PMID- 26799522
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR  - 20211203
IS  - 1875-9114 (Electronic)
IS  - 0277-0008 (Linking)
VI  - 36
IP  - 2
DP  - 2016 Feb
TI  - Time-Dependent and Immunosuppressive Drug-Associated Adverse Event Profiles in De 
      Novo Kidney Transplant Recipients Converted from Tacrolimus to Sirolimus 
      Regimens.
PG  - 152-65
LID - 10.1002/phar.1692 [doi]
AB  - STUDY OBJECTIVE: To 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. DESIGN: Prospective safety analysis of data from a 
      prospective, randomized, open-label, controlled study. PATIENTS: A 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 RESULTS: Both 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. CONCLUSION: SRL/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.
CI  - (c) 2016 Pharmacotherapy Publications, Inc.
FAU - Felix, Maria Julia Pereira
AU  - Felix MJ
AD  - Nephrology Division, Hospital do Rim, Universidade Federal de Sao Paulo, Sao 
      Paulo, Brazil.
FAU - Felipe, Claudia Rosso
AU  - Felipe CR
AD  - Nephrology Division, Hospital do Rim, Universidade Federal de Sao Paulo, Sao 
      Paulo, Brazil.
FAU - Tedesco-Silva, Helio
AU  - Tedesco-Silva H
AD  - Nephrology Division, Hospital do Rim, Universidade Federal de Sao Paulo, Sao 
      Paulo, Brazil.
FAU - Osmar Medina-Pestana, Jose
AU  - Osmar Medina-Pestana J
AD  - Nephrology Division, Hospital do Rim, Universidade Federal de Sao Paulo, Sao 
      Paulo, Brazil.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20160122
PL  - United States
TA  - Pharmacotherapy
JT  - Pharmacotherapy
JID - 8111305
RN  - 0 (Calcineurin Inhibitors)
RN  - 0 (Immunosuppressive Agents)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - HU9DX48N0T (Mycophenolic Acid)
RN  - VB0R961HZT (Prednisone)
RN  - W36ZG6FT64 (Sirolimus)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - Adult
MH  - Brazil/epidemiology
MH  - Calcineurin Inhibitors/adverse effects/therapeutic use
MH  - Drug Eruptions/*epidemiology/immunology/physiopathology
MH  - Drug Monitoring
MH  - Drug Therapy, Combination/adverse effects
MH  - Female
MH  - Gastrointestinal Diseases/*chemically 
      induced/epidemiology/immunology/physiopathology
MH  - Humans
MH  - Immunosuppressive Agents/*adverse effects/therapeutic use
MH  - Incidence
MH  - Kidney Failure, Chronic/immunology/metabolism/surgery
MH  - Kidney Transplantation/*adverse effects
MH  - Male
MH  - Middle Aged
MH  - Mycophenolic Acid/adverse effects/therapeutic use
MH  - Prednisone/adverse effects/therapeutic use
MH  - Severity of Illness Index
MH  - Sirolimus/*adverse effects/therapeutic use
MH  - Subcutaneous Tissue/*drug effects/immunology
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
MH  - Tacrolimus/adverse effects/therapeutic use
OTO - NOTNLM
OT  - adverse event
OT  - conversion
OT  - safety
OT  - sirolimus
OT  - tacrolimus
EDAT- 2016/01/23 06:00
MHDA- 2016/12/15 06:00
CRDT- 2016/01/23 06:00
PHST- 2016/01/23 06:00 [entrez]
PHST- 2016/01/23 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
AID - 10.1002/phar.1692 [doi]
PST - ppublish
SO  - Pharmacotherapy. 2016 Feb;36(2):152-65. doi: 10.1002/phar.1692. Epub 2016 Jan 22.