fosaprepitant dimeglumine: clinical use

Prescribing considerations

• Use only as part of combination antiemetic therapy for highly or moderately emetogenic chemotherapy.
• Complete a thorough interaction review, particularly for CYP3A4 substrates with a narrow therapeutic range, CYP3A4 inhibitors or inducers, warfarin and hormonal contraceptives.
• Use caution in moderate hepatic impairment; evidence is limited, and there are no data in severe hepatic impairment.
• Ensure appropriate venous administration and promptly stop or relocate the infusion if local irritation develops.
• For paediatric patients aged 6 months and over, check product-specific age, weight, vascular-access and administration requirements.

Contraindications and cautions

• Hypersensitivity to fosaprepitant, polysorbate 80 or another formulation excipient.
• Concurrent pimozide, terfenadine, astemizole or cisapride.

Monitoring

• Observe during and shortly after administration for immediate hypersensitivity.
• Monitor the infusion site, especially when vesicant chemotherapy uses the same access.
• Monitor INR closely in people receiving chronic warfarin.
• Consider additional toxicity or concentration monitoring for clinically sensitive CYP3A4 substrates and interacting anticancer treatments.
• Assess liver function when clinically indicated, particularly with hepatic impairment or hepatotoxic co-treatment.

Clinical pharmacology

Fosaprepitant is an intravenous phosphorylated prodrug rapidly and almost completely converted to aprepitant. Aprepitant selectively antagonises substance P at human NK1 receptors. Fosaprepitant is a weak, transient CYP3A4 inhibitor; interaction effects may also involve CYP2C9 induction associated with aprepitant exposure.

Formulation and product differences

• The product is a white to off-white powder requiring reconstitution and dilution before intravenous infusion.
• It contains polysorbate 80, lactose, disodium edetate and pH-adjusting agents and is essentially sodium-free.
• It is incompatible with solutions containing divalent cations, including Hartmann's and lactated Ringer's solutions.
• Inspect the prepared solution for particles and discolouration and follow product-specific compatibility and storage instructions.
• Oral aprepitant is a separate formulation of the active metabolite and should replace intravenous treatment only where the oncology protocol specifies this.

Solution for infusion

Route: Intravenous

Strengths: 150 mg