Cyclophosphamide
Alkylating agents
Alkylating agentsHigh alert
An error with this medicine can cause serious harm: double checks and protocols are used.
A nitrogen mustard prodrug activated in the liver. It cross-links DNA in lymphomas, leukaemias and breast cancer, and its acrolein can make the bladder bleed.
Also called: CPA
Quick facts
- Group
- Alkylating agents
- Target
- DNA (guanine N7), cross-linked by phosphoramide mustard
- Used for
- Hodgkin and non-Hodgkin lymphomas · Multiple myeloma
- Key effects
- Neutropenia and infections · Nausea · Hair loss
- Monitor
- Complete blood count before each cycle · Serum sodium
- ATC
- L01AA01
No doses: the clinician sets them by the current guideline.
Mechanism of action
Cyclophosphamide itself is inactive. Liver cytochrome P450 enzymes (CYP2B6, 2C9, 3A and others) turn it into 4-hydroxycyclophosphamide, which is in balance with aldophosphamide. Aldophosphamide splits into two products: phosphoramide mustard, which bonds to guanines on both DNA strands and cross-links them, and acrolein, which has no anticancer effect but injures the bladder lining. It also strongly suppresses B and T lymphocytes, which is why it is used in severe autoimmune disease.
- Liver CYP enzymes turn the prodrug into 4-hydroxycyclophosphamide
- This splits into phosphoramide mustard and acrolein
- Phosphoramide mustard cross-links the two DNA strands
- Acrolein in the urine irritates the bladder lining
Indications
- Hodgkin and non-Hodgkin lymphomas, in combination regimens. Non-Hodgkin lymphoma →
- Multiple myeloma. Multiple myeloma →
- Leukaemias (acute and chronic). Acute leukaemia (AML and ALL) →
- Breast and ovarian cancer. Breast cancer →
- Childhood tumours: neuroblastoma, retinoblastoma. Neuroblastoma →
- Biopsy-proven minimal change nephrotic syndrome in children that does not respond to corticosteroids. Nephrotic syndrome →
Adverse effects
Common
- Neutropenia and infections
- Nausea, vomiting, diarrhoea
- Hair loss
- Amenorrhoea and low sperm counts (infertility)
- Slow wound healing
Contraindications
- Severe hypersensitivity to cyclophosphamide or its metabolites (cross-sensitivity with other alkylators is possible)
- Urinary outflow obstruction
Key interactions
- HIV protease inhibitors
- Raise cytotoxic metabolites: more infections, neutropenia and mucositis.
- Metronidazole
- Acute encephalopathy has been reported.
- Tamoxifen
- Higher risk of blood clots with cyclophosphamide-containing regimens.
- Radiotherapy and other myelotoxic, cardiotoxic or nephrotoxic drugs
- Add to the same toxicities.
What is monitored
- Complete blood count before each cycle
- Urinalysis for red cells (microscopic haematuria)
- Serum sodium, kidney and liver function
- Heart and lung symptoms, especially with high doses
Administration and safety
- Hazardous drug: prepared and disposed of with chemotherapy precautions.
- Plenty of fluids and frequent voiding protect the bladder; it is usually given early in the day so the bladder is not full of metabolites overnight.
- Mesna is added in high-dose regimens to protect the bladder.
- Urinary obstruction is excluded or corrected before treatment.
Pregnancy and breastfeeding
Can cause fetal harm: first-trimester exposure has been linked to skeletal, palate, limb and eye malformations and miscarriage; effective contraception is needed.
Nursing care
- Check blood counts and urinalysis before each dose.
- Encourage fluids and voiding often; report pink or red urine, or painful, urgent urination, at once.
- Watch for fever and other signs of infection during the low-count period.
- Track weight and sodium: water retention and hyponatraemia can occur.
- Teaching: hair loss and infertility are possible (discuss fertility preservation); effective contraception during and after treatment.
Pharmacokinetics
- Absorption
- Oral (well absorbed) or intravenous.
- Distribution
- Low protein binding of the parent drug; some metabolites bind more.
- Metabolism
- Activated by liver CYP enzymes; aldehyde dehydrogenase inactivates part of it. It induces its own metabolism.
- Elimination
- Mostly as metabolites in the urine, which brings acrolein into the bladder.
- Half-life
- 3 to 12 hours for the parent drug (label).
Test yourself
Think of the answer, then tap the question to see it.
Which metabolite of cyclophosphamide causes haemorrhagic cystitis, and how is it prevented?
Acrolein; hydration with frequent voiding, and mesna in high-dose regimens.
Why does cyclophosphamide need the liver to work?
It is a prodrug: CYP enzymes convert it to 4-hydroxycyclophosphamide, which releases phosphoramide mustard, the alkylating species.
Which electrolyte disorder can cyclophosphamide cause?
Hyponatraemia from water retention, resembling SIADH.
Which urinary condition contraindicates cyclophosphamide?
Urinary outflow obstruction.
Connections
← Back to the class: Alkylating agents
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - CYCLOPHOSPHAMIDE injection, powder, for solution (DailyMed (U.S. National Library of Medicine), 2026); Cyclophosphamide: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); eEML - Electronic Essential Medicines List (World Health Organization, 2025).
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