No

Antineoplastic Agent, Antibiotic

In combination treatment of acute myeloid leukemia (AML), this includes classifications M1 through M7 of the French-American-British (FAB) classification system; also used for the treatment of acute lymphocytic leukemia (ALL) in children

D

Hypersensitivity to idarubicin, daunorubicin, or any component

The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered. Administer I.V. slowly into a freely flowing I.V. infusion; do not administer I.M. or S.C., severe necrosis can result if extravasation occurs; can cause myocardial toxicity and is more common in patients who have previously received anthracyclines or have pre-existing cardiac disease; reduce dose in patients with impaired hepatic function; irreversible myocardial toxicity may occur as total dosage approaches 137.5 mg/m²; severe myelosuppression is also possible.

>10%:

Central nervous system: Headache, fever

Dermatologic: Alopecia, rash, urticaria

Gastrointestinal: Mucositis, nausea, vomiting, diarrhea, stomatitis

Genitourinary: Reddish urine

Hematologic: Hemorrhage, anemia

Leukopenia (nadir: 8-29 days)

Thrombocytopenia (nadir: 10-15 days)

Local: Tissue necrosis upon extravasation, erythematous streaking

Vesicant chemotherapy

Miscellaneous: Infection

1% to 10%:

Central nervous system: Seizures

Neuromuscular & skeletal: Peripheral neuropathy

Miscellaneous: Pulmonary allergy

<1%: Arrhythmias, EKG changes, cardiomyopathy, congestive heart failure, myocardial toxicity, acute life-threatening arrhythmias, hyperuricemia, elevated liver enzymes or bilirubin

Symptoms of overdose include severe myelosuppression and increased GI toxicity

Treatment is supportive; it is unlikely that therapeutic efficacy or toxicity would be altered by conventional peritoneal or hemodialysis

Patients may experience impaired immune response to vaccines; possible infection after administration of live vaccines in patients receiving immunosuppressants

Store intact vials of lyophilized powder at room temperature and protect from light

Dilute powder with sterile water for injection to a concentration of 1 mg/mL as follows: Solution is stable for 72 hours at room temperature and 7 days under refrigeration. Bacteriostatic diluents are not recommended.

5 mg = 5 mL

10 mg = 10 mL

Further dilution in D₅W or NS is stable for 4 weeks at room temperature and protected from light

Incompatible with dexamethasone, etoposide, fluorouracil, heparin, hydrocortisone, methotrexate, vincristine

Standard I.V. dilution:

I.V. push: Dose/syringe (concentration: 1 mg/mL)

Maximum syringe size for IVP: 30 mL syringe and syringe should be less than or equal to 75% full

IVPB: Dose/100 mL D₅W or NS

Syringe and IVPB solutions are stable for 72 hours at room temperature and 7 days under refrigeration

Derivative of daunorubicin; the only structural difference between idarubicin and the parent compound, daunorubicin, is lack of the methoxyl group at the C4 position of the aglycone. Similar to daunorubicin, idarubicin exhibits inhibitory effects on DNA and RNA polymerase in vitro. Idarubicin has an affinity for DNA similar to the parent compound and somewhat higher efficacy than daunorubicin in stabilizing the DNA double helix against heat denaturation.

Absorption: Oral: Rapid but erratic (20% to 30%) from the GI tract

Distribution: Large V_d due to extensive tissue binding and distributes into CSF

Protein binding: 94% to 97%

Metabolism: In the liver to idarubicinol, which is pharmacologically active

Half-life, elimination: Oral: 14-35 hours; I.V.: 12-27 hours

Time to peak serum concentration: Within 2-4 hours and varies considerably

Elimination: ~15% of an I.V. dose has been recovered in urine as idarubicin and idarubicinol; urinary recovery of idarubicin and idarubicinol is lower following oral doses; similar amounts are excreted via the bile

I.V.:

Leukemia: 10-12 mg/m² once daily for 3 days and repeat every 3 weeks

Solid tumors: 5 mg/m² once daily for 3 days and repeat every 3 weeks

Adults: 12 mg/m²/day for 3 days by slow (10-15 minutes) intravenous injection in combination with Ara-C

The Ara-C may be given as 100 mg/m²/day by continuous infusion for 7 days or as Ara-C 25 mg/m² bolus followed by Ara-C 200 mg/m²/day for 5 days continuous infusion

Dosing adjustment in renal impairment: Dose reduction is recommended

Serum creatinine greater than or equal to 2 mg/dL: Reduce dose by 25%

Hemodialysis: Significant drug removal is unlikely based on physiochemical characteristics

Peritoneal dialysis: Significant drug removal is unlikely based on physiochemical characteristics

Dosing adjustment/comments in hepatic impairment:

Bilirubin 1.5-5.0 mg/dL or AST 60-180 units/L: Reduce dose 50%

Bilirubin >5 mg/dL or AST >180 units/L: Do not administer

CBC with differential, platelet count, ECHO, EKG, serum electrolytes, creatinine, uric acid, ALT, AST, bilirubin, signs of extravasation

None reported

Leukopenia is common; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

This drug can only be administered I.V. Maintain adequate nutrition and hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). May cause hair loss (will grow back); nausea or vomiting (consult prescriber for antiemetic medication); you will be susceptible to infection (avoid crowds and exposure to infection); or urine may turn red-brown (normal). Report immediately any pain, burning, or stinging at infusion site; difficulty breathing; or swelling of extremities. Pregnancy/breast-feeding precautions: Use appropriate contraceptive measures; do not get pregnant while taking this drug (serious fetal damage has occurred). Consult prescriber if breast-feeding.

Local erythematous streaking along the vein may indicate too rapid a rate of administration

Unless specific data available, do not mix with other drugs

Extravasation management:

Apply ice immediately for 30-60 minutes; then alternate off/on every 15 minutes for one day

Topical cooling may be achieved using ice packs or cooling pad with circulating ice water. Cooling of site for 24 hours as tolerated by the patient. Elevate and rest extremity 24-48 hours, then resume normal activity as tolerated. Application of cold inhibits vesicant's cytotoxicity.

Application of heat or sodium bicarbonate can be harmful and is contraindicated

If pain, erythema, and/or swelling persist beyond 48 hours, refer patient immediately to plastic surgeon for consultation and possible debridement

Injection: 1 mg/mL (5 mL, 10 mL, 20 mL)

Powder for injection, lyophilized, as hydrochloride: 5 mg, 10 mg

Arlin ZA, "Idarubicin in Acute Leukemia: An Effective New Therapy for the Future," Semin Oncol, 1989, 16(1 Suppl 2):35-6.

Berman E, "A Review of Idarubicin in Acute Leukemia," Oncology, 1993, 7(10):91-8, 104.

Borchmann P, Hubel K, Schnell R, et al, "Idarubicin: A Brief Overview on Pharmacology and Clinical Use," Int J Clin Pharmacol Ther, 1997, 35(2):80-3.

Fields SM and Koeller JM, "Idarubicin: A Second Generation Anthracycline," DICP, 1991, 25(5):505-17.

Hollingshead LM and Faulds D, "Idarubicin: A Review of Its Pharmacodynamic and Pharmacokinetic Properties, and Therapeutic Potential in the Chemotherapy of Cancer," Drugs, 1991, 42(4):690-719.

Jeffrey LP, Chairman, National Study Commission on Cytotoxic Exposure. Position Statement. "The Handling of Cytotoxic Agents by Women Who Are Pregnant, Attempting to Conceive, or Breast-Feeding," January 12, 1987.

Reid JM, Pendergrass TW, Krailo MD, et al, "Plasma Pharmacokinetics and Cerebrospinal Fluid Concentrations of Idarubicin and Idarubicinol in Pediatric Leukemia Patients: A Children's Cancer Study Group Report," Cancer Res, 1990, 50(20):6525-8.