Navegando por Palavras-chave "sirolimus"

Agora exibindo 1 - 18 de 18
  • Nenhuma Miniatura disponível
    Item
    Somente Metadadados
    Análise prospectiva do perfil de segurança do estudo de conversão planejada do regime imunossupressor com base no sirolimo introduzido 3 meses após transplante renal, em comparação com um regime contínuo com base no tacrolimo em pacientes com novo transpl
    (Universidade Federal de São Paulo (UNIFESP), 2016-06-30) Felix, Maria Julia Pereira [UNIFESP]; Silva Junior, Helio Tedesco Silva Junior [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The safety and tolerability of immunosuppressive regimens derive from complex interactions of factors including known drug-related off-target adverse events, drug doses/concentrations and combinations, demography and time after transplantation. This study investigated regimen-associated and time-dependent incidences of adverse events (AE) and serious adverse events (SAE) in kidney transplant recipients (KTR). This was a prospective study enrolling 119 low immunological risk KTR who received tacrolimus (TAC), mycophenolate sodium (MPS) and prednisone and were randomized at 3 months to be converted (n=60) or not (n=59) from TAC to SRL and followed till month 24. Before conversion, the cumulative incidence of AE was 98%, being 25% SAE. Gastrointestinal (66%) and Infection (58%) were the most frequent disorders. The incidences of TAC or MPS dose reductions due to AE were 1.7% and 12%, respectively. After conversion, the cumulative incidence of AE and SAE were 100% and 27% in the SRL group and 98% and 30% in the TAC group, respectively. The most common disorders were gastrointestinal (70% vs. 54% p=0.23) and infection (77% vs. 73%, p=0.79) in SRL and TAC, respectively. The incidence of aphthous ulcer (28 vs. 0%, p=0.00), 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 SRL compared to TAC. COX regression analysis showed higher relative risk for Gastrointestinal (HR: 1.9, 1.2?3.01 95 %CI, p=0.05) and Skin and Subcutaneous tissue (HR: 2.5, 1.1?4.1 95 %CI, p=0.02) in SRL compared to TAC. AE-related dose reduction occurred in 18% with SRL and in 3% with TAC while MPS dose reduction occurred in 12% of patients receiving SRL and in 10% in TAC. The incidence, type and severity of AE are associated with time after transplantation and the immunosuppression. Nevertheless, careful drug dose adjustments were associated with low rates of early treatment discontinuation.
  • Nenhuma Miniatura disponível
    Item
    Somente Metadadados
    Calcineurin Inhibitor Minimization in the Symphony Study: Observational Results 3 Years after Transplantation
    (Wiley-Blackwell, 2009-08-01) Ekberg, H.; Bernasconi, C.; Tedesco-Silva Junior, Hélio [UNIFESP]; Vitko, S.; Hugo, C.; Demirbas, A.; Reyes Acevedo, R.; Grinyo, J.; Frei, U.; Vanrenterghem, Y.; Daloze, P.; Halloran, P. F.; Lund Univ; F Hoffmann La Roche Ltd; Universidade Federal de São Paulo (UNIFESP); IKEM; FAU Erlangen Nurnberg; Akdeniz Univ; Hosp Miguel Hidalgo; Ciutat Univ Bellvitge; Charite Virchow Klinikum; Katholieke Univ Leuven; CHUM Montreal; Univ Alberta
    The Symphony study showed that at 1 year posttransplant, a regimen based on daclizumab induction, 2 g mycophenolate mofetil (MMF), low-dose tacrolimus and steroids resulted in better renal function and lower acute rejection and graft loss rates compared with three other regimens: two with low-doses of cyclosporine or sirolimus instead of tacrolimus and one with no induction and standard cyclosporine dosage. This is an observational follow-up for 2 additional years with the same endpoints as the core study. Overall, 958 patients participated in the follow-up. During the study, many patients changed their immunosuppressive regimen (e.g. switched from sirolimus to tacrolimus), but the vast majority (95%) remained on MMF. During the follow-up, renal function remained stable (mean change: -0.6 ml/min), and rates of death, graft loss and acute rejection were low (all about 1% per year). the MMF and low-dose tacrolimus arm continued to have the highest GFR (68.6 +/- 23.8 ml/min vs. 65.9 +/- 26.2 ml/min in the standard-dose cyclosporine, 64.0 +/- 23.1 ml/min in the low-dose cyclosporine and 65.3 +/- 26.2 ml/min in the low-dose sirolimus arm), but the difference with the other arms was not significant (p = 0.17 in an overall test and 0.077, 0.039 and 0.11, respectively, in pair-wise tests). the MMF and low-dose tacrolimus arm also had the highest graft survival rate, but with reduced differences between groups over time, and the least acute rejection rate. in the Symphony study, the largest ever prospective study in de novo kidney transplantation, over 3 years, daclizumab induction, MMF, steroids and low-dose tacrolimus proved highly efficacious, without the negative effects on renal function commonly reported for standard CNI regimens.
  • Nenhuma Miniatura disponível
    Item
    Somente Metadadados
    Concentration-controlled use of sirolimus associated with reduced exposure of cyclosporine in black recipients of primarily living renal allograft donors: 12-month results
    (Blackwell Publishing, 2005-10-01) Ferreira, A. N.; Machado, P. G.; Felipe, C. R.; Motegi, S. A.; Hosaka, B. H.; Tanaka, M. K.; Kamura, L. A.; Park, S. I.; Garcia, R.; Franco, M.; Alfieri, F.; Casarini, D. E.; Tedesco-Silva, H.; Medina-Pestana, J. O.; Universidade Federal de São Paulo (UNIFESP); Labs Wyeth Whitehall
    Aim: This study was designed to identify optimal therapeutic sirolimus (SRL) concentrations in black kidney transplant recipients on reduced cyclosporine (CsA) exposure and prednisone.Methods: Seventy patients (64 living/six deceased) received CsA (8-10 mg/kg/d), prednisone, and 15 mg loading dose followed by 5-mg fixed doses of SRL till day 7 when they were randomized to maintain SRL trough concentrations (high-performance liquid chromatography) of 8-12 (GI = 34) or 15-20 (GII = 36) ng/mL.Results: Mean CsA concentrations were 109 +/- 53 vs. 89 +/- 41 ng/mL and 75 +/- 54 vs. 60 +/- 35 ng/mL (ns) at 2 and 6 months. Accordingly, mean SRL trough concentrations were 12.4 +/- 6.1 vs. 20.0 +/- 9.5 ng/mL (p < 0.001) and 10.8 +/- 5.8 vs. 18.0 +/- 6.1 ng/mL (p < 0.001). the incidence of biopsy-proven acute rejection [13% (GI: 18% vs. GII: 8%, ns)], graft loss or death was 16% (GI: 21% vs. GII: 11%, ns]. There were no deaths and three graft losses (GI = 1; GII = 2). Creatinine clearance was higher in GI (64.5 +/- 17 vs. 54.4 +/- 14.7 mL/min, p = 0.011). the incidence of post-transplant diabetes mellitus was 13% and no CMV disease was observed.Conclusion: in black recipients of primarily living renal allograft donors reduced CsA exposure and SRL concentration-controlled regimens produced low incidences of acute rejection, post-transplant diabetes mellitus and CMV disease, with no significant impairment in graft function.
  • Nenhuma Miniatura disponível
    Item
    Somente Metadadados
    Cyclosporine and sirolimus pharmacokinetics and drug-to-drug interactions in kidney transplant recipients
    (Wiley-Blackwell, 2009-10-01) Felipe, Claudia R. [UNIFESP]; Park, Sung-In [UNIFESP]; Pinheiro-Machado, Paula G. [UNIFESP]; Garcia, Riberto [UNIFESP]; Casarini, Dulce E. [UNIFESP]; Moreira, Silvia [UNIFESP]; Tedesco-Silva, Helio [UNIFESP]; Medina-Pestana, Jose O. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    This study was conducted to evaluate the pharmacokinetics (pk) and drug interactions between cyclosporine (CsA) and sirolimus (SRL) in kidney transplant recipients. the morning (a.m.) and evening (p.m.) pk of CsA (4-5 mg/kg/dose) and SRL (2 mg, n = 20; 5 mg, n = 33) were evaluated on day 7 (n = 53). CsA showed circadian variation when comparing a.m. and p.m. administration [AUC: 8066 vs. 6699, P < 0.001 (CI 970.9; 1763.6); C0: 272 vs. 245, P = 0.007 (CI 7.5; 46.1)]. SRL showed dose-proportional pk. Significant and drug-to-drug concentration-dependent pk interactions were observed within a narrow concentration range for both drugs. A fivefold increase in SRL AUC (from a mean of 130 to 538 ng h/mL) was associated with a 25% increase in mean a.m. CsA AUC [7021 to 8811 ng h/mL, P = 0.037, CI (-3461.2; -118.9)] and with a 42% increase in mean p.m. CsA AUC [5386-7639, P = 0.024, CI (-4164.4; -340.7)]. A twofold increase in a.m. CsA AUC (from 5860 to 10 974 ng h/mL) was associated with a 70% increase in mean SRL AUC [223 to 380 ng h/mL, P = 0.0026, CI (-291.7; -22.8)]. A twofold increase in p.m. CsA AUC (from 4573 to 9692 ng h/mL) was associated with a 63% increase in mean SRL AUC [246 to 400 ng h/mL, P = 0.032, CI (-290.7; -16.6)]. CSA shows circadian pk regardless of sirolimus dose or blood concentration. Significant drug-to-drug interactions occur within narrow blood drug concentrations. the magnitude of the effect of CsA on SRL blood concentration is higher than that of SRL on CsA blood concentrations. These findings emphasize the need for therapeutic drug monitoring using this drug combination.
  • Nenhuma Miniatura disponível
    Item
    Somente Metadadados
    Decreased Cytomegalovirus infection after antilymphocyte therapy in sirolimus-treated renal transplant patients
    (Elsevier B.V., 2005-01-01) Ozaki, K. S.; Camara, NOS; Galante, N. Z.; Camargo, LFA; Pacheco-Silva, A.; Universidade Federal de São Paulo (UNIFESP)
    Cytomegalovirus (CMV) infection is highly prevalent in transplant patients, especially in those submitted to a more intense immunosuppression. We monitored CMV infection in 34 patients during 60 days after antilymphocyte therapy without CMV prophylaxis. Six patients received sirolimus and 28 received no sirolimus as immunosuppression. During 60 days, of follow-up time, 24/28 (86%) patients who did not use sirolimus developed CMV infection at a mean time of 32.43 +/- 13.61 days after antilymphocyte treatment. in contrast, no patient on sirolimus had CMV infection during the same follow-up (p<0.001). During a further 4-month follow-up, six patients on sirolimus-free therapy had recurrence of CMV 46.5 +/- 18.5 days after them first episode. During this same period, one patient receiving sirolimus had one positive cell for CMV antigenemia, 169 days, after antilymphocyte therapy. in conclusion, the use of sirolimus significantly reduced the incidence of CMV infection in patients treated with antilymphocyte antibodies. (C) 2004 Elsevier B.V. All rights reserved.
  • Imagem de Miniatura
    Item
    Acesso aberto (Open Access)
    Eficácia, tolerabilidade e segurança do uso do sirolimo após o transplante renal
    (Sociedade Brasileira de Nefrologia, 2009-12-01) Oliveira, Nagilla Ione de [UNIFESP]; Harada, Kelly Miyuki [UNIFESP]; Spinelli, Glaucio Amaral [UNIFESP]; Park, Sung In [UNIFESP]; Sampaio, Edison Luiz Mandia [UNIFESP]; Felipe, Claudia Rosso [UNIFESP]; Tedesco-Silva Junior, Hélio [UNIFESP]; Pestana, Jose Osmar Medina [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    INTRODUCTION: Sirolimus (SRL) is an immunosuppressive drug with confirmed efficacy and safety profile in the prophylaxis of acute rejection after renal transplantation. OBJECTIVES: To assess the efficacy, safety, and tolerability of SRL and prednisone in combination with cyclosporine (CSA) or tacrolimus (TAC) after renal transplantation. METHODS: Retrospective study of 332 renal transplant recipients from 1999 to 2006. Primary outcome included treatment failure, defined as the cumulative incidence of biopsy-proven acute rejection, graft loss, death, or SRL discontinuation. RESULTS: Living donors were the primary source of kidneys (92%). Regarding the recipients, mean age was 37 years, 65% were males, 46% were white, and the prevalence of diabetes was 6%. Sirolimus was combined with CSA and TAC in 70.8% and 29.2% of patients, respectively. Treatment failure rates at the first and fifth year of transplantation were 22.2% and 47.8%, respectively, without difference between the groups receiving CSA and TAC. At five years, the survival rates were as follows: patient's, 92.8%; graft's, 86.1%; deathcensored graft's, 92.7%; and free from biopsy-proven acute rejection, 82.2%. Treatment with SRL was discontinued in 27.1% of the patients, due to adverse effects (22.9%) and inefficacy (3.3%). The main reasons for SRL discontinuation were as follows: dyslipidemia (6%); graft dysfunction (5.2%); proteinuria (4.5%); infection (1.5%); delayed wound healing (1.2%); and anemia (0.9%). CONCLUSION: In this cohort of patients, SRL efficacy and safety were similar when combined with either CSA or TAC. Oral tolerability was adequate, considering the relatively low SRL discontinuation rate.
  • Imagem de Miniatura
    Item
    Acesso aberto (Open Access)
    Fundamento e desenho do teste randomizado PAINT
    (Sociedade Brasileira de Cardiologia - SBC, 2009-12-01) Lemos, Pedro A.; Moulin, Bruno; Perin, Marco A.; Oliveira, Ludmilla A.r.r.; Arruda, J. Airton; Lima, Valter C. [UNIFESP]; Lima, Antonio A.g.; Caramori, Paulo R.a.; Medeiros, Cesar R.; Barbosa, Mauricio R.; Brito Jr, Fabio S.; Ribeiro, Expedito E.; Martinez, Eulógio E.; Universidade de São Paulo (USP); Hospital Universitário Cassiano Antonio de Moraes; Hospital Santa Marcelina; Natal Hospital Center; Hospital Meridional; Universidade Federal de São Paulo (UNIFESP); Hospital Universitário Walter Cantidio; PUC-RS Hospital São Lucas; Rede D'Or de Hospitais; Hospital Biocor; São Camilo Hospital
    BACKGROUND: We describe the rationale and design for the PercutAneous INTervention with biodegradable-polymer based paclitaxel-eluting or sirolimus-eluting versus bare stents for de novo coronary lesions - PAINT trial. OBJECTIVES: To evaluate two novel formulations of paclitaxel-eluting stent and the sirolimus-eluting stent against a stent with the same metallic structure but without polymer coating or drug elution. METHODS: The PAINT is a multicenter 3-arm randomized trial, conducted in Brazilian tertiary institutions, which included 275 patients allocated for the InfinniumR paclitaxel-eluting stent, the SupralimusR sirolimus-eluting stent or the Milennium MatrixR bare metal stent in a 2:2:1 ratio. Patients had de novo coronary lesions in native vessels with a diameter between 2.5 and 3.5 mm, amenable for treatment with a single stent of 29 mm or less in length. The primary objetive was to compare the in-stent late loss at 9 months of both paclitaxel- and sirolimus-eluting versus the late loss of control bare metal stents. Important secondary objectives included the comparison in outcomes between sirolimus and paclitaxel stents, as well as the analysis of the incidence of major adverse cardiac events. RESULTS AND CONCLUSIONS: The PAINT trial had a unique design that allowed for the evaluation of the safety and efficacy profiles of two novel drug-eluting stent formulations, with a biodegradable-polymer carrier and releasing paclitaxel or sirolimus, which were compared against a bare metal stent (primary objective). As the drug-eluting stents differed by the drug, but were identical otherwise, the trial also allowed the comparison of the anti-restenosis effects of sirolimus versus paclitaxel (secondary objective).
  • Imagem de Miniatura
    Item
    Acesso aberto (Open Access)
    Impacto dos stents e do sirolimus por via oral na vasomotilidade coronariana dependente e independente do endotelio
    (Sociedade Brasileira de Cardiologia - SBC, 2012-04-01) Fernandes, Rósley Weber Alvarenga [UNIFESP]; Dantas, João Miguel [UNIFESP]; Oliveira, Dinaldo Cavalcanti [UNIFESP]; Bezerra, Hiram Grando [UNIFESP]; Brito Jr., Fabio Sandoli [UNIFESP]; Lima, Valter C. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    BACKGROUND: There is no consensus regarding the impact of stenting on long-term endothelial function. There have been reports of increased endothelial dysfunction with sirolimus-eluting stents as compared to bare metal stenting (BMS). OBJECTIVE: This study aims to assess the impact of BMS and the effect of oral sirolimus on endothelial function. METHODS: Forty-five patients were randomized into three groups: BMS + high-dose oral sirolimus (initial dose of 15 mg, followed by 6 mg/day for four weeks); BMS + low-dose sirolimus (6 mg followed by 2 mg daily for four weeks); and BMS without sirolimus. Changes in vasoconstriction or vasodilation in a 15 mm segment starting at the distal stent end in response to acetylcholine and nitroglycerin were assessed by quantitative angiography. RESULTS: The groups had similar angiographic characteristics. The percent variation in diameter in response to acetylcholine was similar in all groups at the two time points (p = 0.469). Four hours after stenting, the target segment presented an endothelial dysfunction that was maintained after eight months in all groups. In all groups, endothelium-independent vasomotion in response to nitroglycerin was similar at four hours and eight months, with increased target segment diameter after nitroglycerin infusion (p = 0.001). CONCLUSION: The endothelial dysfunction was similarly present at the 15 mm segment distal to the treated segment, at 4 hours and 8 months after stenting. Sirolimus administered orally during 4 weeks to prevent restenosis did not affect the status of endothelium-dependent and independent vasomotion.
  • Nenhuma Miniatura disponível
    Item
    Somente Metadadados
    Long-Term Follow-Up of De Novo Use of mTOR and Calcineurin Inhibitors After Kidney Transplantation
    (Lippincott Williams & Wilkins, 2016) de Paula, Mayara Ivani [UNIFESP]; Medina-Pestana, Jose Osmar [UNIFESP]; Ferreira, Alexandra Nicolau [UNIFESP]; Cristelli, Marina Pontello [UNIFESP]; Franco, Marcello Fabiano [UNIFESP]; Aguiar, Wilson Ferreira [UNIFESP]; Tedesco-Silva, Helio [UNIFESP]; Felipe, Claudia Rosso [UNIFESP]
    Background:Long-term efficacy and safety of de novo use of the mammalian target of rapamycin inhibitors (mTORi) have been evaluated primarily using registry data.Methods:This was a pooled retrospective analysis of data obtained from 10 prospective randomized trials in de novo kidney transplant recipients (n = 581) receiving calcineurin inhibitors (CNIs) combined with sirolimus (n = 329), everolimus (n = 128), or antimetabolites (n = 124).Results:There were no differences in patient (84.5 versus 80.9 versus 89.7%, P = 0.996), graft (65.4 versus 59.5 versus 73.1%, P = 0.868), and biopsy-confirmed acute rejection-free (78.1 versus 77.3 versus 79.0%, P = 0.976) survivals, respectively. The incidence of cytomegalovirus infection was lower (6 versus 3 versus 11%, P = 0.024) but treatment discontinuation was higher among patients receiving mTORi (66.0 versus 47.7 versus 31.5%, P < 0.001), respectively. At 5 years, median estimated glomerular filtration rate (49.6 versus 43.9 versus 53.2 mL/min, P = 0.006) was lower and the proportion of patients with proteinuria (53 versus 40 versus 23%, P < 0.001) was higher among patients receiving mTORi, respectively.Conclusions:The efficacy of de novo use of mTORi is comparable with that of antimetabolites in kidney transplant recipients receiving calcineurin inhibitor. Apart from the lower cytomegalovirus infection rate, the safety profile is unfavorable, showing higher treatment discontinuation rates and higher incidence of proteinuria.
  • Nenhuma Miniatura disponível
    Item
    Somente Metadadados
    Long-Term Follow-Up of De Novo Use of mTOR and Calcineurin Inhibitors After Kidney Transplantation
    (Lippincott Williams & Wilkins, 2016) de Paula, Mayara Ivani [UNIFESP]; Medina-Pestana, Jose Osmar [UNIFESP]; Ferreira, Alexandra Nicolau [UNIFESP]; Cristelli, Marina Pontello [UNIFESP]; Franco, Marcello Fabiano [UNIFESP]; Aguiar, Wilson Ferreira [UNIFESP]; Tedesco-Silva, Helio [UNIFESP]; Felipe, Claudia Rosso [UNIFESP]
    Background:Long-term efficacy and safety of de novo use of the mammalian target of rapamycin inhibitors (mTORi) have been evaluated primarily using registry data.Methods:This was a pooled retrospective analysis of data obtained from 10 prospective randomized trials in de novo kidney transplant recipients (n = 581) receiving calcineurin inhibitors (CNIs) combined with sirolimus (n = 329), everolimus (n = 128), or antimetabolites (n = 124).Results:There were no differences in patient (84.5 versus 80.9 versus 89.7%, P = 0.996), graft (65.4 versus 59.5 versus 73.1%, P = 0.868), and biopsy-confirmed acute rejection-free (78.1 versus 77.3 versus 79.0%, P = 0.976) survivals, respectively. The incidence of cytomegalovirus infection was lower (6 versus 3 versus 11%, P = 0.024) but treatment discontinuation was higher among patients receiving mTORi (66.0 versus 47.7 versus 31.5%, P < 0.001), respectively. At 5 years, median estimated glomerular filtration rate (49.6 versus 43.9 versus 53.2 mL/min, P = 0.006) was lower and the proportion of patients with proteinuria (53 versus 40 versus 23%, P < 0.001) was higher among patients receiving mTORi, respectively.Conclusions:The efficacy of de novo use of mTORi is comparable with that of antimetabolites in kidney transplant recipients receiving calcineurin inhibitor. Apart from the lower cytomegalovirus infection rate, the safety profile is unfavorable, showing higher treatment discontinuation rates and higher incidence of proteinuria.
  • Nenhuma Miniatura disponível
    Item
    Somente Metadadados
    Mycophenolate mofetil vs. sirolimus in kidney transplant recipients receiving tacrolimus-based immunosuppressive regimen
    (Blackwell Publishing, 2008-03-01) Sampaio, Edison L. [UNIFESP]; Pinheiro-Machado, Paula G. [UNIFESP]; Garcia, Riberto [UNIFESP]; Felipe, Claudia R. [UNIFESP]; Park, Sung I. [UNIFESP]; Casarini, Dulce E. [UNIFESP]; Moreira, Silvia [UNIFESP]; Franco, Marcello F. [UNIFESP]; Tedesco-Silva, Helio [UNIFESP]; Medina-Pestana, Jose O. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Mycophenolate mofetil (MMF) and sirolimus (SRL) are effective immunosuppressive drugs with distinct safety profile.Methods: Kidney transplant recipients receiving tacrolimus (TAC)-based immunosuppressive regimen were randomized to receive fixed daily doses of MMF (2 g/d, n = 50) or SRL (one loading dose of 15 mg, 5 mg/d till day 7 and 2 mg/d thereafter, n = 50) without induction therapy.Results: No differences were observed in the incidence of the composite (biopsy-confirmed acute rejection, graft loss or death) end-point (18% vs. 16%, p = 1.000), biopsy confirmed acute rejection (12% vs. 14%, p = 1.000), one-yr patient (94% vs. 98%, p = 0.308), graft (92% vs. 98%, p = 0.168), and death-censored graft survival (98% vs. 100%, p = 0.317) comparing patients receiving MMF or SRL respectively. Patients receiving SRL showed worse safety outcomes, higher mean creatinine (1.6 +/- 0.5 mg/dL vs. 1.4 +/- 0.3 mg/dL, p = 0.007), higher proportion of patients with proteinuria (52.0% vs. 10.7%, p = 0.041), higher mean urinary protein concentrations (0.3 +/- 0.5 g/L vs. 0.1 +/- 0.2 g/L, p = 0.012), higher mean cholesterol concentration (217 mg/dL vs. 190 mg/dL, p = 0.030), and higher proportion of patients prematurely discontinued from randomized therapy (26% vs. 8%, p = 0.031).Conclusion: in patients receiving TAC, MMF produced similar efficacy but superior safety profile compared with SRL.
  • Nenhuma Miniatura disponível
    Item
    Somente Metadadados
    An open-label randomized trial of the safety and efficacy of sirolimus vs. azathioprine in living related renal allograft recipients receiving cyclosporine and prednisone combination
    (Blackwell Munksgaard, 2004-02-01) Machado, P. G.; Felipe, C. R.; Hanzawa, N. M.; Park, S. I.; Garcia, R.; Alfieri, F.; Franco, M.; Silva, H. T.; Medina-Pestana, J. O.; Universidade Federal de São Paulo (UNIFESP); Labs Wyeth Brasil
    Background: the ability of sirolimus (SRL), in combination with reduced exposure of cyclosporine, was investigated to prevent acute rejection and associated side effects.Methods: Between June 1999 and February 2000, 70 recipients of primary one-haplotype living-related donor renal allografts were randomized to receive SRL (2 mg/d) or azathioprine (AZA) (2 mg/kg/d) combined with cyclosporine and prednisone. the primary end-point was a composite of first occurrence of biopsy-confirmed acute rejection, graft loss, or death during the first 3 months after transplantation.Results: From week 4 to month 12, SRL patients received lower cyclosporine (week 4: 364 mg/d vs. 455 mg/d, p = 0.004; month 12: 195 mg/d vs. 255 mg/d, p = 0.038) doses and showed lower cyclosporine concentrations (week 4: 247 ng/mL vs. 309 ng/mL, p = 0.04; month 12: 143 ng/mL vs. 188 ng/mL, p = 0.045). Compared with AZA, SRL patients showed reduced 3-month primary end point (0% vs. 17.1%, p = 0.025), and reduced incidence of biopsy-confirmed acute rejection at 3 months (0% vs. 14.3%, p = 0.01) but not at 12 months (11.4% vs. 14.3%, NS). Mean creatinine at 12 months were not different (1.8 +/- 0.6 vs. 1.6 +/- 0.6, p = 0.23). Hyperlipidemia was the only adverse event more frequent among SRL patients (49% vs. 17%, p = 0.01). There were no differences in infections and no malignancies in both groups.Conclusions: the combination of 2 mg fixed doses of SRL, reduced cyclosporine exposure and prednisone was associated with a low incidence of acute rejection and did not result in significantly impaired graft function compared with patients receiving AZA, standard doses of cyclosporine and prednisone.
  • Nenhuma Miniatura disponível
    Item
    Somente Metadadados
    Planned Randomized Conversion From Tacrolimus to Sirolimus-Based Immunosuppressive Regimen in de Novo Kidney Transplant Recipients
    (Wiley-Blackwell, 2013-12-01) Tedesco-Silva Junior, Hélio [UNIFESP]; Felipe, Claudia Rosso [UNIFESP]; Garcia, V. D.; Neto, E. D.; Filho, M. A.; Contieri, F. L. C.; Carvalho, D. D. B. M. de; Pestana, Jose Osmar Medina [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Santa Casa de Misericordia; Universidade de São Paulo (USP); Inst Urol & Nefrol; Med Sch FAMERP HB FUNFARME; Hosp Univ Evangel Curitiba; Bonsucesso Gen Hosp
    Planned conversion from tacrolimus to sirolimus was evaluated in de novo kidney transplant recipients. in this multicenter, randomized, open-label study, 297 patients were initially treated with tacrolimus, mycophenolate sodium and prednisone. of the 283 patients reaching 3 months, 97 were converted to sirolimus (SRL), 107 were maintained on tacrolimus (TAC) and 79 were patients receiving TAC without criteria to undergo intervention at month 3 (TACex). the primary objective was to show superior estimated glomerular filtration rate (eGFR) in the SRL group at month 24. of the 258 patients who completed 24 months, 91 (94%) were in the SRL group, 101 (94%) in the TAC group and 66 (84%) in the TACex group. in the intention-to-treat population there were no differences in eGFR (66.225.3 vs. 70.7 +/- 25.1, p=0.817) or in the severity of chronic sclerosing lesions scores in 24-month protocol biopsies. Higher mean urinary protein-to-creatinine ratio (0.36 +/- 0.69 vs. 0.15 +/- 0.53, p=0.03) and higher incidence of treated acute rejection between months 3-24 (13.4% vs. 4.7%, p=0.047) were observed in SRL compared to TAC group. in this population planned conversion from TAC to SRL 3 months after kidney transplantation was not associated with improved renal function at 24 months.
  • Nenhuma Miniatura disponível
    Item
    Somente Metadadados
    Sirolimus quantification by high-performance liquid chromatography with ultraviolet detection
    (Blackwell Publishing Ltd, 2005-03-01) Andrade, Maria Claudina Camargo de [UNIFESP]; Di Marco, Giovana Seno [UNIFESP]; Felipe, Claudia Rosso [UNIFESP]; Alfieri, Fernando; Tedesco-Silva Junior, Hélio [UNIFESP]; Pestana, José Osmar Medina [UNIFESP]; Casarini, Dulce Elena [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Wyeth Ayerst Res
    The need to adapt optimal conditions of sirolimus blood level monitoring in laboratories led us to optimize an high-performance liquid chromatography-ultraviolet method and compare the elution performances using the mobile phase A, 68% MeOH/2% acetonitrile (ACN)/30% H2O and mobile phase B, 30% MeOH/42% ACN/28% H2O. Samples were assayed with 1-chlorobutane, redissolved in MeOH/water and injected onto a C-18 column at 50 degrees C. the assay achieved sensitivity of 2.5-150 ng/ml (CV = 10.6%) and recovery of 92-103.6%. the intra- and interassay precisions ranged from 3.3% to 13% and from 5.9% to 15% for quality controls of 7.5, 60 and 120 ng/ml. the mobile phase A was unable to elute and recover sirolimus and internal standard in the expected retention time and concentration. Under our working conditions, the assay was precise, accurate and sensible, stressing the importance of establishing for the best working conditions according to the staff and demands of the laboratory.
  • Nenhuma Miniatura disponível
    Item
    Somente Metadadados
    Tacrolimus pharmacokinetic drug interactions: effect of prednisone, mycophenolic acid or sirolimus
    (Wiley-Blackwell, 2009-02-01) Park, Sung-In [UNIFESP]; Felipe, Claudia R. [UNIFESP]; Pinheiro-Machado, Paula G. [UNIFESP]; Garcia, Riberto [UNIFESP]; Fernandes, Fernanda B. [UNIFESP]; Casarini, Dulce E. [UNIFESP]; Tedesco-Silva, Helio [UNIFESP]; Medina-Pestana, Jose O. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    This study was conducted to evaluate time-dependent pharmacokinetic changes and drug interactions over the first 6 months after transplantation in kidney transplant recipients receiving tacrolimus (TAC), prednisone (PRED) and mycophenolate mofetil (MMF) or sirolimus (SRL). Pharmacokinetic assessments were carried out at day 7 and months 1, 3, and 6 in kidney transplant recipients receiving TAC plus PRED with either MMF (2 g/day, n = 13) or SRL (15 mg loading dose, 5 mg for 7 days followed by 2 mg/day, n = 12). There were no differences in the main demographic characteristics or in mean PRED doses during the first 6 months after transplant. From day 7 to month 6, there was a 65% increase in TAC dose corrected exposure (dose corrected area under the curve; AUC) in patients receiving MMF (P = 0.005) and a 59% increase in TAC dose corrected exposure in patients receiving SRL (P = 0.008). From day 7 to month 6, there was a 72% increase in mycophenolate dose corrected exposure (P = 0.001) and a 65% increase in SRL dose corrected exposure (P = 0.008). TAC dose corrected exposure was 23% lower in patients receiving SRL compared with MMF (P = 0.012) on average over the study period. PRED dose reduction was associated with increase in TAC (in patients receiving SRL, P = 0.040) and mycophenolic acid (MPA) (P = 0.070) drug exposures. Tercile distribution of TAC drug exposure showed a positive correlation with mean SRL exposures (P = 0.016). Conversely, tercile distribution of SRL drug exposure showed a positive correlation with mean TAC exposures (P = 0.004). Time-dependent increases in TAC, MPA and SRL drug exposures occur up to 6 months after transplantation. Drug-to-drug interactions indicate that intense therapeutic drug monitoring is required to avoid under-or over-immunosuppression.
  • Nenhuma Miniatura disponível
    Item
    Somente Metadadados
    Time-Dependent and Immunosuppressive Drug-Associated Adverse Event Profiles in De Novo Kidney Transplant Recipients Converted from Tacrolimus to Sirolimus Regimens
    (Wiley-Blackwell, 2016) Felix, Maria Julia Pereira [UNIFESP]; Felipe, Claudia Rosso [UNIFESP]; Tedesco-Silva, Helio [UNIFESP]; Medina-Pestana, Jose Osmar [UNIFESP]
    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.
  • Nenhuma Miniatura disponível
    Item
    Somente Metadadados
    Time-Dependent and Immunosuppressive Drug-Associated Adverse Event Profiles in De Novo Kidney Transplant Recipients Converted from Tacrolimus to Sirolimus Regimens
    (Wiley-Blackwell, 2016) Felix, Maria Julia Pereira [UNIFESP]; Felipe, Claudia Rosso [UNIFESP]; Tedesco-Silva, Helio [UNIFESP]; Medina-Pestana, Jose Osmar [UNIFESP]
    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.
  • Nenhuma Miniatura disponível
    Item
    Somente Metadadados
    The use of sirolimus in ganciclovir-resistant cytomegalovirus infections in renal transplant recipients
    (Blackwell Publishing, 2007-09-01) Ozaki, Kikumi Suzete; Camara, Niels Olsen Saraiva; Nogueira, Eliana; Pereira, Mauricio Galvao; Granato, Celso; Melaragno, Claudio; Camargo, Luis Fernando Aranha; Pacheco-Silva, Alvaro; Universidade Federal de São Paulo (UNIFESP); Hosp Rim & Hipertensao; Hosp Israelita Albert Einstein
    Background: the widespread use of prophylactic ganciclovir and anti-lymphocyte/thymocyte therapies are associated with increased induction of ganciclovir-resistant cytomegalovirus (CMV) strains. the use of sirolimus has been associated with a lower incidence of CMV infection in transplant recipients. We questioned whether it could also be effective as a therapeutic treatment of resistant CMV infection.Methods: Patients with ganciclovir-resistant CMV infections determined clinically and by DNA sequencing analysis were enrolled. Antigenaemia and DNA sequencing were used to diagnosis and follow the mutations.Results: Nine transplant patients were given sirolimus plus mycophenolate mofetil (n = 4) or a calcineurin inhibitor (n = 5). Seven out of nine recipients were CMV IgG negative before transplantation. We observed a rapid decrease in antigenaemia levels, reaching zero in eight out of nine (88.9%) patients within a median of 20.3 +/- 10.1 d. Graft function remained stable and no patient presented acute rejection or recurrence of the CMV infection.Conclusions: This suggests that the use of sirolimus plus ganciclovir therapy could be useful in ganciclovir-resistant CMV infections.