PATIENT Brochure for BOSULIF (bosutinib)

Transcription

1 PATIENT Brochure for BOSULIF PATIENT Brochure for BOSULIF (bosutinib) A guide for adult patients who have a type of leukemia called Philadelphia chromosome positive chronic myelogenous leukemia (Ph+ CML) who no longer benefit from or did not tolerate other treatment.

2 Table of Contents What is the goal of treatment for CML?...4 What are the treatment milestones for CML?...5 What is resistance?...6 What is intolerance?...6 The importance of taking your CML medicine as prescribed...7 What is BOSULIF?...8 What are the possible side effects?...8 What you should know about diarrhea and BOSULIF How should I take BOSULIF?...12 What should I tell my doctor? What were the clinical results for BOSULIF? How do I get BOSULIF and patient assistance?...20 Important Safety Information for patients...23 Notes...25 What are the terms to know?

3 introduction Helping you get where you want to be Your doctor has prescribed BOSULIF, a prescription medicine used to treat adults who have a type of leukemia called Ph+ CML who no longer benefit from or did not tolerate other treatment. When you download materials from the Patient Support and Resources page on you ll find resources to help you get started with your new medicine. With these tools in hand, you can: Discover more about your disease and why BOSULIF may be right for you Use the Side Effect Management Worksheet to learn about some side effect management tips to discuss with your doctor Use the Monthly Tracker booklet to keep track of your doctor visits, other medicines, and side effects Remember to always speak with your doctor if you have questions about this or other medicines you take. 3

4 What is the goal of treatment for CML? Chronic phase (CP): Less than 10% of cancer cells in blood or bone marrow Accelerated phase (AP): 10% to 19% of cancer cells in blood or bone marrow Blast phase (BP): Greater than or equal to 20% of cancer cells in blood or bone marrow CML has 3 phases: CP, AP, and BP. Most patients are diagnosed in CP, so the goal of treatment is to control the disease in CP and keep it from getting worse for as long as possible. To do this, tyrosine kinase inhibitors (TKIs) are used to slow the growth of CML cells. There are 3 types of responses that your doctor will measure to see if you are meeting treatment goals: Types of responses in CML Hematologic response Cytogenetic response Molecular response A return of blood cells to normal levels, a decrease of immature cells in peripheral blood (blood outside the bones), and no signs and symptoms of the disease A decrease in the number of Philadelphia (Ph) chromosomes in blood or bone marrow cells A decrease in the amount of Bcr-Abl messenger ribonucleic acid (mrna) in blood or bone marrow cells 4

5 What are the treatment milestones for CML? The following is a general set of recommendations for monitoring CML treatment that may be used for some patients. These are based on the NCCN Clinical Practice Guidelines In Oncology (NCCN Guidelines ) for Chronic Myelogenous Leukemia (V ). a Follow-up point 3 months 6 months b 12 months 18 months Treatment milestone 10% or less of Bcr-Abl detected in the blood OR Partial cytogenetic response in bone marrow 10% or less of Bcr-Abl detected in the blood OR Partial cytogenetic response in bone marrow Complete cytogenetic response No Ph chromosomes detected in the bone marrow Complete cytogenetic response No Ph chromosomes detected in the bone marrow 1% to 35% Ph chromosomes detected in the bone marrow 1% to 35% Ph chromosomes detected in the bone marrow b 6-month evaluation not needed if 3-month milestone is achieved. If tests at any of these follow-up points, or others not listed, show that you are not meeting your treatment milestones, your doctor may select a different treatment or adjust your dose. To get the most out of any treatment, it is important for you to always take your medicine as your doctor prescribed. a Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ) for Chronic Myelogenous Leukemia V National Comprehensive Cancer Network, Inc. All rights reserved. Accessed January 16, To view the most recent and complete version of the NCCN Guidelines, go online to NATIONAL COMPREHENSIVE CANCER NETWORK, NCCN, NCCN GUIDELINES, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc. 5

6 What is resistance? a Resistance is when a disease fails to respond or stops responding to a given therapy. Your doctor will schedule regular check-ups to measure your response to therapy. This will be done using blood and bone marrow tests. Resistance can occur at any time during treatment, even if you have been taking your medication successfully for several years. Because of this, resistance may be a possible cause for not meeting treatment goals. There are 2 types of resistance: Primary resistance is when you do not respond when first starting treatment Secondary resistance is when you lose your response or stop responding later in treatment Resistance is often, but not always, the result of mutations in the Bcr-Abl gene that causes Ph+ CML. What is intolerance? b Intolerance is when a patient can no longer take his or her current medicine due to unmanageable side effects. If your side effects are severe, occur too often, or are damaging to your health, your doctor may switch you to another medicine. However, having side effects does not always mean that treatment should be switched. Often, your doctor will be able to treat or manage side effects (for example, by reducing your dose) without having to switch your medicine for Ph+ CML. Always tell your doctor or nurse if you have side effects, even if you think they aren t serious. a References: 1. American Cancer Society. Leukemia chronic myeloid (myelogenous) overview. Accessed September 13, American Society of Clinical Oncology. Leukemia chronic myeloid CML. /treatment-options. Accessed December 3, Leukemia & Lymphoma Society. Chronic phase CML treatment. chronicmyeloidleukemia/treatment/chronicphasecml. Accessed December 3, b Reference: Hochhaus A, O Brien SG, Guilhot F, et al; IRIS Investigators. Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia. 2009;23:

7 The importance of taking your CML medicine as prescribed While resistance and intolerance may lead to treatment not working as expected, there s another critical issue: taking your medicine exactly as your doctor prescribed. Skipping doses or taking less medicine may affect your response to treatment. In fact, several studies have shown that patients with CML who do not take their medicine as prescribed are more likely to experience poor response and treatment outcomes. That s why it is very important to stick to the prescribed dose of your CML medicine. If you ever have questions about how much BOSULIF to take, talk with your doctor. See pages for more tips that may help you take BOSULIF as your doctor prescribed. If you are interested in co-pay support or financial assistance for BOSULIF, turn to pages

8 What is Bosulif? BOSULIF is a prescription medicine used to treat adults who have a type of leukemia called Ph+ CML who no longer benefit from or did not tolerate other treatment. Keep in mind that BOSULIF may not work the same for everyone. It is not known if BOSULIF is safe and works in children less than 18 years of age. What are the possible side effects? BOSULIF may cause serious side effects, including: Stomach problems. BOSULIF may cause stomach (abdomen) pain, nausea, diarrhea, or vomiting. Tell your doctor about any stomach problems Low blood cell counts. BOSULIF may cause low platelet counts (thrombocytopenia), low red blood cell counts (anemia), and low white blood cell counts (neutropenia). Your doctor should do blood tests to check your blood cell counts regularly during your treatment with BOSULIF. Call your doctor right away if you have unexpected bleeding or bruising, blood in your urine or stools, fever, or any signs of an infection Liver problems. BOSULIF may cause liver problems. Your doctor should do blood tests to check your liver function regularly during your treatment with BOSULIF. Call your doctor right away if your skin or the white part of your eyes turns yellow (jaundice) or you have dark tea color urine 8

9 What are the possible side effects? (cont d) Your body may hold too much fluid (fluid retention). Fluid may build up in the lining of your lungs, the sac around your heart, or your stomach cavity. Call your doctor right away if you get any of the following symptoms during your treatment with BOSULIF: shortness of breath and cough swelling all over your body chest pain weight gain swelling in your hands, ankles, or feet The most common side effects of BOSULIF include: diarrhea nausea low blood cell counts vomiting stomach pain rash fever tiredness or weakness Tell your doctor right away if you get respiratory tract infections, loss of appetite, headache, dizziness, back pain, joint pain, or itching while taking BOSULIF. These may be symptoms of a severe allergic reaction. Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of BOSULIF. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to the FDA at FDA

10 What you should know about diarrhea and BOSULIF BOSULIF may cause a range of side effects. Among the most common are stomach problems, including diarrhea. 82% of patients in the clinical trial experienced episodes of diarrhea while taking BOSULIF. Diarrhea experienced by patients in the clinical trial Median length of each episode of diarrhea Median length of time after starting treatment that first episode occurred 1 day 2 days Median number of episodes each patient experienced 3 (range per patient was 1-221) Percentage of patients with episodes of severe diarrhea 8% 10

11 What you should know about diarrhea and BOSULIF (cont d) Definitions of diarrhea Severe 7 or more loose or watery stools/bowel movements in 1 day Moderate Mild Between 4 and 6 loose or watery stools/bowel movements in 1 day Less than 4 loose or watery stools/bowel movements in 1 day If you have diarrhea, call your doctor. Your doctor may recommend you take medicine to treat diarrhea. Always talk to your doctor before taking any over-the-counter medicines. Your doctor may choose to have you stop taking BOSULIF for a period of time or change your dose to help manage diarrhea. You can also discuss the following tips with your doctor: Avoid spicy foods, fatty foods, caffeine, and raw fruit Eat mild foods Drink water often For more information on tips for managing side effects, download the Side Effects Management Worksheet from 11

12 How should I take BOSULIF? It is important to take BOSULIF exactly as prescribed by your doctor. Follow the instructions below and talk with your healthcare provider for more information. BOSULIF is taken by mouth once a day BOSULIF should be taken with food Swallow BOSULIF tablets whole Tips that may help you take BOSULIF as your doctor prescribed Make BOSULIF a part of your daily routine. Take your medicine every day at the same time. For example, you may want to take BOSULIF in the morning with breakfast or in the evening with dinner Use a pill container to organize your medicines Take your dose of BOSULIF with you in a pill container when you travel Keep a list of all the medicines you take, and tell your doctor before taking any new medicine 12

13 How should I take BOSULIF? (cont d) Remember to take BOSULIF exactly as prescribed by your doctor. Do not change your dose or stop taking BOSULIF without first talking with your doctor Your doctor may change your dose of BOSULIF or tell you to stop taking BOSULIF depending on how you are doing on treatment Do not crush or cut BOSULIF tablets. Do not touch or handle crushed or broken BOSULIF tablets You should avoid grapefruit, grapefruit juice, and supplements that contain grapefruit extract during treatment with BOSULIF. Grapefruit products increase the amount of BOSULIF in your body If you miss a dose of BOSULIF, take it as soon as you remember. If you miss a dose by more than 12 hours, skip that dose and take your next dose at your regular time. Do not take 2 doses at the same time If you take too much BOSULIF, call your doctor or go to the nearest hospital emergency room right away Red tablets are 500 mg Yellow tablets are 100 mg Tablets not shown actual size. 13

14 What should I tell my doctor? Your doctor needs to know about any other medical conditions or diseases that you have. Below are some items to discuss with your doctor. Because BOSULIF and certain other medicines can affect each other, talk to your doctor about the other medicines you take. This includes prescription medicines, non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take: Medicines that increase the amount of BOSULIF in your blood stream, such as: Amprenavir (Agenerase ) Aprepitant (Emend ) Atazanavir (Reyataz ) Boceprevir (Victrelis ) Ciprofloxacin (Cipro, Proquin XR ) Clarithromycin (Biaxin, Prevpac ) Conivaptan (Vaprisol ) Crizotinib (Xalkori ) Darunavir (Prezista ) Digoxin (Lanoxin ) Diltiazem (Cardizem, Dilacor XR, Tiazac ) Erythromycin (Ery-tab ) Fluconazole (Diflucan ) Fosamprenavir (Lexiva ) Imatinib (Gleevec ) Indinavir (Crixivan ) Itraconazole (Onmel, Sporanox ) Ketoconazole (Nizoral ) Nefazodone (Serzone ) Nelfinavir (Viracept ) Posaconazole (Noxafil ) Ritonavir (Kaletra, Norvir ) Saquinavir (Invirase, Fortovase ) Telaprevir (Incivek ) Telithromycin (Ketek ) Verapamil (Calan, Covera-HS, Tarka, Verelan PM ) Voriconazole (Vfend ) Brand names mentioned above are the registered trademarks of their respective companies. 14

15 What should I tell my doctor? (cont d) Medicines that decrease the amount of BOSULIF in your blood stream, such as: Bosentan (Tracleer ) Phenobarbital (Solfoton ) Carbamazepine (Carbatrol, Equetro, Tegretol ) Efavirenz (Sustiva ) Etravirine (Intelence ) Modafinil (Provigil ) Nafcillin (Unipen, Nallpen ) Phenytoin (Dilantin ) Rifabutin (Mycobutin ) Rifampin (Rifamate, Rifater, Rifadin ) St. John s wort BOSULIF is best absorbed from your stomach into your blood stream in the presence of stomach acid. You should avoid taking BOSULIF with medicines that reduce stomach acid, such as: Esomeprazole (Nexium ), esomeprazole strontium Omeprazole (Prilosec, Vimovo, Zegerid ) Dexlansoprazole (Dexilant ) Lansoprazole (Prevacid ) Pantoprazole sodium (Protonix ) Rabeprazole (AcipHex ) Medicines that neutralize stomach acid, such as: cimetidine (Tagamet ), famotidine (Pepcid ), ranitidine (Zantac ), aluminum hydroxide/magnesium hydroxide (Maalox ), calcium carbonate (Tums ), or calcium carbonate and magnesia (Rolaids ) may be taken up to 2 hours before or 2 hours after BOSULIF. Brand names mentioned above are the registered trademarks of their respective companies. 15

16 What should I tell my doctor? (cont d) Before you take BOSULIF, tell your doctor if you: have liver problems have heart problems have kidney problems have any other medical conditions are pregnant or plan to become pregnant. BOSULIF can harm your unborn baby. You should not become pregnant while taking BOSULIF. Tell your doctor right away if you become pregnant while taking BOSULIF are a woman who may become pregnant. Use effective contraception (birth control) during and for at least 30 days after completing treatment with BOSULIF. Talk to your doctor about forms of birth control are breastfeeding or plan to breastfeed. It is not known if BOSULIF passes into your breast milk or if it can harm your baby. You and your doctor should decide if you will take BOSULIF or breastfeed. You should not do both 16

17 What should I tell my doctor? (cont d) Tell your doctor right away if you get respiratory tract infections, loss of appetite, headache, dizziness, back pain, joint pain, or itching while taking BOSULIF. These may be symptoms of a severe allergic reaction. Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of BOSULIF. For more information, ask your doctor or pharmacist. If you have diarrhea, call your doctor. Your doctor may recommend you take medicine to treat diarrhea. Always talk to your doctor before taking any over-the-counter medicines. Your doctor may choose to have you stop taking BOSULIF for a period of time or change your dose to help you manage diarrhea. If you miss a dose of BOSULIF, take it as soon as you remember. If you miss a dose by more than 12 hours, skip that dose and take your next dose at your regular time. Do not take 2 doses at the same time. If you take too much BOSULIF, call your doctor or go to the nearest hospital emergency room right away. 17

18 What were the clinical trial results for BOSULIF? BOSULIF was studied in adult patients with Ph+ CML in: CP who had been treated with 1 prior TKI CP who had been treated with 2 or more prior therapies AP or BP who had been treated with at least 1 prior TKI To see if BOSULIF worked in the clinical trial, doctors looked at patients blood and bone marrow samples regularly. In patients in CP, response was measured by the decrease in the number of white blood cells (WBCs) that had the Philadelphia chromosome. This is called cytogenetic response. A major cytogenetic response (MCyR) is when the medicine reduces the number of patients WBCs with the Philadelphia chromosome to less than or equal to 35%. In patients in AP and BP, response was measured by overall hematologic response (OHR). 18

19 What were the clinical trial results for BOSULIF? (cont d) Efficacy results Patients in CP who had been treated with 1 prior TKI (Gleevec [imatinib]) At 6 months from the start of therapy with BOSULIF, 34% of these patients had an MCyR When these patients were followed for a longer period (at least 23 months), 53% of patients achieved an MCyR at some point during that period Patients in CP who had been treated with 2 or more prior TKIs By 6 months from the start of therapy with BOSULIF, 27% of these patients had an MCyR When these patients were followed for a longer period (at least 13 months), 32% of patients achieved an MCyR at some point during that period Patients in AP or BP who had been treated with at least 1 prior TKI When patients were followed for 11 months, 55% of patients in AP achieved an OHR at some point during that period When patients were followed for 11 months, 28% of patients in BP achieved an OHR at some point during that period Gleevec is a registered trademark of Novartis AG. 19

20 How do I get BOSULIF and patient assistance? Learn how to get BOSULIF, co-pay support, other financial assistance, and additional resources. BOSULIF is available only by prescription through retail and specialty pharmacies Specialty pharmacies offer a range of services, including mail order, to help with access and are able to coordinate delivery of BOSULIF regardless of where you live. If you need help determining which specialty pharmacy to use, your doctor s office may be able to help you find one that works with your insurance. A Pfizer First Resource program counselor may also be able to help you or your doctor s office identify an appropriate specialty pharmacy. Call for more information. 30-day free trial supply If you are new to BOSULIF and are eligible for the program, you can receive a 30-day free trial supply. Terms and Conditions apply. Please see below. You may only be offered enrollment in the program through your healthcare provider. Enrolling is easy just follow these steps: 1. With your healthcare provider, fill out an Enrollment form and a Patient Authorization form. 2. Have the forms faxed to The 30-day free trial supply will then be mailed to you. Terms and Conditions for Voucher Program The trial voucher is not a prescription for BOSULIF beyond 30 days and there is no obligation to continue BOSULIF. To continue a patient on therapy, a separate prescription must be written to be filled at the patient s pharmacy of choice. Patients may be offered enrollment in the trial voucher program exclusively through their healthcare provider. This offer is valid once per patient for a 30-day supply through 12/31/14. By enrolling in the 30-day trial voucher offer for BOSULIF, you acknowledge that you currently meet the eligibility criteria and will comply with the Terms and Conditions described below: 1. Voucher is valid for 30 days of dosing of BOSULIF, not to exceed 500 mg once daily for 30 days, for new patients. 2. A Patient Authorization form and Patient Enrollment form should be completed and returned. 3. No claim for reimbursement for product dispensed pursuant to this voucher may be submitted to any third-party payer, whether a private or government payer. 4. This free trial voucher cannot be combined with any other rebate/coupon, free trial, or similar offer for the specified prescription. 5. This free trial is not health insurance. 6. Offer good only in the United States and Puerto Rico. 7. Only patients new to BOSULIF may use this voucher. By redeeming this voucher, you certify that you are not currently using BOSULIF. Only 1 voucher per person may be redeemed under this program. This voucher is not transferable. 8. Pfizer reserves the right to rescind, revoke, or amend this free trial voucher without notice. 9. The free trial voucher expires 12/31/ Typical savings with this voucher for insured patients is estimated to be $65, or the full out-of-pocket cost for the patient for a 30-day prescription. 20

21 How do I get BOSULIF and patient assistance? (cont d) BOSULIF Co-pay Program for eligible commercially insured patients a Pay no more than $10for each 30-day prescription of BOSULIF (bosutinib) Expires: 12/31/2014 BIN: Group: ID#: Terms and Conditions apply. This card is not health insurance. You may be eligible for the BOSULIF Co-pay Program to lower your out-of-pocket costs for BOSULIF. If eligible, you will pay no more than $10 for each 30-day prescription of BOSULIF with maximum annual savings of $25,000. Terms and Conditions apply. Enroll online at or call BOSULIF ( ) 24 hours a day Monday Friday, Saturday 8 am 7 pm (EST), and Sunday 9 am 5 pm (EST). a Also available for cash-paying patients. Maximum annual savings will apply. Terms and Conditions for Co-pay Program By enrolling in the co-pay offer for BOSULIF (bosutinib), you acknowledge that you currently meet the eligibility criteria and will comply with the Terms and Conditions described below: 1. The offer is not valid for prescriptions that are eligible to be reimbursed, in whole or in part, by Medicaid, Medicare, or other federal or state healthcare programs (including any state prescription drug assistance programs and the Government Health Insurance Plan available in Puerto Rico [formerly known as La Reforma de Salud ]). 2. The offer is not valid for prescriptions that are eligible to be reimbursed by private insurance plans or other health or pharmacy benefit programs, which reimburse you for the entire cost of your prescription drugs. 3. Maximum annual savings of $25, You must deduct the value received under this program from any reimbursement request submitted to your insurance plan, either directly by you or on your behalf. 5. Cannot be combined with any other rebate/coupon, free trial, or similar offer for the specified prescription. 6. The offer will be accepted only at participating pharmacies. 7. This offer is not health insurance. 8. Offer good only in the United States and Puerto Rico. 9. Pfizer reserves the right to rescind, revoke, or amend the program without notice. 10. Program expires 12/31/ No membership fees. 12. The offer is limited to 1 per person during this offering period and is not transferable. 13. This offer can be used by cash-paying patients. The maximum annual savings of $25,000 still applies. 14. Typical savings with the card for a 30-day prescription of BOSULIF, for a commercially insured patient with a co-pay benefit design, is estimated to be $55. For a commercially insured patient with co-insurance requirements, savings could be greater and depend on the benefit design. Pfizer Inc., 235 East 42 nd Street, New York, NY

22 How do I get BOSULIF and patient assistance? (cont d) Pfizer First Resource Program Call , Monday Friday 9 AM 8 pm (EST) to learn more. If you are uninsured or do not have enough prescription drug coverage, you may be able to get your prescription for BOSULIF for free through the Pfizer First Resource program. A program counselor can help you find which programs you may be eligible for, as well as help you find an appropriate specialty pharmacy. Patient Advocate Foundation The Patient Advocate Foundation offers assistance to patients with specific issues they are facing with their insurer, employer, and/or creditor regarding insurance, job retention, and/or debt crisis matters relative to their diagnosis of life-threatening or debilitating diseases. Caregiver Action Network The Caregiver Action Network provides education, peer support, and resources to family caregivers across the United States free of charge. Well Spouse Association The Well Spouse Association advocates for and addresses the needs of individuals caring for a chronically ill and/or disabled spouse/partner. 22

23 Important Safety Information for patients Do not take BOSULIF if you are allergic to bosutinib or any of the ingredients in BOSULIF. BOSULIF may cause serious side effects, including: Stomach problems. BOSULIF may cause stomach (abdomen) pain, nausea, diarrhea, or vomiting. Tell your doctor about any stomach problems Low blood cell counts. BOSULIF may cause low platelet counts (thrombocytopenia), low red blood cell counts (anemia) and low white blood cell counts (neutropenia). Your doctor should do blood tests to check your blood cell counts regularly during your treatment with BOSULIF. Call your doctor right away if you have unexpected bleeding or bruising, blood in your urine or stools, fever, or any signs of an infection Liver problems. BOSULIF may cause liver problems. Your doctor should do blood tests to check your liver function regularly during your treatment with BOSULIF. Call your doctor right away if your skin or the white part of your eyes turns yellow (jaundice) or you have dark tea color urine Your body may hold too much fluid (fluid retention). Fluid may build up in the lining of your lungs, the sac around your heart, or your stomach cavity. Call your doctor right away if you get any of the following symptoms during your treatment with BOSULIF: shortness of breath and cough chest pain swelling in your hands, ankles, or feet swelling all over your body weight gain The most common side effects of BOSULIF include: diarrhea stomach pain nausea rash low blood cell counts fever vomiting tiredness or weakness Please see 23

24 Important Safety Information for patients (cont d) Tell your doctor right away if you get respiratory tract infections, loss of appetite, headache, dizziness, back pain, joint pain, or itching while taking BOSULIF. These may be symptoms of a severe allergic reaction. Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of BOSULIF. For more information, ask your doctor or pharmacist. Tell your doctor about the medicines you take, including prescription medicines, non-prescription medicines, vitamins, and herbal supplements. BOSULIF and certain other medicines can affect each other. Before you take BOSULIF, tell your doctor if you: have liver problems have heart problems have kidney problems have any other medical conditions are pregnant or plan to become pregnant. BOSULIF can harm your unborn baby. You should not become pregnant while taking BOSULIF. Tell your doctor right away if you become pregnant while taking BOSULIF are a woman who may become pregnant. Use effective contraception (birth control) during and for at least 30 days after completing treatment with BOSULIF. Talk to your doctor about forms of birth control are breastfeeding or plan to breastfeed. It is not known if BOSULIF passes into your breast milk or if it can harm your baby. You and your doctor should decide if you will take BOSULIF or breastfeed. You should not do both Please see full Prescribing Information, including Patient Information, beginning on page

25 Keep going determination is inspiring Notes Use this space to write down any questions you have for your doctor or nurse. 25

26 What are the terms to know? Bcr-Abl: An abnormal gene that causes bone marrow to grow white blood cells faster than normal. Bone marrow: The soft, sponge-like tissue in the center of most bones. It makes white blood cells, red blood cells, and platelets. Chromosomes: The part of a cell that holds genetic information. Clinical study: A type of research study that tests how well a new medicine works in people. These studies can test new methods of screening, prevention, diagnosis, or treatment of a disease. Genes: Pieces of deoxyribonucleic acid (DNA) that parents pass on to a child. Genes determine hair and eye color, as well as many other traits. Median: The median is a kind of average. Median number of episodes of diarrhea means that half of the patients in the study experienced more episodes of diarrhea and half experienced fewer episodes of diarrhea. Messenger ribonucleic acid (mrna): A type of RNA found in cells. mrna molecules carry the genetic information needed to make proteins. They carry the information from the DNA in the nucleus of the cell to the cytoplasm where the proteins are made. Philadelphia chromosome: An abnormality in your genes that results in an unnatural protein called Bcr-Abl. This gene causes CML cells to grow uncontrollably. Tyrosine kinase inhibitor (TKI): A medicine that works to block CML cell growth in patients with cancer. In CML, a TKI is used to block Bcr-Abl. BSW Pfizer Inc. All rights reserved. February

27 HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use BOSULIF safely and effectively. See full prescribing information for BOSULIF BOSULIF (bosutinib) tablets, for oral use Initial U.S. Approval: RECENT MAJOR CHANGES Dosage and Administration, Renal Impairment (2.8) 4/ INDICATIONS AND USAGE BOSULIF is a kinase inhibitor indicated for the treatment of adult patients with chronic, accelerated, or blast phase Ph+ chronic myelogenous leukemia (CML) with resistance or intolerance to prior therapy. (1) Myelosuppression: Monitor blood counts and manage as necessary. (2.4, 5.2) Hepatic toxicity: Monitor liver enzymes at least monthly for the first three months and as needed. Withhold, dose reduce, or discontinue BOSULIF. (2.3, 5.3) Fluid retention: Monitor patients and manage using standard of care treatment. Withhold, dose reduce, or discontinue BOSULIF. (2.3, 5.4) Embryofetal toxicity: May cause fetal harm. Females of reproductive potential should avoid becoming pregnant while being treated with BOSULIF. (5.5) ADVERSE REACTIONS Most common adverse reactions (incidence greater than 20%) are diarrhea, nausea, thrombocytopenia, vomiting, abdominal pain, rash, anemia, pyrexia, and fatigue. (6) DOSAGE AND ADMINISTRATION Recommended Dose: 500 mg orally once daily with food. (2.1) Consider dose escalation to 600 mg daily in patients who do not reach complete hematologic response by week 8 or complete cytogenetic response by week 12 and do not have Grade 3 or greater adverse reactions. (2.2) Adjust dosage for hematologic and non-hematologic toxicity. (2.3, 2.4) Adjust dosage for hepatic and renal impairment. (2.7, 2.8) DOSAGE FORMS AND STRENGTHS Tablets: 100 mg and 500 mg. (3) CONTRAINDICATIONS Hypersensitivity to BOSULIF. (4) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at or FDA at FDA-1088 or DRUG INTERACTIONS CYP3A Inhibitors and Inducers: Avoid concurrent use of BOSULIF with strong or moderate CYP3A inhibitors and inducers. (2.5, 2.6, 7.1, 7.2) Proton Pump Inhibitors: May decrease bosutinib drug levels. Consider shortacting antacids in place of proton pump inhibitors. (7.2) See 17 for PATIENT COUNSELING INFORMATION and FDAapproved patient labeling Revised: 9/ WARNINGS AND PRECAUTIONS Gastrointestinal toxicity: Monitor and manage as necessary. Withhold, dose reduce, or discontinue BOSULIF. (2.3, 5.1) FULL PRESCRIBING INFORMATION: CONTENTS* 1 INDICATIONS AND USAGE 2 DOSAGE AND ADMINISTRATION 2.1 Recommended Dosing 2.2 Dose Escalation 2.3 Dose Adjustments for Non-Hematologic Adverse Reactions 2.4 Dose Adjustments for Myelosuppression 2.5 Concomitant Use With CYP3A Inhibitors 2.6 Concomitant Use With CYP3A Inducers 2.7 Hepatic Impairment 2.8 Renal Impairment 3 DOSAGE FORMS AND STRENGTHS 4 CONTRAINDICATIONS 5 WARNINGS AND PRECAUTIONS 5.1 Gastrointestinal Toxicity 5.2 Myelosuppression 5.3 Hepatic Toxicity 5.4 Fluid Retention 5.5 Embryofetal Toxicity 6 ADVERSE REACTIONS 6.1 Imatinib-Resistant or -Intolerant Ph+ Chronic Phase (CP), Accelerated Phase (AP), and Blast Phase (BP) CML 6.2 Additional Data from Multiple Clinical Trials 7 DRUG INTERACTIONS 7.1 Drugs That May Increase Bosutinib Plasma Concentrations 7.2 Drugs That May Decrease Bosutinib Plasma Concentrations 7.3 Drugs That May Have Their Plasma Concentration Altered By Bosutinib 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy 8.3 Nursing Mothers 8.4 Pediatric Use 8.5 Geriatric Use 8.6 Hepatic Impairment 8.7 Renal Impairment 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 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. 1

28 FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE BOSULIF is indicated for the treatment of adult patients with chronic, accelerated, or blast phase Philadelphia chromosomepositive (Ph+) chronic myelogenous leukemia (CML) with resistance or intolerance to prior therapy. 2 DOSAGE AND ADMINISTRATION 2.1 Recommended Dosing The recommended dose and schedule of BOSULIF is 500 mg orally once daily with food. Continue treatment with BOSULIF until disease progression or patient intolerance. If a dose is missed beyond 12 hours, the patient should skip the dose and take the usual prescribed dose on the following day. 2.2 Dose Escalation Consider dose escalation to 600 mg once daily with food in patients who do not reach complete hematological response (CHR) by week 8 or a complete cytogenetic response (CCyR) by week 12, who did not have Grade 3 or higher adverse reactions, and who are currently taking 500 mg daily. 2.3 Dose Adjustments for Non-Hematologic Adverse Reactions Elevated liver transaminases: If elevations in liver transaminases greater than 5 institutional upper limit of normal (ULN) occur, withhold BOSULIF until recovery to less than or equal to 2.5 ULN and resume at 400 mg once daily thereafter. If recovery takes longer than 4 weeks, discontinue BOSULIF. If transaminase elevations greater than or equal to 3 ULN occur concurrently with bilirubin elevations greater than 2 ULN and alkaline phosphatase less than 2 ULN (Hy s law case definition), discontinue BOSULIF [see Warnings and Precautions (5.3)]. Diarrhea: For NCI CTCAE Grade 3-4 diarrhea (increase of greater than or equal to 7 stools/day over baseline/pretreatment), withhold BOSULIF until recovery to Grade less than or equal to 1. BOSULIF may be resumed at 400 mg once daily [see Warnings and Precautions (5.1)]. For other clinically significant, moderate or severe non-hematological toxicity, withhold BOSULIF until the toxicity has resolved, then consider resuming BOSULIF at 400 mg once daily. If clinically appropriate, consider re-escalating the dose of BOSULIF to 500 mg once daily. 2.4 Dose Adjustments for Myelosuppression Dose reductions for severe or persistent neutropenia and thrombocytopenia are described below (Table 1). Table 1: Dose Adjustments for Neutropenia and Thrombocytopenia ANC a less than 1000x10 6 /L or Platelets less than 50,000x10 6 /L Withhold BOSULIF until ANC greater than or equal to1000x10 6 /L and platelets greater than or equal to 50,000x10 6 /L. Resume treatment with BOSULIF at the same dose if recovery occurs within 2 weeks. If blood counts remain low for greater than 2 weeks, upon recovery, reduce dose by 100 mg and resume treatment. If cytopenia recurs, reduce dose by an additional 100 mg upon recovery and resume treatment. a Absolute Neutrophil Count Doses less than 300 mg/day have not been evaluated. 2.5 Concomitant Use With CYP3A Inhibitors Avoid the concomitant use of strong or moderate CYP3A and/or P-gp inhibitors with BOSULIF as an increase in bosutinib plasma concentration is expected (strong CYP3A inhibitors include ritonavir, indinavir, nelfinavir, saquinavir, ketoconazole, boceprevir, telaprevir, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, nefazodone and conivaptan. Moderate CYP3A inhibitors include fluconazole, darunavir, erythromycin, diltiazem, atazanavir, aprepitant, amprenavir, fosamprevir, crizotinib, imatinib, verapamil, grapefruit products and ciprofloxacin) [see Drug Interactions (7.1)]. 2.6 Concomitant Use With CYP3A Inducers Avoid the concomitant use of strong or moderate CYP3A inducers with BOSULIF as a large reduction in exposure is expected (strong CYP3A inducers include rifampin, phenytoin, carbamazepine, St. John s Wort, rifabutin and phenobarbital. Moderate CYP3A inducers include bosentan, nafcillin, efavirenz, modafinil and etravirine) [see Drug Interactions (7.2)]. 2.7 Hepatic Impairment In patients with pre-existing mild, moderate, and severe hepatic impairment, the recommended dose of BOSULIF is 200 mg daily. A daily dose of 200 mg in patients with hepatic impairment is predicted to result in an area under the concentration curve 2

29 (AUC) similar to the AUC seen in patients with normal hepatic function receiving 500 mg daily. However, there are no clinical data for efficacy at the dose of 200 mg once daily in patients with hepatic impairment and CML [see Use in Special Populations (8.6) and Clinical Pharmacology (12.3)]. 2.8 Renal Impairment In patients with pre-existing severe renal impairment (CLcr less than 30 ml/min), the recommended dose of BOSULIF is 300 mg daily. A daily dose of 300 mg in patients with severe renal impairment is predicted to result in an area under the concentration curve (AUC) similar to the AUC seen in patients with normal renal function receiving 500 mg daily. However, there are no clinical data for efficacy at the dose of 300 mg once daily in patients with severe renal impairment and CML [see Use in Special Populations (8.7) and Clinical Pharmacology (12.3)]. 3 DOSAGE FORMS AND STRENGTHS 100 mg tablets: yellow, oval, biconvex, film-coated tablets debossed with Pfizer on one side and 100 on the other. 500 mg tablets: red, oval, biconvex, film-coated tablets debossed with Pfizer on one side and 500 on the other. 4 CONTRAINDICATIONS Hypersensitivity to BOSULIF. In the BOSULIF clinical trials, anaphylactic shock occurred in less than 0.2% of treated patients. 5 WARNINGS AND PRECAUTIONS 5.1 Gastrointestinal Toxicity Diarrhea, nausea, vomiting, and abdominal pain occur with BOSULIF treatment. Monitor and manage patients using standards of care, including antidiarrheals, antiemetics, and/or fluid replacement. In the single-arm Phase 1/2 clinical trial, the median time to onset for diarrhea (all grades) was 2 days and the median duration per event was 1 day. Among the patients who experienced diarrhea, the median number of episodes of diarrhea per patient during treatment with BOSULIF was 3 (range 1-221). To manage gastrointestinal toxicity, withhold, dose reduce, or discontinue BOSULIF as necessary [see Dosage and Administration (2.3) and Adverse Reactions (6)]. 5.2 Myelosuppression Thrombocytopenia, anemia and neutropenia occur with BOSULIF treatment. Patients with CML who are receiving BOSULIF should have a complete blood count performed weekly for the first month and then monthly thereafter, or as clinically indicated. To manage myelosuppression, withhold, dose reduce, or discontinue BOSULIF as necessary [see Dosage and Administration (2.4) and Adverse Reactions (6)]. 5.3 Hepatic Toxicity One case consistent with drug induced liver injury (defined as concurrent elevations in ALT or AST greater than or equal to 3 ULN with total bilirubin greater than 2 ULN and alkaline phosphatase less than 2 ULN) occurred in a trial of BOSULIF in combination with letrozole. The patient recovered fully following discontinuation of BOSULIF. This case represented 1 out of 1209 patients in BOSULIF clinical trials. In the 546 patients from the safety population, the incidence of ALT elevation was 17% and AST elevation was 14 %. Twenty percent of the patients experienced an increase in either ALT or AST. Most cases of transaminase elevations occurred early in treatment; of patients who experienced transaminase elevations of any grade, more than 80% experienced their first event within the first 3 months. The median time to onset of increased ALT and AST was 30 and 33 days, respectively, and the median duration for each was 21 days. Perform monthly hepatic enzyme tests for the first three months of treatment with BOSULIF and as clinically indicated. In patients with transaminase elevations, monitor liver enzymes more frequently. Withhold, dose reduce, or discontinue BOSULIF as necessary [see Dosage and Administration (2.3) and Adverse Reactions (6)]. 5.4 Fluid Retention Fluid retention occurs with BOSULIF and may manifest as pericardial effusion, pleural effusion, pulmonary edema, and/or peripheral edema. In the single-arm Phase 1/2 clinical trial in 546 patients with CML treated with prior therapy, severe fluid retention was reported in 14 patients (3%). Specifically, 9 patients had a Grade 3 or 4 pleural effusion, 3 patients experienced both Grade 3 or Grade 4 pleural and pericardial effusions, 1 patient experienced Grade 3 peripheral and pulmonary edema, and 1 patient had a Grade 3 edema. Monitor and manage patients using standards of care. Interrupt, dose reduce or discontinue BOSULIF as necessary [see Dosage and Administration (2.3) and Adverse Reactions (6)]. 5.5 Embryofetal Toxicity There are no adequate and well controlled studies of BOSULIF in pregnant women. BOSULIF can cause fetal harm when administered to a pregnant woman. Bosutinib caused embryofetal toxicities in rabbits at maternal exposures that were greater than the clinical exposure at the recommended bosutinib dose of 500 mg/day. Females of reproductive potential should be advised to avoid pregnancy while being treated with BOSULIF. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus [see Use in Specific Populations (8.1)]. 3

30 6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Gastrointestinal toxicity [see Dosage and Administration (2.3) and Warnings and Precautions (5.1)]. Myelosuppression [see Dosage and Administration (2.4) and Warnings and Precautions (5.2)]. Hepatic toxicity [see Dosage and Administration (2.5) and Warnings and Precautions (5.3)]. Fluid retention [see Warnings and Precautions (5.4)]. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Serious adverse reactions reported include anaphylactic shock [see Contraindications (4)], myelosuppression, gastrointestinal toxicity (diarrhea), fluid retention, hepatotoxicity and rash. Adverse reactions of any toxicity grade reported for greater than 20% of patients in the Phase 1/2 safety population (n=546) were diarrhea (82%), nausea (46%), thrombocytopenia (41%), vomiting (39%), abdominal pain (37%), rash (35%), anemia (27%), pyrexia (26%), and fatigue (24%). 6.1 Imatinib-Resistant or -Intolerant Ph+ Chronic Phase (CP), Accelerated Phase (AP), and Blast Phase (BP) CML The single-arm Phase 1/2 clinical trial enrolled patients with Ph+ chronic, accelerated, or blast phase chronic myelogenous leukemia (CML) and Ph+ acute lymphoblastic leukemia (ALL) with resistance or intolerance to prior therapy. The safety population (received at least 1 dose of BOSULIF) included 546 CML patients. Within the safety population there were 287 patients with CP CML previously treated with imatinib only who had a median duration of BOSULIF treatment of 24 months, and a median dose intensity of 484 mg/day. There were 119 patients with CP CML previously treated with both imatinib and at least 1 additional TKI who had a median duration of BOSULIF treatment of 9 months and a median dose intensity of 475 mg/day. There were 76 patients with AP CML, and 64 patients with BP CML. In the patients with AP CML and BP CML, the median duration of BOSULIF treatment was 10 months and 3 months, respectively. The median dose intensity was 483 mg/day, and 500 mg/day, in the AP CML and BP CML cohorts, respectively. Table 2 identifies adverse reactions greater than or equal to 10% for all grades and grades 3 or 4 for the Phase 1/2 CML safety population. Table 2: Adverse Reactions (10% or greater) in patients with CML System Organ Class Preferred Term Gastrointestinal Disorders Diarrhea Nausea Abdominal Pain a Vomiting Blood and Lymphatic System Disorders Thrombocytopenia Anemia Neutropenia General Disorders and Administrative Site Conditions Fatigue b Pyrexia Edema c Asthenia Infections and Infestations Respiratory tract infection d Nasopharyngitis Investigations Alanine aminotransferase increased Aspartate aminotransferase increased CP CML N=406 n (%) All Grades Grade 3/4 342 (84) 186 (46) 162 (40) 152 (37) 163 (40) 94 (23) 65 (16) 104 (26) 90 (22) 56 (14) 45 (11) 49 (12) 47 (12) 81 (20) 64 (16) 4 38 (9) 5 (1) 6 (1) 12 (3) 105 (26) 35 (9) 43 (11) 6 (1) 2 (<1) 1 (<1) 5 (1) 2 (<1) 0 30 (7) 15 (4) AdvP CML N=140 n (%) All Grades 107 (76) 66 (47) 41 (29) 59 (42) 59 (42) 52 (37) 26 (19) 28 (20) 51 (36) 19 (14) 14 (10) 14 (10) 7 (5) 14(10) 15(11) All CP and AdvP CML N=546 n (%) Grade 3/4 All Grades Grade 3/4 7 (5) 3 (2) 7 (5) 5 (4) 52 (37) 37 (26) 25 (18) 6 (4) 4 (3) 1 (1) 1 (1) 0 0 7(5) 4 (3) 449 (82) 252 (46) 203 (37) 211 (39) 222 (41) 146 (27) 91 (17) 132 (24) 141 (26) 75 (14) 59 (11) 63 (12) 54 (10) 95(17) 79(14) Metabolism and nutrition disorder Decreased appetite 53 (13) 3 (1) 19 (14) 0 72 (13) 3 (1) Musculoskeletal and Connective Tissue Disorder Arthralgia Back pain Nervous System Disorders Headache Dizziness 58 (14) 49 (12) 82 (20) 39 (10) 2 (<1) 3 (1) 3 (1) 0 18 (13) 10 (7) 25 (18) 18 (13) 0 2 (1) 6 (4) 1 (1) 76 (14) 59 (11) 107 (20) 57 (10) 45 (8) 8 (1) 13 (2) 17 (3) 157 (29) 72 (13) 68 (12) Respiratory, Thoracic and Mediastinal Disorders Dyspnea 41 (10) 4 (1) 26 (19) 8 (6) 67 (12) 12 (2) 12 (2) 6 (1) 2 (<1) 6 (1) 2 (<1) 0 37(7) 19(3) 2 (<1) 5 (1) 9 (2) 1 (<1)

31 System Organ Class Preferred Term CP CML N=406 n (%) AdvP CML N=140 n (%) All CP and AdvP CML N=546 n (%) All Grades Grade All Grade 3/4 All Grades Grade 3/4 3/4 Grades Cough 80(20) 0 30(21) 0 110(20) 0 Skin and Subcutaneous Disorders Rash e Pruritus 140 (34) 43 (11) 32 (8) 3 (1) 49 (35) 11 (8) 6 (4) (35) 54 (10) 38 (7) 3 (1) CP CML = Chronic Phase CML; AdvP CML = Advanced Phase CML (includes patients with Accelerated Phase and Blast Phase CML) a Abdominal pain includes the following preferred terms: Abdominal pain, Abdominal pain upper, Abdominal pain lower, Abdominal tenderness, Gastrointestinal pain, Abdominal discomfort b Fatigue includes the following preferred terms: Fatigue, Malaise c Edema includes the following preferred terms: Edema, Edema peripheral, Localized edema, Face edema d Respiratory tract infection includes the following preferred terms: Respiratory tract infection, Upper respiratory tract infection, Lower respiratory tract infection, Viral upper respiratory tract infection, Respiratory tract infection viral e Rash includes the following preferred terms: Rash, Rash macular, Rash pruritic, Rash generalized, Rash papular, Rash maculo-papular In the single-arm Phase 1/2 clinical trial, one patient (0.2%) experienced QTcF interval of greater than 500 ms. Patients with uncontrolled or significant cardiovascular disease including QT interval prolongation were excluded by protocol. Table 3 identifies the clinically relevant or severe Grade 3/4 laboratory test abnormalities for the Phase 1/2 CML safety population. Table 3: Number (%) of Patients with Clinically Relevant or Severe Grade 3/4 Laboratory Test Abnormalities In the Phase 1/2 Clinical Study, Safety Population CP CML N=406 n (%) AdvP CML N=140 n (%) All CP and AdvP CML N=546 n (%) Hematology Parameters Platelet Count (Low) less than /L 102 (25) 80 (57) 182 (33) Absolute Neutrophil Count less than /L 74 (18) 52 (37) 126 (23) Hemoglobin (Low) less than 80 g/l 53 (13) 49 (35) 102 (19) Biochemistry Parameters SGPT/ALT greater than 5.0 ULN 39 (10) 8 (6) 47 (9) SGOT/AST greater than 5.0 ULN 17 (4) 4 (3) 21 (4) Lipase greater than 2 ULN 33 (8) 4 (3) 37 (7) Phosphorus (Low) less than 0.6 mmol/l 30 (7) 10 (7) 40 (7) Total Bilirubin greater than 3.0 ULN 3 (1) 2 (1) 5 (1) 6.2 Additional Data from Multiple Clinical Trials The following adverse reactions were reported in patients in clinical trials with BOSULIF (less than 10% of BOSULIF-treated patients). They represent an evaluation of the adverse reaction data from 870 patients with Ph+ leukemia who received at least 1 dose of single-agent BOSULIF. These adverse reactions are presented by system organ class and are ranked by frequency. These adverse reactions are included based on clinical relevance and ranked in order of decreasing seriousness within each category. Blood and Lymphatic System Disorders: 1% and less than 10% - febrile neutropenia Cardiac Disorders: 1% and less than 10% - pericardial effusion; 0.1% and less than 1% - pericarditis Ear and Labyrinth Disorders: 1% and less than 10% - tinnitus Gastrointestinal Disorders: 1% and less than 10% - gastritis; 0.1% and less than 1% - acute pancreatitis, gastrointestinal hemorrhage a General Disorders and Administrative Site Conditions: 1% and less than 10% - chest pain b, pain Hepatobiliary Disorders: 1% and less than 10% - hepatotoxicity c, abnormal hepatic function d ; 0.1% and less than 1% - liver injury 5