Drugs

, Volume 66, Supplement 2, pp 1–8 | Cite as

Enteric-coated Mycophenolate Sodium (myfortic®): An Overview of Current and Future Use in Transplantation

Review Article

Abstract

Mycophenolic acid (MPA) exerts a potent immunosuppressive effect via a number of distinct mechanisms. Use of the mycophenolate mofetil (MMF) formulation is associated with significant efficacy benefits, but gastrointestinal adverse events frequently necessitate dose reductions, interruptions or discontinuation. Enteric-coated mycophenolate sodium (EC-MPS) delays the release of MPA until the small intestine. Pivotal trials in renal transplant patients have demonstrated equivalent efficacy and safety of EC-MPS and MMF. The myfortic® Prospective Multicenter Study (myPROMS) is an international clinical trial of EC-MPS, with 14 subprotocols and 1700 patients, in de novo and maintenance renal transplant patients receiving cyclosporine, with or without corticosteroids. Results from three myPROMS studies have confirmed that maintenance patients can be safely converted from MMF to EC-MPS. Evidence from the US and European myPROMS studies have shown that EC-MPS and cyclosporine provide good efficacy with a favorable safety profile (including gastrointestinal tolerability) regardless of whether higher or lower cyclosporine C2 targets are used. In terms of quality of life, interim results from the Patient Reported Outcomes in renal transplant patients with or without GastroIntestinal Symptoms (PROGIS) study suggest that the conversion of MMF-treated patients with gastrointestinal complaints to EC-MPS may be associated with a significant improvement in gastrointestinal burden, health-related quality of life and psychological well-being. However these data will need to be confirmed in a true controlled trial. Only limited data from clinical trials of EC-MPS in non-renal transplantation are currently available.

Keywords

Acute Rejection Mycophenolate Mofetil Renal Transplant Recipient Renal Transplant Patient Gastrointestinal Adverse Event 

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References

  1. 1.
    Allison AC, Eugui EM. Purine metabolism and immunosuppressive effects of mycophenolate mofetil (MMF). Clin Transplant 1996; 10: 77–84PubMedGoogle Scholar
  2. 2.
    Mele TS, Halloran PF. The use of mycophenolate mofetil in transplant recipients. Immunopharmacology 2000; 47: 215–45PubMedCrossRefGoogle Scholar
  3. 3.
    Barten MJ, Gummert JF, van Gelder T, et al. Flow cytometric quantitation of calcium-dependent and -independent mitogen-stimulation of T cell functions in whole blood: inhibition by immunosuppressive drugs in vitro. J Immunol Methods 2001; 253: 95–112PubMedCrossRefGoogle Scholar
  4. 4.
    Barten MJ, van Gelder T, Gummert JF, et al. Novel assays of multiple lymphocyte functions in whole blood measure: new mechanisms of action of mycophenolate mofetil in vivo. Transpl Immunol 2002; 10: 1–14PubMedCrossRefGoogle Scholar
  5. 5.
    European Mycophenolate Mofetil Cooperative Study Group. Placebo-controlled study of mycophenolate mofetil combined with cyclosporin and corticosteroids for prevention of acute rejection. Lancet 1995; 345: 1231–325Google Scholar
  6. 6.
    Sollinger HW, for the US Renal Transplant Mycophenolate Mofetil Study Group. Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients. Transplantation 1995; 60: 225–32PubMedCrossRefGoogle Scholar
  7. 7.
    The Tricontinental Mycophenolate Mofetil Renal Transplantation Study Group. A blinded, randomized clinical trial of mycophenolate mofetil for the prevention of acute rejection in cadaveric renal transplantation. Transplantation 1996; 61: 1029–37CrossRefGoogle Scholar
  8. 8.
    Meier-Kriesche HU, Steffen BJ, Hochberg AM, et al. Mycophenolate mofetil versus azathioprine therapy is associated with a significant protection against long-term renal allograft function deterioration. Transplantation 2003; 75: 1341–6PubMedCrossRefGoogle Scholar
  9. 9.
    Meier-Kriesche HU, Ojo AO, Leichtman AB, et al. Effect of mycophenolate mofetil on long-term outcomes in African American renal transplant recipients. J Am Soc Nephrol 2000; 11: 2366–70PubMedGoogle Scholar
  10. 10.
    Ojo AO, Meier-Kriesche HU, Hanson JA, et al. Mycophenolate mofetil reduces late renal allograft loss independent of acute rejection. Transplantation 2000; 69: 2405–9PubMedCrossRefGoogle Scholar
  11. 11.
    van Gelder T, Hilbrands LB, Vanrenterghem Y, et al. A randomized double-blind, multicenter plasma concentration controlled study of the safety and efficacy of oral mycophenolate mofetil for the prevention of acute rejection after kidney transplantation. Transplantation 1999; 27: 261–6CrossRefGoogle Scholar
  12. 12.
    Knoll GA, MacDonald I, Khan A, et al. Mycophenolate mofetil dose reduction and the risk of acute rejection after renal transplantation. J Am Soc Nephrol 2003; 14: 2381–6PubMedCrossRefGoogle Scholar
  13. 13.
    Pelletier RP, Akin B, Henry ML, et al. The impact of mycophenolate mofetil dosing patterns on clinical outcome after renal transplantation. Clin Transplant 2003; 17: 200–5PubMedCrossRefGoogle Scholar
  14. 14.
    Hardinger KL, Brennan DC, Lowell J, et al. Long-term outcome of gastrointestinal complications in renal transplant patients treated with mycophenolate mofetil. Transplant Int 2004; 17: 609–16CrossRefGoogle Scholar
  15. 15.
    Tierce JC, Porterfield-Baxa J, Petrilla AA, et al. Impact of mycophenolate mofetil (MMF)-related gastrointestinal complications and MMF dose alterations on transplant outcomes and healthcare costs in renal transplant recipients. Clin Transplant 2006; 19: 779–84CrossRefGoogle Scholar
  16. 16.
    Arms W, Breuer S, Choudhury GT, et al. Enteric-coated mycophenolate sodium delivers bioequivalent MPA exposure compared with mycophenolate mofetil. Clin Transplant 2005; 19: 199–206CrossRefGoogle Scholar
  17. 17.
    Hawthorne AB, Mahida YR, Cole AT, et al. Aspirin-induced gastric mucosal damage: prevention by enteric-coating and relation to prostaglandin synthesis. Br J Clin Pharmacol 1991; 32: 77–83PubMedCrossRefGoogle Scholar
  18. 18.
    Budde K, Glander P, Diekmann F, et al. Review of the immunosuppressant enteric-coated mycophenolate sodium. Exp Opin Pharmacother 2004; 5: 1333–45CrossRefGoogle Scholar
  19. 19.
    Novartis Pharma AG. myfortic® (mycophenolic acid) summary of product characteristics. 10 October 2003Google Scholar
  20. 20.
    Arns W, Gies M, Choi L, et al. Absorption characteristics of myfortic®, an enteric-coated formulation of mycophenolic acid. Int J Clin Pharmacol Therapeut 2006; in press.Google Scholar
  21. 21.
    Pescovitz MD, Conti D, Dunn J, et al. Intravenous mycophenolate mofetil: safety, tolerability and pharmacokinetics. Clin Transplant 2000; 14: 179–88PubMedCrossRefGoogle Scholar
  22. 22.
    Tedesco-Silva H, Bastien M-C, Choi L, et al. Mycophenolic acid metabolite profile in renal transplant patients receiving enteric-coated mycophenolate sodium or mycophenolate mofetil. Transplant Proc 2005; 37: 852–5PubMedCrossRefGoogle Scholar
  23. 23.
    Shaw LM, Holt DW, Oellerich M, et al. Current issues in therapeutic drug monitoring of mycophenolic acid: report of a roundtable discussion. Ther Drug Monit 2001; 23: 305–15PubMedCrossRefGoogle Scholar
  24. 24.
    Hale MD, Nicholls AJ, Bullingham RE, et al. The pharmacokinetic-pharmacodynamic relationship for mycophenolate mofetil in renal transplantation. Clin Pharmacol Ther 1998; 64: 672–83PubMedCrossRefGoogle Scholar
  25. 25.
    Mourad M, Malaise J, Chaib Eddour D, et al. Correlation of mycophenolic acid pharmacokinetic parameters with adverse events in kidney transplant patients treated with mycophenolate mofetil. Clin Chem 2001; 47: 88–94PubMedGoogle Scholar
  26. 26.
    Granger DK. Enteric-coated mycophenolate sodium: results of two pivotal global multicenter trials. Transplant Proc 2001; 33: 3241–4PubMedCrossRefGoogle Scholar
  27. 27.
    Salvadori M, Holzer H, de Mattos A, et al. Enteric-coated mycophenolate sodium is therapeutically equivalent to mycophenolate mofetil in de novo renal transplant patients. Am J Transplant 2004; 4: 231–6PubMedCrossRefGoogle Scholar
  28. 28.
    Budde K, Curtis J, Knoll G, et al. Enteric-coated mycophenolate sodium can be safely administered in maintenance renal transplant patients: results of a 1-year study. Am J Transplant 2004; 4: 237–43PubMedCrossRefGoogle Scholar
  29. 29.
    Budde K, Knoll G, Curtis J, et al. Safety and efficacy after conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium: results of a 1-year extension study. Transplant Proc 2005; 37: 912–5PubMedCrossRefGoogle Scholar
  30. 30.
    Kumar M, Chan L, Oppenheimer F, et al. on behalf of the ERL 301 and 302 study groups. Experience with myfortic® (EC-MPS) in elderly de novo and maintenance renal transplant patients. J Am Soc Nephrol 2005; 16: 823AGoogle Scholar
  31. 31.
    Chan L, Arns W, Knoll G, on behalf of the ERL 301 and 302 study groups. Myfortic® (enteric coated mycophenolate sodium, EC-MPS) is safe alternative to mycophenolate acid therapy in de novo and maintenance diabetic kidney transplant patients. J Am Soc Nephrol 2005; 16: 239AGoogle Scholar
  32. 32.
    Curtis J, Weir M, on behalf of ERL 302 study group. Experience with enteric coated mycophenolate sodium (EC-MPS, myfortic®) within African-American kidney transplant patients. J Am Soc Nephrol 2005; 16: 237AGoogle Scholar
  33. 33.
    Sollinger H, Tomlanovich S, Margreiter R, on behalf of the ERL 301 study group. Safety of myfortic® (enteric-coated mycophenolate sodium, EC-MPS) when administered in combination with induction treatment in renal transplantation. J Am Soc Nephrol 2005; 16: 828AGoogle Scholar
  34. 34.
    Abbud-Filho M, Giron F, Hernandez E, et al. Stable renal transplant recipients can be safely converted from MMF to enteric-coated mycophenolate sodium tablets: Interim results of a multicenter Latin American study. Transplant Proc 2004; 36: 1647–9PubMedCrossRefGoogle Scholar
  35. 35.
    Massari P, Duro-Garcia V, Girón F, et al. Safety assessment of the conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in stable renal transplant patients. Transplant Proc 2005; 37: 916–9PubMedCrossRefGoogle Scholar
  36. 36.
    Nashan B, Ivens K, Suwelack B, et al. Conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in maintenance renal transplant patients: preliminary results from the myfortic® prospective multicenter study. Transplant Proc 2004; 36: 521S–3SPubMedCrossRefGoogle Scholar
  37. 37.
    David-Neto E, Turconi A, Giron F, et al. A study about the safety and tolerability of the conversion to enteric-coated mycophenolate sodium from mycophenolate mofetil in stable pediatric renal transplant recipients [Abstract 1517]. Am J Transplant 2004; 4 (Suppl 8): 575Google Scholar
  38. 38.
    Kamar N, Garrigue V, Karras A, et al. Impact of early or delayed cyclosporine on delayed graft function in renal transplant recipients. A randomized multicenter study. American Journal Transplantation 2006; 6: 1042–8CrossRefGoogle Scholar
  39. 39.
    Cibrik DM, Meier-Kriesche H-H, Bresnahan B, et al. Renal function with cyclosporine C2 monitoring, enteric-coated mycophenolate sodium and basiliximab: a 12 month randomized trial in renal transplant recipients. Transplantation 2006 (in press)Google Scholar
  40. 40.
    Budde K, Bosmans J-L, Zeier M, et al. Safety and efficacy of reduced or full dose of cyclosporine (Neoral1) incombination with mycophenolate sodium (myfortic®), basiliximab (Simulect1), and steroids in de novo kidney transplant recipients. Transplantation 2004; 78 (Suppl 2): 83CrossRefGoogle Scholar
  41. 41.
    Chan L, Mulgaonkar S, Walker R, et al. Patient-reported gastrointestinal symptom burden and health-related quality of life following conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium. Transplantation 2006; 81: 1290–7PubMedCrossRefGoogle Scholar
  42. 42.
    Kleinman L, Faull R, Walker R, et al. Gastrointestinal-specific patient-reported outcome instruments differentiate between renal transplant patients with or without GI complications. Transplant Proc 2005; 37: 846–9PubMedCrossRefGoogle Scholar
  43. 43.
    Baryalei M, Zenker D, Pieske B, et al. Renal function and safety of heart transplant recipients switched to mycophenolate mofetil and low-dose cyclosporine. Transplant Proc 2003; 35: 1539–42PubMedCrossRefGoogle Scholar
  44. 44.
    Cantarovich M, Tzimas GN, Barkun J, et al. Efficacy of mycophenolate mofetil combined with very low-dose cyclosporine microemulsion in long-term liver transplant patients with renal dysfunction. Transplantation 2003; 76: 98–102PubMedCrossRefGoogle Scholar
  45. 45.
    Lama R, Santos F, Algar FJ, et al. Lung with tacrolimus and mycophenolate mofetil: a review. Transplant Proc 2003; 35: 1968–73PubMedCrossRefGoogle Scholar
  46. 46.
    Moreno JM, Rubio E, Gomez A, et al. Effectiveness and safety of mycophenolate mofetil as monotherapy in liver transplantation. Transplant Proc 2003; 35: 1874–6PubMedCrossRefGoogle Scholar
  47. 47.
    Kobashigawa JA, Renlund DG, Gerosa G, et al. Similar efficacy and safety of enteric-coated mycophenolate sodium (EC-MPS, myfortic®) compared with mycophenolate mofetil (MMF) in de novo heart transplant recipients: results of a 12-month, single-blind, randomized, parallel-group, multicenter study. J Heart Lung Transplant 2006; 25: 935–41PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  1. 1.UIC Transplant CenterUniversity of Illinois at ChicagoChicagoUSA

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