What is the recommended dose of mycophenolate mofetil (MMF) for a patient with autoimmune hepatitis?

Mycophenolate Mofetil Dosing in Autoimmune Hepatitis

The recommended dose of mycophenolate mofetil for autoimmune hepatitis is 2 g daily (1 g twice daily), typically used in combination with corticosteroids. 1

Clinical Context for MMF Use

MMF is not a first-line agent for treatment-naïve autoimmune hepatitis. The standard approach remains corticosteroids with azathioprine. 1 However, MMF serves two specific roles:

Primary Indications for MMF

• Azathioprine intolerance (nausea, vomiting, fever, arthralgias, rash) - where MMF achieves approximately 58% response rate 1, 2
• Refractory disease (failure to normalize transaminases despite standard therapy) - where MMF achieves only 23% response rate 1, 2
• Post-transplant settings (recurrent or de novo AIH after liver transplantation) 1

Dosing Regimen

Standard Dosing

• Initial and maintenance dose: 2 g daily (1 g twice daily) in divided doses 1
• Some protocols initiate at 1 g daily with escalation to 1.5-2 g daily for maintenance 2

Dose Range for Refractory Cases

• Adjustable between 500 mg/day to 3 g/day depending on response and tolerance 2
• Most studies have consistently used 2 g/day as the target dose 1, 3, 4

Combination Therapy

• MMF should be combined with corticosteroids initially 1
• The goal is to taper prednisolone from typical starting doses (20 mg/day) down to minimal maintenance (2-5 mg/day) over 8-9 months 3, 5
• In post-transplant settings, MMF is added to existing corticosteroid and calcineurin inhibitor regimens 1

Treatment Algorithm

For Azathioprine Intolerance

1. Discontinue azathioprine when intolerance symptoms emerge
2. Initiate MMF 2 g daily (1 g twice daily) while continuing corticosteroids 1
3. Expect biochemical response within 3 months in most responders 3, 5
4. Gradually taper prednisolone dose as transaminases normalize 3

For Refractory Disease

1. Confirm inadequate response (persistent elevated transaminases despite adequate azathioprine dosing) 1
2. Add MMF 2 g daily to existing corticosteroid regimen, or replace azathioprine with MMF 1
3. Recognize that response rates are lower (23%) compared to intolerance cases 1, 2
4. If response remains inadequate after 3-6 months, consider calcineurin inhibitors (tacrolimus or cyclosporine) 1

For Post-Transplant AIH

1. Optimize calcineurin inhibitor levels first 1
2. If transaminases remain elevated, add MMF 2 g daily to corticosteroid and calcineurin inhibitor regimen 1
3. Continue indefinitely as part of immunosuppressive maintenance 1

Critical Monitoring Requirements

Initial Phase (First Month)

• Weekly complete blood counts to detect neutropenia, anemia, or thrombocytopenia 2, 6
• Baseline comprehensive metabolic panel including liver and renal function 6

Months 2-3

• CBC twice monthly 6
• Liver function tests every 2-3 weeks 6

Long-term Maintenance

• CBC and liver function tests every 1-3 months indefinitely 6
• Monitor for signs of infection (fever, respiratory symptoms) given immunosuppression risk 6

Important Safety Considerations

Absolute Contraindications

• Pregnancy - FDA Category D with severe teratogenic risk (cranial, facial, cardiac anomalies) 2, 6
• Severe neutropenia 2

Common Adverse Effects Requiring Dose Adjustment or Discontinuation

• Gastrointestinal toxicity (diarrhea, nausea, vomiting) occurs in 3-34% of patients 6, 7
• Hematologic suppression (anemia, leukopenia, thrombocytopenia) 6
• Up to one-third of patients may discontinue due to poor tolerance or side effects 1, 7

Drug Interactions to Avoid

• Do not combine with azathioprine - increases purine metabolism inhibition 6
• Avoid live vaccines during treatment 6
• Separate administration from antacids, iron supplements, and bile acid sequestrants by several hours 6

Clinical Pearls and Pitfalls

Response Expectations

• Patients with azathioprine intolerance respond significantly better (58%) than those with refractory disease (23%) 1, 2
• Biochemical improvement typically occurs within 3 months if MMF will be effective 3, 5
• Histological improvement follows biochemical response, with inflammatory scores and fibrosis scores decreasing significantly 3, 4

When MMF Fails

• Children with autoimmune hepatitis and sclerosing cholangitis are invariably non-responders 1
• If MMF proves ineffective for refractory disease, escalate to calcineurin inhibitors (tacrolimus preferred over cyclosporine) 1
• Consider liver transplantation for progressive disease despite maximal medical therapy 1

Cost Considerations

• MMF is approximately 6-7 times more expensive than azathioprine 2
• Treatment duration is typically lifelong 2
• This cost differential is justified when azathioprine causes intolerance, but less compelling for refractory disease given the modest 23% response rate 1, 2

Steroid-Sparing Effect

• A major benefit of MMF is enabling significant corticosteroid dose reduction, from median 20 mg/day to 2 mg/day within 8-9 months 3, 5
• Approximately 37-58% of patients can achieve complete remission off prednisolone entirely 5