IDARUBICIN HYDROCHLORIDE
Clinical safety rating: avoid
Contraindicated (not allowed)
Idarubicin is an anthracycline antineoplastic agent. It intercalates between DNA base pairs, inhibits topoisomerase II, and generates free radicals, leading to DNA damage and cell death.
| Metabolism | Primarily hepatic metabolism via aldo-keto reductases to idarubicinol (active metabolite); also metabolized by CYP450 enzymes. |
| Excretion | Primarily hepatic metabolism and biliary excretion (40-50% unchanged drug and metabolites in bile); renal excretion accounts for <15% as unchanged drug and metabolites. |
| Half-life | Terminal elimination half-life is 20-30 hours (mean 22 hours); prolonged in hepatic impairment. |
| Protein binding | Approximately 97% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Large Vd of 25-30 L/kg; extensive tissue distribution with high concentrations in liver, lungs, and kidneys. |
| Bioavailability | Not available orally; only administered intravenously (100% bioavailability by IV route). |
| Onset of Action | Intravenous: within 2-3 days (bone marrow suppression); clinical antileukemic effect seen after 7-10 days. |
| Duration of Action | Myelosuppression lasts 2-3 weeks; recovery begins around day 14-21. |
12 mg/m2 IV over 5-10 minutes, daily for 3 days, every 3 weeks (total dose per cycle 36 mg/m2) or as part of combination regimens; alternate regimen: 8-12 mg/m2 IV daily for 3 days.
| Dosage form | SOLUTION |
| Renal impairment | GFR < 60 mL/min: no specific dose adjustment, but monitor for increased toxicity; GFR < 30 mL/min: consider dose reduction by 25-50% or alternative agent; severe impairment (GFR < 15 mL/min) avoid use. |
| Liver impairment | Child-Pugh Class A: standard dose; Child-Pugh Class B: reduce dose by 25-50%; Child-Pugh Class C: contraindicated or reduce dose by 50% with close monitoring; if bilirubin > 3 mg/dL, avoid use. |
| Pediatric use | 10-12 mg/m2 IV daily for 3 days, every 3 weeks; for acute lymphoblastic leukemia, 10 mg/m2/day for 3 days; weight-based equivalent for children < 0.5 m2: 0.3-0.4 mg/kg/day for 3 days. |
| Geriatric use | No specific dose adjustment based on age alone; monitor for increased myelosuppression and cardiotoxicity; start at lower end of dosing range (e.g., 8 mg/m2/day for 3 days) in patients >70 years or with comorbidities. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Other cardiotoxic drugs (eg trastuzumab) increase risk Can cause severe and irreversible cardiotoxicity and myelosuppression.
| Breastfeeding | Excreted in human milk; M/P ratio unknown. Due to potential for serious adverse reactions (neutropenia, thrombocytopenia, cardiotoxicity) in nursing infants, breastfeeding is contraindicated during therapy and for at least 10 days after the last dose. |
| Teratogenic Risk | Pregnancy Category D. First trimester: High risk of major congenital malformations including cardiac, CNS, and skeletal defects. Second/third trimesters: Increased risk of fetal growth restriction, preterm birth, and neonatal myelosuppression. Contraindicated in pregnancy. |
■ FDA Black Box Warning
Severe myelosuppression; cumulative dose-dependent cardiotoxicity (risk increases with prior anthracycline exposure or pre-existing heart disease); tissue necrosis with extravasation; reduce dose in hepatic impairment.
| Common Effects | Myelosuppression |
| Serious Effects |
Hypersensitivity to idarubicin or other anthracyclines; severe hepatic impairment; severe renal impairment; uncontrolled infection; baseline severe myelosuppression; pre-existing cardiomyopathy; recent myocardial infarction; severe arrhythmias; pregnancy; breastfeeding.
| Precautions | Cardiotoxicity (monitor LVEF, cumulative dose limit ~150 mg/m²); myelosuppression; extravasation (use central line); secondary leukemia; tumor lysis syndrome; hepatotoxicity; renal impairment (dose adjustment); pregnancy category D. |
| Food/Dietary |
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| Fetal Monitoring | Monitor maternal CBC with differential, liver function tests, renal function, and cardiac function (ECG, echocardiogram) before and during therapy. Evaluate fetal growth via ultrasound, consider antenatal fetal monitoring (nonstress test, biophysical profile) if continued pregnancy. Assess for signs of preterm labor. |
| Fertility Effects | Gonadal suppression, amenorrhea, and premature ovarian failure in females; azoospermia or oligospermia in males. May cause irreversible infertility. Risk increases with cumulative dose and patient age. |
| Avoid grapefruit and grapefruit juice as they inhibit CYP3A4 and may increase idarubicin levels. No other specific food restrictions; however, maintain adequate nutrition and hydration. Avoid alcohol due to hepatotoxicity risk. |
| Clinical Pearls | Idarubicin is a potent anthracycline with 4-5 times greater potency than daunorubicin. It is lipophilic, allowing oral bioavailability, but IV formulation is standard. Requires cardiac monitoring due to dose-dependent cardiomyopathy (cumulative dose limit ~150 mg/m²). Extravasation causes severe tissue necrosis; administer via central line or secure peripheral IV. Idarubicin is metabolized to idarubicinol, which has antileukemic activity and prolongs effects. Dose adjustment needed for hepatic impairment (bilirubin >2 mg/dL). Do not co-administer with live vaccines. Premedicate with antiemetics (e.g., 5-HT3 antagonists) as it is highly emetogenic. Monitor for tumor lysis syndrome; maintain hydration and allopurinol. Can cause red-orange urine discoloration (harmless). |
| Patient Advice | This medication may cause a red-orange discoloration of your urine, sweat, and tears for 1-2 days after treatment; this is harmless and temporary. · Avoid contact with people who have recent live vaccines (e.g., MMR, nasal flu) as your immune system will be suppressed. · You may experience hair loss, nausea, vomiting, and mouth sores; report severe symptoms to your doctor. · Notify your doctor immediately if you have chest pain, shortness of breath, or swelling of ankles/feet (signs of heart damage). · Inform your doctor if you are pregnant, planning to become pregnant, or breastfeeding. · Do not take aspirin, ibuprofen, or other NSAIDs without approval due to bleeding risk. · Stay well hydrated; drink plenty of fluids to prevent kidney issues from tumor lysis syndrome. · Use effective contraception during and for at least 6 months after treatment for both men and women. |