Idarubicin Hydrochloride

Idarubicin Hydrochloride is a DNA-intercalating analog of daunorubicin which has an inhibitory effect on nucleic acid synthesis and interacts with the enzyme topoisomerase II. The absence of a methoxy group at position 4 of the anthracycline structure gives the compound a high lipophilicity which results in an increased rate of cellular uptake compared with other anthracyclines.

• Acute myeloid leukemia (AML) in adults - FAB classifications M1 through M7

Adult Dose (Intravenous):

• Induction Therapy (AML): 12 mg/m2 daily for 3 days (slow IV injection, 10-15 min) in combination with cytarabine
• Cytarabine: 100 mg/m2 daily for 7 days (continuous infusion) or 25 mg/m2 IV bolus then 200 mg/m2 daily for 5 days (continuous infusion)
• Second course: After recovery from severe mucositis, with 25% dose reduction
• Hepatic/Renal impairment: Consider dose reduction; do not administer if bilirubin >5 mg%

Child Dose: Safety and effectiveness in children have not been established

Side Effects:

• Severe myelosuppression (in all therapeutic doses)
• Death due to infection and/or bleeding (during severe myelosuppression)
• Cardiac toxicity (congestive heart failure, arrhythmias, cardiomyopathies)
• Nausea, vomiting
• Mucositis
• Alopecia (hair loss)

Precautions:

• Idarubicin is a potent bone marrow suppressant
• Caution in patients with pre-existing bone marrow suppression (from prior drug therapy or radiotherapy)
• Careful hematologic monitoring required
• Pre-existing heart disease and prior anthracycline therapy increase risk of cardiac toxicity
• Facilities for rapid treatment of severe hemorrhagic conditions and infections must be available

Contraindications:

• Hypersensitivity
• Pre-existing severe bone marrow suppression (unless benefit warrants risk)

Use in Pregnancy: Category D; embryotoxic and teratogenic in animal studies; no adequate human studies; if used during pregnancy, apprise of potential hazard to fetus; women of childbearing potential should avoid pregnancy.

Use in Lactation: It is not known whether this drug is excreted in human milk; due to potential for serious adverse reactions, mothers should discontinue nursing.

Renal Impairment: Consider dose reduction in hepatic and/or renal impairment; caution in severe renal impairment.

Hepatic Impairment: Do not administer if bilirubin exceeds 5 mg%; consider dose reduction in hepatic impairment.