Bosutinib

Bosutinib is a prescription medication used for the treatment of chronic myelogenous leukemia. 

• Bosutinib is available under the following different brand names: Bosulif 

Common side effects of Bosutinib include:

• Diarrhea,
• Nausea,
• Low blood platelet cell count (thrombocytopenia),
• Vomiting,
• Abdominal pain,
• Stomach discomfort,
• Itching or rash,
• Anemia,
• Fever,
• Fatigue,
• Tired feeling,
• Weakness,
• Headache,
• Dizziness,
• Joint pain,
• Back pain,
• Cold symptoms such as stuffy nose, sneezing, sore throat, or cough,
• Swelling (edema),
• Decreased appetite,
• Respiratory tract infection, or
• Low white blood cell count (neutropenia).

Serious side effects of Bosutinib include:

• severe or ongoing nausea, vomiting, stomach pain, or diarrhea.
• blood in your stools.
• urinating more or less than usual.
• feeling light-headed or short of breath.
• heart problems--swelling, rapid weight gain, feeling short of breath.
• low blood cell counts--fever, chills, tiredness, flu-like symptoms, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands, and feet.
• liver problems--upper stomach pain, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or
• swelling or fluid build-up in the lungs--anxiety, sweating, pain when you breathe, feeling short of breath while lying down, wheezing, gasping for breath, cough with foamy mucus, chest pain, fast or uneven heart rate.

Rare side effects of Bosutinib include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 100 mg
• 400 mg
• 500 mg

Chronic Myelogenous Leukemia

Adult dosage

• Newly diagnosed chronic phase Philadelphia chromosome-positive
  • 400 mg orally once a day with food
  • Continue until disease progression or unacceptable toxicity
• Chronic, accelerated, or blast phase Philadelphia chromosome-positive
  • 500 mg orally once a day with food
  • Continue until disease progression or unacceptable toxicity

Dose escalation

• May increase dose by 100-mg/day increments; not to exceed 600 mg/day

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Bosutinib has severe interactions with the following drug:
  • Lefamulin
• Bosutinib has serious interactions with at least 96 other drugs.
• Bosutinib has moderate interactions with at least 109 other drugs.
• Bosutinib has minor interactions with no other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Hypersensitivity 

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Bosutinib?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Bosutinib?”

Cautions

• Diarrhea, nausea, vomiting, and abdominal pain may occur; monitor and manage patients using standards of care, including antidiarrheals, antiemetics, and fluid replacement
• Thrombocytopenia, anemia, and neutropenia occur with treatment; perform CBC weekly for the first month and then monthly thereafter, or as clinically indicated
• Fluid retention may occur and manifest as pericardial effusion, pleural effusion, pulmonary edema, and/or peripheral edema
• Cardiac failure and left ventricular dysfunction have been reported in patients taking; monitor for signs and symptoms consistent with cardiac failure and treat as clinically indicated; interrupt, dose reduce, or discontinue as necessary
• A decline in glomerular filtration rate reported in patients receiving therapy, which in turn increases bosutinib exposure in patients; use caution in patients with moderate renal impairment; dosage adjustment recommended
• Fetal harm may occur when administered to pregnant females
• Hepatic toxicity
  • Elevated ALT, AST, and/or bilirubin may occur; perform monthly hepatic enzyme tests for the first 3 months during treatment, and then as clinically indicated
  • Median time to onset of increased ALT and AST was 35 and 33 days; the median duration for each was 21 days
  • Perform hepatic enzyme tests monthly for the first 3 months of treatment and as clinically indicated; in patients with transaminase elevations, monitor liver enzymes more frequently
• QT Prolongation
• Caution in patients with a history of QTc prolongation, who have uncontrolled or significant cardiac disease (e.g., myocardial infarction, congestive heart failure, unstable angina, clinically significant bradycardia), or who are taking drugs that prolong QT interval
• Hypokalaemia and hypomagnesemia may further increase this effect
• Monitor QT interval at baseline before initiating therapy and as clinically indicated
• Correct hypokalaemia or hypomagnesemia before administration and monitor periodically during therapy
• Drug interaction overview
  • CYP3A4 substrate
    • Strong or moderate CYP3A4 inhibitors
    • Avoid coadministration
  • Strong or moderate CYP3A4 inhibitors increase bosutinib Cmax and AUC, which may increase the risk of toxicities
  • Strong CYP3A4 inducers
    • Avoid coadministration
    • Strong CYP3A4 inducers decrease bosutinib Cmax and AUC, which may reduce the efficacy
  • Proton pump inhibitors (PPI)
    • Use short-acting antacids or H2-blockers as an alternant; separate dosing by more than 2 hours from bosutinib dosing
    • PPIs decrease bosutinib Cmax and AUC, which may reduce the efficacy

Pregnancy and Lactation

• No data are available on pregnant women to inform the drug-associated risk; however, fetal harm may occur when administered to pregnant women based on the mechanism of action and findings from animal studies
• Verify pregnancy status in females of reproductive potential before starting treatment
• Contraception
  • Based on findings from animal studies, fetal harm may occur when administered to pregnant females
  • Females of reproductive potential: Use effective contraception during treatment and for at least 2 weeks after the last dose
• Infertility
  • Risk of infertility in females or males of reproductive potential has not been studied in humans
  • Based on findings from animal studies, reduced fertility may occur in females and males of reproductive potential
• Lactation
  • No data are available regarding the presence of bosutinib or its metabolites in human milk or its effects on a breastfed child or milk production
  • Bosutinib is present in the milk of lactating rats
  • Owing to the potential for serious adverse reactions in a nursing child, breastfeeding is not recommended during treatment and for at least 2 weeks after the last dose