IDAMYCIN PFS
Clinical safety rating
cautionComprehensive clinical and safety monograph for IDAMYCIN PFS (IDAMYCIN PFS).
Comprehensive clinical and safety monograph for IDAMYCIN PFS (IDAMYCIN PFS).
Treatment of acute myeloid leukemia (AML) in adultsTreatment of acute lymphocytic leukemia (ALL) (off-label)
Idarubicin is an anthracycline antineoplastic antibiotic that intercalates with DNA and inhibits topoisomerase II, resulting in DNA strand breaks and inhibition of nucleic acid synthesis.
| Metabolism | Hepatic metabolism primarily via aldo-keto reductases to idarubicinol (active metabolite); further metabolism via glucuronidation. |
| Excretion | Renal (approximately 5-12% as unchanged drug and metabolites), biliary/fecal (significant, with 40-50% recovered in feces over 7 days). |
| Half-life | Terminal elimination half-life of idarubicin is 20-30 hours; idarubicinol (active metabolite) has a terminal half-life of 45-60 hours, extending myelosuppression duration. |
| Protein binding | Idarubicin: 94-97% bound to plasma proteins (primarily albumin); idarubicinol: 90-95% bound. |
| Volume of Distribution | Vd: 40-90 L/kg (extensive tissue distribution, indicating high affinity for intracellular sites such as DNA). |
| Bioavailability | Oral bioavailability: approximately 30% (limited clinical use; idarubicin is typically administered IV). |
| Onset of Action | IV administration: clinical antileukemic effect observed within 1-2 weeks (bone marrow clearing). |
| Duration of Action | Myelosuppression duration: 2-3 weeks; cardiac toxicity risk persists long-term (months to years). |
| Molecular Weight | 497.5 |
12 mg/m² intravenously over 10 to 15 minutes daily for 3 days (induction) or 12 mg/m² intravenously daily for 2 days (consolidation).
| Dosage form | SOLUTION |
| Renal impairment | GFR 20-50 mL/min: Administer 75% of dose; GFR <20 mL/min: Administer 50% of dose. Not dialyzable; no supplemental dose needed post-dialysis. |
| Liver impairment | Child-Pugh Class B: Reduce dose by 25%; Child-Pugh Class C: Reduce dose by 50%. Severe hepatic dysfunction (bilirubin >3 mg/dL): Contraindicated unless benefit outweighs risk. |
| Pediatric use | Children: 12 mg/m² intravenously daily for 3 days (induction) or 12 mg/m² daily for 2 days (consolidation). For infants <0.5 m²: 0.75 mg/kg intravenously daily for 3 days. |
| Geriatric use | No specific dose adjustment, but monitor for increased myelosuppression and cardiotoxicity. Consider dose reduction based on renal function and performance status. |
| 1st trimester | Idarubicin is contraindicated in the first trimester due to high teratogenic risk; cases of fetal cardiac anomalies, limb malformations, and growth restriction have been reported. |
| 2nd trimester | Use only if benefit outweighs risk; may cause fetal myelosuppression, growth restriction, and premature labor; consider close fetal monitoring. |
| 3rd trimester | Use only if benefit outweighs risk; risk of neonatal myelosuppression, cardiotoxicity, and premature delivery; monitor for hydrops fetalis and fetal distress. |
Clinical note
Comprehensive clinical and safety monograph for IDAMYCIN PFS (IDAMYCIN PFS).
| Placental transfer | Idarubicin and its active metabolite idarubicinol cross the placenta; detectable fetal plasma concentrations approximate maternal levels, indicating substantial transfer. |
| Breastfeeding | Idarubicin is excreted into breast milk in low concentrations; due to potential serious adverse reactions (myelosuppression, cardiotoxicity) in the breastfed infant, breastfeeding is not recommended during therapy and for at least 3-4 weeks after last dose. |
| Lactation Rating | L5 - Contraindicated |
| Teratogenic Risk | Idarubicin is embryotoxic and teratogenic in animal studies. Human data are limited, but it is classified as FDA Pregnancy Category D. There is evidence of fetal risk in the first trimester, including malformations and spontaneous abortion. In the second and third trimesters, there is risk of fetal growth restriction, preterm labor, and neonatal myelosuppression. Use only if potential benefit justifies risk. |
| Fetal Monitoring | Monitor complete blood count with differential, cardiac function (echocardiogram, ECG), hepatic function, renal function, and tumor lysis syndrome parameters. In pregnancy, monitor fetal growth and well-being with ultrasound and non-stress testing. Assess for signs of myelosuppression and cardiotoxicity. |
| Fertility Effects | Idarubicin may cause gonadal suppression, amenorrhea, and azoospermia. Prepubertal patients may experience permanent infertility. Reduced ovarian reserve and testicular function have been reported. Consider fertility preservation prior to treatment. |
■ FDA Black Box Warning
Severe myelosuppression when used at therapeutic doses; cardiac toxicity including potentially fatal congestive heart failure, acute left ventricular failure, and arrhythmias; secondary malignancies including acute myeloid leukemia and myelodysplastic syndrome; extravasation leading to severe tissue necrosis; reduce dose in patients with hepatic impairment.
| Serious Effects |
Severe hepatic impairment (Child-Pugh Class C)Severe renal impairment (CrCl < 20 mL/min)Hypersensitivity to idarubicin or any componentPre-existing myelosuppression (absolute neutrophil count < 1500/μL)Severe cardiac dysfunction (LVEF < 40%)Recent or ongoing cardiotoxic therapy (e.g., cumulative anthracycline exposure)Acute infections (e.g., sepsis)Pregnancy (first trimester) and breastfeeding
| Precautions | Monitor cardiac function before and during therapy; cumulative dose increases risk of cardiotoxicity, Severe myelosuppression with risk of infection and bleeding, Extravasation risk: administer via secure IV line, Secondary malignancies reported, Hepatic and renal impairment may require dose adjustment, Tumor lysis syndrome, May impair fertility |
| Food/Dietary | Avoid grapefruit and grapefruit juice due to potential CYP3A4 inhibition affecting drug metabolism. No other significant food interactions. |
| Clinical Pearls | Administer IV only; extravasation causes severe tissue necrosis. Premedicate with antiemetics. Monitor for cardiotoxicity with cumulative doses >550 mg/m2 (or 450 mg/m2 with prior chest irradiation). Urine may turn reddish for 1-2 days. Leukocyte nadir occurs 10-14 days after administration. |
| Patient Advice | This drug can cause severe nausea and vomiting; take antiemetics as prescribed. · Your urine may appear red or orange for 1-2 days after treatment; this is normal. · Report any pain, redness, or swelling at the injection site immediately. · Avoid receiving live vaccines during treatment and for 6 months after. · Use effective contraception during and for at least 6 months after therapy. |
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