idarubicin hydrochloride: clinical use

Prescribing considerations

• Restrict use to clinicians experienced in cytotoxic chemotherapy, with facilities to manage severe infection, haemorrhage, cardiac toxicity and extravasation.
• Ensure recovery from important acute toxicities of previous cytotoxic treatment before starting.
• Review lifetime exposure to idarubicin, other anthracyclines and anthracenediones because cardiotoxicity is cumulative and additive.
• Assess cardiovascular disease, previous mediastinal or pericardial radiotherapy, prior cardiotoxic therapy and age-related risk; children require long-term cardiac follow-up.
• Evaluate active gastrointestinal disease carefully before oral therapy because severe bleeding or perforation has occurred.
• Discuss effective contraception and fertility preservation before treatment.

Contraindications and cautions

• Hypersensitivity to idarubicin, excipients, other anthracyclines or anthracenediones
• Severe hepatic or renal impairment
• Severe cardiomyopathy, recent myocardial infarction or severe arrhythmia
• Uncontrolled infection
• Persistent myelosuppression
• Previous maximum cumulative exposure to idarubicin or related anthracyclines or anthracenediones
• Breastfeeding during treatment

Monitoring

• Full blood count with differential before and during treatment
• Baseline and repeated cardiac assessment using ECG and a consistent quantitative left-ventricular function method
• Liver and renal function before and during treatment
• Uric acid, potassium, calcium, phosphate and creatinine where tumour lysis is a concern
• Injection site continuously during intravenous administration
• Clinical surveillance for infection, bleeding, mucositis, gastrointestinal toxicity and delayed heart failure

Clinical pharmacology

Idarubicin is a lipophilic anthracycline that intercalates DNA, inhibits topoisomerase II and suppresses nucleic-acid synthesis. It is converted to idarubicinol, an active metabolite with slower elimination; biliary elimination predominates.

Formulation and product differences

• The injection is a clear orange-red solution for intravenous use only and must never be given intrathecally.
• The intravenous product is licensed for defined adult and paediatric acute-leukaemia settings.
• The hard capsules are swallowed whole and may be taken with a light meal.
• The oral product has distinct licensed roles when intravenous idarubicin cannot be used and in selected advanced breast cancer.
• The injection should not be mixed with heparin or kept in prolonged contact with alkaline solutions.

Capsule

Route: Oral

Strengths: 5 mg, 10 mg

Injection

Route: Parenteral

Strengths: 1 mg/mL