What are the indications, uses, and monitoring requirements for Mycophenolate (MMF) Mofetil in dermatology?

Mycophenolate Mofetil in Dermatology: Indications, Dosing, and Monitoring

Mycophenolate mofetil (MMF) is conditionally recommended as an off-label, steroid-sparing immunosuppressant for refractory moderate-to-severe atopic dermatitis and autoimmune blistering diseases, particularly pemphigus vulgaris and bullous pemphigoid, when first-line therapies have failed. 1

FDA-Approved vs. Off-Label Use

• MMF is FDA-approved only for prophylaxis of organ rejection in renal, cardiac, and hepatic transplantation 2
• All dermatologic uses are off-label 1
• The evidence quality for dermatologic indications is very low to low, but clinical experience supports its use when conventional therapies fail 1

Primary Dermatologic Indications

Atopic Dermatitis

• Use MMF for adults with refractory moderate-to-severe atopic dermatitis who have failed conventional systemic therapies 1
• Expect a delayed onset of action: clinical improvement typically begins after 10 weeks, with efficacy equal to cyclosporine by that time 1
• MMF demonstrates longer clinical remission after discontinuation compared to cyclosporine 1
• In one retrospective analysis, 85% of patients reported improvement within the first month, and 50% achieved complete disease clearance 1

Pemphigus Vulgaris

• Add MMF 2-3 g/day immediately at treatment initiation as a steroid-sparing agent alongside prednisolone 1 mg/kg/day 3
• Expect a 6-8 week latent period before clinical effect becomes apparent 3
• MMF is preferred over cyclophosphamide in some contexts due to comparable efficacy with potentially fewer severe toxicities 1, 3
• Continue MMF during corticosteroid taper to minimize relapse risk 3

Bullous Pemphigoid

• MMF shows similar efficacy to azathioprine when combined with corticosteroids for inducing remission 1
• Liver toxicity occurs less frequently with MMF compared to azathioprine, though infections may be more common 1

Psoriasis

• MMF has mixed efficacy in psoriasis and should be reserved for moderate disease or psoriatic arthritis, not severe plaque psoriasis 4, 5
• Dosing of 2 g/day (1 g twice daily) for 3 weeks showed 40-70% PASI reduction in 7 of 11 patients with severe psoriasis 4
• Patients with severe psoriasis generally do not respond adequately to MMF monotherapy 5
• MMF may be more effective for psoriatic arthritis than for cutaneous psoriasis 5

Other Dermatologic Conditions

• Case reports and small series support use in pyoderma gangrenosum, Crohn's disease (cutaneous manifestations), bullous lichen planus, lupus erythematosus, and dermatomyositis 6, 7, 8
• Evidence for these conditions consists primarily of case reports and should be considered experimental 7

Dosing Protocols

Standard Dosing

• Start at 500 mg twice daily and increase by 500 mg weekly to reach target dose of 1000 mg twice daily (2 g/day) 9
• For severe autoimmune blistering diseases, doses may range from 2-3 g/day in divided doses 1, 3
• In select cases requiring higher immunosuppression, doses up to 1500 mg twice daily (3 g/day) may be used if tolerated 9
• For psoriasis and Crohn's disease, lower doses of 500 mg twice daily may be sufficient 6

Pediatric Dosing

• For children ≥2 years with refractory atopic dermatitis, use 600-1200 mg/m² body surface area 1
• MMF is relatively safe in pediatric patients without significant hematologic, hepatic, or infectious complications 1

Formulation Options

• Available as oral suspension, capsules, and tablets, administered twice daily 1
• Enteric-coated mycophenolate sodium (mycophenolic acid 720-1080 mg twice daily) can be substituted if gastrointestinal intolerance occurs 3, 10

Mechanism of Action

• MMF inhibits inosine monophosphate dehydrogenase (IMPDH), blocking the de novo purine biosynthesis pathway 1, 9, 10
• This selectively affects B-cells and T-cells, which lack compensatory purine salvage mechanisms 1, 10
• Results in decreased B and T cell proliferation, T cell apoptosis, and suppression of dendritic cells and IL-1 10

Monitoring Requirements

Baseline Testing

• Complete blood count (CBC) with differential 9
• Comprehensive metabolic panel including liver function tests 9
• Pregnancy test in women of childbearing potential (MMF is teratogenic and contraindicated in pregnancy) 9, 2

Ongoing Monitoring

• Monitor CBC and liver function tests every 2-4 weeks initially, then monthly once stable 9
• Watch for leukopenia, anemia, and thrombocytopenia 1, 9, 10
• Consider monitoring MMF glucuronide levels to ensure therapeutic range, though this is not routinely performed in dermatology 9
• Maintain vigilance for infections, as theoretical risk exists (though less clearly defined in dermatology patients compared to transplant recipients) 1

Critical Monitoring Period

• The 6-8 week lag period before MMF becomes clinically effective is crucial—do not prematurely reduce corticosteroids during this time 3
• Maintain adequate corticosteroid coverage (typically ≤10 mg/day prednisone) while awaiting MMF effect 3

Adverse Effects and Safety Considerations

Common Side Effects

• Gastrointestinal symptoms (nausea, vomiting, abdominal cramping, diarrhea) are most common, occurring in up to 35% of patients 1, 10
• These GI symptoms are not dose-dependent and typically do not impact compliance 1
• Switching to enteric-coated formulation may reduce GI symptoms 1, 3
• Headaches and fatigue occur but are generally mild 1

Hematologic Toxicity

• Leukopenia, anemia, and thrombocytopenia can occur but are rare in dermatology patients 1, 10
• Hematologic effects are less severe than with azathioprine or cyclophosphamide 1

Infection Risk

• Theoretical increased susceptibility to viral and bacterial infections exists 1
• The clinical significance in dermatology patients is less clear than in transplant recipients 1
• When used with cyclophosphamide, add Pneumocystis jirovecii prophylaxis with trimethoprim/sulfamethoxazole 800/160 mg on alternate days 3

Malignancy Risk

• Potential risk of cutaneous malignancy and lymphoma exists, though difficult to quantify in dermatology patients, especially with multidrug regimens 1

Pregnancy and Contraception

• MMF is teratogenic and absolutely contraindicated in pregnancy 9, 2
• Coadminister with hormonal contraceptives plus mandatory additional barrier methods 2
• MMF reduces levonorgestrel AUC by approximately 15%, potentially compromising contraceptive efficacy 2

Drug Interactions

Significant Interactions to Avoid

• Do not coadminister with cholestyramine—it decreases MPA AUC by approximately 40% by interrupting enterohepatic recirculation 2
• Avoid combination of norfloxacin plus metronidazole—reduces MPA AUC by 33% 2
• Telmisartan decreases MPA concentrations by approximately 30% 2
• Sevelamer and calcium-free phosphate binders decrease MPA Cmax by 36% and AUC by 26%—administer 2 hours after MMF if needed 2

Cyclosporine Interaction

• Cyclosporine reduces MPA exposure by 30-50% by inhibiting enterohepatic recirculation 2
• When switching from cyclosporine to tacrolimus or other agents that don't interfere with MPA recycling, expect increased MPA levels 2

Neutral Interactions

• Trimethoprim/sulfamethoxazole does not affect MPA bioavailability 2
• Ganciclovir shows no pharmacokinetic interaction, but both drugs compete for tubular secretion in renal impairment—monitor carefully 2
• Ciprofloxacin and amoxicillin/clavulanic acid can be used without significant interaction 2

Clinical Pitfalls and Caveats

Common Errors to Avoid

• Do not withdraw MMF prematurely—47% of successfully treated pemphigus patients relapse when treatment stops after only 1 year 3
• Do not reduce corticosteroids during the 6-8 week latent period before MMF takes effect 3
• Do not use MMF as monotherapy for severe plaque psoriasis—efficacy is poor 5
• Do not ignore the need for dual contraception in women of childbearing potential 2

Patient Selection

• Comorbidities or drug interactions that may exacerbate toxicity make MMF inappropriate for select patients 1
• MMF's lack of hepatic or renal toxicity is a significant advantage over cyclosporine, methotrexate, and azathioprine, making it suitable for patients with these comorbidities 8

Switching Between Immunosuppressants

• When switching from cyclophosphamide to MMF in pemphigus, maintain current prednisone dose (typically ≤10 mg daily) or temporarily increase to 1 mg/kg/day if disease is not controlled 3
• Higher MMF doses (2.5-3 g/day) may be required to induce remission in some patients 3

Comparative Efficacy

• MMF shows slower onset compared to cyclosporine but longer remission duration after discontinuation 1
• MMF demonstrates similar efficacy to azathioprine in bullous pemphigoid with different toxicity profiles 1
• A randomized controlled trial showed no significant differences in efficacy or adverse events between pulsed cyclophosphamide and MMF in pemphigus vulgaris 3
• For pemphigus vulgaris, MMF's steroid-sparing effect appears greater than cyclophosphamide but evidence quality is limited 1