Cyclophosphamide
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Dosing and administration[3]
For severe or organ-threatening disease (vasculitis, severe lupus). Given as intermittent IV pulses or lower-dose oral therapy, with vigorous hydration and (for higher-dose IV) mesna for uroprotection.
| Indication | Starting dose | Titration and maximum |
|---|---|---|
| IV pulse (vasculitis, severe lupus) | 500 to 1000 mg/m2 IV every 2 to 4 weeks; the low-dose Euro-Lupus regimen is 500 mg IV every 2 weeks for 6 doses. | Adjust for renal function, age, and the white-cell nadir; limit cumulative exposure. |
| Oral | 1 to 2 mg/kg/day orally. | Adjust to the white-cell count; use for the shortest effective duration. |
Renal adjustment. Reduce the dose in renal impairment; hydrate well.
Uroprotection (hydration, and mesna for higher-dose IV) reduces hemorrhagic cystitis and bladder-cancer risk; the drug is gonadotoxic, so discuss fertility preservation before starting, and Pneumocystis prophylaxis is standard.
Monitoring
- CBC with attention to the nadir; urinalysis for hematuria.
- Uroprotection (hydration, mesna for higher-dose IV); Pneumocystis prophylaxis.
- Monitor for infection; long-term bladder cancer and malignancy risk; gonadotoxicity.
Contraindications
- Pregnancy.
- Severe bone marrow suppression or active serious infection.
- Active urinary tract bleeding or hemorrhagic cystitis.
Key interactions
- Additive myelosuppression with other cytotoxic or immunosuppressive agents.
- Allopurinol may increase myelosuppression.
- Avoid live vaccines.
Clinical notes
How it is used in lupus
Reserved for organ- or life-threatening SLE and severe lupus nephritis. The low-dose Euro-Lupus regimen is favoured in nephritis for its better tolerability and lower toxicity, including a lower infertility risk.[1, 2]
Common side effects
Nausea, cytopenias, infection risk, alopecia, and bladder toxicity occur; it is gonadotoxic and can impair fertility. Described from background clinical knowledge with fertility risk noted in the guidelines; reconcile with the product monograph.
Tests and monitoring
CBC with differential and creatinine weekly for 4 weeks, then monthly. Urine pregnancy testing before each infusion for people of reproductive age. Urinalysis with infusions per local protocol, then every 6 months after the course. Mesna is not routinely needed for standard-dose intravenous dosing. Urine cytology to screen for bladder cancer if the cumulative dose exceeds 36 g.[1]
Important cautions
Teratogenic and gonadotoxic; generally avoided in pregnancy and stopped before conception. Offer fertility protection: a gonadotropin-releasing hormone agonist as co-therapy in females, and consider sperm cryopreservation in males. Full reproductive-health guidance is maintained on the pregnancy record.[1, 2]
References
- Sammaritano LR, Askanase A, Bermas BL, et al. 2025 American College of Rheumatology (ACR) Guideline for the Treatment of Systemic Lupus Erythematosus. Arthritis Care Res (Hoboken). 2025. doi:10.1002/acr.25690 https://doi.org/10.1002/acr.25690
- Sammaritano LR, Askanase A, Bermas BL, et al. 2024 American College of Rheumatology (ACR) Guideline for the Screening, Treatment, and Management of Lupus Nephritis. Arthritis Care Res (Hoboken). 2025;77(9):1045-1065. doi:10.1002/acr.25528 https://doi.org/10.1002/acr.25528
- PROCYTOX (cyclophosphamide) Product Monograph. Health Canada authorized product monograph. https://health-products.canada.ca/dpd-bdpp/