Immunosuppression with Tacrolimus Early after Orthotopic Heart Transplantation: A Comparison of Prograf and Advagraf
Background: We compared trough levels and clinical outcomes in patients who received Prograf or Advagraf (tacrolimus) de novo following heart transplantation surgery.
Methods: Eighty-two patients were included in this follow-up study. Biopsy results were controlled for the first 3 months after orthotopic heart transplantation. Trough levels were monitored for 4 weeks: daily during the first 7 days and once every week thereafter. The lengths of stay in the hospital and in intensive care were compared. The end point of the study was the 1-year mortality rate.
Results: We found significant differences between the groups for both biopsy results and trough levels. Trough levels differed for the first 5 days and then converged on the sixth day. The levels remained comparable throughout the monitoring period. The 1-year mortality rates for Prograf and Advagraf were 20% and 15%, respectively.
Conclusions: Trough levels were comparable after an adjustment period. There were no differences between the 2 groups in their 1-year mortality rates. These results suggest that Advagraf is a safe alternative to Prograf for patients who have undergone heart transplantation.
Comuzzi C, Lorenzin D, Rossetto A, et al. 2010. Safety of conversion from twice-daily tacrolimus (Prograf) to once-daily prolonged-release tacrolimus (Advagraf) in stable liver transplant recipients. Transplant Proc 42:1320-1.nCrespo M, Mir M, Marin M, et al. 2009. De novo kidney transplant recipients need higher doses of Advagraf compared with Prograf to get therapeutic levels. Transplant Proc 41:2115-7.nDew MA, Dabbs AD, Myaskovsky L, et al. 2009. Meta-analysis of medical regimen adherence outcomes in pediatric solid organ transplantation. Transplantation 88:736-46.nDobbels F, Berben L, De Geest S, et al; Transplant360 Task Force. 2010. The psychometric properties and practicability of self-report instruments to identify medication nonadherence in adult transplant patients: a systematic review. Transplantation 90:205-19.nEmre S, Genyk Y, Schluger LK, et al. 2000. Treatment of tacrolimus-related adverse effects by conversion to cyclosporine in liver transplant recipients. Transpl Int 13:73-8.nFirst MR. 2008. First clinical experience with the new once-daily formulation of tacrolimus. Ther Drug Monit 2:159-66.nFischer RG. 1980. Compliance-oriented prescribing: simplifying drug regimens. J Fam Pract 10:427-35.nKrämer BK, Charpentier B, Bäckman L, et al, for the Tacrolimus Prolonged Release Renal Study Group. 2010. Tacrolimus once daily (ADVAGRAF) versus twice daily (PROGRAF) in de novo renal transplantation: a randomized phase III study. Am J Transplant 10:2632-43.nKuypers DR, Naesens M, de Jonge H, Lerut E, Verbeke K, Vanrenterghem Y. 2010. Tacrolimus dose requirements and CYP3A5 genotype and the development of calcineurin inhibitor-associated nephrotoxicity in renal allograft recipients. Ther Drug Monit 32:394-404.nMarin-Gomez LM, Gomez-Bravo MA, Alamo-Martinez JA, et al. Evaluation of clinical safety of conversion to Advagraf therapy in liver transplant recipients: observational study. Transplant Proc 41:2184-6.nMeçule A, Poli L, Nofroni I, et al. 2010. Once daily tacrolimus formulation: monitoring of plasma levels, graft function, and cardiovascular risk factors. Transplant Proc 42:1317-9.nMeier M, Nitschke M, Weidtmann B, et al. 2006. Slowing the progression of chronic allograft nephropathy by conversion from cyclosporine to tacrolimus: a randomized controlled trial. Transplantation. 81:1035-40.nMorath C, Mueller M, Goldschmidt H, Schwenger V, Opelz G, Zeier M. 2004. Malignancy in renal transplantation. J Am Soc Nephrol 15:1582-8.nNankivell BJ, Borrows RJ, Fung CL, O'Connell PJ, Chapman JR, Allen RD. 2004. Calcineurin inhibitor nephrotoxicity: longitudinal assessment by protocol histology. Transplantation 78:557-65.nSommerer C, Hergesell O, Nahm AM, et al. 2002. Cyclosporin A toxicity of the renal allograft—a late complication and potentially reversible. Nephron 92:339-45.nStaatz CE, Goodman LK, Tett SE. 2010. Effect of CYP3A and ABCB1 single nucleotide polymorphisms on the pharmacokinetics and pharmacodynamics of calcineurin inhibitors: part II. Clin Pharmacokinet 2010;49:207-21.nTrune?ka P, Boillot O, Seehofer D, et al, for the Tacrolimus Prolonged Release Liver Study Group. 2010. Once-daily prolonged-release tacrolimus (ADVAGRAF) versus twice-daily tacrolimus (PROGRAF) in liver transplantation. Am J Transplant 10:2313-23.nvan Hooff JP, Alloway RR, Trune?ka P, Mourad M. 2011. Four-year experience with tacrolimus once-daily prolonged release in patients from phase II conversion and de novo kidney, liver, and heart studies. Clin Transplant 25:E1-12.nVincenti F, Jensik SC, Filo RS, Miller J, Pirsch J. 2002. A long-term comparison of tacrolimus (FK506) and cyclosporine in kidney transplantation: evidence for improved allograft survival at five years. Transplantation 73:775-82.n
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