What is the use and dosing of mycophenolate mofetil (Cellcept) in adult patients with a history of organ transplant or autoimmune diseases?

Mycophenolate Mofetil: Clinical Use and Dosing

Primary Indication and Mechanism

Mycophenolate mofetil (MMF) is FDA-approved for prophylaxis of solid organ transplant rejection and serves as an off-label alternative for refractory autoimmune diseases, working by selectively inhibiting T and B lymphocyte proliferation through blockade of de novo purine synthesis. 1, 2

• MMF is a prodrug rapidly hydrolyzed to mycophenolic acid (MPA), which inhibits inosine monophosphate dehydrogenase (IMPDH), an enzyme critical for guanosine nucleotide synthesis 2, 3
• This mechanism preferentially affects lymphocytes because they depend critically on the de novo pathway, unlike other cells that can use salvage pathways 4, 2

FDA-Approved Dosing for Transplantation

Renal Transplantation

• Standard dose: 1 g orally twice daily (2 g total daily dose) 1
• Higher doses of 1.5 g twice daily (3 g/day) were studied but showed no efficacy advantage and worse safety profile 1
• Administer on an empty stomach when possible (food decreases peak concentration by 40%), though stable patients may take with food if needed 1

Cardiac Transplantation

• Dose: 1.5 g orally twice daily (3 g total daily dose) 1

Hepatic Transplantation

• Dose: 1.5 g orally twice daily (3 g total daily dose) 1

Pediatric Dosing (Ages 3 months to 18 years)

• 600 mg/m² twice daily using oral suspension (maximum 2 g/day) 1
• Body surface area 1.25-1.5 m²: 750 mg capsules twice daily 1
• Body surface area >1.5 m²: 1 g capsules/tablets twice daily 1

Dose Adjustments for Special Populations

Severe Chronic Renal Impairment

• In renal transplant patients with GFR <25 mL/min/1.73 m² beyond immediate post-transplant period, avoid doses exceeding 1 g twice daily 1
• No adjustment needed for delayed graft function immediately post-transplant 1
• For cardiac/hepatic transplant patients with severe renal impairment, use only if benefits outweigh risks 1
• In renal insufficiency, the inactive metabolite MPAG accumulates 3-6 fold and MPA increases by 50% 3

Neutropenia Management

• If absolute neutrophil count drops below 1.3 × 10³/µL, interrupt dosing or reduce dose immediately 1

Hepatic Impairment

• No dose adjustment recommended for severe hepatic parenchymal disease in renal patients 1
• Insufficient data for cardiac transplant patients with severe hepatic disease 1

Off-Label Use in Autoimmune Diseases

Systemic Autoimmune Rheumatic Disease-Associated Interstitial Lung Disease

• MMF is conditionally recommended as a preferred first-line treatment option 2
• Start at 500 mg twice daily, increase by 500 mg weekly to target 1000 mg twice daily (2 g/day) 4
• May increase to 1500 mg twice daily (3 g/day) if tolerated 4

Autoimmune Hepatitis (Second-Line)

• For patients failing steroids and azathioprine, MMF is conditionally recommended as initial second-line therapy 2

Refractory Atopic Dermatitis

• Consider MMF as an alternative therapy for severe, refractory cases 5
• Dosing ranges from 0.5-3 g/day divided twice daily, though optimal dosing is not established 5
• Efficacy is inconsistent; initial response may be delayed (10 weeks), but clinical remission may last longer than cyclosporine upon discontinuation 5
• In one study, 85% reported improvement within first month, and 50% achieved disease clearance 5

Pediatric Atopic Dermatitis

• MMF is a relatively safe alternative for children ≥2 years with refractory disease 5
• Suggested dosing: 600-1200 mg/m² based on transplant literature 5

Adverse Effects and Monitoring

Common Side Effects

• Gastrointestinal disturbances are most common: nausea, vomiting, diarrhea, abdominal cramping (up to 35% of patients) 2, 5, 4
• Consider enteric-coated formulation (mycophenolate sodium) if GI symptoms develop 5, 2
• If GI effects occur, interrupt therapy or reduce dose 2
• Headaches and fatigue may occur but are not dose-dependent and rarely affect compliance 5

Hematologic Effects

• Leukopenia, anemia, and thrombocytopenia can occur 2, 5
• Monitor CBC every 1-3 months during therapy 2

Infectious Risk

• Theoretical increased susceptibility to viral and bacterial infections (clearly observed in transplant patients, applicability to autoimmune disease patients unknown) 5
• Monitor for signs of progressive multifocal leukoencephalopathy and cease treatment if suspected 2

Malignancy Risk

• Potential risk of cutaneous malignancy and lymphoma, though difficult to delineate given multidrug therapy in many reports 5

Additional Monitoring

• Obtain renal and hepatic profiles every 1-3 months 2
• Consider monitoring MMF glucuronide levels to ensure therapeutic range 4

Critical Contraindications and Warnings

• Absolutely contraindicated in pregnancy due to teratogenic effects 4
• Lacks nephrotoxicity, cardiovascular toxicity, or diabetogenic potential compared to other immunosuppressants 6
• Primarily metabolized by glucuronidation, not through cytochrome P450 system 6