What are the differences between enteric‑coated mycophenolate sodium and mycophenolate mofetil, including dosing, efficacy, side‑effects, and which should be used first‑line?

Mycophenolate Sodium vs Mycophenolate Mofetil: Clinical Comparison

Either enteric-coated mycophenolate sodium (EC-MPS) or mycophenolate mofetil (MMF) can be used first-line as they are therapeutically equivalent in efficacy, with EC-MPS 720 mg twice daily roughly equivalent to MMF 1000 mg twice daily. 1

Mechanism and Formulation Differences

Both formulations deliver the same active metabolite, mycophenolic acid (MPA), which selectively inhibits inosine monophosphate dehydrogenase (IMPDH), thereby blocking T and B lymphocyte proliferation 2, 3. The key difference lies in drug delivery:

• MMF is rapidly hydrolyzed to MPA upon reaching systemic circulation, with peak levels (Tmax) at approximately 1.0 hour 4
• EC-MPS has an enteric coating that dissolves at pH >5, delaying MPA release until the small intestine, with peak levels (Tmax) at approximately 2.5 hours 4, 5

Dose Equivalency

The established dose conversion is EC-MPS 720 mg = MMF 1000 mg 1, 5. This equivalency has been validated through bioavailability studies showing both formulations deliver comparable MPA exposure (AUC) 5, 6.

For Asian populations specifically, lower doses may be appropriate: target 2 grams daily total dose of MMF (or equivalent EC-MPS 1440 mg daily) compared to 3 grams daily in non-Asians 1.

Efficacy Comparison

Both formulations demonstrate therapeutic equivalence across all measured outcomes 1, 6:

• A pivotal 12-month randomized controlled trial in de novo renal transplant patients showed identical efficacy failure rates (EC-MPS 25.8% vs MMF 26.2%; 95% CI [-8.7, +8.0]) 6
• Both formulations are equally effective for lupus nephritis treatment 1
• In extrarenal systemic lupus erythematosus, EC-MPS demonstrated superiority over azathioprine in achieving remission and reducing flares 1

Side Effect Profile

The gastrointestinal tolerability advantage of EC-MPS over MMF remains controversial and not definitively established 1:

• Overall adverse event rates are comparable between formulations 6
• Some evidence suggests EC-MPS may reduce upper GI symptoms, particularly in patients converted from MMF due to GI intolerance 7, 8
• In conversion studies, 70% of patients switching from MMF to EC-MPS experienced reduction in GI symptoms, especially diarrhea 8
• However, the pivotal phase III trial showed similar overall GI side effect rates, though EC-MPS had fewer dose reductions/discontinuations (15.0% vs 19.5% at 12 months) 6

Both formulations carry identical risks for:

• Leukopenia and other hematologic effects 3
• Infectious complications 3
• Teratogenicity (must discontinue ≥6 weeks before conception) 1

First-Line Recommendation

Choose either formulation based on practical considerations rather than efficacy 1:

• Start with MMF if cost is a primary concern, as it is generally less expensive 1
• Start with EC-MPS if the patient has known upper GI sensitivity or history of gastric/duodenal disease 7
• Convert from MMF to EC-MPS if significant GI symptoms develop on MMF, using equivalent dosing (MMF 1000 mg = EC-MPS 720 mg) 7, 8

Monitoring Requirements

Regardless of formulation chosen 7, 3:

• Monitor CBC and renal/hepatic profiles every 1-3 months
• Check MPA blood levels if GI intolerance develops—high levels suggest drug-related diarrhea 7
• Rule out infectious causes (stool analysis for enteropathogens, C. difficile) before attributing diarrhea to medication 7
• In renal insufficiency, expect MPAG accumulation (3-6 fold) and MPA increases (50%), though dose adjustment guidelines are not firmly established 2

Management of GI Intolerance

If diarrhea develops on either formulation 7:

1. Mild diarrhea: Continue medication with anti-diarrheal agents and fluid/electrolyte support
2. Persistent/severe diarrhea: Either reduce dose or switch from MMF to EC-MPS at equivalent dosing
3. Refractory cases: Consider alternative immunosuppressants (azathioprine, cyclophosphamide, calcineurin inhibitors, or leflunomide depending on indication) 7