Idarubicin Hydrochloride

Idarubicin Hydrochloride is indicated for the treatment of:

• Acute Myeloid Leukemia (AML): Used as induction and consolidation therapy in adult and pediatric patients with newly diagnosed AML.
• Acute Lymphoblastic Leukemia (ALL): Utilized in combination chemotherapy regimens for some ALL protocols.
• Other hematologic malignancies: Occasionally used off-label in certain leukemias or myelodysplastic syndromes based on clinical discretion.

Adults:

• Induction therapy for AML: 12 mg/m² administered intravenously once daily for 3 consecutive days, typically combined with cytarabine or other agents according to treatment protocols.
• Consolidation therapy: Dosage and duration are regimen-dependent and generally involve lower doses for fewer days.

Pediatrics:

• Dose is generally 10 to 12 mg/m² IV daily for 3 days during induction therapy, adjusted per clinical protocol.

Elderly:

• Dose adjustment may be necessary due to increased susceptibility to toxicity. Lower initial doses or modified schedules are often used.

Renal Impairment:

• Use with caution; no formal dosing adjustments available.

Hepatic Impairment:

• Dose reduction recommended in moderate to severe hepatic dysfunction due to reduced metabolism.

Administration:

• Administer by slow intravenous injection or infusion over several minutes.
• Use central venous access if available to minimize local toxicity.
• Avoid intramuscular or subcutaneous administration.

Idarubicin is an anthracycline antibiotic that exerts antineoplastic effects primarily by intercalating between DNA base pairs, thereby disrupting DNA replication and transcription. It inhibits the topoisomerase II enzyme, preventing the relegation of DNA strands during replication and inducing DNA breaks, leading to apoptosis of rapidly dividing malignant cells. Additionally, idarubicin generates reactive oxygen species causing oxidative cellular damage, contributing to its cytotoxic effects.

• Absorption: Complete bioavailability via intravenous administration.
• Distribution: Widely distributed in tissues with high affinity for cardiac tissue; volume of distribution approximately 15-30 L/m².
• Metabolism: Extensively metabolized in the liver via carbonyl reductases and cytochrome P450 enzymes into active and inactive metabolites.
• Half-life: Terminal elimination half-life ranges from 22 to 29 hours.
• Excretion: Primarily eliminated via biliary excretion; minimal renal clearance.

• Pregnancy: FDA Pregnancy Category D. Idarubicin is teratogenic and embryotoxic; contraindicated during pregnancy. Women of reproductive potential should use effective contraception.
• Lactation: Unknown if excreted in human milk; breastfeeding is contraindicated during therapy and for an appropriate period afterward due to potential toxicity.

• Primary Class: Antineoplastic agent
• Subclass: Anthracycline antibiotic, topoisomerase II inhibitor

• Hypersensitivity to idarubicin, other anthracyclines, or formulation components.
• Severe cardiac impairment or recent myocardial infarction.
• Severe bone marrow suppression not related to malignancy.
• Pregnancy and lactation.

• Cardiotoxicity: Dose-dependent risk of cardiomyopathy and congestive heart failure; cardiac function should be assessed before and monitored during treatment.
• Myelosuppression: Severe neutropenia and thrombocytopenia are common; regular complete blood count monitoring is essential.
• Extravasation: Severe tissue necrosis can occur with extravasation; use central venous access if possible and monitor injection sites.
• Secondary Malignancies: Risk of therapy-related leukemia or myelodysplastic syndrome.
• Hepatic impairment: Dose adjustment required; monitor liver function.
• Infection Risk: Due to immunosuppression; monitor and manage infections promptly.

Common:

• Myelosuppression (neutropenia, anemia, thrombocytopenia)
• Nausea and vomiting
• Mucositis and stomatitis
• Alopecia
• Injection site reactions

Serious/Rare:

• Cardiotoxicity including arrhythmias and heart failure
• Severe infections due to immunosuppression
• Hepatic toxicity
• Secondary malignancies
• Tissue necrosis from extravasation

• Increased myelosuppression with other bone marrow suppressive agents.
• Enhanced cardiotoxicity with concurrent use of other cardiotoxic drugs (e.g., trastuzumab).
• CYP3A4 inhibitors or inducers may alter idarubicin metabolism.
• Radiation therapy can increase hematologic toxicity.
• Live vaccines should be avoided due to immunosuppression.

• Idarubicin remains a key anthracycline in AML induction protocols per current oncology guidelines.
• Updated recommendations emphasize rigorous cardiac monitoring to detect early cardiotoxicity.
• Dose adjustments in hepatic impairment and elderly patients are now standard practice.
• Increased focus on long-term monitoring for secondary malignancies after treatment.

• Store at 20°C to 25°C (68°F to 77°F); short excursions between 15°C and 30°C (59°F to 86°F) allowed.
• Protect from light and moisture; keep in original packaging.
• Keep vial tightly closed.
• Use reconstituted solutions promptly and discard unused portions appropriately.
• Store out of reach of children.