Usual Adult Dose for Chronic Myelogenous Leukemia

Philadelphia chromosome-positive chronic myeloid leukemia I chronic phase (Ph+ CML-CP)

Ph+ CML-CP Previously Treated with 2 or More TKIs (tyrosine kinase inhibitors):
Recommended dose: 80 mg orally once a day OR 40 mg orally every 12 hours
Duration of therapy: Continue as long as clinical benefit is observed or until unacceptable toxicity occurs

Ph+ CML-CP with the T315I Mutation:
Recommended dose:: 200 mg orally every 12 hours

Comments:

• This drug is approved under accelerated approval based on major molecular response; continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials
• For recommended dosage modifications for the management of adverse reactions; see Dose Adjustments.

• Treatment of Ph+ CML in CP, previously treated with 2 or more tyrosine kinase inhibitors (TKIs)
• Treatment of Ph+ CML in CP with the T315I mutation

Renal Dose Adjustments

Mild to severe renal impairment (eGFR 15 to 89 mL/min/1.73 m2): No adjustment recommended
ESRD (eGFR less than 15 mL/min/1.73 m2) Data not available

Liver Dose Adjustments

Mild to severe hepatic impairment: No adjustment recommended

Dose Adjustments

Dose Reductions for Adverse Reactions:

Ph+ CML-CP Previously treated with 2 or more TKIs:

• FIRST REDUCTION: 40 mg once a day OR 20 mg twice a day
• SUBSEQUENT REDUCTION: Permanently discontinue in patients unable to tolerate reduced dose

• FIRST REDUCTION: 160 mg twice a day
• SUBSEQUENT REDUCTION: Permanently discontinue in patients unable to tolerate reduced dose

• WITHHOLD therapy until resolved to ANC of 1 x 10(9)/L or greater and/or PLT of 50 x 10(9)/L or greater
• If resolved within 2 weeks: Resume at starting dose
• If resolved after more than 2 weeks: Resume at reduced dose

• WITHHOLD until resolved to less than 1.5 x ULN
• If resolved, restart at reduced dose; if event recurs at reduced dose, permanently discontinue
• If not resolved, permanently discontinue; perform diagnostic tests to exclude pancreatitis

• WITHHOLD until recovery to Grade 1 or less
• If resolved, resume at reduced dose
• If not resolved, permanently discontinue

Precautions

CONTRAINDICATIONS: None

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Take orally without food; avoid consuming food for 2 hours before and 1 hour after dosing.
• Once-daily doses should be taken at the same time each day; twice-daily doses should be taken at approximately 12-hour intervals.
• Tablets should be swallowed whole; do not break, crush, or chew tablets.

• Once-daily regimen: If a dose is missed by more than approximately 12 hours, skip the dose and take the next dose as scheduled
• Twice-daily regimen: If a dose is missed by more than approximately 6 hours, skip the dose and take the next dose as scheduled

• Dispense and store in the original container to protect from moisture
• Store at 20C to 25C (68F to 77F), with excursions permitted between 15C and 30C (59F and 86F)

• This drug is approved under accelerated approval based on major molecular response; continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.

• Obtain complete blood counts (CBC) every 2 weeks for the first 3 months, then monthly thereafter, or as clinically indicated; monitor for signs and symptoms of myelosuppression.
• Obtain serum lipase and amylase levels monthly, or as clinically indicated; monitor for signs and symptoms of pancreatic toxicity, especially in patients with a history of pancreatitis.
• Monitor blood pressure.
• Monitor for hypersensitivity reactions.
• Monitor for patients with cardiovascular risk factors for worsening or new cardiovascular signs and symptoms.

• Patients should be instructed to read the US FDA-approved patient labeling (Patient Information).
• Patients should be advised to report signs and symptoms of infection, bleeding, pancreatitis, hypersensitivity, hypertension, or cardiovascular toxicity.
• Women of childbearing potential should understand the potential risk to fetus if this drug is used during pregnancy; women should be advised to use effective contraception during treatment and for 1 week after the last dose.
• Women should not breastfeed during treatment and for 1 week after the last dose.
• Patients should be advised that this drug may interact with other medications and alter the effects of this drug; patients should be advised to report all medication use including over the counter and herbal supplements, to their healthcare provider.