What is the recommended dose of cyclophosphamide (CYC) and hydration protocol for a patient with Systemic Lupus Erythematosus (SLE) presenting with lupus myocarditis and nephritis?

Cyclophosphamide Dosing and Hydration Protocol for SLE with Lupus Myocarditis and Nephritis

For patients with SLE presenting with lupus myocarditis and nephritis, the recommended cyclophosphamide regimen is low-dose intravenous cyclophosphamide at 500 mg every 2 weeks for 6 doses, combined with glucocorticoids. 1

Cyclophosphamide Dosing Options

Preferred Regimen: Low-Dose IV Cyclophosphamide

• Administer 500 mg IV every 2 weeks for a total of 6 doses (cumulative dose 3 grams) 1
• This "Euro-Lupus" protocol has shown comparable efficacy to high-dose regimens with fewer adverse effects 2
• Particularly beneficial for reducing risk of infertility compared to high-dose regimens 1

Alternative Regimen: High-Dose IV Cyclophosphamide

• Consider only in patients with adverse clinical or histological prognostic factors (crescents or necrosis in >25% of glomeruli, rapidly declining renal function) 1
• Dosing: 0.5-0.75 g/m² monthly for 6 months 1
• Higher risk of adverse effects including severe infections and gonadal toxicity 1

Oral Cyclophosphamide Option

• 1.0-1.5 mg/kg/day for 3 months 1
• Less preferred due to higher cumulative dose and increased risk of adverse events 1
• Weekly monitoring for neutropenia required (versus monthly with IV regimen) 1

Hydration Protocol

• Administer 1-2 liters of intravenous normal saline before cyclophosphamide infusion 3
• Continue hydration for 24 hours post-infusion to minimize risk of hemorrhagic cystitis 3
• Instruct patient to void frequently and maintain high oral fluid intake (2-3 liters daily) on the day of treatment 4
• Consider co-administration with mesna for bladder protection 1

Glucocorticoid Protocol

• Initial treatment: IV methylprednisolone 0.25-0.50 g/day for 1-3 days based on disease severity 1
• Follow with oral prednisone 0.35-1.0 mg/kg/day (not exceeding 80 mg/day) 1
• Taper over several months to maintenance dose of ≤7.5 mg/day by 3-6 months 1

Monitoring and Follow-up

• Complete blood count weekly for the first month, then every 2 weeks during treatment 5
• Hold cyclophosphamide if white blood cell count <3,000/mm³ or neutrophil count <1,500/mm³ 5
• Monitor renal function and urinalysis before each dose 1
• Evaluate response by measuring proteinuria, serum creatinine, and complement levels 1
• Expect at least 25% reduction in proteinuria and/or normalization of complement levels after 8 weeks of treatment 1

Special Considerations

• For patients concerned about fertility preservation:

  • Consider mycophenolate mofetil as first-line alternative 1
  • If cyclophosphamide is necessary, use the low-dose regimen 1
  • Consider gonadotropin-releasing hormone agonists (leuprolide) for women 1
  • Sperm banking for men prior to treatment 1

• For patients with severe disease (crescentic nephritis):

  • Higher-dose cyclophosphamide may be warranted 1
  • More aggressive initial glucocorticoid therapy (1 mg/kg/day) 1

Pitfalls and Caveats

• Minimize lifetime cyclophosphamide exposure to <36 grams to reduce risk of malignancy 1
• Screen for tuberculosis, hepatitis B, hepatitis C, and HIV before initiating therapy 1
• Consider Pneumocystis jirovecii prophylaxis during treatment 1
• Ensure adequate contraception, as cyclophosphamide is teratogenic 1
• Monitor for hemorrhagic cystitis, which can be minimized with adequate hydration and mesna 1