Mycophenolate mofetil (MMF) in heart transplantation: rejection prevention and treatment

Mycophenolate mofetil (MMF), the morpholinoethylester of mycophenolic acid, inhibits the de novo pathway for purine synthesis. Evidence suggests that MMF suppresses lymphocyte function more than that of neutrophils, erythrocytes, and other rapidly dividing cell lines that can utilize salvage pathways for purine synthesis. While rigorous efficacy data await the completion of an ongoing, multicenter, prospectively randomized, placebo-controlled trial, long-term safety data are, however, available from numerous uncontrolled trials in cardiac transplantation. Dose-ranging trials in 49 heart recipients suggest that doses > or = 4000 mg/d are associated with significant, reversible gastrointestinal toxicity when compared with doses < 4000 mg/d (p < 0.001). Patients receiving > or = 1000 mg/d may have fewer rejection episodes. Even in the long term, changing from azathioprine to MMF is associated with increases in hematocrit (p < 0.001), total WBC count (p < 0.005), and absolute neutrophil count (p < 0.005). Successful use of MMF in refractory cardiac allograft rejection suggests an advantage over azathioprine. MMF is safe and appears to be at least as effective as azathioprine for immunosuppression following heart transplantation.