Time-Dependent and Immunosuppressive Drug-Associated Adverse Event Profiles in De Novo Kidney Transplant Recipients Converted from Tacrolimus to Sirolimus Regimens

Time-Dependent and Immunosuppressive Drug-Associated Adverse Event Profiles in De Novo Kidney Transplant Recipients Converted from Tacrolimus to Sirolimus Regimens

Author Felix, Maria Julia Pereira Autor UNIFESP Google Scholar
Felipe, Claudia Rosso Autor UNIFESP Google Scholar
Tedesco-Silva, Helio Autor UNIFESP Google Scholar
Medina-Pestana, Jose Osmar Autor UNIFESP Google Scholar
Abstract Study ObjectiveTo evaluate the safety and tolerability of immunosuppressive drugs used in a planned randomized conversion from a calcineurin inhibitor, tacrolimus, to a mammalian target of rapamycin inhibitor, sirolimus, in de novo kidney transplant recipients. DesignProspective safety analysis of data from a prospective, randomized, open-label, controlled study. PatientsA total of 119 adult kidney transplant recipients who received tacrolimus (TAC), mycophenolate sodium (MPS), and prednisone between February 2008 and May 2010; after 3 months of this regimen, 60 of these patients were randomized to conversion from TAC to sirolimus (SRL/MPS group), and 59 patients continued with the TAC regimen (TAC/MPS group). Measurements and Main ResultsBoth groups were followed for 24 months after transplantation for immunosuppressive regimen-associated and time-dependent occurrences of adverse events (AEs) and serious adverse events (SAEs). Before conversion from TAC to SRL, the cumulative incidence of AEs was 98%; 25% were SAEs. Gastrointestinal AEs (66%) and infections (58%) were the most frequent AEs. The incidences of TAC and MPS dose reductions due to AEs were 1.7% and 12%, respectively. After conversion, no significant differences were noted in the SRL/MPS group versus the TAC/MPS group in the cumulative incidences of AEs (100% vs 98%) and SAEs (27% vs 30%). The most common AEs were gastrointestinal (70% vs 54%, p=0.23) and infection (77% vs 73%, p=0.79) in the SRL/MPS versus TAC/MPS groups. The incidence of aphthous ulcer (28% vs 0%, p=< 0.01), sinusitis (10% vs 0%, p=0.01), dermatitis (15% vs 3%, p=0.03), and dyslipidemia (35% vs 14%, p=0.02) were higher in the SRL/MPS group compared with the TAC/MPS group. Cox proportion regression analysis showed a higher relative risk for gastrointestinal (hazard ratio [HR] 1.9, 95% confidence interval [CI] 1.2-3.01, p<0.05) and skin and subcutaneous tissue (HR 2.5, 95% CI 1.1-4.1, p<0.05) AEs in the SRL/MPS group compared with the TAC/MPS group. AE-related dose reductions occurred in 18.3% of patients receiving SRL and 3.3% of patients receiving TAC. MPS dose reductions due to AEs occurred in 11.7% of patients receiving SRL and 13.6% of patients receiving TAC. ConclusionSRL/MPS treatment was associated with a time-dependent higher incidence of gastrointestinal and skin and subcutaneous tissue AEs, which occurred mainly during the first 6 months after conversion from TAC/MPS. Although the treatments with SRL or TAC after 3 months of transplantation showed different safety profiles, both regimens demonstrated adequate tolerability, with low rates of early discontinuation related to AEs.
Keywords safety
conversion
sirolimus
tacrolimus
adverse event
xmlui.dri2xhtml.METS-1.0.item-coverage Hoboken
Language English
Date 2016
Published in Pharmacotherapy. Hoboken, v. 36, n. 2, p. 152-165, 2016.
ISSN 0277-0008 (Sherpa/Romeo, impact factor)
Publisher Wiley-Blackwell
Extent 152-165
Origin https://accpjournals.onlinelibrary.wiley.com/doi/10.1002/phar.1692
Access rights Closed access
Type Article
Web of Science ID WOS:000371145500005
URI https://repositorio.unifesp.br/handle/11600/58596

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