IDAMYCIN
Clinical safety rating
cautionComprehensive clinical and safety monograph for IDAMYCIN (IDAMYCIN).
Comprehensive clinical and safety monograph for IDAMYCIN (IDAMYCIN).
Treatment of acute myeloid leukemia (AML) in adults, including induction therapy in combination with other agentsTreatment of acute lymphoblastic leukemia (ALL) (off-label)
Idarubicin is an anthracycline antineoplastic agent that intercalates with DNA and inhibits topoisomerase II, leading to inhibition of DNA replication and transcription, and ultimately cell death. It also generates free radicals and induces apoptosis.
| Metabolism | Idarubicin is extensively metabolized in the liver to its active metabolite idarubicinol, which has similar antineoplastic activity. The primary enzyme involved is aldo-keto reductase. Idarubicin and idarubicinol are eliminated via biliary excretion and renal excretion. |
| Excretion | Primarily hepatic metabolism; biliary excretion of metabolites accounts for ~50% of total elimination. Renal excretion of unchanged drug is minimal (<10%). Approximately 30-40% of the dose is recovered in urine as metabolites. Fecal elimination of metabolites accounts for ~50%. |
| Half-life | Terminal elimination half-life: 20-30 hours (mean ~22 hours). Prolonged in severe hepatic impairment (up to 40 hours) and may be extended in patients with renal impairment due to accumulation of active metabolite idarubicinol (half-life > 60 hours). |
| Protein binding | Parent drug: 94-97% bound, primarily to albumin. Idarubicinol (active metabolite): ~95% bound to albumin. |
| Volume of Distribution | Vd: 20-30 L/kg (mean ~25 L/kg). Very large distribution indicates extensive tissue binding and penetration into cells, particularly in bone marrow. |
| Bioavailability | Oral bioavailability: approximately 28% (range 10-40%) due to first-pass metabolism. Not available orally in typical clinical practice; IV administration is standard. Oral formulations exist for investigational use but not FDA-approved. |
| Onset of Action | IV: Onset of antileukemic effect within 1-3 days (due to DNA intercalation), with earliest evidence of bone marrow suppression (myelosuppression) seen at 3-5 days post-dose. |
| Duration of Action | Duration of myelosuppression: 3-4 weeks post-administration. Antitumor effect persists as long as cellular idarubicinol is present (intracellular half-life ~72 hours). Clinical response (remission) may require 1-2 cycles of therapy. |
| Molecular Weight | 497.49 |
12 mg/m² IV daily for 3 days (acute myeloid leukemia) or 12 mg/m² IV daily for 3 days (acute lymphoblastic leukemia); maximum cumulative dose 600 mg/m².
| Dosage form | POWDER |
| Renal impairment | If serum creatinine > 2 mg/dL or creatinine clearance < 30 mL/min, reduce dose by 25-50% and monitor cardiac function. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 25%; Child-Pugh C: reduce dose by 50% or consider alternative therapy. |
| Pediatric use | 10-12 mg/m² IV daily for 3 days; maximum cumulative dose 600 mg/m²; adjust for renal/hepatic impairment. |
| Geriatric use | Start at lower end of dosing range (e.g., 10-12 mg/m²), monitor cardiac function closely due to increased risk of cardiomyopathy; reduce dose for renal impairment. |
| 1st trimester | Contraindicated due to teratogenicity; embryotoxicity, fetal malformations observed. |
| 2nd trimester | Contraindicated; risk of fetal harm outweighs benefits. |
| 3rd trimester | Contraindicated; may cause fetal toxicity and neonatal myelosuppression. |
Clinical note
Comprehensive clinical and safety monograph for IDAMYCIN (IDAMYCIN).
| Placental transfer | Idarubicin and its active metabolite idarubicinol cross the placenta. Fetal plasma concentrations similar to maternal levels, indicating significant transfer. |
| Breastfeeding | Idarubicin is excreted into human milk. Because of the potential for serious adverse reactions in nursing infants, breastfeeding is contraindicated during treatment and for at least 10 days after the last dose. |
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | Pregnancy category D. First trimester: high risk of fetal malformations (central nervous system, cardiovascular, skeletal). Second and third trimesters: increased risk of fetal growth restriction, preterm birth, and neonatal myelosuppression. Avoid use unless maternal benefit outweighs risks. |
| Fetal Monitoring | Monitor maternal CBC, cardiac function (LVEF), and hepatic/renal function. Fetal monitoring: serial ultrasound for growth restriction, amniotic fluid index, and fetal echocardiography. |
| Fertility Effects | Causes ovarian failure in women (premature menopause) and azoospermia in men. Risk correlates with cumulative dose and age at treatment. |
■ FDA Black Box Warning
Idarubicin should be administered only under the supervision of physicians experienced in leukemia chemotherapy. Severe myelosuppression occurs. Cardiotoxicity (including heart failure, arrhythmias, and cardiomyopathy) may occur, especially with cumulative doses exceeding 150 mg/m². Extravasation can cause severe tissue necrosis. Reduction of left ventricular ejection fraction (LVEF) and congestive heart failure have been reported.
| Serious Effects |
Hypersensitivity to idarubicin or other anthracyclinesSevere hepatic impairmentSevere cardiac impairmentPre-existing bone marrow suppressionPregnancy
| Precautions | Myelosuppression: severe bone marrow suppression leading to infection, bleeding, and anemia, Cardiotoxicity: acute (arrhythmias, myocardial depression) and chronic (cumulative dose-related cardiomyopathy); monitor LVEF, Secondary malignancies: higher risk of therapy-related myelodysplasia or acute leukemia, Extravasation: severe tissue damage if extravasation occurs; use central line administration, Tumor lysis syndrome: rapid lysis of tumor cells can cause uric acid nephropathy, Hepatic impairment: requires dose reduction, Renal impairment: requires dose reduction, Immunosuppression: live vaccines contraindicated |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may inhibit CYP3A4 metabolism and increase idarubicin toxicity. No other significant food interactions are reported. Maintain adequate hydration to prevent tumor lysis syndrome; avoid alcohol as it may exacerbate hepatic toxicity. |
| Clinical Pearls | Idarubicin is a potent anthracycline with significant cardiotoxicity; cumulative lifetime dose should not exceed 150 mg/m² in adults. Administer IV slowly over 5-10 minutes to reduce risk of extravasation, which causes severe tissue necrosis. Monitor for acute infusion reactions and premedicate with antiemetics. Renal and hepatic impairment require dose adjustment; check bilirubin and creatinine levels before each cycle. Concomitant use with other cardiotoxic agents increases risk of heart failure. |
| Patient Advice | Tell your doctor if you have heart, liver, or kidney problems before starting treatment. · You will need regular blood tests to monitor blood counts and heart function. · Report any chest pain, shortness of breath, or swelling in your ankles immediately. · Avoid grapefruit and grapefruit juice during treatment as it may increase side effects. · Use effective contraception during and for at least 6 months after treatment. · Notify your healthcare provider if you experience fever, chills, or signs of infection. · This medication may cause your urine to turn reddish-orange for 1-2 days after administration. |
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