pemetrexed diarginine: clinical use

Prescribing considerations

• Restrict use to specialist-supervised systemic anticancer treatment.
• Ensure folic acid and vitamin B12 supplementation and corticosteroid premedication are in place.
• Assess renal function, hydration, concurrent nephrotoxins and NSAID exposure.
• Consider previous or planned radiotherapy because radiation pneumonitis and recall reactions have occurred.
• Discuss contraception and potential fertility impairment before treatment.

Contraindications and cautions

• Hypersensitivity to pemetrexed or an excipient
• Breastfeeding
• Concomitant yellow fever vaccination
• Use is not recommended when creatinine clearance is below 45 mL/min because evidence is insufficient

Monitoring

• Full blood count, including differential and platelets, before administration
• Renal and hepatic biochemistry before administration
• Treatment toxicity, infection, mucositis, skin reactions and hydration status
• Symptoms or biochemical evidence of acute tubular injury or nephrogenic diabetes insipidus

Clinical pharmacology

Pemetrexed is a multitargeted antifolate inhibiting thymidylate synthase, dihydrofolate reductase and GARFT. Intracellular polyglutamation increases retention and enzyme inhibition. Hepatic metabolism is limited, and most elimination is as unchanged pemetrexed in urine.

Formulation and product differences

• The selected product is a pemetrexed-diarginine liquid concentrate rather than a pemetrexed-disodium powder or concentrate.
• It contains L-arginine, L-cysteine and propylene glycol and requires dilution before intravenous use.
• It may be diluted with sodium chloride or glucose solution as specified in the product information; calcium-containing diluents are incompatible.
• L-arginine is incompatible with cisplatin, so the medicines must not be mixed and the intravenous line should be flushed after pemetrexed.
• Inspect for particles or discolouration before administration; the preparation is single-use cytotoxic material.

Solution for infusion

Route: Intravenous

Strengths: 25 mg/mL