Usual Adult Dose for Acute Myeloid Leukemia

50 mg orally twice a day at approximately 12 hour intervals on Days 8 to 21 of each cycle of induction AND on Days 8 to 21 of each cycle of consolidation.

Comments:

• This drug is not indicated as a single-agent induction therapy for acute myeloid leukemia (AML) patients.
• Information on FDA-approved tests for the detection of FLT3 mutation in AML is available at: http://www.fda.gov/CompanionDiagnostics.

Use: In combination with standard cytarabine and daunorubicin induction and cytarabine consolidation
chemotherapy, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) who are FLT3
mutation-positive, as detected by a FDA approved test

Usual Adult Dose for Systemic Mastocytosis

100 mg orally twice a day at approximately 12 hour intervals

Comments:

• Monitor for toxicity at least weekly for the first 4 weeks, every other week for the next 8 weeks, and monthly thereafter while on treatment.
• Treatment should be continued until disease progression or unacceptable toxicity.

Uses: For the treatment of adult patients with aggressive systemic mastocytosis (ASM), systemic
mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL)

Usual Adult Dose for Leukemia

100 mg orally twice a day at approximately 12 hour intervals

Comments:

• Monitor for toxicity at least weekly for the first 4 weeks, every other week for the next 8 weeks, and monthly thereafter while on treatment.
• Treatment should be continued until disease progression or unacceptable toxicity.

Uses: For the treatment of adult patients with aggressive systemic mastocytosis (ASM), systemic
mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL)

Renal Dose Adjustments

Data not available.

Liver Dose Adjustments

Data not available.

Dose Adjustments

FOR PATIENTS WITH SYSTEMIC MASTOCYTOSIS:

ABSOLUTE NEUTROPHIL COUNT (ANC) LESS THAN 1 x 10(9)/L WITHOUT MCL OR ANC LESS THAN 0.5 x 10(9)/L WITH BASELINE ANC VALUE of 0.5 to 1.5 x 10(9)/L:

• Interrupt treatment until ANC 1 x 10(9)/L or greater, then resume treatment at 50 mg twice a day; increase to 100 mg twice a day if tolerated.
• Discontinue treatment if low ANC persists for more than 21 days and is suspected to be drug-related.

PLATELET COUNT LESS THAN 50 X 10(9)/L WITHOUT MCL OR PLATELET COUNT LESS THAN 25 x 10(9)/L WITH BASELINE PLATELET COUNT of 25 to 75 x 10(9)/L:

• Interrupt treatment until platelet count 50 x 10(9)/L or greater, then resume treatment at 50 mg twice a day; increase to 100 mg twice a day if tolerated.
• Discontinue treatment if low platelet count persists for more than 21 days and is suspected to be drug-related.

HEMOGLOBIN LESS THAN 8 g/L WITHOUT MCL OR LIFE-THREATENING ANEMIA WITH BASELINE HEMOGLOBIN VALUE of 8 to 10 g/L:

• Interrupt treatment until hemoglobin 8 g/L or greater, then resume treatment at 50 mg twice a day; increase to 100 mg twice a day if tolerated.
• Discontinue treatment if low hemoglobin persists for more than 21 days and is suspected to be drug-related.

GRADE 3/4 NAUSEA AND/OR VOMITING DESPITE OPTIMAL ANTI-EMETIC THERAPY: Interrupt treatment for 3 days (6 doses), then resume treatment at 50 mg twice a day; increase to 100 mg twice a day if tolerated.

OTHER GRADE 3/4 NON-HEMATOLOGICAL TOXICITIES: Interrupt treatment until event has resolved to Grade 2 or less, then resume treatment at 50 mg twice a day; increase to 100 mg twice a day if tolerated.

Precautions

CONTRAINDICATIONS:

• Hypersensitivity to the active component or any of the ingredients

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:

• To reduce the risk of nausea and vomiting, administer prophylactic anti-emetics prior to treatment with this drug.
• Swallow capsules whole with food; do not open or crush the drug capsules.
• Do not make up a missed or vomited dose; administer the next dose at the usual scheduled time.

Storage Requirements:

• Store this drug at 20C to 25C (68F to 77F); excursions permitted at 15C to 30C (59F to 86F).
• Keep this drug in its original package to protect it from moisture.

Monitoring:

• Respiratory: Signs/symptoms of interstitial lung disease and pneumonitis