Efficacy and Safety of Elective Conversion From Sotrastaurin (STN) to Tacrolimus (TAC) or Mycophenolate (MPS) in Stable Kidney Transplant Recipients. Issue 3 (June 2016)

• Record Type: Journal Article
• Authors: Hannun, Pedro; Felipe, Claudia; Ferreira, Alexandra; Sandes-Freitas, Tainá; Cristelli, Marina; Aguiar, Wilson; Franco, Marcello; Campos, Erika; Gerbase de Lima, Maria; Tedesco-Silva, Hélio; Medina-Pestana, José
• Is Part Of: Therapeutic drug monitoring. Volume 38:Issue 3(2016:Jun.)
• Publication Date: 2016-06
• Subjects: sotrastaurin -- tacrolimus -- everolimus -- mycophenolate -- late immunosuppression conversion -- kidney transplant; Pharmacokinetics -- Periodicals; Patient monitoring -- Periodicals; Drugs -- Analysis -- Periodicals; Body fluids -- Analysis -- Periodicals; Drug Therapy -- Periodicals; Monitoring, Physiologic -- Periodicals; Pharmacology -- Periodicals; 615.7
• DOI: 10.1097/FTD.0000000000000292
• Languages: English
• ISSNs: 0163-4356

Abstract

Abstract : Background: This study aimed to evaluate the efficacy and safety outcomes of conversion strategies in stable kidney transplant recipients after premature termination of the sotrastaurin (STN) development program. Methods: This is an exploratory and prospective study, including 38 stable renal transplant recipients. Tacrolimus (TAC) group [STN → mycophenolate sodium (MPS)] consisted of 9 patients receiving TAC, STN, and prednisone that were converted from STN to MPS. Everolimus (EVR) group (STN → TAC) consisted of 29 patients receiving EVR, STN, and prednisone that were converted from STN to TAC. Results: In TAC (STN → MPS) group, dose-adjusted TAC concentrations decreased from baseline to first week (2.3 ± 1.1 versus 1.5 ± 1.0 ng·mL −1 ·mg −1, P < 0.05). Two patients experienced a first acute rejection episode. Conversion to MPS was associated with a higher incidence of adverse events. In EVR (STN → TAC) group, dose-adjusted EVR concentrations decreased from baseline to first week (3.6 ± 2.3 ng·mL −1 ·mg −1 versus 1.9 ± 0.8 ng·mL −1 ·mg −1, P < 0.01). The proportion of patients with donor-specific antibodies was lower in TAC (STN → MPS) (11%) compared to EVR (STN → TAC) (31%) before conversion. Conversion from STN to TAC was associated with a reduction in estimated glomerular filtration rate (69.6 ± 16.9 versus 61.0 ± 18.8 mL·min −1 ·1.73 m −2, P < 0.01) and a decreased proportion of patients with donor-specific antibodies (31% versus 14%) at 12 months. Conclusions: Conversion from TAC/STN to TAC/MPS or from EVR/STN to TAC/EVR was associated with significant pharmacokinetic changes in both TAC and EVR whole-blood trough concentrations due to known drug-to-drug interaction, which were associated with changes in efficacy and safety. Abstract : Supplemental Digital Content is Available in the Text.