# Cyclophosphamide: veterinary dose and monograph

> Cyclophosphamide is a veterinary drug. An alkylating-agent CHEMOTHERAPY / IMMUNOSUPPRESSANT dosed by BODY SURFACE AREA (mg/m²), not mg/kg. Indications include lymphoma / lymphoid leukaemia (CHOP and other multidrug protocols); various sarcomas and carcinomas (per protocol); severe immune-mediated disease (immunosuppression) — less commonly now. This monograph lists 6 reference doses for dogs, cats, horses and rabbits, each with route, frequency and source.

Source: https://vetmasterji.com/drugs/cyclophosphamide · Last reviewed: 2026-10-01

## 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

*Cyclophosphamide doses for dogs*

| Indication | Dose | Route | Frequency | Duration |
| --- | --- | --- | --- | --- |
| Lymphoma / neoplasia (BSA dosing) | 200–250 mg/m² PO or IV once every 3 weeks (per protocol), or 50 mg/m² PO 4 days a week | PO | per protocol | — |
| Metronomic therapy (e.g. incompletely excised sarcoma) | 10–15 mg/m² PO once daily (often with piroxicam 0.3 mg/kg q24h) | PO | q24h (or q48h if poorly tolerated) | — |
| Immunosuppression (IMHA / ITP / polyarthritis) | 50 mg/m² PO every other day, or 4 days on / 3 days off | PO | q48h or 4 days/week | — |

- 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

*Cyclophosphamide doses for cats*

| Indication | Dose | Route | Frequency | Duration |
| --- | --- | --- | --- | --- |
| Lymphoma / neoplasia | 6.25–12.5 mg per cat PO once daily 4 days a week (or 200 mg/m² per protocol) | PO | per protocol | — |

- 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

*Cyclophosphamide doses for horses*

| Indication | Dose | Route | Frequency | Duration |
| --- | --- | --- | --- | --- |
| Lymphoma (protocol) | 200 mg/m² IV (usually about 1 g per horse) every 1–2 weeks | IV | every 1–2 weeks | — |

- 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

*Cyclophosphamide doses for rabbits*

| Indication | Dose | Route | Frequency | Duration |
| --- | --- | --- | --- | --- |
| Lymphoma | 50 mg/m² PO daily 3 days a week, or 100–200 mg/m² IV every 7 days | PO | per protocol | — |

- 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

> **Caution:** 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

> **Caution:** 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

### What is the dose of Cyclophosphamide for dogs?

Reference doses for Cyclophosphamide in dogs: 200–250 mg/m² PO or IV once every 3 weeks (per protocol), or 50 mg/m² PO 4 days a week PO per protocol (Lymphoma / neoplasia (BSA dosing)); 10–15 mg/m² PO once daily (often with piroxicam 0.3 mg/kg q24h) PO q24h (or q48h if poorly tolerated) (Metronomic therapy (e.g. incompletely excised sarcoma)); 50 mg/m² PO every other day, or 4 days on / 3 days off PO q48h or 4 days/week (Immunosuppression (IMHA / ITP / polyarthritis)). Confirm against the label and the patient before use.

### What is the dose of Cyclophosphamide for cats?

Reference doses for Cyclophosphamide in cats: 6.25–12.5 mg per cat PO once daily 4 days a week (or 200 mg/m² per protocol) PO per protocol (Lymphoma / neoplasia). Confirm against the label and the patient before use.

### What is the dose of Cyclophosphamide for horses?

Reference doses for Cyclophosphamide in horses: 200 mg/m² IV (usually about 1 g per horse) every 1–2 weeks IV every 1–2 weeks (Lymphoma (protocol)). Confirm against the label and the patient before use.

### When should Cyclophosphamide not be used?

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.

### What are the side effects of Cyclophosphamide in animals?

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.

## Sources

- Plumb's Veterinary Drug Handbook
- Merck Veterinary Manual, 11th edition
- Papich, Papich Handbook of Veterinary Drugs, 5th edition

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VetMasterJi is a clinical decision-support and education platform for veterinary professionals and students. It does not provide veterinary advice, diagnosis or treatment for specific animals. All drug doses, calculators and differentials are references that must be independently verified before clinical use; the attending registered veterinarian remains solely responsible for every clinical decision.