doxorubicin hydrochloride: clinical use

Prescribing considerations

• Administration must be supervised by clinicians experienced in cytotoxic therapy.
• Document previous anthracycline exposure, cardiac disease, mediastinal radiotherapy and concomitant cardiotoxic treatments.
• Confirm recovery from significant toxicity of previous treatment before conventional doxorubicin.
• Assess hepatic function because impaired biliary elimination can increase exposure and toxicity.
• Consider fertility preservation and pregnancy-prevention counselling before treatment.
• Use the complete formulation name throughout prescribing, dispensing, preparation and administration.

Contraindications and cautions

• Conventional intravenous doxorubicin: hypersensitivity to doxorubicin, another anthracycline or anthracenedione; persistent myelosuppression; severe hepatic impairment; severe myocardial insufficiency; recent myocardial infarction; severe arrhythmias; or previous maximum cumulative anthracycline exposure.
• Selected pegylated-liposomal product: hypersensitivity to doxorubicin, peanut, soya or an excipient.
• Selected pegylated-liposomal product must not be used for AIDS-related Kaposi’s sarcoma that can be treated effectively with local therapy or systemic alfa-interferon.

Monitoring

• Full blood count before and during treatment.
• Baseline and ongoing cardiac assessment, including left-ventricular function where appropriate; delayed cardiotoxicity can occur after treatment.
• Liver function, including bilirubin, before and during treatment.
• Infusion site and acute infusion reactions during administration.
• Clinical and biochemical features of tumour-lysis syndrome in susceptible patients.
• For prolonged pegylated-liposomal exposure, monitor oral ulceration or persistent oral discomfort.

Clinical pharmacology

Doxorubicin is an anthracycline cytotoxic agent that intercalates DNA, impairs nucleic-acid and protein synthesis and generates reactive species. It is extensively distributed, converted partly to active doxorubicinol and eliminated mainly through the hepatobiliary route. Pegylated liposomal encapsulation prolongs circulation and changes tissue distribution and pharmacokinetics.

Formulation and product differences

• Conventional solution and pegylated-liposomal concentrate have different pharmacokinetic properties, licensed indications, administration requirements and toxicity patterns.
• The pegylated-liposomal product contains soy-derived phospholipid and sucrose and is diluted in glucose infusion solution.
• Pegylated-liposomal doxorubicin must not be substituted for conventional doxorubicin or another liposomal formulation.

Solution for infusion

Route: Intravenous

Strengths: 2 mg/mL