ZAVEDOS

What it is

ZAVEDOS is a semi synthetic antineoplastic anthracycline for intravenous use. Each vial contains 5 mg/5 mL or 10 mg/10 mL of idarubicin hydrochloride. It is supplied as a solution for injection that is red-orange, clear, and mobile, free from particles.

Approved indications

— Remission induction in untreated patients with acute myelogenous leukaemia (AML) in adults. — Remission induction in relapsed or refractory patients with acute myelogenous leukaemia (AML) in adults.

Dosing overview

For induction therapy in adult patients with AML, ZAVEDOS 12 mg/m² is given daily for three days by slow intravenous injection (10–15 minutes) in combination with cytarabine 100 mg/m² daily given by continuous infusion for seven days. A dose reduction of 25% is recommended if a second induction course is given in patients who experienced severe mucositis, with administration delayed until recovery from this toxicity has occurred.

Key safety warnings

ZAVEDOS is a potent bone marrow suppressant, and myelosuppression, primarily of leucocytes, will occur in all patients given a therapeutic dose and careful haematological monitoring including granulocytes, red cells and platelets is required. Cardiotoxicity is a risk of anthracycline treatment that may be manifested by early or late events; delayed cardiotoxicity usually develops late in the course of therapy or within 2 to 3 months after completion of treatment, and is manifested by reduced left ventricular ejection fraction and/or signs and symptoms of congestive heart failure such as dyspnoea, pulmonary oedema, dependent oedema, cardiomegaly and hepatomegaly. Assessment of cardiac function with an ECG and either a multiple gated acquisition scan or an echocardiogram should be performed prior to starting therapy with ZAVEDOS, and repeated determinations of left ventricular ejection fraction should be performed, particularly with higher cumulative anthracycline doses. Severe enterocolitis with perforation has been reported rarely, with the risk of perforation potentially increased by instrumental intervention; the possibility of perforation should be considered in patients who develop severe abdominal pain and appropriate diagnostic and management steps should be taken. With intravenously administered ZAVEDOS, extravasation at the site of injection can cause pain, severe local tissue lesions and necrosis, and may occur with or without accompanying stinging or burning sensation, even if blood returns well on aspiration of the infusion needle.

Contraindications

ZAVEDOS therapy is contraindicated in patients with severe renal and liver impairment or patients with uncontrolled infections. It should not be administered to individuals with hypersensitivity to idarubicin or any other component of the product and/or other anthracyclines. ZAVEDOS therapy is contraindicated in patients with severe myocardial insufficiency, recent myocardial infarction, severe arrhythmias, persistent myelosuppression, or previous treatment with maximum cumulative doses of idarubicin and/or other anthracyclines and anthracenediones. ZAVEDOS therapy is contraindicated in pregnant women or women wishing to become pregnant.

PBS listing

ZAVEDOS solution for intravenous injection containing idarubicin hydrochloride 5 mg in 5 mL is listed on the PBS with restriction and an ex-manufacturer price of A$29.91.

Regulatory history

ZAVEDOS idarubicin hydrochloride was first registered on the ARTG on 19 August 1999, with two registered variants: 5 mg/5 mL injection vial (ARTG 67397) and 10 mg/10 mL injection vial (ARTG 67398).