cyclophosphamide monohydrate: clinical use

Prescribing considerations

• Specialist initiation with facilities for clinical, biochemical and haematological monitoring.
• Assess infection, marrow reserve, previous cytotoxic therapy or radiotherapy, urinary-tract disease, renal and hepatic function, and cardiac or pulmonary risk.
• Review pregnancy risk, contraception and fertility preservation before treatment.
• Plan hydration, frequent bladder emptying and appropriate uroprotection.
• Review vaccination status and interacting medicines before immunosuppression.
• Use cytotoxic handling, preparation and disposal precautions.

Contraindications and cautions

• Hypersensitivity to cyclophosphamide or its metabolites
• Acute infection
• Bone-marrow aplasia or significant pre-treatment marrow depression
• Urinary-tract infection
• Acute urothelial toxicity following cytotoxic therapy or radiotherapy
• Urinary outflow obstruction
• Breastfeeding
• Non-malignant disease unless immunosuppression is required for a life-threatening condition; pregnancy restrictions differ slightly between selected formulations

Monitoring

• Full blood count before administration and regularly during treatment
• Clinical assessment for infection and immunosuppression
• Urinalysis or urine sediment and assessment of haematuria or urinary symptoms
• Renal and liver function
• Fluid balance and serum electrolytes where clinically indicated
• Cardiac, pulmonary and hepatic toxicity in patients with relevant risk factors or symptoms
• Long-term vigilance for secondary malignancy and fertility effects

Clinical pharmacology

An inactive nitrogen-mustard prodrug activated by hepatic CYP enzymes to alkylating metabolites. DNA cross-linking impairs replication; metabolites and parent compound are primarily eliminated through the kidneys. Acrolein causes urotoxicity.

Formulation and product differences

• The oral product is a coated tablet containing lactose and sucrose; it should not be divided or crushed.
• Injectable products are powders requiring reconstitution by trained staff. The solvent and further dilution depend on whether the preparation is used for infusion or direct intravenous injection.
• The selected injectable powders contain no excipients; intravenous administration is preferably by infusion.

Tablet

Route: Oral

Strengths: 50 mg

Injection

Route: Parenteral

Strengths: 500 mg, 1000 mg, 2000 mg, 1 g