cyclophosphamide: clinical use

Prescribing considerations

• Specialist administration with clinical, biochemical and haematological monitoring facilities.
• Exclude or correct urinary outflow obstruction; assess infection, marrow reserve, urinary toxicity and relevant organ dysfunction.
• Ensure appropriate hydration, regular bladder emptying and consideration of mesna.
• Review fertility preservation where relevant.
• Review interactions, vaccination plans, previous radiotherapy and cardiac, pulmonary, renal or hepatic risks.

Contraindications and cautions

• Hypersensitivity to cyclophosphamide or its metabolites
• Acute infection
• Pre-existing bone-marrow aplasia or depression
• Urinary tract infection
• Acute urothelial toxicity following cytotoxic treatment or radiotherapy
• Urinary outflow obstruction
• Breastfeeding
• For non-malignant disease, use is restricted to immunosuppression in life-threatening situations

Monitoring

• Full blood count, including leukocytes and platelets, before administration and regularly during treatment
• Urinary sediment and other evidence of urotoxicity or nephrotoxicity
• Renal and hepatic function, hydration and serum electrolytes
• Infection, bleeding, bladder toxicity and cardiac, pulmonary or hepatic complications
• Long-term infertility and secondary malignancy risks

Clinical pharmacology

Cyclophosphamide is a hepatic CYP-activated nitrogen-mustard prodrug. Active metabolites produce cytostatic effects principally through DNA alkylation, while acrolein is urotoxic. Cyclophosphamide and its metabolites are mainly renally eliminated and are dialysable.

Formulation and product differences

• Single-use white crystalline powder for intravenous injection or infusion.
• Contains no excipients.
• Reconstitution solvent depends on the intended route; material reconstituted with water is hypotonic and must not be injected directly.
• Preparation requires designated cytotoxic-handling facilities and trained staff; pregnant personnel should not handle it.

Injection

Route: Parenteral

Strengths: 500 mg, 1000 mg, 2000 mg