Cyclophosphamide

Cyclophosphamide is a nitrogen-mustard alkylating prodrug used mainly in veterinary oncology. It is an established component of multidrug chemotherapy for lymphoma and several other malignancies in dogs and cats. Lower-intensity metronomic regimens and selected immunosuppressive uses represent additional applications, with evidence and treatment goals varying by disease.

Group

Alkylating antineoplastic and immunosuppressant

Mechanism of Action

Hepatic cytochrome P450 enzymes convert cyclophosphamide to active intermediates that generate phosphoramide mustard. This metabolite alkylates DNA and forms cross-links, disrupting replication and transcription and promoting cell death. Suppression of proliferating lymphocytes contributes to immunosuppressive activity. In metronomic regimens, proposed additional actions include inhibition of tumor-associated angiogenesis and modulation of regulatory immune cells, with clinical relevance varying by tumor.

Dose Rates

Dogs

Use / stage	Dose	Route	Instructions
Cancer chemotherapy	Reference only	PO	50 mg/m² orally every 48 hours or once daily for four days each week. Alternative IV protocols use 150–300 mg/m² repeated after 21 days. Do not flatten the four-days-per-week regimen or assume mg/kg equivalence across patient sizes.
Metronomic chemotherapy	Reference only	PO	10–15 mg/m² orally every 24 hours. The approximate 0.3 mg/kg equivalence is not a universal conversion.
Immunosuppression	Reference only	PO	50 mg/m² orally every 48 hours, or 2.2 mg/kg once daily for four days each week. The weekly schedule requires protocol support.
Pulse chemotherapy	Reference only	PO	200–250 mg/m² once every 3 weeks; the dosage bullet does not specify the route. Dividing 250 mg/m² over three treatment days may reduce cystitis. The parenthetical 10 mg/kg is not a universal surface-area conversion.
Metronomic soft-tissue sarcoma combination	Reference only	PO	Cyclophosphamide 10 mg/m² orally daily with piroxicam 0.3 mg/kg daily has been described after incomplete resection. Increase the interval only for an individualized toxicity plan; this is not single-agent calculator dosing.
Additional oncology schedules	Reference only	IV	Historical alternatives include 250 mg/m² orally every three weeks or 100–300 mg/m² IV weekly depending on the actual oncology protocol. Do not exchange schedules between protocols.
Immune-mediated polyarthritis protocol	Reference only	PO	After inadequate response or relapse on corticosteroids: cyclophosphamide orally on four consecutive days each week, 1.5 mg/kg per treatment for dogs over 30 kg, 2 mg/kg for 15–30 kg and 2.5 mg/kg below 15 kg, with prednisolone 0.25–0.5 mg/kg daily. Continue 2–4 months, never beyond four months in this protocol because of bladder toxicity. Tablets must not be split; this is a specialist protocol, not verified product weight-band dosing.
Glomerulonephritis immunosuppression alternative	Reference only	PO	2.2 mg/kg orally daily for four days, followed by three days off and repetition, is described as an alternative. Benefit, infectious risks and current case selection require separate review.

Cats

Use / stage	Dose	Route	Schedule	Instructions
Cancer chemotherapy	Reference only	PO		6.25–12.5 mg per cat orally once daily for four days each week. Some protocols use 25 mg per cat twice weekly; another alternative is 200 mg/m². The weekly schedule and surface-area dose are not supported by the simple calculator.
Historical FIP immunosuppression	Reference only	PO		An older regimen used 2–4 mg/kg orally four times weekly. This is not current antiviral treatment for FIP and is retained only as historical context, not an enabled treatment recommendation.

Horses

Use / stage	Dose	Route	Schedule	Instructions
Cancer chemotherapy	Reference only	IV		200 mg/m² IV every 1–2 weeks in a defined oncology protocol. The example of about 1 g per horse is not a universal fixed dose.

Rabbits

Use / stage	Dose	Route	Schedule	Instructions
Lymphoma chemotherapy	Reference only	PO		50 mg/m² orally daily for three days each week, or 100–200 mg/m² IV every seven days; choose one defined protocol and use managed venous access.

Indications

Combination chemotherapy for lymphoma and selected leukemias in dogs and cats, including COP- and CHOP-based protocols.
Treatment of selected carcinomas, sarcomas, mammary tumors and other malignancies as part of tumor-specific chemotherapy.
Metronomic treatment of selected solid tumors, aimed at disease stabilization or palliation; evidence of benefit is tumor- and protocol-dependent.
Specialist immunosuppression for selected refractory immune-mediated disorders, including some cases of pemphigus or systemic lupus erythematosus; controlled veterinary efficacy evidence is limited.

Contraindications

Pregnancy because of embryotoxicity and teratogenicity.
Use cautiously with infection risk or marrow suppression.

Interactions

Other myelosuppressive drugs increase toxicity.

Adverse effects

Myelosuppression
Sterile hemorrhagic cystitis, especially in dogs
Vomiting and diarrhea
Alopecia in susceptible coat types

Toxicity

Marrow suppression may nadir at 7–10 days with recovery over 21–28 days. Sterile hemorrhagic cystitis is an important treatment-limiting toxicity.

Preparations

Preparation	Form	Strength	Route
Cyclophosphamide 25 mg tablet Coated cytotoxic tablet; do not split. Whole tablets only.	Tablet	25 mg / tablet	PO
Cyclophosphamide 50 mg tablet Coated cytotoxic tablet; do not split. Whole tablets only.	Tablet	50 mg / tablet	PO
Cyclophosphamide 25 mg/mL injection	Injection	25 mg / mL	IV

Monitoring and Administration

Monitor CBC and urinalysis. Use cytotoxic handling precautions and maintain hydration and frequent urination according to the oncology protocol.

Mesna binds urinary metabolites. Concurrent furosemide 2.2 mg/kg has been described to reduce cystitis risk; the source does not specify its route in that discussion, so it is not added as a dosing instruction.

Do not split coated tablets. Keep below 30°C; reconstituted solutions are subject to hydrolysis. The conservative periods described are 24 hours at room temperature or 6 days refrigerated, with longer refrigerated stability reported only for some preparations.

Evidence does not show added benefit over prednisolone alone for canine IMHA in the cited study. Metronomic efficacy remains incompletely established.

For the historical polyarthritis protocol, check urine weekly and CBC every 7–14 days. Gross hematuria requires stopping. The source reduces dose for WBC below 6000/µL or platelets below 125000/µL and holds treatment for two weeks when WBC falls below 4000/µL or platelets below 100000/µL, then resumes at half dose after recovery. These thresholds belong to that protocol, not every oncology course.

Do not mathematically redistribute weekly whole tablets without an oncology/immunosuppression plan; active ingredient may be unevenly distributed in coated tablets. A smaller compounded dosage form is preferable to unsupported splitting.