What is the recommended dosing regimen for cyclophosphamide (CYTOXAN) in patients with inflammatory myositis?

Cyclophosphamide Dosing Regimen for Inflammatory Myositis

For patients with inflammatory myositis, cyclophosphamide should be administered at 0.6-1.0 g/m² IV every 4 weeks or 1-2 mg/kg/day orally (not exceeding 200 mg daily) for 3-12 months, with appropriate supportive measures to prevent complications. 1

Indications for Cyclophosphamide in Myositis

• Cyclophosphamide should be reserved for patients with severe organ manifestations, particularly interstitial lung disease (ILD) associated with dermatomyositis (DM) or polymyositis (PM) 1
• It is typically used after failure of first-line therapies or in cases with life-threatening complications 1

Administration Protocols

Intravenous Regimen:

• Dose: 0.6-1.0 g/m² IV 1
• Frequency: Every 4 weeks 1
• Duration: Typically 3-6 months, occasionally extended to 12 months for refractory cases 1
• Supportive care:
  • Intravenous hydration with normal saline 1
  • Antiemetics to control nausea 1
  • Mesna (40% of cyclophosphamide dose) to prevent hemorrhagic cystitis 1

Oral Regimen:

• Dose: 1-2 mg/kg/day 1
• Maximum dose: 200 mg daily 1
• Duration: 3-12 months 1
• Hydration: Patients should maintain adequate fluid intake (2-3 L within 24 hours) 1

Dose Adjustments

• For patients over 60 years old, consider reducing the dose 1
• For patients with renal impairment (GFR <30 ml/min/1.73 m²), reduce dose by 0.5 mg/kg/day for oral or 2.5 mg/kg for IV administration 1
• Monitor white blood cell count for nadir 8-14 days after infusion; maintain nadir above 3.0 x 10⁹/L 1

Monitoring and Safety Measures

• Complete blood count: Monitor regularly, especially 8-14 days post-infusion when nadir occurs 1
• Urinalysis: Monitor for hematuria as sign of hemorrhagic cystitis 1
• Mesna administration:
  • For IV cyclophosphamide: Give oral mesna 4 and 8 hours after infusion (20% of cyclophosphamide dose per dose) 1
  • For oral cyclophosphamide: Consider daily mesna 1
• Hydration: Advise patients to maintain adequate hydration (2-3 L/day) 1
• Frequent urination: Recommend patients urinate frequently, especially first thing in the morning, to prevent acrolein metabolite accumulation 1
• Pneumocystis jiroveci prophylaxis: Trimethoprim/sulfamethoxazole (800/160 mg on alternate days or 400/80 mg daily) 1

Efficacy and Evidence

• In a study of 17 patients with PM/DM with progressive interstitial pneumonia, IV cyclophosphamide improved symptoms, pulmonary function tests, and high-resolution CT findings 2
• Yamasaki et al. found that 11 of 17 patients with DM/PM or amyopathic DM treated with cyclophosphamide and prednisolone had improvement in dyspnea, and 8 patients had at least 10% improvement in vital capacity 1
• Some studies have shown limited efficacy in refractory cases without pulmonary involvement 3

Combination Therapy

• Cyclophosphamide is typically used in combination with corticosteroids 1, 4
• For severe interstitial pneumonia, a combination of high-dose prednisolone, cyclosporine A (2-4 mg/kg/day), and IV pulse cyclophosphamide (10-30 mg/kg every 3-4 weeks) has shown benefit 4
• Rituximab is becoming an alternative to cyclophosphamide for refractory cases 1

Potential Adverse Effects

• Hemorrhagic cystitis (preventable with mesna and adequate hydration) 1
• Cytopenias requiring dose adjustment or discontinuation 1
• Increased risk of infections 3
• Premature ovarian failure and sterility 1
• Nausea and vomiting 1
• Long-term risk of malignancy 1

Practical Considerations

• For patients with childbearing potential, discuss fertility preservation options before initiating therapy 1
• Consider switching to less toxic alternatives like mycophenolate mofetil after achieving disease control 1
• In cases of treatment failure after 3-6 months, consider alternative therapies such as rituximab 1