Enteric-coated mycophenolate sodium for transplant immunosuppression.

PURPOSE: The pharmacology, pharmacokinetics, drug interactions, clinical efficacy, adverse effects, monitoring, and dosage and administration of enteric-coated (EC) mycophenolate sodium are reviewed. SUMMARY: EC mycophenolate sodium is the EC salt form of mycophenolic acid (MPA), the active component of the pro-drug, mycophenolate mofetil. EC mycophenolate sodium was developed to reduce the upper-gastrointestinal (GI) effects of mycophenolate mofetil. Unlike oral mycophenolate mofetil, which releases MPA in the stomach, EC mycophenolate sodium releases MPA in the small intestine. The absolute bioavailability of EC mycophenolate sodium is 72%. MPA undergoes hepatic metabolism by glucuronyl transferase to the inactive mycophenolic acid glucuronide (MPAG), the predominant metabolite. The majority of an administered dose of EC mycophenolate sodium is found as MPAG in the urine. The mean terminal half-life of MPA ranges from 8 to 16 hours. EC mycophenolate sodium and mycophenolate mofetil have equivalent mechanisms of action and drug interaction profiles. Thus far, EC mycophenolate sodium has demonstrated similar efficacy and safety to mycophenolate mofetil in two Phase III clinical trials of adult renal transplant recipients. One study demonstrated improved health-related quality of life in patients switched from mycophenolate mofetil to EC mycophenolate sodium. Ongoing Phase IV studies are trying to further determine advantages of the EC product. CONCLUSION: EC mycophenolate sodium is a safe and effective immunosuppressive agent approved for use in the prevention of acute rejection after renal transplantation. It offers an excellent addition to the current armamentarium of immunosuppressive drugs for transplant immunosuppression.

Cyclosporine-sparing effects of daclizumab in renal allograft recipients.

PURPOSE: The safety and efficacy of reduced-dose cyclosporine in renal transplantation were studied. METHODS: Patients receiving their first renal transplant received daclizumab 1 mg/kg every 14 days for a total of five doses, mycophenolate mofetil 1 g twice daily, corticosteroids per the institution's routine protocol, and half of the institution's usual cyclosporine dosage. Trough cyclosporine concentrations targeted were half the customary goals, or 150-200 ng/mL for the first six months and 125-175 ng/mL for months 7-12. A retrospective control group included 15 matched patients who had received full-dose cyclosporine, mycophenolate mofetil, and corticosteroids without daclizumab induction therapy. RESULTS: Thirty patients were studied (15 in each group). At baseline, the control group had a significantly lower panel reactive antibody level (0.13%) than the treatment group (5.2%) (p = 0.01). Mean cyclosporine concentrations at 1, 6, and 12 months were significantly lower in the treatment group (p < 0.0001). No patient in either group had an acute rejection episode. All control patients had cyclosporine-associated adverse effects, compared with seven treatment-group patients (p = 0.0022). The treatment group had 19 infections, versus 29 in the control group (p = 0.39). Three study-group patients and eight control patients required a fine-needle aspiration or biopsy (p = 0.13). CONCLUSION: Among kidney transplant patients at low risk of acute rejection, those treated with daclizumab and low-dose cyclosporine had an identical rate of acute rejection (none) and fewer cyclosporine-associated adverse effects compared with patients in a retrospective control group who received full-dose cyclosporine without daclizumab.