What is the recommended induction dosing of mycophenolate (Cellcept) for pediatric patients with lupus nephritis?

Mycophenolate Mofetil Dosing for Pediatric Lupus Nephritis Induction Therapy

For pediatric patients with lupus nephritis, mycophenolate mofetil (MMF) should be dosed at 600 mg/m² per dose given twice daily, with a target total daily dose of 1200 mg/m²/day (maximum 3 g/day) for induction therapy. 1

Dosing Recommendations Based on Patient Characteristics

Standard Dosing

• Initial dose: Start at 300 mg/m²/day and titrate up 1
• Target dose: 1200 mg/m²/day (600 mg/m² twice daily) 1
• Maximum dose: 3 g/day total for non-Asian patients 2

Race-Based Dosing Considerations

• Non-Asian patients: Target 3 g/day total daily dose 2
• Asian patients: Target 2 g/day total daily dose 2
• African American/Hispanic patients: May benefit from MMF over cyclophosphamide due to better response rates 2

Clinical Scenario-Based Dosing

• Class III/IV lupus nephritis without crescents: 2-3 g/day total dose 2
• Class III/IV lupus nephritis with crescents: 3 g/day preferred 2
• Proteinuria with stable creatinine: 2-3 g/day total dose 2
• Proteinuria with recent significant rise in creatinine: 3 g/day preferred 2

Administration Protocol

1. Initial phase: Begin with 300 mg/m²/day and increase gradually 1
2. Titration: Increase to target dose of 1200 mg/m²/day (600 mg/m² twice daily) 1
3. Duration: Induction therapy should continue for 6 months 2
4. Monitoring: Check mycophenolic acid (MPA) levels during treatment 3
   • Target MPA-AUC₀₋₁₂ₕ: >25.24 μg·h·mL⁻¹ at 6 months for renal remission 4

Combination Therapy

• MMF should be combined with glucocorticoids 2
• Initial glucocorticoid regimen:
  • Three consecutive pulses of IV methylprednisolone 500-750 mg 2
  • Followed by oral prednisone 0.5 mg/kg/day for 4 weeks 2
  • Taper to ≤10 mg/day by 4-6 months 2

Maintenance Therapy After Induction

• Reduce MMF dose to 750-1000 mg twice daily (1.5-2 g/day total) 2
• Continue maintenance therapy for at least 36 months total (including induction phase) 2, 5
• Consider azathioprine as alternative if MMF not tolerated or pregnancy planned 2

Monitoring Response

• Complete response: Proteinuria <0.5 g/1.73 m² per day or <300 mg/m² per day 2
• Partial response: ≥50% reduction in proteinuria to <3 g/g creatinine 2
• No response: Failure to achieve partial or complete response within 6-12 months 2

Potential Adverse Events

• Common: Gastrointestinal symptoms (nausea, diarrhea)
• Serious: Infections (particularly herpes zoster) 1
• Hematologic: Leukopenia, anemia
• Other: Hair loss 1

Clinical Pearls

1. MMF has shown superior efficacy compared to cyclophosphamide in some pediatric studies, with 66% of patients achieving complete remission at 6 months 6
2. MMF has a better safety profile with fewer adverse events than cyclophosphamide 6, 7
3. Low-dose MMF (1.5 g/day) has shown effectiveness in some populations 7, but standard dosing based on body surface area is recommended for pediatric patients
4. MPA-G (glucuronidated metabolite) levels may better correlate with clinical response than MPA levels 3

By following this dosing algorithm and monitoring protocol, clinicians can optimize the induction therapy for pediatric lupus nephritis patients while minimizing potential adverse effects.