Semisynthetic anthracycline glycoside analog of daunorubicin.
Inhibits topoisomerase II by forming a cleavable complex with topoisomerase II and DNA.
In the presence of iron, drug forms oxygen free radicals, which cause single- and double-stranded DNA breaks.
Intercalates into DNA, which results in inhibition of DNA synthesis and function.
Specificity, in part, for the late S- and G2-phases of the cell cycle.
Increased expression of the multidrug-resistant gene with enhanced drug efflux. This results in decreased intracellular drug accumulation.
Decreased expression of topoisomerase II.
Mutations in topoisomerase II, with decreased binding affinity to drug.
Increased expression of sulfhydryl proteins, including glutathione and glutathione-associated enzymes.
Rapid and extensive tissue distribution. Peak concentrations in nucleated blood and bone marrow cells are achieved within minutes of administration and are 100-fold greater than those in plasma. Parent drug and its major metabolite, idarubicinol, are extensively bound (>90%) to plasma proteins.
Acute myelogenous leukemia.
Acute lymphoblastic leukemia.
Chronic myelogenous leukemia in blast crisis.
Myelodysplastic syndromes.
Acute myelogenous leukemia, induction therapy—12 mg/m2 IV on days 1-3 in combination with cytarabine, 100 mg/m2/day IV continuous infusion for 7 days.
Probenecid and sulfinpyrazone—Avoid concomitant use of probenecid and sulfinpyrazone, as these are uricosuric agents and may lead to uric acid nephropathy.
Heparin—Idarubicin is incompatible with heparin, as it forms a precipitate.
Use with caution in patients with abnormal liver function. Dose modification should be considered in patients with liver dysfunction. Dose reduction by 50% is recommended for serum bilirubin in the range of 2.6-5.0 mg/dL. Absolutely contraindicated in patients with bilirubin >5.0 mg/dL.
Careful administration of drug, usually through a central venous catheter, is necessary, as it is a strong vesicant. If peripheral venous access is used, careful monitoring of drug administration is necessary to avoid extravasation. If extravasation is suspected, stop infusion immediately, withdraw fluid, elevate arm, and apply ice to site. In severe cases, consult a plastic surgeon.
Alkalinization of the urine, allopurinol, and vigorous IV hydration are recommended to prevent tumor lysis syndrome in patients with acute myelogenous leukemia.
Monitor cardiac function before (baseline) and periodically during therapy with either MUGA radionuclide scan or echocardiogram to assess LVEF. Risk of cardiac toxicity is higher in elderly patients >70 years of age, in patients with prior history of hypertension or pre-existing heart disease, in patients previously treated with anthracyclines, or in patients with prior radiation therapy to the chest. While maximum dose of idarubicin that may be administered safely is not known, cumulative doses of >150 mg/m2 have been associated with decreased LVEF.
Caution patients against sun exposure and to wear sun protection when outside.
Caution patients about the potential for red discoloration of urine for 1-2 days after drug administration.
Pregnancy category D. Breastfeeding should be avoided.
Myelosuppression is dose-limiting, with neutropenia and thrombocytopenia. Nadir typically occurs at 10-14 days after treatment, with recovery of counts by day 21. Risk of myelosuppression is greater in elderly patients and in those previously treated with chemotherapy and/or radiation therapy.
Nausea and vomiting. Usually mild and occur in up to 80%-90% of patients.
Cardiac toxicity. Cardiac effects are similar to but less severe than those of doxorubicin. Acute toxicity presents as atrial arrhythmias, chest pain, and myopericarditis syndrome that typically occur within the first 24-48 hours of drug administration. Dilated cardiomyopathy with congestive heart failure can occur, usually with higher cumulative doses above 150 mg/m2.
Alopecia is nearly universal but reversible.
Generalized skin rash, increased sensitivity to sunlight, and hyperpigmentation of nails and at the injection site. Radiation-recall skin reactions can occur.
Potent vesicant, and extravasation can lead to extensive tissue damage.
Mucositis and diarrhea are common.
Hepatotoxicity with alterations in SGOT and SGPT.
Red discoloration of urine. Usually within the first 1-2 days after drug administration.
