATIENT COUNSELING INFORMATION *Sections or subsections omitted from the full prescribing information are not listed.