raltitrexed: clinical use

Prescribing considerations

• Treatment should be supervised by a clinician experienced in cytotoxic chemotherapy and toxicity management.
• Assess renal function carefully because reduced clearance increases exposure; serum creatinine may underestimate impairment in older or underweight patients.
• Use caution with reduced marrow reserve, poor performance status, previous radiotherapy, older age or mild-to-moderate hepatic impairment.
• Gastrointestinal toxicity can coincide with severe myelosuppression and requires prompt assessment.

Contraindications and cautions

• Hypersensitivity to raltitrexed or an excipient
• Pregnancy, potential pregnancy during treatment or breastfeeding
• Severe renal impairment
• Folinic acid, folic acid or vitamin preparations containing them immediately before or during treatment

Monitoring

• Full blood count with differential and platelets before treatment and each subsequent administration
• Serum creatinine and calculated or measured renal function
• Liver transaminases and bilirubin
• Clinical assessment for diarrhoea, mucositis, infection, bleeding and dehydration; increase blood-count monitoring when gastrointestinal toxicity develops

Clinical pharmacology

A folate analogue transported into cells and polyglutamated intracellularly. Its retained polyglutamate forms potently inhibit thymidylate synthase. Elimination is mainly unchanged through the kidneys, with some faecal excretion and prolonged intracellular retention.

Formulation and product differences

• The selected product is a white-to-cream powder for solution for intravenous infusion in a single vial containing 2 mg raltitrexed.
• Excipients include mannitol, dibasic sodium phosphate and sodium hydroxide; the product is essentially sodium-free.
• After reconstitution it requires further dilution and should not be mixed with other medicines in the same container.