Usual Adult Dose for Chronic Myelogenous Leukemia

Newly-diagnosed:
400 mg orally once daily
Duration of therapy: Until disease progression or patient intolerance

Chronic/accelerated/blast phase:
500 mg orally once daily
Duration of therapy: Until disease progression or patient intolerance

Comments:

• Take this drug with food.
• If a dose is missed beyond 12 hours, the patient should skip the dose and take the usual prescribed dose on the following day.

• For newly-diagnosed chronic phase (CP) Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML)
• For chronic phase, accelerated phase (AP), or blast phase (BP) Ph+ CML with resistance or intolerance to prior therapy

Renal Dose Adjustments

RECOMMENDED STARTING DOSE for newly-diagnosed chronic phase Ph+ CML:

• Normal renal function: 400 mg orally once a day
• Moderate renal dysfunction (CrCl 30 to 50 mL/min): 300 mg orally once a day
• Severe renal dysfunction (CrCl less than 30 mL/min): 200 mg orally once a day

• Normal renal function: 500 mg orally once a day
• Moderate renal dysfunction (CrCl 30 to 50 mL/min): 400 mg orally once a day
• Severe renal dysfunction (CrCl less than 30 mL/min): 300 mg orally once a day

Liver Dose Adjustments

RECOMMENDED STARTING DOSE for newly-diagnosed chronic phase Ph+ CML:

• Normal liver function: 400 mg orally once a day
• Mild, moderate, or severe liver dysfunction (Child-Pugh A, B, or C): 200 mg orally once a day (There are no clinical data for efficacy at the dose of 200 mg once daily in patients with CML)

• Normal liver function: 500 mg orally once a day
• Mild, moderate, or severe liver dysfunction (Child-Pugh A, B, or C): 200 mg orally once a day (There are no clinical data for efficacy at the dose of 200 mg once daily in patients with CML)

Dose Adjustments

DOSE ESCALATION:

• The dose can be escalated by increments of 100 mg once daily to a maximum of 600 mg once daily in patients who did not achieve or maintain a hematologic, cytogenetic, or molecular response and who did not have Grade 3 or higher adverse reactions at the recommended starting dosage.

• Liver transaminases greater than 5 times the institutional upper limit of normal (ULN): Withhold therapy until recovery to less than or equal to 2.5 x ULN and resume at 400 mg orally once daily thereafter. If recovery takes longer than 4 weeks, discontinue therapy.
• Liver transaminases greater than or equal to 3 x ULN concurrently with bilirubin greater than 2 x ULN and alkaline phosphatase less than 2 x ULN (Hy's law case definition): Discontinue therapy

• For NCI CTCAE Grade 3 to 4 diarrhea (increase of greater than or equal to 7 stools/day over baseline/pretreatment): Withhold therapy until recovery to Grade 1 or less. Treatment may be resumed at 400 mg orally once a day.

• Withhold therapy until resolved, then consider resuming therapy at a dose reduced by 100 mg orally once a day.
• If appropriate, consider re-escalating the dose to the starting dose once a day.
• Doses less than 300 mg/day have been used in patients; however, efficacy has not been established

• Absolute neutrophil count (ANC) less than 1000 x 10(6)/L OR platelets less than 50,000 x 10(6)/L: Withhold therapy until ANC is greater than or equal to 1000 x 10(6)/L AND platelets are greater than or equal to 50,000 x 10(6)/L.
• Resume therapy at the same dose if recovery occurs within 2 weeks. If blood counts remain low for more than 2 weeks, upon recovery, reduce dose by 100 mg and resume therapy.
• If cytopenia recurs, reduce dose by an additional 100 mg upon recovery and resume therapy.
• Doses less than 300 mg/day have been used in patients; however, efficacy has not been established.

Precautions

CONTRAINDICATIONS:

• Hypersensitivity to the active component or any of the ingredients. Reactions have included anaphylaxis.

Dialysis

Data not available

Other Comments

Administration advice:

• This drug should be taken with food.
• Tablets should be swallowed whole and not be broken or cut.
• If a dose is missed beyond 12 hours, the patient should skip the dose and take the usual prescribed dose on the following day.

• Store at 20C to 25C (68F to 77F); excursions permitted to 15C to 30C (59F to 86F).

• Procedures for proper disposal of anticancer drugs should be considered.
• Touching or handling crushed or broken tablets should be avoided.
• Any unused product or waste material should be disposed of in accordance with local requirements, or drug take back programs.

• Advise the patient to read the approved patient labeling (Patient Information).
• This drug may cause dizziness, fatigue, visual impairment, and other adverse effects which may impair ability to drive or operate machinery. If affected, avoid such tasks for as long as the side effects persist.
• Advise patients that they may experience respiratory tract infections, rash, fatigue, loss of appetite, headache, dizziness, back pain, arthralgia, or pruritus and to seek medical attention if symptoms are significant.
• Advise patients that there is a possibility of anaphylactic shock.
• 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.
• Advise patients to seek immediate medical attention if any symptoms suggestive of cardiac failure and cardiac ischemia occur, such as shortness of breath, weight gain, or fluid retention.
• Advise patients to immediately report to the health care provider frequent urination, polyuria or oliguria.
• Advise patients of the possibility of developing liver function abnormalities and to immediately report jaundice.
• 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.
• Advise patients that they may experience diarrhea, nausea, vomiting, abdominal pain, or blood in their stools and to seek medical attention promptly for these symptoms
• Due to nausea and vomiting the efficacy of oral contraceptives may be reduced because of inadequate absorption.