Mycophenolic acid, enteric-coated

Mycophenolate mofetil was approved by the FDA in 1995, and enteric-coated mycophenolic acid was approved in 2004. Both agents are considered to be adjunctive immunosuppressants. Mycophenolic acid acts by inhibiting inosine monophosphate deydrogenase, a vital enzyme in the de novo pathway of purine synthesis. Inhibition of this enzyme prevents the proliferation of most cells that are dependent on the de novo pathway for purine synthesis, including T cells.7,11,26-28... 

Mycophenolate mofetil is available in 250 mg capsules and 500 mg tablets, an oral suspension (100 mg/mlL, in cherry syrup), and an injectable.11 Usual doses of mycophenolate mofetil range from 1000 to 3000 mg/day in two to four divided doses. The conversion between oral and IV mycophenolate mofetil is 1 1. Enteric-coated mycophenolic acid is available in 180 and 360 mg tablets. For conversion between mycophenolate mofetil and enteric-coated MPA, 1000 mg mycophenolate mofetil is equivalent to 720 mg enteric-coated MPA.26,29 The recommended starting dose of enteric-coated mycophenolic acid is 720 mg given twice daily.11 It appears that conversion of mycophenolate mofetil to enteric-coated mycophenolic acid is safe, but more studies are needed to determine the exact role of enteric-coated MPA in the immunosuppressive armamentarium. Mycophenolic acid trough concentrations can be monitored, but they are not recommended routinely. 

The most common adverse events associated with these agents are GI (18% to 54%, namely, diarrhea, nausea, vomiting, and gastritis) and myelosuppression (20% to 40%).7,11,26-28 Despite its enteric coating, to date, mycophenolic acid has shown no significant benefit in terms of reduction in GI adverse events compared with mycophenolate mofetil in renal transplant recipients.26... 

MPA derivatives have replaced azathioprine as the antiproliferative agent of choice in most organ transplant centers. The MPA derivatives generally are considered to provide a more specific immunosuppressive effect compared with azathioprine. Mycophenolate mofetil and enteric-coated mycophe-nolic acid have similar safety and efficacy data in renal transplant recipients. 

Mycophenolate sodium is an enteric-coated formulation of the sodium salt of mycophenohc acid designed to reduce the GI side effects of MMF. This formulation allows for mycophenohc acid to be released directly in the small intestine for absorption rather than in the stomach. Because mycophenohc acid is the activated form of MMF, the actions... 

A common strategy to mitigate mycophenolic acid-related gastrointestinal adverse events includes dose manipulations, such as split dosing, dose reduction, and withdrawal. However, dose alterations are associated with poorer graft outcomes. Enteric-coated mycophenolate mofetil sodium was associated with fewer dose reductions and withdrawals in a retrospective single-center comparison in 1709 consecutive kidney transplant patients [97 ]. 

An enteric-coated delivery system of MPA was developed with the aim that it would minimize gastrointestinal side effects [55]. Myfortic, approved by the FDA in 2004, is an enteric formulation of mycophenolate sodium (EC-MPS), which releases the active MPA moiety. The enteric coating of the tablet consists of the polymer, hypromellose phthalate combined with titanium dioxide, iron oxide yellow, and indigotine (180 mg tablet) or iron oxide red (360 mg tablet) [56]. Hypromellose phthalate is a monoph-thalic acid ester of hydroxypropyl methylcellulose which dissolves at pH 5-5.5, thereby affording delivery of MPA to the small intestine rather than the stomach. 

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