What is the proper use and dosage of Mycophenolate (Mycophenolate mofetil) for treating autoimmune diseases and preventing organ rejection in transplant patients?

Mycophenolate: Proper Use and Dosing

Mycophenolate mofetil (MMF) is a critical immunosuppressant that inhibits lymphocyte proliferation by blocking inosine monophosphate dehydrogenase, making it highly effective for preventing organ rejection in transplant recipients and treating select autoimmune diseases, with dosing ranging from 2-3 g/day for most indications. 1

Mechanism of Action

• MMF is converted to its active form, mycophenolic acid (MPA), which selectively inhibits inosine monophosphate dehydrogenase—an enzyme essential for de novo purine synthesis in T and B lymphocytes 2, 3
• This preferential effect on lymphocytes occurs because they critically depend on the de novo pathway for DNA synthesis, unlike other cells that can utilize salvage pathways 4, 3
• The result is potent inhibition of T and B cell proliferation, T cell apoptosis, and suppression of dendritic cells and IL-1 3

Dosing for Transplant Rejection Prophylaxis

Kidney Transplantation

• Adults: 1 g orally or IV twice daily (total 2 g/day) 1
• Pediatrics (≥3 months): 600 mg/m² twice daily, maximum 2 g/day total 1
• For pediatric patients with BSA ≥1.5 m²: 1 g twice daily 1

Heart Transplantation

• Adults: 1.5 g orally or IV twice daily (total 3 g/day) 1
• Pediatrics (≥3 months): Start at 600 mg/m² twice daily, increase to maintenance of 900 mg/m² twice daily if tolerated (maximum 3 g/day) 1

Liver Transplantation

• Adults: 1.5 g orally twice daily OR 1 g IV twice daily 1
• Pediatrics (≥3 months): Start at 600 mg/m² twice daily, increase to 900 mg/m² twice daily if tolerated (maximum 3 g/day) 1

IV Administration Guidelines

• IV formulation should only be used when patients cannot tolerate oral medication 1
• Administer within 24 hours of transplantation 1
• Maximum duration: 14 days, then switch to oral as soon as tolerated 1
• Must infuse over ≥2 hours via peripheral or central vein—never as bolus 1
• Rapid infusion increases risk of phlebitis and thrombosis 1

Dosing for Autoimmune Diseases

Lupus Nephritis (Class III-IV)

• Target dose: 2-3 g/day (or MPA 1.44-2.16 g/day) for induction therapy 2
• MMF is a first-line option equivalent to cyclophosphamide, with possible superior efficacy in African-Americans 2
• Dose adjustment based on tolerance, efficacy, and trough MPA blood levels 2
• Combination with tacrolimus may be considered, particularly with nephrotic-range proteinuria 2

Systemic Autoimmune Rheumatic Disease-Associated Interstitial Lung Disease (SARD-ILD)

• Mycophenolate is the preferred first-line therapy across multiple SARD subtypes including systemic sclerosis, rheumatoid arthritis, mixed connective tissue disease, inflammatory myopathies, and Sjögren's disease 2
• Typical starting dose: 500 mg twice daily, increased by 500 mg weekly to target of 1000 mg twice daily (2 g/day) 4
• May increase to 1500 mg twice daily (3 g/day) if tolerated 4
• Monitoring of MMF levels (glucuronide) may optimize therapeutic range 4

Immune Thrombocytopenia (ITP)

• Dose: 500-2000 mg/day in adults 2
• Pediatric dose: 1300 mg/m²/day (maximum 2000 mg) 2
• Response is relatively slow: ~15% at 1 week, ~50% by 1 month 2
• Durable response: 56.7-61.9% 2

Inflammatory Myopathy

• Dose range: 500 mg twice daily, titrated to 1 g twice daily 5
• Used as alternative when conventional immunosuppressives are ineffective or poorly tolerated 5

Critical Safety Considerations

Absolute Contraindications

• Pregnancy: MMF is a potent teratogen with 49% miscarriage rate, 2% stillbirth rate, and 23% structural anomaly rate 2, 1
• Specific malformations include hypoplastic nails, shortened fifth fingers, microtia, cleft lip/palate, auditory canal absence, and cardiac defects 2
• Requires 12-week washout period before attempting pregnancy 2
• Contraindicated during lactation 2
• Hypersensitivity to mycophenolate, mycophenolic acid, or Polysorbate 80 (in IV formulation) 1

Females of Reproductive Potential

• Must use two reliable forms of contraception 2, 1
• Requires comprehensive counseling on pregnancy prevention and planning 1

Boxed Warnings (FDA)

• Embryofetal toxicity with increased first trimester pregnancy loss and congenital malformations 1
• Increased risk of lymphoma and other malignancies, particularly skin cancers 1
• Increased susceptibility to serious infections including opportunistic infections, bacterial, viral, fungal, and protozoal infections with potential fatal outcomes 1
• Risk of viral reactivation of hepatitis B and C 1

Monitoring Requirements

Laboratory Monitoring

• Complete blood count: Monitor for neutropenia, anemia, and thrombocytopenia 2, 4, 3
• Liver function tests: Monitor for transaminitis, at least monthly 2, 4
• Consider therapeutic drug monitoring of MPA levels to optimize efficacy and minimize toxicity 2, 4

Dose Adjustments for Adverse Effects

• Reduce or interrupt dosing for neutropenia 1
• Common gastrointestinal side effects (diarrhea 6.8%, nausea, vomiting) may require dose reduction 2, 4, 3
• Enteric-coated mycophenolate sodium formulation may reduce GI side effects 3

Additional Precautions

Infection Risk Management

• Avoid live attenuated vaccines during therapy 1
• Monitor for opportunistic infections including progressive multifocal leukoencephalopathy 2
• Pure red cell aplasia has been reported 2

Blood and Semen Donation

• Avoid blood donation during therapy and for 6 weeks after discontinuation 1
• Avoid semen donation during therapy and for 90 days after discontinuation 1

Drug Interactions

• IV formulation is incompatible with other IV solutions and must not be mixed or administered concurrently via the same catheter 1

Special Populations

• Patients with hypoxanthine-guanine phosphoribosyl-transferase deficiency should avoid MMF 1
• May impair ability to drive or operate machinery 1

Combination Therapy Considerations

• In transplantation, MMF is used with cyclosporine or tacrolimus (calcineurin inhibitors) and corticosteroids 1
• In lupus nephritis, combination with tacrolimus may enhance efficacy, particularly with nephrotic-range proteinuria 2
• In rapidly progressive SARD-ILD, upfront combination therapy (double or triple therapy) is conditionally recommended over monotherapy 2
• Limited evidence supports combining with azathioprine 2