What is the recommended dosing regimen for mycophenolate mofetil in an adult with rheumatoid arthritis‑associated interstitial lung disease, including adjustments for low body weight, impaired renal function, side‑effect tolerance, monitoring schedule, infection prophylaxis, and alternative therapies?

Mycophenolate Mofetil Dosing for Rheumatoid Arthritis-Associated Interstitial Lung Disease

For adults with RA-ILD, initiate mycophenolate mofetil at 2–3 g per day (1–1.5 g twice daily), as this is the conditionally recommended preferred first-line immunosuppressive therapy. 1

Standard Dosing Regimen

• Start with mycophenolate mofetil 1 g twice daily (total 2 g/day) and titrate up to 1.5 g twice daily (total 3 g/day) as tolerated to achieve optimal immunosuppression for RA-ILD 1
• The enteric-coated formulation (mycophenolate sodium) can be used at equivalent dosing: 720 mg twice daily is bioequivalent to mycophenolate mofetil 1 g twice daily 2, 3
• Maximum recommended dose is 1.5 g twice daily (3 g total daily) for mycophenolate mofetil 1, 3

Dose Adjustments for Special Populations

Low Body Weight

• No specific weight-based dose reduction is recommended in guidelines for RA-ILD; however, consider starting at the lower end of the dosing range (1 g twice daily) in patients with significantly low body weight and titrate based on tolerance 1

Renal Impairment

• In severe renal impairment (creatinine clearance <25 mL/min), avoid doses exceeding 1 g twice daily due to accumulation of the glucuronide metabolite (MPAG), which reaches approximately five times normal levels in end-stage renal disease 4
• Monitor free (unbound) mycophenolic acid levels in patients with severe renal dysfunction, as total drug levels may underestimate therapeutic exposure 5
• Dose adjustments should be guided by clinical response and toxicity monitoring rather than routine therapeutic drug monitoring in most cases 3

Managing Side Effects and Dose Modifications

Gastrointestinal Intolerance

• If gastrointestinal side effects develop (diarrhea, nausea, vomiting occur in up to 35% of patients), first attempt dose reduction or temporary interruption 4
• Switch to enteric-coated mycophenolate sodium 720–1080 mg twice daily if symptoms persist, as this formulation may reduce upper GI symptoms 1, 3
• Consider checking mycophenolic acid blood levels if GI intolerance necessitates dose reduction to ensure adequate immunosuppression 4, 3

Hematologic Toxicity

• Reduce dose or temporarily discontinue if absolute neutrophil count falls below 1.3 × 10⁹/L or if significant anemia or thrombocytopenia develops 4
• Resume at a lower dose once counts recover, typically reducing by 250–500 mg per dose 4

Monitoring Schedule

Initial Phase (First Year)

• CBC with differential: weekly for the first 4 weeks, then twice monthly for months 2–3, then monthly for months 4–12 4
• Comprehensive metabolic panel (including liver and renal function): every 2–3 weeks after initiation and dose changes, then every 3 months once stable 4
• Baseline hepatitis B, hepatitis C, and tuberculosis screening before initiation if combining with other highly immunosuppressive agents 4

Long-Term Monitoring

• CBC and metabolic panel every 1–3 months indefinitely while on therapy, as hematologic toxicity can occur at any time 4
• Full-body skin examination at baseline and periodically (at least annually) to monitor for skin malignancies 4
• Instruct patients to check temperature frequently and report fever, infection symptoms, or neurologic changes immediately 4

Infection Prophylaxis

• Avoid all live vaccines during mycophenolate therapy 4
• Consider Pneumocystis jirovecii prophylaxis (trimethoprim-sulfamethoxazole single-strength daily or double-strength three times weekly) when combining mycophenolate with high-dose corticosteroids or other potent immunosuppressants 1
• Screen for latent tuberculosis before initiation if using combination immunosuppression 4

Critical Drug Interactions to Avoid

• Do not coadminister with antacids containing aluminum or magnesium, iron supplements, cholestyramine, or activated charcoal, as these significantly reduce mycophenolate absorption; separate administration by at least 2 hours if unavoidable 4, 3
• Never combine with azathioprine due to additive purine metabolism inhibition and excessive bone marrow suppression 4
• Mycophenolate may reduce effectiveness of hormonal contraceptives; use barrier methods or alternative contraception 4

Pregnancy Considerations

• Discontinue mycophenolate at least 6 weeks before planned conception due to FDA black box warning for severe teratogenic effects, including cranial, facial, and cardiac abnormalities 2, 4
• Counsel all patients of childbearing potential about this risk before initiating therapy 4

Alternative and Combination Therapies for RA-ILD

If Mycophenolate Fails or Is Not Tolerated

• Switch to rituximab (1 g IV × 2 doses, 2 weeks apart) or azathioprine (2–3 mg/kg/day if TPMT normal), which are also conditionally recommended first-line options for RA-ILD 1
• Consider adding nintedanib 150 mg twice daily if progression occurs despite immunosuppression, particularly in patients with usual interstitial pneumonia (UIP) pattern on imaging 1, 6

Glucocorticoid Use

• Short-term glucocorticoids (≤3 months) may be used as a bridge when initiating mycophenolate or switching therapies, but long-term glucocorticoids are conditionally recommended against for RA-ILD due to infection risk and lack of proven benefit 1
• If glucocorticoids are used, taper aggressively once mycophenolate reaches therapeutic effect (typically 4–6 weeks) 1

Common Pitfalls to Avoid

• Do not use mycophenolate trough levels to guide dosing, as single time-point measurements (especially troughs) do not reliably reflect drug exposure; if therapeutic drug monitoring is needed, measure area under the curve (AUC₀₋₁₂) with limited sampling strategies 5
• Do not assume enteric-coated mycophenolate sodium and mycophenolate mofetil are interchangeable at equal doses; use the established conversion ratio (720 mg EC-MPS = 1000 mg MMF) 2
• Do not delay treatment initiation in symptomatic or progressing RA-ILD; retrospective data suggest mycophenolate is effective even in UIP patterns, and early treatment may prevent irreversible fibrosis 6
• Do not stop monitoring CBC after the first year; hematologic toxicity can emerge at any time during chronic therapy 4