Usage
Idarubicin is primarily used to treat acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). It is an anthracycline antineoplastic agent. It acts by intercalating into DNA, inhibiting topoisomerase II, and creating free radicals, ultimately causing cell death.
Alternate Names
Idarubicin hydrochloride; 4-Demethoxydaunorubicin.
Brand Name: Idamycin®, Idamycin PFS®, Zavedos®.
How It Works
Pharmacodynamics: Idarubicin exerts its anti-cancer effect by multiple mechanisms:
- DNA intercalation: Inserts itself between DNA base pairs, disrupting DNA structure and function.
- Topoisomerase II inhibition: Prevents this enzyme from relieving DNA supercoiling necessary for DNA replication and transcription.
- Free radical generation: Produces reactive oxygen species that damage cell membranes and other cellular components.
These actions combined disrupt nucleic acid synthesis and function, leading to cell death. The lack of a methoxy group at position 4 increases lipophilicity, enhancing cellular uptake compared to other anthracyclines.
Pharmacokinetics:
- Absorption: After IV administration, idarubicin quickly distributes throughout the body and into tissues. Oral absorption is rapid, with peak plasma concentrations in 2–4 hours.
- Metabolism: Primarily metabolized in the liver to the active metabolite idarubicinol, which also contributes to the cytotoxic effects.
- Elimination: Excreted primarily in bile and, to a lesser extent, in urine, mainly as idarubicinol. Plasma clearance is high, suggesting significant extrahepatic metabolism.
Dosage
Standard Dosage
Adults (AML):
- Induction: 12 mg/m² IV daily for 3 days in combination with cytarabine.
- Consolidation: 10-12 mg/m² IV daily for 2 days.
- Maximum Cumulative Lifetime Dose: 150 mg/m² IV.
Children (AML):
- 10-12 mg/m² IV daily for 3 days every 3 weeks. Doses for children < 0.5 m² should be calculated based on mg/kg (divide mg/m² by 30).
Special Cases:
- Elderly Patients: Increased risk of adverse events, particularly cardiotoxicity. Consider lower doses.
- Patients with Renal Impairment: Dose reduction may be necessary:
- CrCl 10-50 mL/min: 75% of the dose.
- CrCl < 10 mL/min: 50% of the dose.
- Patients with Hepatic Dysfunction: Dose reduction may be necessary:
- Bilirubin 2.6-5 mg/dL: 50% of the dose.
- Bilirubin > 5 mg/dL: Avoid use.
- Patients with Comorbid Conditions: Careful monitoring for cardiotoxicity is essential, especially with pre-existing cardiac disease, prior mediastinal radiation, or concomitant use of other cardiotoxic agents.
Clinical Use Cases
Idarubicin’s primary use is for the treatment of leukemias (AML, ALL). Dosages in these clinical settings adhere to the standard dosage guidelines mentioned above. Intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations do not have specific dosage recommendations for idarubicin; dosage is dependent on indication.
Dosage Adjustments
Dosage adjustments are necessary for patients with renal or hepatic impairment as outlined above. Modification may also be required for patients experiencing myelosuppression or other toxicities. Genetic polymorphisms affecting drug metabolism are not explicitly addressed in current guidelines.
Side Effects
Common Side Effects
Nausea, vomiting, diarrhea, mucositis, alopecia, myelosuppression (neutropenia, thrombocytopenia, anemia), abdominal pain, headache, and injection site reactions.
Rare but Serious Side Effects
Cardiomyopathy, congestive heart failure, arrhythmias, secondary malignancies, severe infections (due to myelosuppression).
Long-Term Effects
Cardiotoxicity, including cardiomyopathy and congestive heart failure, can be a long-term consequence, especially with cumulative doses above 150 mg/m². Secondary AML can occur.
Adverse Drug Reactions (ADR)
Severe myelosuppression, anaphylaxis, severe cardiotoxicity, including arrhythmias and heart failure, extravasation-related tissue necrosis.
Contraindications
Hypersensitivity to idarubicin or other anthracyclines, severe hepatic or renal impairment, severe cardiomyopathy, recent myocardial infarction, severe arrhythmias, pre-existing myelosuppression.
Drug Interactions
Idarubicin interacts with numerous drugs, including:
- Other myelosuppressive agents (e.g., cyclophosphamide): Increased myelosuppression.
- Cardiotoxic agents (e.g., trastuzumab): Increased risk of cardiotoxicity.
- Live attenuated vaccines: Reduced vaccine efficacy and increased risk of infection.
- Heparin: Precipitation may occur when mixed.
- CYP450 interactions have been identified, influencing metabolism of idarubicin and co-administered drugs. Always consult interaction checkers for potential interactions with specific medications, OTC drugs, and supplements.
Pregnancy and Breastfeeding
Idarubicin is contraindicated during pregnancy (FDA Pregnancy Category D). It is mutagenic, genotoxic, embryotoxic, fetotoxic, and teratogenic in animals. It should not be used during breastfeeding.
Drug Profile Summary
- Mechanism of Action: DNA intercalation, topoisomerase II inhibition, free radical generation.
- Side Effects: Myelosuppression, nausea, vomiting, mucositis, alopecia, cardiotoxicity.
- Contraindications: Hypersensitivity, severe hepatic/renal impairment, severe heart disease.
- Drug Interactions: Many; see Drug Interactions section.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: See Dosage section.
- Monitoring Parameters: CBC, LFTs, cardiac function (e.g., LVEF), renal function.
Popular Combinations
Idarubicin is often used in combination with cytarabine for induction therapy in AML.
Precautions
- Assess cardiac, hepatic, and renal function before and during treatment.
- Monitor closely for myelosuppression.
- Implement appropriate infection control measures.
- Ensure adequate hydration.
- Avoid extravasation during IV administration.
- Advise patients on contraception and risks during pregnancy and breastfeeding.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Idarubicin?
A: See Dosage section for detailed adult and pediatric dosing, including adjustments for special populations.
Q2: What is the mechanism of action of Idarubicin?
A: Idarubicin acts through DNA intercalation, topoisomerase II inhibition, and free radical generation, ultimately disrupting cell growth and causing cell death.
Q3: What are the common side effects of Idarubicin?
A: Common side effects include nausea, vomiting, diarrhea, mucositis, alopecia, and myelosuppression.
Q4: What are the most serious side effects of Idarubicin?
A: Cardiomyopathy, congestive heart failure, severe infections (due to myelosuppression), and secondary malignancies.
Q5: Is Idarubicin safe during pregnancy or breastfeeding?
A: No, idarubicin is contraindicated during pregnancy and breastfeeding due to its potential for serious harm to the fetus or infant.
Q6: What are the key drug interactions with Idarubicin?
A: Idarubicin interacts with many drugs, notably other myelosuppressive or cardiotoxic agents. Consult drug interaction resources for a comprehensive list.
Q7: How is Idarubicin administered?
A: Idarubicin is usually administered as a slow intravenous infusion over 5–10 minutes via a freely running IV line.
Q8: What should be monitored during Idarubicin treatment?
A: Close monitoring of complete blood counts, liver function tests, cardiac function (including left ventricular ejection fraction), and renal function is essential during treatment.
Q9: What are the contraindications for Idarubicin?
A: Contraindications include hypersensitivity to the drug or other anthracyclines, severe hepatic or renal impairment, and severe heart disease.
Q10: What precautions should be taken during IV administration of Idarubicin?
A: Administer as a slow infusion through the sidearm of a freely running IV line to avoid extravasation, which can cause severe tissue necrosis.
