Idarubicin Hydrochloride

Indications

Idarubicin Hydrochloride is used for: Acute myeloid leukemia, in combination with other antileukemic drugs. This includes French-American-British (FAB) classifications M1 through M7.

Adult Dose

IV Infusion Idarubicin Injection 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. The benefit of consolidation in prolonging the duration of remissions and survival is not proven. Hepatic Impairment Bilirubin 2.6-5 mg/dL: 50% of dose Bilirubin >5 mg/dL: Avoid use

Child Dose

Renal Dose

Renal Impairment CrCl 10-50 mL/min: 75% of dose CrCl <10 mL/min: 50% of dose Hemodialysis: Supplemental dose not necessary Peritoneal dialysis: Supplemental dose not necessary

Administration

IV Preparation Vials: reconstitute with NS to a concentration of 1 mg/mL Standard dilution IV push: dose/syringe (concentration is 1 mg/mL); maximum syringe size for IVP is 30 mL syringe & syringe should be <75% full IVPB: dose/100 mL D5W or NS IV Administration Vesicant Administer by intermittent infusion over 10-15 min Administer into a free flowing IV solution of NS or D5W Local erythematous streaking along the vein may indicate rapid administration

Contra Indications

Hypersensitivity Serum bilirubin >5 mg/dL [>85.5 umol/L]

Precautions

The drug should be administered under the supervision of a cancer chemotherapy physician experienced in acute leukemia treatment in a facility with appropriate equipment to monitor patients compromised by drug toxicity. Severe hemorrhagic conditions or overwhelming infection resulting from the therapy should also be able to be treated at the facility. Only administer intravenously into a freely flowing IV infusion. Do not administer intramuscularly or subcutaneously. Severe local tissue damage can occur with extravasation. Myocardial toxicity leading to CHF may occur. Toxicity is more common with prior anthracycline use or preexisting cardiac disease. Myelosuppression can be severe at therapeutic doses Reduce dose in renal or hepatic impairment

Pregnancy-Lactation

Pregnancy There is no conclusive information about therapy adversely affecting human fertility or causing teratogenesis; there has been one report of a fetal fatality after maternal exposure to drug during second trimester There are no adequate and well-controlled studies in pregnant women; drug should be used during pregnancy only if potential benefit justifies potential risk to fetus If drug is to be used during pregnancy, or if patient becomes pregnant during therapy, patient should be apprised and informed of potential hazard to fetus Women of childbearing potential should be advised to avoid pregnancy and advised to use effective contraception during treatment and for at least 6.5 months after the last dose Men with female partners of childbearing potential should be advised to use effective contraception during treatment and for at least 3.5 months after last dose Both men and women should seek advice for fertility preservation before treatment and/or seek genetic counseling after treatment Animal data Drug was embryotoxic and teratogenic in rat at dose of 1.2 mg/m2/day or one-tenth the human dose, which was nontoxic to dams; Drug was embryotoxic but not teratogenic in rabbit even at a dose of 2.4 mg/m2/day or two tenths the human dose, which was toxic to dams Lactation Not known whether drug is excreted in human milk; because many drugs are excreted in human milk and because of potential for serious adverse reactions in nursing infants from drug; mothers should discontinue nursing prior to taking drug and do not breastfeed during treatment and for 14 days after last dose

Interactions

Idarubicin hydrochloride is a potent myelosuppressant and combination chemotherapy regimens that contain other agents with similar action may lead to additive toxicity, especially with regard to bone marrow/hematologic and gastrointestinal effects. The use of idarubicin hydrochloride in combination chemotherapy with other potentially cardiotoxic drugs, as well as the concomitant use of other cardioactive compounds (e.g., calcium channel blockers), requires monitoring of cardiac function throughout treatment. Changes in hepatic or renal function induced by concomitant therapies may affect idarubicin hydrochloride metabolism, pharmacokinetics, and therapeutic efficacy and/or toxicity. An additive myelosuppressant effect may occur when radiotherapy is given concomitantly or within 2-3 weeks prior to treatment with idarubicin hydrochloride.

Adverse Effects

Side effects of Idarubicin Hydrochloride : >10% Infection (95%) Nausea (30-60%) Vomiting (30-60%) Alopecia (25-30%) Hemorrhage (63%) Stomatitis (11%) Fever (26%) Elevated bilirubin and transaminases (20-30%) Myelosuppression: > 10% 1-10% Seizure (4%) CHF (2%) Peripheral neuropathy (8%) Frequency Not Defined Fever Chills Headache Flushing Myocardial infarction Cardiac dysrhythmia Chest pain Diarrhea Inflammatory disease of mucous membrane Hyperuricemia Red discoloration of urine Rash

Mechanism of Action

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.