Mycophenolate Mofetil MMF

Current indication:

All patients receiving a kidney and/or pancreas graft should be treated with MMF in the first instance. If they are unable to tolerate it, a switch to Mycophenolic Acid (Myfortic) or Azathioprine may be made.

Dose:

500 mg to 1g twice daily, depending on concomitant immunosuppression and renal function.
MMF is best absorbed on an empty stomach, either one hour before or two hours after a meal, but gastrointestinal side effects may be alleviated by taking it with food and further splitting the daily dose.

Mode of action:

MMF is rapidly hydrolysed following absorption to mycophenolic acid (MPA), the active metabolite. MPA is a potent inhibitor of inosine monophosphate dehydrogenase (IMPDH) and therefore inhibits the de-novo pathway of guanosine nucleotide synthesis. B and T lymphocytes are critically dependent on the de novo pathway and so MPA inhibits B and T lymphocyte proliferation and also B-cell antibody formation.

Preparation:

MMF is available as 250 mg capsules (blue-brown) and 500 mg tablets (lavender). The brand name is CELLCEPT. The equivalent doses of MYFORTIC are 180mg and 360mg respectively.

Monitoring:

Monitoring of MMF blood levels is not needed.

Contra-indications:

Pregnancy see important information on the Long Term Immunsuppression page.

Side-effects:

Gastrointestinal side-effects are common. Consider an an alternative cause of diarrhoea and exclude infection. If felt to be due to MMF, consider:

  • Splitting dose to 500mg qds is the first line approach
  • Switching to Myfortic (720mg bd = 1g MMF bd)
  • Reducing dose
  • Switch to azathioprine

Leucopenia may occur. Exclude CMV infection. Consider a dose reduction and monitor white cell count.

Interactions:

  • Tacrolimus increases the AUC of MPA, the active metabolite of MMF. By 3 months past transplant the increase is such that the dose of MMF may need to be reduced with time post-transplant to maintain stable systemic exposure to MPA.
  • Cholestyramine and antacids – may bind MMF and significantly reduce absorption.
  • Drugs which undergo tubular secretion, e.g. acyclovir, theoretically may impair secretion of MMF and have raised blood levels themselves during concurrent administration.
  • Drugs which interfere with entero-hepatic recirculation may reduce the efficacy of MMF.