Brand Information

Strength	Rate	Packing Style
mg	0.00	unit

Drug Interaction:

CYP3A Inhibitors and Inducers: Avoid concurrent use of BOSULIF with strong

or moderate CYP3A inhibitors and inducers.

Proton Pump Inhibitors: May decrease bosutinib drug levels.

Consider short-acting antacids in place of proton pump inhibitors.

Indication:

BOSULIFR (bosutinib) tablets, for oral use

Initial U.S. Approval: 2012

RECENT MAJOR CHANGES

Dosage and Administration, Renal Impairment (2.8) 4/2013

Drug Name- Bosulif

Active Ingredient - Bosutinib

To treat chronic myelogenous leukemia (CML) , a blood and bone marrow

disease that usually affects older adults

Indication-

To treat chronic myelogenous leukemia (CML) , a blood and bone marrow

disease that usually affects older adults

Approved by FDA on 4-9-2012 (Ref- FDA Approved List- 2012)

Adverse Reaction:

Most common adverse reactions (incidence greater than 20%) are diarrhea,

nausea, thrombocytopenia, vomiting, abdominal pain, rash, anemia, pyrexia,

and fatigue.

Contra-Indications:

CONTRAINDICATIONS

Hypersensitivity to BOSULIF.

WARNINGS AND PRECAUTIONS

Gastrointestinal toxicity: Monitor and manage as necessary.

Withhold, dose reduce, or discontinue BOSULIF

Myelosuppression: Monitor blood counts and manage as necessary.

Hepatic toxicity: Monitor liver enzymes at least monthly for the first three months

and as needed. Withhold, dose reduce, or discontinue BOSULIF.

Fluid retention: Monitor patients and manage using standard of care treatment.

Withhold, dose reduce, or discontinue BOSULIF.

Embryofetal toxicity: May cause fetal harm. Females of reproductive potential

should avoid becoming pregnant while being treated with BOSULIF.

Dosages/ Overdosage Etc:

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.

DOSAGE AND ADMINISTRATION

-

Recommended Dose: 500 mg orally once daily with food.

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.

Adjust dosage for hematologic and non-hematologic toxicity.

Adjust dosage for hepatic and renal impairment.

DOSAGE FORMS AND STRENGTHS

Tablets: 100 mg and 500 mg.

Patient Information:

PATIENT COUNSELING INFORMATION

See FDA-approved patient labeling (Patient Information).

Dosing and Administration

Instruct patients to take BOSULIF exactly as prescribed, not to change their dose

or to stop taking BOSULIF unless they are told to do so by their doctor.

If patients miss a dose beyond 12 hours, they should be advised to take

the next scheduled dose at its regular time.

A double dose should not be taken to make up for any missed dose.

Advise patients to take BOSULIF withfood. Patients should be advised:

Do not crush or cut tablet. Do not touch or handle crushed or broken tablets

Gastrointestinal Problems

Advise patients that they may experience diarrhea, nausea, vomiting, abdominal pain,

or blood in their stools with BOSULIF and to seek medical attention promptly

for these symptoms.

Low Blood Cell Counts

Advise patients of the possibility of developing low blood cell counts and to

immediately report fever, any suggestion of infection, or signs or symptoms

suggestive of bleeding or easy bruising.

Liver Problems

Advise patients of the possibility of developing liver function abnormalities and

to immediately report jaundice.

Fluid Retention

Advise patients of the possibility of developing fluid retention (swelling, weight gain,

or shortness of breath) and to seek medical attention promptly if these symptoms arise.

Other Adverse Reactions

Advise patients that they may experience other adverse reactions such as respiratory

tract infections, rash, fatigue, loss of appetite, headache, dizziness, back pain,

arthralgia, or pruritus with BOSULIF and to seek medical attention if symptoms are

significant. There is a possibility of anaphylactic shock.

Pregnancy and Breast-feeding

Advise patients that BOSULIF can cause fetal harm when administered to a pregnant

woman. Advise women of the potential hazard to the fetus and to avoid becoming

pregnant. If BOSULIF is used during pregnancy, or if the patient becomes pregnant

while taking BOSULIF, the patient should be apprised of the potential hazard

to the fetus. Because a potential risk to the nursing infant cannot be excluded,

women that are taking BOSULIF should not breast-feed or provide breast

milk to infants.

Counsel females of reproductive potential to use effective contraceptive measures

to prevent pregnancy during and for at least 30 days after completing treatment

with BOSULIF.

Instruct patients to contact their physicians immediately if they become pregnant

during treatment.

Advise patients not to take BOSULIF treatment while pregnant or breastfeeding.

If a patient wishes to restart breastfeeding after treatment, advise her to discuss

the appropriate timing with her physician.

Drug Interactions

Advise patients that BOSULIF and certain other medicines, including over the counter

medications or herbal supplements (such as St. Johns wort) can interact with each

other and may alter the effects of BOSULIF

Pharmacology/ Pharmacokinetics:

CLINICAL PHARMACOLOGY

1 Mechanism of Action

Bosutinib is a tyrosine kinase inhibitor. Bosutinib inhibits the Bcr-Abl kinase that

promotes CML; it is also an inhibitor of Src-family kinases including Src, Lyn,

and Hck. Bosutinib inhibited 16 of 18 imatinib-resistant forms of Bcr-Abl expressed

in murine myeloid cell lines. Bosutinib did not inhibit the T315I and V299L mutant cells.

In mice, treatment with bosutinib reduced the size of CML tumors relative to controls

and inhibited growth of murine myeloid tumors expressing several imatinib-resistant forms

of Bcr-Abl.

2. Pharmacokinetics

Absorption

Following administration of a single dose of BOSULIF 500 mg with food in patients

with cancer, the median time-to-peak concentration (tmax) was 4-6 hours. Bosutinib

exhibits dose proportional increases in AUC and Cmax, over the dose range of 200

to 800 mg. After 15 daily doses of BOSULIF (500 mg) with food in patients with CML,

the mean (SD) Cmax value was 200 (12) ng/mL, and the mean (SD) AUC was

3650 (425) ng•h/mL. When given with a high fat meal, the Cmax and AUC of bosutinib

increased 1.8and 1.7-fold, respectively.

Pregnancy and lactation:

USE IN SPECIFIC POPULATIONS

1. Pregnancy

Pregnancy Category D

Based on its mechanism of action and findings in animals, BOSULIF can cause fetal

harm when administered to a pregnant woman. Studies in animals showed

reproductive toxicities

If BOSULIF is used during pregnancy, or if the patient becomes pregnant while

taking BOSULIF, the patient should be apprised of the potential hazard to

the fetus.Fetal exposure to bosutinib-derived radioactivity during pregnancy

was demonstrated

2. Nursing Mothers

It is not known whether bosutinib is excreted in human milk. Bosutinib and/or its

metabolites were excreted in the milk of lactating rats. Radioactivity was present

in the plasma of suckling offspring 24 to 48 hours after lactating rats received

a single oral dose of radioactive bosutinib.

Because many drugs are excreted in human milk and because of the potential

for serious adverse reactions in nursing infants from BOSULIF, a decision

should be made whether to discontinue nursing or to discontinue the drug, taking

into account the importance of the drug to the mother.

3. Pediatric Use

The safety and efficacy of BOSULIF in patients less than 18 years of age have

not been established.

4. Geriatric Use

In the Phase 1/2 clinical trial of BOSULIF in patients with Ph+ CML, 20% were age

65 and over, 4% were 75 and over. No overall differences in safety or effectiveness

were observed between these patients and younger patients, and other reported

clinical experience has not identified differences in responses between the

elderly and younger patients, but greater sensitivity of some older individuals

cannot be ruled out.

BOSULIF*

Drug Interaction

Indication

Adverse Reaction

Contra-Indications

Dosages/ Overdosage Etc

Patient Information

Pharmacology/ Pharmacokinetics

Pregnancy and lactation