Mycophenolate Mofetil (MMF) in Interstitial Lung Disease: Prescription and Risks
Mycophenolate mofetil should be initiated at 500 mg twice daily and gradually increased by 500 mg weekly to a target dose of 1000-1500 mg twice daily for the treatment of interstitial lung disease associated with systemic autoimmune rheumatic diseases. 1
Dosing Protocol
Initial Dosing and Titration
- Start with 500 mg twice daily
- Increase by 500 mg weekly until reaching target dose
- Target maintenance dose: 1000-1500 mg twice daily (2-3 g/day total)
- Maximum dose: 3 g/day in divided doses
Monitoring Schedule
- Baseline labs: Complete blood count, liver function tests, renal function
- Follow-up labs: Every 1-2 weeks during initial titration, then monthly for 3 months
- Once stable: Monitor every 2-3 months
- Pulmonary function tests: Every 3-6 months to assess efficacy
Efficacy in Different ILD Types
MMF has emerged as a first-line agent for ILD across multiple systemic autoimmune rheumatic diseases:
- Systemic Sclerosis-ILD: First-line therapy, superior to cyclophosphamide for long-term outcomes 1
- Inflammatory Myopathy-ILD: First-line therapy, particularly effective in anti-synthetase syndrome 2
- Sjögren's-ILD: First-line steroid-sparing agent 1
- Rheumatoid Arthritis-ILD: Effective for stabilizing lung function 3
MMF has demonstrated significant improvements in forced vital capacity (FVC) and diffusing capacity (DLCO) across multiple studies, with improvements of 4.9-7.3% in FVC and 6.3-7.1% in DLCO over 1-3 years of treatment 3.
Major Risks and Side Effects
Common Side Effects (10-30%)
- Gastrointestinal: Nausea, vomiting, diarrhea, abdominal cramping 1
- Management: Split daily dose into 3-4 smaller doses or consider enteric-coated formulation
- Note: GI symptoms are typically not dose-dependent
Less Common but Serious Risks (1-10%)
- Hematologic: Leukopenia, anemia, thrombocytopenia 1
- Infections: Increased susceptibility to bacterial and viral infections 1
- Hepatotoxicity: Transaminitis requiring monitoring 1
Rare but Critical Risks (<1%)
- Malignancy: Small increased risk with prolonged use, particularly skin cancers 1
- Progressive multifocal leukoencephalopathy: Very rare but serious 1
- Pure red cell aplasia: Rare hematologic complication 1
Important Drug Interactions
- Proton pump inhibitors/H2 blockers: Reduce MMF bioavailability by 21-33% 4
- Consider monitoring drug levels or adjusting dosing when co-prescribed
- Antacids: May decrease absorption
- Medications affecting enterohepatic circulation: May alter MMF levels
Special Considerations
Pregnancy
- Absolutely contraindicated in pregnancy and lactation 1, 2
- Women of childbearing potential must use reliable contraception
Combination Therapy
- With Nintedanib: Effective combination for progressive fibrosing ILD, particularly in systemic sclerosis 1
- With Rituximab: Consider for refractory cases or rapidly progressive ILD 1, 2
- With Corticosteroids: Allows for steroid dose reduction to minimize long-term steroid toxicity 5
Monitoring for Efficacy
- Pulmonary Function Tests: Every 3-6 months (FVC, DLCO)
- HRCT: Baseline and as clinically indicated (typically annually)
- Symptom assessment: Dyspnea, cough, exercise tolerance
- Oxygen saturation: At rest and with activity
Clinical Pearls
- MMF typically takes 4-8 weeks to demonstrate clinical effect, with maximum benefit seen after 3-6 months 1
- In patients with UIP-pattern injury, MMF may stabilize rather than improve lung function 3
- MMF has a better safety profile than cyclophosphamide for long-term use 5
- For patients who cannot tolerate MMF, consider calcineurin inhibitors (tacrolimus, cyclosporine) as alternatives 2
By following this structured approach to MMF prescription and monitoring, clinicians can optimize outcomes while minimizing risks in patients with ILD associated with systemic autoimmune diseases.