IDAMYCIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for IDAMYCIN (IDAMYCIN).
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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for IDAMYCIN (IDAMYCIN).
| Breastfeeding | Not recommended. Idarubicin is excreted into breast milk; M/P ratio not available. Potential for severe adverse effects in nursing infant including neutropenia and cardiotoxicity. |
| 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 |
■ 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 any component of the formulation","Severe hepatic impairment (bilirubin >5 mg/dL)","Severe renal impairment (creatinine clearance <15 mL/min)","Inadequate bone marrow reserve due to prior chemotherapy or radiotherapy","Pregnancy (category D): can cause fetal harm","Lactation: discontinue nursing or drug"]
| 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"] |
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| 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. |