Version July 2025
| Intermittent (pulse) CYC protocol | Euro-Lupus protocol (shorter, lower-dose regimen) | NIH protocol (longer, higher-dose regimen) |
| CYC dosing*[1,2] | ||
| Initial dose | 500 mg | 750 to 1000 mg/m2 of estimated BSA |
| Subsequent doses | Same as the initial dose | Adjust based on the patient's response and nadir of the WBC count¶ |
| Typical frequency and duration | Every 2 weeks for 6 doses | Every 4 weeks for 3 to 6 dosesΔ |
| Prevention of adverse effects | ||
| Fertility preservation | Facilitate for patients if desired and feasible prior to CYC infusion◊. May not be necessary for females receiving the Euro-Lupus protocol who do not have other risk factors for developing ovarian dysfunction (eg, age >30 years, non-nephritis patients at low risk for multiple rounds of CYC over lifetime). | |
| Hydration | Give 1 to 2 L of half normal or normal saline IV starting approximately 30 minutes prior to the CYC infusion§. | |
| Bladder protection | Give mesna approximately 15 to 30 minutes prior to the CYC infusion, then again several hours after the infusion¥. | |
| Antiemetics | Give a dose of an antiemetic (eg, ondansetron) approximately 30 minutes prior to the CYC infusion; then repeat as needed for nausea or vomiting. | |
| Laboratory monitoring |
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BSA: body surface area; CBC: complete blood count; CYC: cyclophosphamide; GnRH: gonadotropin-releasing hormone; hCG: human chorionic gonadotropin; IV: intravenous; NIH: National Institute of Health; WBC: white blood cell.
* The CYC dose may need to be adjusted for multiple factors including impaired kidney function, drug interactions, obesity, advanced age, and WBC count. Specific interactions should be assessed using a drug interactions tool such as the drug interactions program included within UpToDate. For more information, refer to UpToDate content on the use of cyclophosphamide in patients with rheumatic disease.
¶ For patients receiving the NIH protocol, a CBC with differential is typically checked 10 to 14 days after each infusion and again on the day of infusion to determine subsequent doses. Refer to UpToDate content for details on monitoring and dose adjustment.
Δ While most patients transition after 3 to 6 months to an alternative, less toxic immunosuppressive agent to maintain remission, historically, the NIH protocol included monthly CYC pulses for 6 months followed by pulses every 3 months for an additional 18 months.
◊ CYC may cause gonadal dysfunction. The optimal method for fertility preservation in males is cryopreservation of sperm, and in females it is cryopreservation of either ovarian tissue or of oocytes or embryos through ovarian stimulation. However, these procedures may not be possible in seriously ill patients with rheumatic disease who require urgent initiation of CYC. An alternative option in females is to administer a GnRH agonist (ie, leuprolide), which is ideally given 10 to 14 days prior to the initial CYC dose or, in the case of critical illness, 10 to 14 days before the second CYC dose. Lupron also reduces the risk of ovarian insufficiency. For more information and dosing, refer to UpToDate content on the use of CYC in patients with rheumatic disease.
§ The type and volume of intravenous fluid should be adjusted based on the individual patient's comorbidities. Some patients may need a dose of furosemide to help maintain strong urinary output (>100 mL/hour). When CYC is given in the outpatient setting, we encourage oral hydration for 24 hours before the infusion and then consumption of at least 1 liter of fluid every 6 to 8 hours for the subsequent 24 hours.
¥ For patients receiving the Euro-Lupus protocol, mesna is reserved for patients at risk of poor hydration or bladder emptying.
