Ifosfamide
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.
Mecanismo: 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.
Dosificación por especie
- 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
- 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
- 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 · Requires saline diuresis and mesna
- Lymphomas and soft tissue sarcomas · 375 mg/m2 · IV · Every 21 days · Follow cat dose 'b' protocol for diuresis and mesna administration
Las dosis son una referencia clínica para médicos veterinarios. Confirme siempre con la información vigente del producto y el paciente individual.
Vías de administración
Contraindicaciones
- Hypersensitivity to ifosfamide
- Severely depressed bone marrow function
- Active hemorrhagic cystitis
Efectos adversos
- 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
Interacciones farmacológicas
- Benzodiazepines (diazepam, chlordiazepoxide, oxazepam) · May increase concentrations of active ifosfamide and increase toxicity (demonstrated in mice; clinical significance in veterinary patients undetermined)
- Cisplatin · Ifosfamide may enhance cisplatin-induced ototoxicity and nephrotoxicity
- Myelosuppressive drugs (chloramphenicol, flucytosine, amphotericin B, colchicine, other antineoplastics) · Additive myelosuppression
Monitoreo
- 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
Sobredosis
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.
La referencia de fármacos de VetSheet está destinada a médicos veterinarios como apoyo a la decisión clínica; no sustituye el juicio profesional ni la información vigente del fabricante.