Your guide to treatment

Transcription

1 Your guide to treatment A complete resource for adult patients with chronic, accelerated, or blast phase Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia (CML) with resistance or intolerance to prior therapy. Please see Important Safety Information for patients on pages and full Prescribing Information, including Patient Information, beginning on page 31.

2 Introduction Getting started on BOSULIF...5 Getting familiar with side effects of BOSULIF treatment Dealing with diarrhea Taking BOSULIF as prescribed Talking to your doctor about other conditions and medications Getting the support you need Specialty pharmacies Pfizer RxPathways...19 Pfizer Co-Pay One Resources Important Safety Information Terms to know Side effects management sheet Please see Important Safety Information for patients on pages and full Prescribing Information, including Patient Information, beginning on page 31.

3 Welcome to the next STEP in your CML journey BOSULIF STEPS a support program created specifically for patients who are prescribed BOSULIF. Transitioning to a new medication can be stressful. The goal of BOSULIF STEPS is to provide you with important information you can use throughout each step of your treatment. Whether this is your first time changing to a new CML medication, or you have changed in the past, this brochure will be a helpful resource to refer back to throughout treatment with BOSULIF. 3 Please see Important Safety Information for patients on pages and full Prescribing Information, including Patient Information, beginning on page 31.

4 How should I use this brochure? Throughout each section you will notice that important terms have been boldfaced. All of these terms have been defined in an easy-touse glossary on pages 28 and 29. Also, you will find a worksheet on page 30 of your brochure. This worksheet contains tips to help manage common side effects, as well as space to write down any additional notes. Why have I been prescribed 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. BOSULIF is part of a group of medications called tyrosine kinase inhibitors (TKIs). You may have taken similar medications in the past. Your doctor may have changed your medicines because they either stopped working or their side effects became unmanageable. Now you have been prescribed BOSULIF as your next treatment for CML. To learn more about how BOSULIF was studied, visit 4 Please see Important Safety Information for patients on pages and full Prescribing Information, including Patient Information, beginning on page 31.

5 Getting started on BOSULIF (bosutinib) Why am I starting BOSULIF???? There are a few possible reasons why your doctor may have changed your medication; two are discussed below. Keep in mind that it s possible for the same issues to occur with BOSULIF. Resistance is when your disease fails to respond or stops responding to a given therapy. It can occur at any time during treatment, even if you have been taking your medication successfully for several years. 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. Always tell your doctor or nurse when you have side effects, even if you think they aren t serious. Another factor to consider Not taking your medicine as prescribed can impact how it works. It is important to take your medicine exactly as prescribed by your doctor. See pages for more tips that may help you take BOSULIF as your doctor prescribed. 5 Please see Important Safety Information for patients on pages and full Prescribing Information, including Patient Information, beginning on page 31.

6 Getting familiar with side effects of BOSULIF (bosutinib) treatment What are the possible side effects of BOSULIF? There may be side effects with BOSULIF. It s important to be familiar with the side effects so you know what may occur. 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 Remember to speak up 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. 6 Please see Important Safety Information for patients on pages and full Prescribing Information, including Patient Information, beginning on page 31.

7 Getting familiar with side effects of BOSULIF (bosutinib) treatment (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 chest pain swelling in your hands, ankles, or feet swelling all over your body weight gain Kidney problems. BOSULIF may cause kidney problems. Your doctor should do tests to check your kidney function when you start treatment with BOSULIF and during your treatment. Call your doctor right away if you get any of the following symptoms during your treatment with BOSULIF: - you urinate more or less often than normal - you make a much larger or smaller amount of urine than normal 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. Call your doctor for medical advice about side effects. You may report side effects to the FDA at FDA The most common side effects of BOSULIF include: diarrhea nausea low blood cell counts vomiting stomach pain rash fever tiredness or weakness 7 Please see Important Safety Information for patients on pages and full Prescribing Information, including Patient Information, beginning on page 31.

8 Dealing with diarrhea What are the most common side effects with BOSULIF? The most common side effects associated with BOSULIF were stomach problems, including diarrhea. In the clinical study for BOSULIF, 82% of patients experienced episodes of diarrhea. Diarrhea experienced by patients in the clinical trial 2 days 1 (range day 3per patient was 1-221) 8 % Median length of time after starting treatment that diarrhea occurred Median length of each episode of diarrhea Median number of episodes each patient experienced Percentage of patients with episodes of severe diarrhea 8 Please see Important Safety Information for patients on pages and full Prescribing Information, including Patient Information, beginning on page 31.

9 Dealing with diarrhea (cont d) If you have diarrhea, call your doctor. Your doctor may recommend taking medicine to treat diarrhea. Always talk to your doctor before taking any over-the-counter medicine. Your doctor may choose to have you stop taking BOSULIF for a period of time or change your dose to help manage diarrhea. For more tips on managing side effects, see the side effects management sheet on page 30. Tips to help manage diarrhea It s a good idea to monitor what you eat and drink. You can discuss the following tips with your doctor: 3 Eat mild foods Drink water often 7 3 Avoid spicy foods, fatty foods, caffeine, and raw fruit 9 Please see Important Safety Information for patients on pages and full Prescribing Information, including Patient Information, beginning on page 31.

10 Taking BOSULIF (bosutinib) as prescribed How should I take BOSULIF? Follow the instructions below and talk with your doctor or nurse for more information. 3BOSULIF is taken by 3BOSULIF should be 3Swallow BOSULIF mouth, once a day taken with food tablets whole 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 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 Do not crush or cut BOSULIF tablets. Do not touch or handle crushed or broken BOSULIF tablets 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 10 Please see Important Safety Information for patients on pages and full Prescribing Information, including Patient Information, beginning on page 31.

11 Taking BOSULIF (bosutinib) as prescribed (cont d) Why is it so important to take my medication? Skipping doses or taking less medicine may affect your response to treatment. That s why it is very important to follow your doctor s instructions. If you ever have trouble taking your medicine or questions about how much to take, talk with your doctor. Red tablets are 500 mg Yellow tablets are 100 mg Tablets are not shown at actual size. Tips to help you take BOSULIF as prescribed Make BOSULIF part of your daily routine by taking your medicine at the same time every day. It may help to take BOSULIF in the morning with breakfast or in the evening with dinner Organize your medicines with a pill container at home and when you travel Use alarms and calendars as reminders to take medication Keep a list of all the medicines you take, and tell your doctor before taking any new medicine 11 Please see Important Safety Information for patients on pages and full Prescribing Information, including Patient Information, beginning on page 31.

12 Talking to your doctor about other conditions 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 12 Please see Important Safety Information for patients on pages and full Prescribing Information, including Patient Information, beginning on page 31.

13 Talking to your doctor about other medications 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, diltiazem (Cardizem, Dilacor XR, Tiazac ) erythromycin (Ery-tab ) fluconazole (Diflucan ) fosamprenavir (Lexiva ) imatinib (Gleevec ) indinavir (Crixivan ) posaconazole (Noxafil ) ritonavir (Kaletra, Norvir ) saquinavir (Invirase, Fortovase ) telaprevir (Incivek ) telithromycin (Ketek ) verapamil (Calan, Prevpac ) itraconazole Covera-HS, Tarka, conivaptan (Vaprisol ) (Onmel, Sporanox ) Verelan PM ) crizotinib (Xalkori ) darunavir (Prezista ) digoxin (Lanoxin ) ketoconazole (Nizoral ) nefazodone (Serzone ) nelfinavir (Viracept ) voriconazole (Vfend ) Brand names mentioned on this page are the registered trademarks of their respective companies. 13 Please see Important Safety Information for patients on pages and full Prescribing Information, including Patient Information, beginning on page 31.

14 Talking to your doctor about other medications (cont d) Medicines that decrease the amount of BOSULIF in your blood stream, such as: bosentan (Tracleer ) efavirenz (Sustiva ) phenobarbital (Solfoton ) rifampin (Rifamate, Rifater, Rifadin ) carbamazepine (Carbatrol, Equetro, Tegretol ) etravirine (Intelence ) modafinil (Provigil ) nafcillin (Unipen, Nallpen ) phenytoin (Dilantin ) rifabutin (Mycobutin ) 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 dexlansoprazole (Dexilant ) lansoprazole (Prevacid ) omeprazole (Prilosec, Vimovo, Zegerid ) pantoprazole sodium (Protonix ) rabeprazole (AcipHex ) 14 Please see Important Safety Information for patients on pages and full Prescribing Information, including Patient Information, beginning on page 31.

15 Talking to your doctor about other medications (cont d) Medicines like the ones below that neutralize stomach acid may be taken up to 2 hours before or 2 hours after BOSULIF: cimetidine (Tagamet ) famotidine (Pepcid ) ranitidine (Zantac ) aluminum hydroxide/magnesium hydroxide (Maalox ) calcium carbonate (Tums ) or calcium carbonate and magnesia (Rolaids ) What should I tell my doctor? Because BOSULIF and certain other medicines can affect each other, your doctor needs to know about any other medicines you take. Make a list of medical conditions or diseases that you have and the medications that you take for them. This includes prescription medicines, non-prescription medicines, vitamins, and herbal supplements. 15 Please see Important Safety Information for patients on pages and full Prescribing Information, including Patient Information, beginning on page 31.

16 Getting the support you need In this section you will discover the patient services offered as part of the BOSULIF STEPS program. 3An extension of your support network Specialty pharmacy personnel are available 24/7 to offer assistance Pfizer RxPathways offers a range of prescription assistance services to help you access BOSULIF 3Assistance with the cost of treatment Pfizer Co-Pay One helps eligible commercially insured patients reduce the cost of their treatment with BOSULIF 3Resources and information External resources that you can turn to for peer support and disease education 16 Please see Important Safety Information for patients on pages and full Prescribing Information, including Patient Information, beginning on page 31.

17 Specialty pharmacies: An extension of your BOSULIF (bosutinib) support network Specialty pharmacies are similar to traditional pharmacies that you are used to, but they offer additional services for patients. This range of services includes: Prescriptions available by mail order and delivered to your home for added convenience Trained staff who are available to speak with you regarding delivery arrangements, side effects, and other treatment-related concerns Care team members that reach out to check on you when initiating treatment 17 Please see Important Safety Information for patients on pages and full Prescribing Information, including Patient Information, beginning on page 31.

18 BOSULIF (bosutinib) is available through select specialty pharmacies A current list of pharmacies is available at Specialty pharmacy contact Pfizer will work with your healthcare provider to find a specialty pharmacy that is compatible with your insurance. For more information, please call Please see Important Safety Information for patients on pages and full Prescribing Information, including Patient Information, beginning on page 31.

19 Pfizer RxPathways : Connecting patients with the help they need When patients have difficulty getting access to their Pfizer medicines, Pfizer RxPathways may provide the support services that can help. Services available to eligible patients include: Specialty pharmacy referral Co-pay help a Reimbursement support services Appeals process information Free medicines a This is not health insurance. Terms and Conditions apply. Some services are available for specialty and oncology medicines only. Pfizer RxPathways is a joint program of Pfizer Inc and the Pfizer Patient Assistance Foundation. Pfizer RxPathways is part of Pfizer s Global Social Investments portfolio. For more information, please visit To access Pfizer RxPathways information or download an application, please visit For program information and questions, please call Please see Important Safety Information for patients on pages and full Prescribing Information, including Patient Information, beginning on page 31.

20 Pfizer Co-Pay One: Reducing the cost of treatment for patients For eligible patients, the Pfizer Co-Pay One program can lower your out-of-pocket costs for BOSULIF. You will pay no more than $10 monthly for each 30-day prescription of BOSULIF. To find out if you are eligible, visit Terms and Conditions a By enrolling in this co-pay offer, 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 ]). a Please see savings card for complete terms and conditions. For any questions, please call or visit 20 Please see Important Safety Information for patients on pages and full Prescribing Information, including Patient Information, beginning on page 31.

21 Pfizer Co-Pay One: Reducing the cost of treatment for patients (cont d) 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. You are responsible for $10 or the full amount of your co-pay, whichever is less, for each 30-day prescription of a covered medicine. The amount of any savings is the difference between your co-pay and $10. You are entitled to maximum savings of $25,000 per calendar year per patient. 4. 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. For reimbursement when using a nonparticipating pharmacy: Mail a copy of your pharmacy receipt indicating patient name, name of medication purchased, price paid, and date purchased, along with a copy of your Pfizer Co-Pay One Savings Card, to: Pfizer Co-Pay One Savings Card Weston Parkway, Suite 103 Cary, NC Pfizer Inc, 235 East 42nd Street, New York, NY Please see Important Safety Information for patients on pages and full Prescribing Information, including Patient Information, beginning on page 31.

22 Resources: Stepping away for more information If you are looking for additional support or information, you can find external programs and networks below. Visit their Web sites or call directly with the phone numbers provided. Cancer Support Community The Cancer Support Community is an international nonprofit dedicated to providing support, education, and hope to people affected by cancer. Phone: Caregiver Action Network The Caregiver Action Network provides education, peer support, and resources to family caregivers across the United States, free of charge. Phone: Patient Advocate Foundation The Patient Advocate Foundation offers assistance to patients with specific issues they are facing with their insurer, employer, or creditors regarding insurance, job retention, or debt crisis matters relating to their diagnosis of life-threatening or debilitating disease. Phone: 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. Phone: Please see Important Safety Information for patients on pages and full Prescribing Information, including Patient Information, beginning on page 31.

23 Resources: Stepping away for more information (cont d) Learn more about CML Leukemia & Lymphoma Society Phone: American Cancer Society Phone: The National CML Society Phone: CancerCare Phone: Please see Important Safety Information for patients on pages and full Prescribing Information, including Patient Information, beginning on page 31.

24 Important safety information that you should know 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 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 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 24 Please see full Prescribing Information, including Patient Information, beginning on page 31.

25 Important safety information that you should know (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 chest pain swelling in your hands, ankles, or feet swelling all over your body weight gain Kidney problems. BOSULIF may cause kidney problems. Your doctor should do tests to check your kidney function when you start treatment with BOSULIF and during your treatment. Call your doctor right away if you get any of the following symptoms during your treatment with BOSULIF: - you urinate more or less often than normal - you make a much larger or smaller amount of urine than normal The most common side effects of BOSULIF include: diarrhea nausea low blood cell counts vomiting stomach pain rash fever tiredness or weakness 25 Please see full Prescribing Information, including Patient Information, beginning on page 31.

26 Important safety information that you should know (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. 26 Please see full Prescribing Information, including Patient Information, beginning on page 31.

27 Important safety information that you should know (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 27 Please see full Prescribing Information, including Patient Information, beginning on page 31.

28 Terms to know Adherence: When a patient takes medicine as it is prescribed by his or her doctor. bcr-abl: An abnormal gene that causes bone marrow to grow white blood cells faster than normal. Blast phase: The stage of CML when 20% or more of the cells in the blood or bone marrow are cancerous. Bone marrow: The soft, sponge-like tissue in the center of most bones. It makes white blood cells, red blood cells, and platelets. Chromosome: Part of a cell that holds genetic information. Clinical study: A type of research study that tests how well a new medicine works in patients. Diarrhea: A common side effect in patients taking BOSULIF, when the bowels discharge frequent loose or watery stools. Severe: 7 or more loose or watery stools/ bowel movements in 1 day Gene: A piece of deoxyribonucleic acid (DNA) that parents pass on to a child. Genes determine hair and eye color, as well as many other traits. Chronic phase: The phase of CML that most patients are diagnosed in. In this phase, less than 10% of the cells in the blood or bone marrow are cancerous. 28 Please see Important Safety Information for patients on pages and full Prescribing Information, including Patient Information, beginning on page 31.

29 Terms to know (cont d) Hematologic response: A return of blood cells to normal levels, absence of cancerous cells in the blood outside of the bones, and no signs and symptoms of the disease. Intolerance a : When a patient can no longer take his or her current medicine due to unmanageable side effects. Major cytogenetic response: When the number of a patient s white blood cells with the Philadelphia chromosome is reduced to 35% or less. Philadelphia chromosome: An abnormality in your genes that results in an unnatural protein called bcr-abl. This gene causes CML cells to grow uncontrollably. Resistance a : When your disease fails to respond or stops responding to a given therapy 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. 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. a References: 1. American Society of Clinical Oncology. Leukemia Chronic Myeloid CML. /leukemia-chronic-myeloid-cml/treatment-options. Accessed June 27, Leukemia & Lymphoma Society. Chronic Phase CML Treatment. Accessed June 27, Please see Important Safety Information for patients on pages and full Prescribing Information, including Patient Information, beginning on page 31.

30 to help manage side effects This sheet contains information about some common side effects of BOSULIF and tips that may help manage them. It s important to discuss this content with your doctor or nurse and set up a plan for managing any side effects you may have. Not all side effects are manageable. Your doctor may change your dose or tell you to stop taking BOSULIF. Common side effects Diarrhea Stomach pain Nausea or vomiting Rash Fever Tiredness or weakness Management tips to discuss with your doctor or nurse 3 Eat mild foods 3 Drink water often 7 Avoid spicy foods, fatty foods, caffeine, and raw fruit 3 Sleep in a more upright position, propped up on a pillow 3 Reduce your stress with meditation, yoga, or music 7 Avoid large meals, coffee, and alcohol 3 Eat smaller, more frequent meals 3 Drink fluids in small amounts 7 Avoid foods that are sweet, fried, or fatty 3 Wear loose clothing that does not rub against your skin too much 7 Avoid hot water when washing hands, bathing, or showering 7 Avoid soaking in long baths 3 Take antibiotics (if your doctor thinks the fever is caused by a bacterial infection) 3 Take nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen 3 Take short naps or breaks 3 Eat well and drink plenty of fluids 3 Take short walks or do light exercise if you feel up to it 3 Do things that are relaxing, such as listening to music or reading Additional notes to track side effects BSW Pfizer Inc. All rights reserved. January Call your doctor for medical advice about side effects. You may report side effects to the FDA at FDA-1088.

31 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, Recommended Starting Dosage with Hepatic Impairment or Renal Impairment (2.7) 11/2014 Warnings and Precautions, Renal Toxicity (5.5) 11/ 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) 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) DOSAGE FORMS AND STRENGTHS Tablets: 100 mg and 500 mg. (3) CONTRAINDICATIONS Hypersensitivity to BOSULIF. (4) WARNINGS AND PRECAUTIONS Gastrointestinal Toxicity: Monitor and manage as necessary. Withhold, dose reduce, or discontinue BOSULIF. (2.3, 5.1) 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) Renal Toxicity Monitor patients for renal function at baseline and during therapy with BOSULIF (5.5) Embryofetal Toxicity: May cause fetal harm. Females of reproductive potential should avoid becoming pregnant while being treated with BOSULIF. (5.6) ADVERSE REACTIONS Most common adverse reactions (incidence greater than 20%) are diarrhea, nausea, thrombocytopenia, vomiting, abdominal pain, rash, anemia, pyrexia, and fatigue. (6) 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 short-acting antacids in place of proton pump inhibitors. (7.2) See 17 for PATIENT COUNSELING INFORMATION and FDAapproved patient labeling Revised: 11/2014 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 Recommended Starting Dosage with Hepatic Impairment or 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 Renal Toxicity 5.6 Embryofetal Toxicity 6 ADVERSE REACTIONS 6.1 Clinical Trials Experience 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

32 FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE BOSULIF is indicated for the treatment of adult patients with chronic, accelerated, or blast phase Philadelphia chromosome-positive (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 reescalating 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

33 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 Recommended Starting Dosage with Hepatic Impairment or Renal Impairment Organ Function Status Recommended Starting Dosage Normal hepatic and renal function 500 mg once daily Hepatic impairment Mild (Child-Pugh A), Moderate (Child-Pugh B) or 200 mg daily severe (Child-Pugh C) Renal impairment Creatinine clearance 30 to 50 ml/min 400 mg daily Creatinine clearance less than 30 ml/min 300 mg daily [see Use in Specific Populations (8.6,8.7) 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 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. Perform complete blood counts weekly for the first month of therapy 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 hepatic enzyme tests monthly for the first three months of BOSULIF treatment 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)]. 3

34 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 Renal Toxicity An on-treatment decline in estimated glomerular filtration rate (egfr) has occurred in patients treated with BOSULIF. Table 2 identifies the shift from baseline to lowest observed estimated glomerular filtration rate (egfr) during BOSULIF therapy for patients in the global Ph+ Leukemia studies. The median duration of therapy with BOSULIF was approximately 17 months (range, 0.03 to 95) for patients in these studies. Table 2: Shift from Baseline to Lowest Observed egfr Group During Treatment Safety Population in Clinical Studies (n=818)* Baseline Follow Up Renal Function Status n Normal n (%) Mild n (%) Mild to Moderate n (%) Moderate to Severe n (%) Severe n (%) Kidney Failure n (%) Normal (19) 174 (64) 30 (11) 14 (5) 1 (<1) 1 (<1) Mild (2) 170 (39) 177 (40) 63 (14) 14 (3) 2 (1) Mild to Moderate (5) 28 (35) 37 (47) 10 (13) 0 Moderate to Severe (4) 1 (4) 6 (25) 15 (63) 1 (4) Severe (100) Total (8) 349 (43) 236 (29) 120 (15) 40 (5) 5 (1) Notes: Grading is based on Modification in Diet in Renal Disease method (MDRD). KDIGO Classification by egfr: Normal: greater than or equal to 90, Mild: 60 to less than 90, Mild to Moderate: 45 to less than 60, Moderate to Severe: 30 to less than 45, Severe: 15 to less than 30, Kidney Failure: less than 15 ml/min/1.73 m 2. *Among the 818 patients, egfr was missing in 5 patients at baseline or on-therapy. There were no patients with kidney failure at baseline. Monitor renal function at baseline and during therapy with BOSULIF, with particular attention to those patients who have preexisting renal impairment or risk factors for renal dysfunction. Consider dose adjustment in patients with baseline and treatment emergent renal impairment [see Dosage and Administration (2.7)]. 5.6 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)]. 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)]. Renal toxicity [see Warnings and Precautions (5.5)]. 4

35 6.1 Clinical Trials Experience 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%) [see Clinical Studies (14)]. Adverse Reactions in Patients with Imatinib-Resistant or -Intolerant Ph+ Chronic Phase (CP), Accelerated Phase (AP), and Blast Phase (BP) CML The single-arm Phase 1/2 clinical trial (Study 1) enrolled patients with Ph+ chronic, accelerated, or blast phase chronic myelogenous leukemia (CML) and with resistance or intolerance to prior therapy [see Clinical Studies (14)]. The safety population (received at least 1 dose of BOSULIF) included 546 CML patients: 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. 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. 140 patients with advanced phase CML including 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 3 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 3: Adverse Reactions (10% or Greater) in Patients with CML in Study 1 Chronic Phase CML N=406 Advanced Phase CML N=140 All Grades (%) Grade 3/4 (%) All Grades (%) Grade 3/4 (%) Diarrhea Nausea Abdominal Pain a Thrombocytopenia Vomiting Rash b Fatigue c Anemia Pyrexia 22 < Increased alanine aminotransferase Headache Cough Increased aspartate aminotransferase Neutropenia Edema d 14 <

36 Chronic Phase CML N=406 Advanced Phase CML N=140 All Grades (%) Grade 3/4 (%) All Grades (%) Grade 3/4 (%) Arthralgia 14 < Decreased appetite Respiratory tract infection e 12 < Nasopharyngitis Back pain Asthenia Pruritus Dizziness Dyspnea Advanced Phase CML includes patients with Accelerated Phase and Blast Phase CML a Abdominal pain includes the following terms: abdominal pain, upper abdominal pain, lower abdominal pain, abdominal tenderness, gastrointestinal pain, abdominal discomfort b Rash includes the following terms: rash, macular rash, pruritic rash, generalized rash, popular rash, maculo-papular rash c Fatigue includes the following terms: fatigue, malaise d Edema includes the following terms: edema, peripheral edema, localized edema, face edema e Respiratory tract infection includes the following terms: respiratory tract infection, upper respiratory tract infection, lower respiratory tract infection, viral upper respiratory tract infection, viral respiratory tract infection In the single-arm Phase 1/2 clinical trial, one patient (0.2%) experienced QTcF interval of greater than 500 milliseconds. Patients with uncontrolled or significant cardiovascular disease including QT interval prolongation were excluded by protocol. Table 4 identifies the clinically relevant or severe Grade 3/4 laboratory test abnormalities for the Phase 1/2 CML safety population. Table 4: Number (%) of Patients with Clinically Relevant or Severe Grade 3/4 Laboratory Test Abnormalities in Patients with CML in Study 1, Safety Population Chronic Phase CML N=406 n (%) Advanced Phase 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