Bosutinib Tablets

BOSULIF®
(BAH-su-lif)
(bosutinib) Tablets

What is BOSULIF?

BOSULIF is a prescription medicine used to treat adults who have a certain type of leukemia called Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML) who no longer benefit from or did not tolerate other treatment.

It is not known if BOSULIF is safe and effective in children less than 18 years of age.

Do not take BOSULIF if you are allergic to bosutinib or any of the ingredients in BOSULIF. See the end of this leaflet for a complete list of ingredients of BOSULIF.

Before taking BOSULIF, tell your doctor about all of your medical conditions, including if you:

• have liver problems
• have heart problems
• have kidney problems
• 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 the final dose of BOSULIF. Talk to your doctor about forms of birth control that may be right for you during this time.
• 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.

Tell your doctor about all the medicines you take, including prescription medicines, over-the-counter medicines, vitamins, and herbal supplements. When taken together, BOSULIF and certain other medicines can affect each other.

Know the medicines you take. Keep a list of your medicines and show it to your doctor and pharmacist when you get a new medicine.

How should I take BOSULIF?

• Take BOSULIF exactly as prescribed by your doctor.
• Do not change your dose or stop taking BOSULIF without first talking with your doctor.
• Take BOSULIF with food.
• Swallow BOSULIF tablets whole. Do not crush or cut BOSULIF tablets. Do not touch or handle crushed or broken BOSULIF tablets.
• If you take an antacid or H2 blocker medicine, take it at least 2 hours before or 2 hours after BOSULIF. If you take a Proton Pump Inhibitor (PPI) medicine, talk to your doctor or pharmacist.
• 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.
• Your doctor may change your dose of BOSULIF or tell you to stop taking BOSULIF depending on how you respond to treatment.
• 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.

What are the possible side effects of 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
• 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 often than normal
  • you urinate less often than normal
  • you make a much larger amount of urine than normal
  • you make a much smaller amount of urine than normal

The most common side effects of BOSULIF include:

• 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 FDA at 1-800-FDA-1088.

How should I store BOSULIF?

• Store BOSULIF between 68°F to 77°F (20°C to 25°C).
• Ask your doctor or pharmacist about the right way to throw away outdated or unused BOSULIF.

Keep BOSULIF and all medicines out of the reach of children.

General information about the safe and effective use of BOSULIF.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use BOSULIF for a condition for which it is not prescribed. Do not give BOSULIF to other people even if they have the same symptoms you have. It may harm them. You can ask your doctor or pharmacist for information about BOSULIF that is written for health professionals.

What are the ingredients in BOSULIF?

Active ingredient: bosutinib.

Inactive ingredients: microcrystalline cellulose, croscarmellose sodium, poloxamer, povidone, magnesium stearate, polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, and iron oxide yellow (for 100 mg tablet) and iron oxide red (for 500 mg tablet).

Your pharmacist can provide more information about bosutinib.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2013 Cerner Multum, Inc. Version: 1.01. Revision date: 2/11/2013.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

The following adverse reactions are discussed in greater detail in other sections of the labeling:

• Gastrointestinal toxicity see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].
• Myelosuppression see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].
• Hepatic toxicity see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].
• Fluid retention [see WARNINGS AND PRECAUTIONS].
• Renal toxicity [see WARNINGS AND PRECAUTIONS].

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], myelosuppression, gastrointestinal toxicity (diarrhea), fluid retention, hepatotoxicity and rash.

Adverse reactions of any toxicity grade reported for greater than 20% of patients in Phase 1/2 trial (n=546) were diarrhea (82%), nausea (47%), thrombocytopenia (42%), rash (41%), vomiting (39%), abdominal pain (39%), respiratory tract infection (39%), anemia (30%), pyrexia (27%), liver test abnormalities (24%), fatigue (25%), cough (22%), and headache (20%) [see Clinical Studies].

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]. The safety population (received at least 1 dose of BOSULIF) included 546 CML patients:

• 284 patients with CP CML previously treated with imatinib only who had a median duration of BOSULIF treatment of 26 months, and a median dose intensity of 442 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 442 mg/day.
• 143 patients with advanced phase CML including 79 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 425 mg/day, and 456 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 based on long-term follow-up.

Table 3:Adverse Reactions (10% or Greater) in Patients with CML in Study 1*

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 based on long-term follow-up.

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*

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 881 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; less than 1% - granulocytopenia

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

Vascular Disorders: 1% and less than 10% - hypertension

Gastrointestinal Disorders: 1% and less than 10% - gastritis, gastrointestinal hemorrhage (Anal hemorrhage, Gastric hemorrhage, Gastrointestinal hemorrhage, Hematemesis, Hematochezia, Intestinal hemorrhage, Lower gastrointestinal hemorrhage, Melena, Rectal hemorrhage, Upper gastrointestinal hemorrhage); 0.1% and less than 1% - acute pancreatitis

General Disorders and Administrative Site Conditions: 1% and less than 10% - pain

Hepatobiliary Disorders: 1% and less than 10% - hepatotoxicity (includes Allergic hepatitis, Ascites, Cholestasis, Drug-induced liver injury, Hepatic steatosis, Hepatitis toxic, Hepatocellular injury, Hepatotoxicity, Liver disorder, Liver injury)

Immune System Disorders: 1% and less than 10% - drug hypersensitivity; 0.1% and less than 1% - anaphylactic shock

Investigations: 1% and less than 10% - electrocardiogram QT prolonged (includes Electrocardiogram QT prolonged, Long QT syndrome), blood creatine phosphokinase increased, amylase increased.

Metabolism and Nutrition Disorder: 1% and less than 10% - hyperkalemia, dehydration, hypophosphatemia

Musculoskeletal and Connective Tissue Disorder: 1% and less than 10% - myalgia

Nervous System Disorders: 1% and less than 10% - dysgeusia

Respiratory, Thoracic and Mediastinal Disorders: 0.1% and less than 1% - respiratory failure, pulmonary hypertension

Skin and Subcutaneous Disorders: 1% and less than 10% - urticaria, pruritus; 0.1% and less than 1% - erythema multiforme, exfoliative rash, drug eruption

Post-Marketing Experience

The following additional adverse reactions have been identified during post-approval use of BOSULIF. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Skin and Subcutaneous Tissue Disorders: Stevens-Johnson syndrome

Read the entire FDA prescribing information for Bosulif (Bosutinib Tablets)