Bosutinib

What is Bosutinib?

• Bosutinib (Bosulif) is a kinase inhibitor used to treat chronic myelogenous leukemia (CML) that is Philadelphia chromosome positive.

Bosutinib

Bosutinib ball-and-stick

Bosutinib3Dan

What are the uses of this medicine?

• 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 are newly-diagnosed or who no longer benefit from or did not tolerate other treatment.

How does this medicine work?

• Bosutinib (boe sue’ ti nib) is an orally available, small molecule inhibitor of the BCR-ABL tyrosine kinase receptor, which is the product of a fusion gene resulting from the reciprocal translocations between chromosomes 9 and 22 that characterize the Philadelphia chromosome of chronic myelogenous leukemia (CML).
• The abnormal tyrosine kinase receptor is constitutively expressed and causes unregulated cell growth and proliferation in myeloid cells.
• Inhibition of the receptor can lead to dramatic reversal of progression of leukemia, although sometimes limited by the development of tumor resistance caused by mutations in the kinase.
• Bosutinib was the fourth BCR-ABL tyrosine kinase receptor inhibitor approved for use in cancer chemotherapy (after imatinib, dasatinib and nilotinib) and, like many of the BCR-ABL tyrosine kinase inhibitors, also has some activity against the abnormal tyrosine kinase (c-Kit) that is found in gastrointestinal stromal tumors (GIST).
• Bosutinib also has activity against the receptors for platelet derived growth factor (PDGF) and vascular endothelial growth factor (VEGF).

Who Should Not Use this medicine ?

This medicine cannot be used in patients who:

• allergic to bosutinib or any of the ingredients in Bosulif.

What drug interactions can this medicine cause?

• Avoid the concomitant use of strong or moderate CYP3A inhibitors with Bosulif.
• Avoid the concomitant use of strong CYP3A inducers with Bosulif.
• Concomitant use with a Proton Pump Inhibitors (PPI) decreased bosutinib Cmax and AUC compared to Bosulif.

Is this medicine FDA approved?

• Bosutinib received approval for use in the United States in 2012.
• Current indications are for adult patients with Philadelphia chromosome-positive CML in the chronic, accelerated or blast stages and with resistance or intolerance to previous therapy.

How should this medicine be used?

Recommended dosage:

• The recommended dose is taken orally once daily with food.

Newly-Diagnosed CP Ph+ CML:

• The recommended dose of Bosulif is 400 mg orally once daily with food.

Chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy:

• 500 mg orally once daily with food.

• Consider dose escalation by increments of 100 mg once daily to a maximum of 600 mg daily in patients who do not reach complete hematologic, cytogenetic, or molecular response and do not have Grade 3 or greater adverse reactions.

Administration:

• Take Bosulif with food.
• Swallow Bosulif tablets whole. Do not crush, break, 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.
• 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 dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Tablets: 100 mg, 400 mg, and 500 mg.

This medicine is available in fallowing brand namesː

• Bosulif

What side effects can this medication cause?

The most common side effects of this medicine include:

• diarrhea
• rash
• nausea
• stomach (abdomen) pain
• vomiting
• tiredness
• liver problems
• respiratory tract infections (infections in nose, throat or lungs)
• fever
• headache
• changes in certain blood tests.

Bosulif may cause serious side effects, including:

• Stomach problems
• Low blood cell counts
• Liver problems
• Heart problems
• fluid retention
• Kidney problems

What special precautions should I follow?

• Diarrhea, nausea, vomiting, and abdominal pain occur with Bosulif treatment. Monitor and manage as necessary. Withhold, dose reduce, or discontinue Bosulif.
• Thrombocytopenia, anemia and neutropenia occur with Bosulif treatment. Monitor blood counts and manage as necessary.
• Bosutinib may cause elevations in serum transaminases (alanine aminotransferase [ALT], aspartate aminotransferase [AST]). Monitor liver enzymes at least monthly for the first 3 months and as needed. Withhold, dose reduce, or discontinue Bosulif.
• Bosulif can cause cardiovascular toxicity including cardiac failure, left ventricular dysfunction, and cardiac ischemic events. Monitor and manage as necessary.
• Fluid retention occurs with Bosulif and may manifest as pericardial effusion, pleural effusion, pulmonary edema, and/or peripheral edema. Monitor patients and manage using standard of care treatment. Withhold, dose reduce, or discontinue Bosulif.
• An on-treatment decline in estimated glomerular filtration rate (eGFR) has occurred in patients treated with Bosulif. Monitor patients for renal function at baseline and during therapy with Bosulif.
• Based on findings from animal studies and its mechanism of action, Bosulif can cause fetal harm when administered to a pregnant woman. Advise female patients of reproductive potential of potential risk to a fetus and to use effective contraception.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• There were no reports of any serious adverse events associated with the overdoses.

Treatment of overdosage:

• Patients who take an overdose of Bosulif should be observed and given appropriate supportive treatment.

Can this medicine be used in pregnancy?

• Based on findings from animal studies and its mechanism of action, Bosulif can cause fetal harm when administered to a pregnant woman

Can this medicine be used in children?

• The safety and efficacy of Bosulif in patients less than 18 years of age have not been established.

What are the active and inactive ingredients in this medicine?

• 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 and 400 mg tablets) and iron oxide red (for 400 mg and 500 mg tablets).

Who manufactures and distributes this medicine?

• Packager: Pfizer Laboratories Div Pfizer Inc

What should I know about storage and disposal of this medication?

• Store Bosulif at room temperature 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.

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• Dailymed label info on Bosutinib
• FDA Bosutinib