Ifosfamide
Also known as: Ifex · Holoxan · Holaxane · Mitoxana · Asoifos · Cuantil · Duvaxan · Fentul · IFO-cell · IFX · Ifocris · Ifolem · Ifomida · Ifosmixan · Ifoxan · Seromida · Troxanol · MJF-9325 · NSC-109724 · Z-4942
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
This is a rate-based continuous infusion (CRI) dose. Calculate the infusion rate; do not use simple weight scaling.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Dogs
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Lymphomas and soft tissue sarcomas | Give IV saline at 18.3 mL/kg/hr for 6 hours. Give ifosfamide at 350 mg/m2 (if patient weighs less than 10 kg), 375 mg/m2 (if greater than 10 kg) IV during the second 30 minutes of the 6-hour infusion. Mesna at a dose of 20% of the ifosfamide dose is given as an IV bolus at the start of the IV infusion and again 2 and 5 hours after the ifosfamide infusion. Repeat every 3 weeks. | IV | Every 3 weeks | — | 🌎 NA |
| Lymphomas and soft tissue sarcomas | 375 mg/m2 | IV | Every 21 days | — | 🌎 NA |
- Lymphomas and soft tissue sarcomas: Requires saline diuresis and mesna
- Lymphomas and soft tissue sarcomas: Follow cat dose 'b' protocol for diuresis and mesna administration
Cats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Vaccine-related sarcomas | 900 mg/m2 every 3 weeks. Mesna bolus and saline diuresis (30 minutes at 18.3 mL/kg/hr) were first given, then ifosfamide and saline diuresis continued for 5 hours after ifosfamide administration completed. | IV | Every 3 weeks | — | 🌎 NA |
| Neoplasia | Normal (0.9%) saline IV diuresis at a fluid rate of 6 times maintenance over 30 minutes. Ifosfamide 900 mg/m2 diluted to 20 mg/mL or less, IV over 20 minutes. Normal saline IV diuresis at 6 times maintenance over 5 hours. Mesna urothelial protectant at 1/5 the patient's calculated mg dose at time zero (immediately before ifosfamide administration), and repeated 2 and 5 hours after ifosfamide. This therapy may be repeated on a 21 day basis. | IV | Every 21 days | — | 🌎 NA |
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Ifosfamide is a potent antineoplastic alkylating agent structurally related to cyclophosphamide.
- Prodrug: It requires hepatic activation to become pharmacologically active.
- Veterinary Use: Primarily used in investigational protocols for lymphomas and soft tissue sarcomas (e.g., feline vaccine-associated sarcomas).
- Toxicity Warning: Highly toxic; requires concurrent administration of mesna (a urothelial protectant) and aggressive saline diuresis to prevent severe hemorrhagic cystitis and nephrotoxicity.
Mechanism of action
Ifosfamide is a cell-cycle phase nonspecific alkylating agent.
- Activation: As a prodrug, it is metabolized primarily by hepatic cytochrome P450 enzymes (and to a lesser extent in the lungs) → ifosfamide mustard (the primary active alkylating metabolite).
- Mechanism: The active mustard metabolite forms covalent bonds with DNA → cross-linking of DNA strands → interferes with DNA replication and RNA transcription → disrupts nucleic acid function and induces cell death.
Safety & warnings
Contraindications
- Hypersensitivity to ifosfamide
- Severely depressed bone marrow function
- Active hemorrhagic cystitis
Adverse effects
- Myelosuppression (neutropenia at 5-7 days, potentially delayed to 14-21 days; thrombocytopenia)
- Hemorrhagic cystitis (bladder epithelial damage)
- Nephrotoxicity (proximal and distal tubular damage, electrolyte abnormalities)
- Volume overload and pulmonary edema (secondary to required saline diuresis)
- Neurotoxicity (somnolence, confusion, coma, encephalopathy)
- Gastrointestinal effects (nausea, vomiting, anorexia)
- Hypersensitivity reactions
- Alopecia
- Abnormal liver function tests
Precautions
Because of its toxicity, ifosfamide should only be used by clinicians experienced with cytotoxic agents. Must be used in conjunction with mesna and saline diuresis to reduce the risk of hemorrhagic cystitis and nephrotoxicity. Use with extreme caution in patients with impaired renal function or preexisting cardiac disease (due to volume overload risk). Handle and dispose of as a hazardous cytotoxic drug. FDA Category D for pregnancy (teratogenic and fetotoxic).
Drug interactions
May increase concentrations of active ifosfamide and increase toxicity (demonstrated in mice; clinical significance in veterinary patients undetermined)
Ifosfamide may enhance cisplatin-induced ototoxicity and nephrotoxicity
Additive myelosuppression
Monitoring
- CBC with platelets (baseline and before re-dosing)
- Renal function with electrolytes (baseline and before re-dosing)
- Urinalysis (baseline and periodic)
- Liver function (baseline and periodic)
- Other adverse effects (volume overload/pulmonary edema, neurotoxicity, GI toxicity)
- Efficacy
Pharmacokinetics
Absorption
Well absorbed after SC injection or oral administration (bioavailability >90%), though normally administered IV.
Distribution
Ifosfamide and its metabolites are widely distributed and enter into both bone and the CNS.
Metabolism
Prodrug requiring biotransformation. Converted primarily via oxidative pathways in the liver (and to a smaller extent in the lungs) into active metabolites, primarily ifosfamide mustard.
Elimination
Ifosfamide and its metabolites are primarily excreted via the kidney into urine.
Overdose
There is limited information available on acute overdoses. Toxicity is expected to be an exacerbation of adverse effects seen at usual doses. No specific antidote (including mesna) is known; treatment is supportive. Methylene blue (50 mg in a ~2% aqueous solution IV over 5 minutes) has been suggested to treat ifosfamide-induced encephalopathy in humans.
Available products
Formulations
- Powder for IV infusion
Human-labeled
- Ifosfamide Powder for IV infusion: 1 gram with 200 mg amps of Mesnex (mesna) in single dose vials
- Ifosfamide Powder for IV infusion: 3 grams with 400 mg amps of Mesnex (mesna) in single dose vials
Regulatory status
No regulatory data for: 🇺🇸 US · 🇪🇺 EU · 🇬🇧 UK · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store powder at 20-25°C (68-77°F). Protect from temperatures >30°C (86°F) as the drug may liquefy at >35°C (95°F). Reconstituted solution is stable for 24 hours when refrigerated. Compatible with D5W, normal saline, or lactated Ringer's. Compatible and stable when mixed with mesna in D5W or lactated Ringer's.
Client information
Important Safety Warning: Ifosfamide is a potent chemotherapy drug with a high risk of severe side effects. It is often used as an investigational treatment in veterinary medicine.
- Handling Precautions: This drug is excreted in your pet's bodily fluids. Avoid direct contact with your pet's saliva or urine for at least 24 hours after treatment. Use gloves when cleaning up waste.
- Side Effects: Watch closely for signs of infection, bleeding, vomiting, or neurological changes (confusion, extreme sleepiness, or abnormal behavior).
- Hospitalization: Treatment requires long intravenous infusions with extra fluids and protective medications (mesna) to safeguard the bladder and kidneys.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.