Performance of modified‐release tacrolimus after conversion in liver transplant patients indicates potentially favorable outcomes in selected cohorts. Issue 1 (January 2015)

• Record Type: Journal Article
• Authors: Considine, Aisling; Tredger, J. Michael; Heneghan, Michael; Agarwal, Kosh; Samyn, Marianne; Heaton, Nigel D.; O'Grady, John G.; Aluvihare, Varuna R.
• Is Part Of: Liver transplantation. Volume 21:Issue 1(2015:Jan.)
• Page Start: 29
• Page End: 37
• Publication Date: 2015-01
• Subjects: Liver -- Transplantation -- Periodicals; Liver -- Diseases -- Periodicals; Liver Transplantation -- Periodicals; Foie -- Greffe -- Périodiques; 617.5560592
• DOI: 10.1002/lt.24022
• Languages: English
• ISSNs: 1527-6465

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Clinical outcomes, dose changes, and dose‐equalized tacrolimus concentrations were examined sequentially in 129 liver transplantation (LT) recipients after successful conversion to once daily modified‐release tacrolimus either early (within 1 month) or late (>1 month) after LT. The data were compared with data for a group of 60 patients maintained on twice daily conventional‐release tacrolimus. Formulation‐ and time‐dependent changes in dose requirements for once and twice daily tacrolimus differed after transplantation. A 1.7‐fold initial increase in the median daily dose was required to achieve target tacrolimus concentrations in the early‐conversion cohort (P = 0.006), whereas a 1.25‐fold increase was required for those converted later (P = 0.013 and P < 0.001 for the difference). In the subsequent 2 months, the median daily dose fell by 20% in the early‐conversion cohort, remained stable for the late‐conversion cohort, but rose by 33% with conventional therapy. Lower median dose‐equalized concentrations persisted for up to 3 months after the conversion to modified‐release therapy. Sex, ethnicity, and the underlying liver disease did not significantly affect these variables. The frequency of treated biopsy‐proven acute rejection episodes fell approximately 4‐fold after the conversion to modified‐release tacrolimus, most notably in the late‐conversion cohort, which experienced a high incidence of rejection before conversion. Posttransplant increases in serum creatinine concentrations were smaller after the introduction of modified‐release tacrolimus in the late‐conversion group (0.7 versus 4 mg/mL for twice daily tacrolimus over 6 months). Reduced interpatient variability in tacrolimus concentrations was evident in the early‐conversion cohort versus the twice daily cohort. A decline in intrapatient variability accompanied the reduction in acute rejection in the late‐conversion cohort. Our data highlight potential benefits for the rejection rate and renal function on conversion to once daily modified‐release tacrolimus late after LT. <italic>Liver Transpl 21:29‐37, 2015</italic>. © 2014 AASLD.</p> </abstract>