[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Alkylating agents](https://durgical.com/en/pharmacology/classes/alkylating-agents/) › Cyclophosphamide # Cyclophosphamide ## Alkylating agents? Alkylating agents ## High 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. Updated Nov 1, 2026 Also called: CPA ## Quick facts **Group** [Alkylating agents](https://durgical.com/en/pharmacology/classes/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. On this page - The basics Mechanism of action - Indications - Adverse effects - Pharmacokinetics - Memory aid - Clinical What the labels mean - Safety Contraindications - Key interactions - What is monitored - Administration and safety - Pregnancy and breastfeeding - Nursing care - Study Test yourself - Connections Connections ## 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 →](https://durgical.com/en/conditions/non-hodgkin-lymphoma/) - Multiple myeloma. [Multiple myeloma →](https://durgical.com/en/conditions/multiple-myeloma/) - Leukaemias (acute and chronic). [Acute leukaemia (AML and ALL) →](https://durgical.com/en/conditions/acute-leukaemia/) - Breast and ovarian cancer. [Breast cancer →](https://durgical.com/en/conditions/breast-cancer/) - Childhood tumours: neuroblastoma, retinoblastoma. [Neuroblastoma →](https://durgical.com/en/conditions/neuroblastoma/) - Biopsy-proven minimal change nephrotic syndrome in children that does not respond to corticosteroids. [Nephrotic syndrome →](https://durgical.com/en/conditions/nephrotic-syndrome/) ## Adverse effects ### Common - Neutropenia and infections - Nausea, vomiting, diarrhoea - Hair loss - Amenorrhoea and low sperm counts (infertility) - Slow wound healing ### Serious (rare, important) - Haemorrhagic cystitis, bladder fibrosis and, later, bladder cancer - Heart toxicity (myocarditis, pericardial effusion, heart failure), mainly at high doses - Pneumonitis and pulmonary fibrosis - Hyponatraemia with water retention (a syndrome like SIADH) - Hepatic veno-occlusive disease; second cancers (myelodysplasia, acute leukaemia) ## 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). ## Memory aid «Cyclophosphamide makes the bladder CRY blood»: Cystitis (acrolein, prevented by mesna and fluids), Retention of water (SIADH-like), Yield of the marrow falls. The liver must activate it first. ## 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. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/cyclophosphamide/) [More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology) ## What the labels mean **High alert** An error with this medicine can cause serious harm: double checks and protocols are used. ## Connections ## Related drugs 4 - [Ifosfamide](https://durgical.com/en/pharmacology/ifosfamide/) - [Mesna](https://durgical.com/en/pharmacology/mesna/) - [Melphalan](https://durgical.com/en/pharmacology/melphalan/) - [Chlorambucil](https://durgical.com/en/pharmacology/chlorambucil/) ## Related conditions 6 - [Non-Hodgkin lymphoma](https://durgical.com/en/conditions/non-hodgkin-lymphoma/) - [Multiple myeloma](https://durgical.com/en/conditions/multiple-myeloma/) - [Acute leukaemia (AML and ALL)](https://durgical.com/en/conditions/acute-leukaemia/) - [Breast cancer](https://durgical.com/en/conditions/breast-cancer/) - [Neuroblastoma](https://durgical.com/en/conditions/neuroblastoma/) - [Nephrotic syndrome](https://durgical.com/en/conditions/nephrotic-syndrome/) [← Back to the class: Alkylating agents](https://durgical.com/en/pharmacology/classes/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](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8627c83f-c057-495d-9f78-8b67bda97b3e) (DailyMed (U.S. National Library of Medicine), 2026); [Cyclophosphamide: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a682080.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=L01AA01) (WHO Collaborating Centre for Drug Statistics Methodology, 2026); [eEML - Electronic Essential Medicines List](https://list.essentialmeds.org/) (World Health Organization, 2025). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/pharmacology/cyclophosphamide/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/cyclophosphamide/