Cyclophosphamide: veterinary dose and monograph

At a glance

Drug class

Veterinary drug

Also known as

Cytoxan, Endoxan, Cyclophosphamide

Species with doses

Dogs, Cats, Horses and Rabbits

Routes

PO, IV

Last reviewed

1 October 2026

Indications

• Lymphoma / lymphoid leukaemia (CHOP and other multidrug protocols)
• Various sarcomas and carcinomas (per protocol)
• Severe immune-mediated disease (immunosuppression) — less commonly now

Cyclophosphamide dose by species

Doses are per administration unless stated. mg/kg doses scale with body weight; per-animal, per-quarter and infusion-rate doses are shown as the reference writes them.

Dogs

• Lymphoma / neoplasia (BSA dosing): Dosed by BODY SURFACE AREA (NOT mg/kg). Papich 5e: 50 mg/m² (≈2.2 mg/kg) PO q48h or 4 days/week; 150–300 mg/m² IV repeated in 21 days; pulse 200–250 mg/m² (≈10 mg/kg) every 3 weeks — dividing the dose over 3 days may reduce sterile haemorrhagic cystitis. Plumb’s p.327 (Kitchell): 250 mg/m² PO every 3 weeks; IV 100–300 mg/m² weekly by protocol. Give in the morning with water access and encourage urination; check CBC before each dose. Consult an oncologist.
• Metronomic therapy (e.g. incompletely excised sarcoma): Papich 5e: 10–15 mg/m² q24h PO (≈0.3 mg/kg). Plumb’s p.327 (Elmslie 2008): 10 mg/m² PO daily with piroxicam 0.3 mg/kg daily to inhibit sarcoma recurrence; move to every other day if adverse effects occur. Monitor urine for haematuria.
• Immunosuppression (IMHA / ITP / polyarthritis): Papich 5e: 50 mg/m² q48h PO or 2.2 mg/kg once daily 4 days/week. Plumb’s p.327: 50 mg/m² every 2nd day (Mackin); polyarthritis 1.5–2.5 mg/kg by size on 4 consecutive days a week for no more than 4 months (Bennett); glomerulonephritis 2.2 mg/kg q24h 4 days on, 3 off (Labato). Azathioprine or ciclosporin are preferred long term (cystitis).

Cats

• Lymphoma / neoplasia: Papich 5e: 6.25–12.5 mg/cat once daily 4 days/week PO; some protocols 25 mg/cat twice weekly; 200 mg/m² also used. Plumb’s p.327: used alone or in COP protocols — consult an oncologist. FIP (slowing progression): 2–4 mg/kg PO four times a week (Foley). Monitor CBC.

Horses

• Lymphoma (protocol): Plumb’s p.327 (Mair & Couto 2006): 200 mg/m² IV every 1–2 weeks; used in the CAP protocol for generalised lymphoma. Consult an oncologist.

Rabbits

• Lymphoma: Plumb’s p.327 (Bryan 2009). Consider an implantable vascular access port for repeated IV chemotherapy.

Contraindications

Pre-existing significant myelosuppression or active urinary tract disease/cystitis. Pregnancy (teratogenic/cytotoxic). Severe hepatic/renal impairment (dose adjust). Known hypersensitivity. Concurrent furosemide may increase myelosuppression (some evidence). Handle with cytotoxic precautions.

Species-specific warnings

Dogs: Sterile haemorrhagic cystitis can be persistent — use cystitis-prevention measures and discontinue at the first urinary sign (chlorambucil is the alkylating alternative).

Adverse effects

• Myelosuppression (neutropenia nadir ~7–10 days)
• STERILE HAEMORRHAGIC CYSTITIS (haematuria, stranguria) — characteristic
• GI: vomiting, diarrhoea, anorexia
• Alopecia (continuously growing coats); delayed bladder tumours with chronic use

Drug interactions

• Other myelosuppressive chemo: additive marrow suppression (built into protocols)
• Furosemide: some evidence of increased myelosuppression
• Phenobarbital and other CYP inducers: increased activation (and toxicity)
• Drugs causing bladder irritation: additive cystitis risk

Pregnancy and lactation

Contraindicated in pregnancy (teratogenic/cytotoxic). Handle with cytotoxic precautions; pregnant staff should not handle/administer.

Monitoring

• CBC before each dose (neutrophil nadir ~7–10 days)
• URINALYSIS / urinary signs — watch closely for haemorrhagic cystitis (haematuria, stranguria); stop the drug if it occurs
• GI signs; renal/hepatic values
• Encourage water intake / morning dosing / frequent urination (cystitis prevention)

Toxicity and overdose

Dose-limiting toxicities are myelosuppression and STERILE HAEMORRHAGIC CYSTITIS (acrolein-mediated — haematuria/stranguria, which can be persistent and predispose to later bladder tumours), plus GI toxicity. Overdose intensifies these. The cystitis is the signature complication to prevent and recognise.

Management: No direct antidote. STOP the drug at the first sign of cystitis (and consider it largely irreversible — switch to chlorambucil for ongoing alkylation). For overdose: manage neutropenic sepsis (antibiotics ± G-CSF), GI support, and aggressive diuresis; the uroprotectant MESNA binds acrolein and is used to prevent/treat haemorrhagic cystitis (mainly with high-dose IV protocols). Monitor CBC closely.

Clinical pearls

• Dose by BODY SURFACE AREA (mg/m²) and double-check the maths — a cytotoxic with a narrow margin
• STERILE HAEMORRHAGIC CYSTITIS is the hallmark toxicity (acrolein): dose in the MORNING with plenty of water and urination; STOP at the first sign of haematuria/stranguria (often irreversible) and switch to chlorambucil
• The "C" of CHOP lymphoma protocols and a classic immunosuppressant — check the CBC before every dose
• Mesna protects the bladder in high-dose IV protocols; handle with full cytotoxic precautions

Mechanism of action

A nitrogen-mustard alkylating pro-drug: hepatic cytochrome-P450 activates it to phosphoramide mustard (the cytotoxic moiety), which cross-links DNA strands, preventing replication/transcription and killing rapidly dividing cells (cell-cycle non-specific) — including cancer cells and lymphocytes (the immunosuppressive effect). A second metabolite, ACROLEIN, is excreted in urine and irritates the bladder urothelium, causing the characteristic sterile haemorrhagic cystitis.

Formulations and products

• 50 mg tablet
• Injection 200 mg / 500 mg / 1 g vial (reconstitute)
• Endoxan — 50 mg tablet; 200 mg / 500 mg / 1 g vial, Tablet / injection (human-label)
• Cytoxan — 25 / 50 mg tablet; injection, Tablet / injection (human-label)

Storage

Tablets/vials: 15–30 °C (per product); reconstituted solution per label. Handle as a hazardous cytotoxic drug (gloves/PPE, do not crush tablets); dispose appropriately.

Before you use this dose

Reference doses for veterinary professionals. Confirm the dose against the product label, the patient’s condition, current guidance and local regulations before use; the attending veterinarian remains responsible for every clinical decision.

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Frequently asked questions