pemetrexed disodium: clinical use

Prescribing considerations

• Administration must be supervised by a clinician experienced in anticancer chemotherapy.
• Ensure folic acid and vitamin B12 supplementation and corticosteroid premedication.
• Assess renal function, marrow reserve, hepatic tests, performance status, hydration and concomitant medicines.
• Review previous or planned radiotherapy because radiation pneumonitis and recall reactions have occurred.
• Discuss contraception and potential male infertility, including sperm-storage counselling where appropriate.

Contraindications and cautions

• Hypersensitivity to pemetrexed or an excipient
• Breastfeeding
• Concurrent yellow-fever vaccination
• Use is not recommended when creatinine clearance is below 45 mL/min

Monitoring

• Full blood count with differential and platelets before treatment
• Renal and hepatic function before treatment
• Clinical evidence of infection, bleeding, mucositis, rash, dehydration, renal toxicity and pulmonary toxicity
• Closer toxicity monitoring when interacting medicines cannot be avoided

Clinical pharmacology

A multitargeted antifolate inhibiting thymidylate synthase, dihydrofolate reductase and GARFT. Intracellular polyglutamation increases retention and inhibitory activity. Hepatic metabolism is limited; elimination is mainly unchanged in urine through filtration and OAT3-mediated tubular secretion.

Formulation and product differences

• The selected product is a powder for concentrate requiring aseptic reconstitution with preservative-free sodium chloride solution and further dilution before intravenous use.
• After reconstitution, the concentration is 25 mg/mL.
• The vial presentations differ in sodium content; the smaller presentation is essentially sodium-free, while the larger contains 54 mg sodium.
• Calcium-containing diluents, including Ringer’s solutions, are incompatible.
• The prepared solution contains no antimicrobial preservative and should be used promptly in accordance with the SmPC.

Solution for infusion

Route: Intravenous

Strengths: 25 mg/mL, 100 mg, 500 mg