Ifosfamide
Alkylating agents
Alkylating agentsHigh alert
An error with this medicine can cause serious harm: double checks and protocols are used.
A cyclophosphamide relative that is always given with mesna. Its metabolites can cause bladder bleeding, kidney damage and confusion (encephalopathy).
Quick facts
- Group
- Alkylating agents
- Target
- DNA (guanine N7), cross-linked by ifosfamide mustard
- Key effects
- Nausea and vomiting · Hair loss · Blood in the urine
- Monitor
- Urinalysis for blood before each dose
- ATC
- L01AA06
No doses: the clinician sets them by the current guideline.
Mechanism of action
Like cyclophosphamide, ifosfamide is a prodrug activated by liver CYP enzymes (mainly CYP3A4) to 4-hydroxyifosfamide, which releases ifosfamide mustard (the DNA cross-linker) and acrolein (toxic to the bladder). A side pathway removes a chloroethyl group and releases chloroacetaldehyde, which is toxic to the brain and kidney tubules; this is why ifosfamide causes more encephalopathy and kidney damage than cyclophosphamide.
- Liver CYP3A4 activates ifosfamide
- Ifosfamide mustard cross-links DNA
- Acrolein reaches the bladder; mesna neutralises it
- Chloroacetaldehyde can injure brain and kidney
Indications
- Third-line combination chemotherapy for germ cell testicular cancer (licensed use). Testicular cancer →
Adverse effects
Common
- Nausea and vomiting
- Hair loss
- Myelosuppression and infections
- Blood in the urine
Contraindications
- Known hypersensitivity to ifosfamide
- Urinary outflow obstruction
Key interactions
- CYP3A4 inducers
- More activation and more chloroacetaldehyde: higher risk of neurotoxicity and nephrotoxicity.
- CYP3A4 inhibitors
- Less activation, possibly less anticancer effect.
- Other cardiotoxic drugs or chest radiotherapy
- Higher risk of heart toxicity.
What is monitored
- Urinalysis for blood before each dose
- Kidney function, serum electrolytes (phosphate, potassium, bicarbonate) and urine chemistry
- Mental status during and after each infusion
- Complete blood count
Administration and safety
- Always given with mesna, timed to cover the whole period when metabolites reach the bladder.
- Generous hydration before and during treatment.
- Hazardous drug: chemotherapy handling precautions.
Pregnancy and breastfeeding
Can cause fetal harm; effective contraception is needed during and after treatment.
Nursing care
- Check the mesna schedule against each ifosfamide dose; a missed mesna dose leaves the bladder unprotected.
- Assess orientation and level of consciousness regularly; stop the infusion and report confusion, drowsiness or hallucinations.
- Record intake and output; test urine for blood.
- Teaching: report red urine, confusion in a family member, fever or bleeding.
Pharmacokinetics
- Absorption
- Intravenous infusion.
- Metabolism
- Liver CYP enzymes, producing active mustard, acrolein and chloroacetaldehyde.
- Elimination
- Mostly in the urine as metabolites.
- Half-life
- Increases with age, linked to a larger volume of distribution.
Test yourself
Think of the answer, then tap the question to see it.
Why is ifosfamide always given with mesna?
Its acrolein reaches the bladder and causes haemorrhagic cystitis; mesna binds it in the urine.
Which ifosfamide metabolite is blamed for encephalopathy and tubular damage?
Chloroacetaldehyde.
What kidney syndrome causes loss of phosphate, glucose and amino acids in the urine after ifosfamide?
Fanconi syndrome (proximal tubular damage).
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 - IFOSFAMIDE injection, solution (DailyMed (U.S. National Library of Medicine), 2026); Ifosfamide Injection: 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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Representative model, for educational purposes only.