Idarubicin Hydrochloride

Idarubicin hydrochloride in combination with other approved antileukemic drugs is indicated for the treatment of acute myeloid leukemia (AML) in adults. This includes French-American- British (FAB) classifications M1 through M7.

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.

For induction therapy in adult patients with AML the following dose schedule is recommended: Idarubicin hydrochloride 12 mg/m2 daily for 3 days by slow (10 to 15 min) intravenous injection in combination with cytarabine. The cytarabine may be given as 100 mg/m2 daily by continuous infusion for 7 days or as cytarabine 25 mg/m2 intravenous bolus followed by cytarabine 200 mg/m2 daily for 5 days continuous infusion. In patients with unequivocal evidence of leukemia after the first induction course, a second course may be administered. Administration of the second course should be delayed in patients who experience severe mucositis, until recovery from this toxicity has occurred, and a dose reduction of 25% is recommended. In patients with hepatic and/or renal impairment, a dose reduction of Idarubicin should be considered. Idarubicin should not be administered if the bilirubin level exceeds 5 mg%. The benefit of consolidation in prolonging the duration of remissions and survival is not proven. There is no consensus regarding optional regimens to be used for consolidation.

Pediatric Use: Safety and effectiveness in children have not been established.

No formal drug interactions studies have been performed.

Pregnancy Category D. Idarubicin was embryotoxic and teratogenic in the rat at a dose of 1.2 mg/m2/day or one tenth the human dose, which was nontoxic to dams. Idarubicin was embryotoxic but not teratogenic in the rabbit even at a dose of 2.4 mg/m2/day or two tenths the human dose, which was toxic to dams. There is no conclusive information about idarubicin adversely affecting human fertility or causing teratogenesis. There has been one report of a fetal fatality after maternal exposure to idarubicin during the second trimester. There are no adequate and well-controlled studies in pregnant women. If Idarubicin is to be used during pregnancy, or if the patient becomes pregnant during therapy, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid pregnancy.

Nursing Mothers: It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from idarubicin, mothers should discontinue nursing prior to taking this drug.

Idarubicin hydrochloride is intended for administration under the supervision of a physician who is experienced in leukemia chemotherapy. Idarubicin is a potent bone marrow suppressant. Idarubicin should not be given to patients with pre-existing bone marrow suppression induced by previous drug therapy or radiotherapy unless the benefit warrants the risk. Severe myelosuppression will occur in all patients given a therapeutic dose of this agent for induction, consolidation or maintenance. Careful hematologic monitoring is required. Deaths due to infection and/or bleeding have been reported during the period of severe myelosuppression. Facilities with laboratory and supportive resources adequate to monitor drug tolerability and protect and maintain a patient compromised by drug toxicity should be available. It must be possible to treat rapidly and completely a severe hemorrhagic condition and/or a severe infection. Pre-existing heart disease and previous therapy with anthracyclines at high cumulative doses or other potentially cardiotoxic agents are co-factors for increased risk of idarubicin-induced cardiac toxicity and the benefit to risk ratio of idarubicin therapy in such patients should be weighed before starting treatment with Idarubicin. Myocardial toxicity as manifested by potentially fatal congestive heart failure, acute life- threatening arrhythmias or other cardiomyopathies may occur following therapy with Idarubicin. Appropriate therapeutic measures for the management of congestive heart failure and/or arrhythmias are indicated.

Store at controlled room temperature, 15° to 30°C, and protect from light.