paclitaxel: clinical use

Prescribing considerations

• Verify whether conventional or albumin-bound paclitaxel is intended; formulations differ in licensing, pharmacokinetics, preparation and administration and are not interchangeable.
• Treatment requires specialist cytotoxic facilities, trained staff and immediate access to supportive treatment for infusion reactions.
• Review hepatic function, baseline neuropathy, infection status, respiratory symptoms, cardiac history, reproductive plans and interacting medicines.
• Conventional solvent-based paclitaxel contains macrogolglycerol ricinoleate and ethanol; account for excipient-related hypersensitivity and ethanol exposure.

Contraindications and cautions

• Hypersensitivity to paclitaxel or formulation-specific excipients.
• Breastfeeding.
• Baseline neutrophil counts below the product-specific threshold.
• For conventional paclitaxel, severe hepatic impairment; serious uncontrolled infection is additionally contraindicated for the Kaposi’s sarcoma indication.

Monitoring

• Full blood count before treatment and during therapy.
• Liver function and clinical evidence of increased toxicity in hepatic impairment.
• Peripheral neuropathy and functional effects.
• Hypersensitivity during infusion and readiness to stop treatment immediately if severe.
• Infusion site for extravasation or infiltration.
• New respiratory symptoms suggesting pneumonitis, particularly with albumin-bound paclitaxel combinations.
• Blood pressure and clinically indicated cardiac monitoring.
• Prompt ophthalmological assessment for new visual impairment.

Clinical pharmacology

Paclitaxel stabilises polymerised microtubules and prevents depolymerisation, disrupting microtubule dynamics and mitosis. It is metabolised mainly through CYP2C8 and CYP3A4 and eliminated predominantly through biliary pathways. Albumin nanoparticle binding changes distribution and pharmacokinetic behaviour compared with solvent-based formulations.

Formulation and product differences

• Conventional paclitaxel is a solvent-based concentrate requiring dilution, an in-line microporous filter and routine hypersensitivity premedication.
• Albumin-bound paclitaxel is a powder reconstituted as an albumin nanoparticle dispersion and uses different filtration and preparation instructions.
• The formulations have different authorised indications, pharmacokinetics, administration requirements and excipients and must not be substituted for one another.

Dispersion for infusion

Route: Intravenous

Strengths: 5 mg/mL

Solution for infusion

Route: Intravenous

Strengths: 6 mg/mL