For Philadelphia positIVe chronic myeloid leukemia in blast crisis (related to inhibition of BCR-ABL tyrosine kinase), accelerated, or in chronic phase after failure with interferon-alfa therapy.?

Antineoplastic Agent / Immunological Agent

Absorption: Tmax, Oral: 2 to 4 hours ;Bioavailability, Oral: 98% Distribution: Protein binding, primarily albumin and alpha-1-acid glycoprotein: 95% Metabolism: Hepatic: primary site via CYP3A4 N-demethylated piperazine derivative (CGP74588): active substrate of CYP3A4 inhibitor of CYP3A4 Excretion: Fecal: 68%; 20% of total dose as unchanged drug Renal: 13%; 5% of total dose as unchanged drug Total body clearance, adults: 8 to 14 L/hr Total body clearance, pediatrics:11 L/hr/m(2) Elimination Half Life approximately 18 hours Children, 14.8 hours N-demethyl derivative (CGP74588): approximately 40 hours

Specific contraindications have not been determined

Fetal risk has been demonstrated

Infant risk cannot be ruled out

• Feeling sleepy. • Feeling tired or weak. • Dizziness. • Not able to sleep. • Belly pain. • Not hungry. • Gas. • Headache. • Hair loss. • Dry skin. • Upset stomach or throwing up. • Loose stools (diarrhea). • Hard stools (constipation). • Change in taste. • Nose and throat irritation. • Joint pain. • Muscle spasm. • Weight gain. • Night sweats. • Back pain. • Anxiety.

Chronic phase Cml 400 mg once daily. May increase to 600 mg Accelerated or blast crisis Cml 600 mg once daily. May increase to 800 mg. Dosage is increased if no haematological response is seen after 3 mth, or in the event of disease progression.

For pediatric patients, imatinib doses can be given once daily or divided into 2 doses (only for children with CML)

(1)Mild impairment (CrCl 40 to 59 mL/min): Maximum dosage 600 mg (2)Moderate impairment (CrCl 20 to 39 mL/min): 50% reduction of the starting dose and increase as tolerated to maximum of 400 mg (3)Severe impairment (CrCl 20 mL/min or less): Use cautiously, a dosage of 100 mg/day was tolerated in 2 patients

1) Mild-to-moderate impairment: No dosage adjustment is necessary. 2) Severe impairment: Reduce dosage by 25% . 3) Adjustments During Therapy Due To Hepatotoxicity a) If liver transaminases are greater than 5 times the institutional upper limit of normal (IULN) or elevations in serum bilirubin are greater than 3 times IULN, imatinib should be stopped. Treatment may then be restarted at a reduced dose (from 400 mg to 300 mg, from 600 mg to 400 mg, or from 800 mg to 600 mg) when the transaminase levels are less than 2.5 times IULN and serum bilirubin is less than 1.5 times IULN . 4) Maximum Tolerated Dose in Mild Hepatic Impairment a) A phase I dose-escalation trial in patients with various solid tumors found that the maximum tolerated dose (MTD) in patients with mild hepatic impairment (n=32) was 500 mg daily. Mild hepatic impairment was defined as total bilirubin of up to 1.5 times the upper limit of normal (ULN) and aspartate transaminase (AST) above the ULN, or AST normal if total bilirubin is above the ULN

Store at a controlled room temperature of 25 degrees C (77 degrees F), with excursions permitted between 15 and 30 degrees C (59 and 86 degrees F). Protect from moisture