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1.
Medicine (Baltimore) ; 98(48): e18150, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770256

RESUMO

The current research aimed to investigate the correlation between the effect of Wuzhi soft capsule (WZC) on FK506 concentration and CYP3A5 gene polymorphism in patients with membranous nephropathy (MN).Seventy-five patients with idiopathic MN were enrolled and divided according to the expression of CYP3A5 gene metabolic enzyme into group A (CP3A5 metabolic enzyme function expression types CYP3A5*1/*1 type and CYP3A5*1/*3 type), and group B (non-expression type CYP3A5*3/*3 type). All patients were given oral administration of tacrolimus capsule at the initial dose of 1 mg for twice a day 1 hour before breakfast and dinner. Afterwards, the oral administration of WZC was added at the dose of 0.5 g for 3 times a day within half an hour after 3 meals.The blood concentrations of FK506 in groups A and B were significantly higher than those before administration. Compared with that before administration, the FK506 blood concentration was increased by 3.051 ±â€Š0.774 ng/ml after adding the WZC. Besides, the blood concentrations of FK506 in group A were lower than those in group B before and after administration; meanwhile, the 24 hours total urine protein and the biochemical indexes in both groups displayed no statistically significant difference. Only 1 case of diarrhea was observed, which was relieved after the reduction of tacrolimus.Wuzhi soft capsule can significantly increase the blood concentration of FK506 in MN patients. Moreover, the CYP3A5 genotyping should be considered when WZC is used to increase the blood concentration of FK506.


Assuntos
Citocromo P-450 CYP3A/genética , Medicamentos de Ervas Chinesas , Glomerulonefrite Membranosa , Tacrolimo , Adulto , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/farmacocinética , Cápsulas , Sinergismo Farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacocinética , Feminino , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulonefrite Membranosa/genética , Glomerulonefrite Membranosa/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Farmacogenômicos , Polimorfismo Genético , Medicina de Precisão/métodos , Tacrolimo/administração & dosagem , Tacrolimo/farmacocinética
2.
Expert Rev Clin Pharmacol ; 12(11): 1047-1057, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31575290

RESUMO

Introduction: The clinical use of tacrolimus is characterized by many side effects which include neurotoxicity. In contrast, tacrolimus has also shown to have neuroregenerative properties. On a molecular level, the mechanisms of action could provide us more insight into understanding the neurobiological effects. The aim of this article is to review current evidence regarding the use of tacrolimus in peripheral nerve injuries.Areas covered: Available data on tacrolimus' indications were summarized and molecular mechanisms were elucidated to possibly understand the conflicting neurotoxic and neuroregenerative effects. The potential clinical applications of tacrolimus, as immunosuppressant and enhancer of nerve regeneration in peripheral nerve injuries, are discussed. Finally, concepts of delivery are explored.Expert opinion: It is unclear what the exact neurobiological effects of tacrolimus are. Besides its known calcineurin inhibiting properties, the mechanism of action of tacrolimus is mediated by its binding to FK506-binding protein-52, resulting in a bimodal dose response. Experimental models found that tacrolimus administration is preferred up to three days prior to or within 10 days post-nerve reconstruction. Moreover, the indication for the use of tacrolimus has been expanding to fields of dermatology, ophthalmology, orthopedic surgery and rheumatology to improve outcomes after various indications.


Assuntos
Regeneração Nervosa/efeitos dos fármacos , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Tacrolimo/administração & dosagem , Animais , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/efeitos adversos , Inibidores de Calcineurina/farmacologia , Esquema de Medicação , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/farmacologia , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/fisiopatologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Tacrolimo/efeitos adversos , Tacrolimo/farmacologia
3.
Ann Hematol ; 98(11): 2579-2591, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31628517

RESUMO

Umbilical cord blood transplantation (UCBT) is a curative treatment for hematological malignancies. However, appropriate prophylaxis against graft-versus-host disease (GVHD), aimed at obtaining rapid and stable engraftment and avoiding toxicity, remains controversial in UCBT. We retrospectively compared outcomes in 409 patients who received calcineurin inhibitors (CIs) plus conventional-dose methotrexate (conv-MTX/CIs, n = 77; methotrexate, 10 mg/m2 on day 1, 7 mg/m2 on days 3 and 6) with those who received CIs plus reduced-dose methotrexate (reduced-MTX/CIs, n = 209; methotrexate, 5 mg/m2 or 5 mg/body on days 1, 3, and 6) or CIs with mycophenolate mofetil (MMF/CIs, n = 123) for GVHD prophylaxis after UCBT. The cumulative incidence of neutrophil engraftment was significantly higher in the reduced-MTX/CI (82.3%) and MMF/CI (86.6%) groups than the conv-MTX/CI (71.4%) group (p = 0.014), although there were no differences in platelet recovery or infectious complications among the three groups. The incidence and severity of GVHD were comparable among the three groups, and there were no significant differences in transplantation-related mortality among the three groups. In conclusion, GVHD prophylaxis with reduced-dose methotrexate and MMF was closely associated with high incidence of neutrophil engraftment without an effect on the incidence and severity of GVHD, which was compared to GVHD prophylaxis with conventional-dose methotrexate.


Assuntos
Inibidores de Calcineurina/uso terapêutico , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro/prevenção & controle , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Ácido Micofenólico/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores de Calcineurina/administração & dosagem , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/terapia , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Incidência , /etiologia , Japão/epidemiologia , Estimativa de Kaplan-Meier , Contagem de Leucócitos , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Neutrófilos , Contagem de Plaquetas , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
4.
Expert Opin Drug Metab Toxicol ; 15(10): 803-811, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31595800

RESUMO

Introduction: Graft-versus-host disease (GVHD) is the most common complication of hematopoietic stem cell transplantation (HSCT); therefore, the prevention of GVHD is important for a successful treatment. Tacrolimus (Tac), a calcineurin inhibitor, has been widely used for the prophylaxis of GVHD in HSCT recipients. Areas covered: This review introduces phase II/III of clinical trials related with Tac's roles in the prevention of GVHD in HSCT. Furthermore, we discuss the normal ranges of Tac concentrations, pharmacogenetics, and drug interactions of Tac, as well as its side effects in adult HSCT recipients. Expert opinion: A series of studies has established the efficacy and safety of Tac alone or in combination with other agents in HSCT. However, successful administration of Tac is complicated by its narrow therapeutic window, inter-patient pharmacokinetic variability, and a spectrum of undesirable side effects. It is necessary to maintain concentrations of Tac within the desired ranges for GVHD prophylaxis. Moreover, various factors contribute to significant variability in Tac pharmacokinetics, including drug interactions and genomic variation.


Assuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Tacrolimo/administração & dosagem , Adulto , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/efeitos adversos , Inibidores de Calcineurina/farmacocinética , Interações de Medicamentos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/farmacocinética , Farmacogenética , Tacrolimo/efeitos adversos , Tacrolimo/farmacocinética
5.
Transplant Proc ; 51(8): 2624-2628, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31563242

RESUMO

INTRODUCTION: Mycophenolate mofetil has improved long-term outcomes of kidney transplantation. However, the impact of mycophenolic acid (MPA) trough level on the development of de novo donor-specific anti-HLA antibody (DSA) is unclear. We examined the relation between MPA trough level and de novo DSA development. METHOD: We retrospectively studied 617 kidney recipients whose MPA trough level and de novo DSA data were available. All patients underwent primary kidney transplant from living donors from 2008 to 2014, and were chronically treated with a calcineurin inhibitor, mycophenolate mofetil, and +/- steroids. They were equally divided into 4 groups according to the mean trough level of MPA (mMPA) at 1 year post-transplantation: Group 1, mMPA < 2.14 ng/mL (n = 152); Group 2, mMPA 2.14-2.83 ng/mL (n = 157); Group 3, mMPA 2.83-3.57 ng/mL (n = 153); and Group 4, mMPA ≥ 3.57 ng/mL (n = 155). The groups were compared by incidence rate of de novo DSA, graft survival rate, and renal function. RESULTS: The incidence rates of de novo DSA were 33.3% in Group 1, 23.7% in Group 2, 22.9% in Group 3, and 30.3% in Group 4 (P = .158). Although there was no significant difference in graft survival rates, a significant difference of renal functions was noted: the higher the renal function, the lower the MPA trough level. CONCLUSION: The mMPA trough level at 1 year post-transplantation was not statistically associated with the incidence rate of de novo DSA after kidney transplantation.


Assuntos
Soro Antilinfocitário/efeitos dos fármacos , Rejeição de Enxerto/prevenção & controle , Imunossupressores/farmacocinética , Transplante de Rim/efeitos adversos , Ácido Micofenólico/farmacocinética , Adulto , Anticorpos/imunologia , Soro Antilinfocitário/imunologia , Inibidores de Calcineurina/administração & dosagem , Feminino , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/efeitos dos fármacos , Sobrevivência de Enxerto/imunologia , Antígenos HLA/imunologia , Humanos , Transplante de Rim/métodos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
6.
Dermatitis ; 30(5): 294-299, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31524757

RESUMO

Atopic dermatitis (AD) often requires combination treatment regimens. However, little is known about treatment combinations and polypharmacy in AD. We sought to characterize patterns of outpatient prescriptions and polypharmacy among US children and adults with AD. Data from the 1993-2015 National Ambulatory Medical Care Survey were analyzed, including 128,300 pediatric and 623,935 adult outpatient visits. Among AD visits, dermatologists prescribed more topical corticosteroids (TCSs, P = 0.01) than any other clinicians, particularly multiple TCSs (P < 0.0001), topical calcineurin inhibitors (TCI, P = 0.009), combination TCIs with TCSs (P = 0.004), and systemic immunosuppressants (P = 0.003). Prescriptions for multiple TCSs increased from ages 0 to 19 years, 20 to 39 years, and peaked at 40 to 59 years (P = 0.0002). Prescriptions for prednisone peaked at ages of 40 to 59 years (P = 0.003). A subset of AD patients was prescribed oral antibiotics (7.1%), although fewer than half had a diagnosis of bacterial infection (42.1%). The proportion of patients receiving multiple prescriptions was higher in visits to primary care practitioners versus dermatologists, those with private versus public insurance, and 50 years or older versus 20 to 49 years versus 0 to 19 years. Visits with 4 or more prescriptions by dermatologists increased between 1993-2000 (10%) and 2011-2015 (29%, P = 0.0001). In conclusion, significant treatment variation exists among specialists managing AD, with increasing polypharmacy over time.


Assuntos
Corticosteroides/uso terapêutico , Inibidores de Calcineurina/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Prescrições de Medicamentos/estatística & dados numéricos , Imunossupressores/uso terapêutico , Padrões de Prática Médica/estatística & dados numéricos , Administração Cutânea , Adolescente , Corticosteroides/administração & dosagem , Adulto , Fatores Etários , Antibacterianos/uso terapêutico , Inibidores de Calcineurina/administração & dosagem , Criança , Pré-Escolar , Dermatologia/estatística & dados numéricos , Quimioterapia Combinada , Glucocorticoides/uso terapêutico , Inquéritos Epidemiológicos , Humanos , Lactente , Recém-Nascido , Seguro Saúde/estatística & dados numéricos , Pessoa de Meia-Idade , Polimedicação , Prednisona/uso terapêutico , Estados Unidos , Adulto Jovem
7.
Clin Drug Investig ; 39(12): 1233-1238, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31522334

RESUMO

BACKGROUND: The efficacy of topical calcineurin inhibitors (TCIs) for the treatment of infants with vitiligo aged less than 2 years remains to be fully determined. OBJECTIVE: This aim of this pilot study was to assess the efficacy and tolerability of the TCIs tacrolimus and pimecrolimus in infants with vitiligo aged under 2 years. METHODS: Infants with vitiligo aged < 2 years were randomly assigned to receive either tacrolimus ointment 0.03% or pimecrolimus cream 1% for a period of 6 months. During this period, topical treatment was applied twice daily. The proportion of body surface area of the treated lesions, locations, and possible adverse effects were recorded. In addition, the overall satisfaction scores of the patients' parents was evaluated by virtue of the visual analog scale (VAS). RESULTS: Forty-six infants with vitiligo were enrolled in this study. The overall response rate (> 0% repigmentation) was 100%, while the effective rate (> 50% repigmentation) of the tacrolimus and pimecrolimus groups was 69.6% and 65.2%, respectively. Meanwhile, the effective rates for vitiligo located on the head and neck, trunk, and extremities were 70%, 64.3% and 50%, respectively, while the response rates for non-segmental and segmental vitiligo were 74.4% and 28.6%, respectively. Only a low incidence of local adverse reactions (including mild redness and skin picking) was reported during the treatment process. CONCLUSIONS: Topical tacrolimus ointment 0.03% or pimecrolimus cream 1% have efficacy for vitiligo in infants, which serves to achieve an appropriate level of safety and tolerability during the 6-month period of applications. Thus, TCIs proved to be a therapeutic option for vitiligo in infants under 2 years of age.


Assuntos
Inibidores de Calcineurina/administração & dosagem , Tacrolimo/análogos & derivados , Tacrolimo/administração & dosagem , Vitiligo/tratamento farmacológico , Administração Tópica , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Projetos Piloto , Tacrolimo/efeitos adversos
8.
J Cutan Med Surg ; 23(4_suppl): 19S-26S, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31476938

RESUMO

The topical calcineurin inhibitors (TCIs), tacrolimus (Protopic) and pimecrolimus (Elidel), were approved in the early 2000s and were widely used as a nonsteroid treatment for atopic dermatitis (AD) in adult and pediatric populations. In 2005, the addition of a boxed warning was mandated for TCIs based on a potential risk of malignancy, and there was subsequently a substantial decline in their use. Since then, evidence has mounted to support the safety of this class of medications and suggests that the increased risk of malignancy remains theoretical. This review aims to dispel some of the common myths surrounding the safety of TCIs by evaluating the key evidence regarding their safety and tolerability in adult and pediatric populations. Four major themes are addressed in a practical question-and-answer format: the risk of harm associated with TCIs including common and serious adverse events; warnings and precautions for their use including the risk of systemic absorption, immunosuppression, and malignancy; the comparative safety of TCIs; and suggestions for counselling patients about the risk of harm with TCIs. Based on the available evidence, international professional dermatological organizations and regulatory authorities have concluded that the benefits of TCIs outweigh their potential risks when used in the appropriate patient populations for the recommended duration of time.


Assuntos
Inibidores de Calcineurina/efeitos adversos , Dermatite Atópica/tratamento farmacológico , Administração Tópica , Inibidores de Calcineurina/administração & dosagem , Humanos
9.
Transplant Proc ; 51(6): 1920-1922, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399176

RESUMO

INTRODUCTION: Following liver transplantation (LT), the majority of patients are treated with reduced-dose calcineurin inhibitors (CNIs) in combination with mycophenolate mofetil. The optimal timing for subsequent conversion to CNI monotherapy is not clearly defined. This study aims to evaluate the safety of conversion to CNI monotherapy after LT. METHODS: This was a single-center retrospective study of 100 consecutive patients who received CNI and mycophenolate mofetil combination regimen after LT at Singapore General Hospital from 2006 to 2018. Patient demographics, clinical parameters, and posttransplant complications (ie, rates of graft rejection, de novo malignancy, cytomegalovirus infection and renal impairment) were recorded. RESULTS: One hundred patients were recruited and mean follow-up time in months ± standard deviation was 60.36 ± 41.73. Patients were divided into 2 groups based on institution of CNI monotherapy within (group 1) or beyond (group 2) 6 months. Twenty-five (25%) patients were on CNI monotherapy within 6 months post-LT. Overall patient survival was 83.7% at 5-years posttransplant. There was no statistical difference in the rates of posttransplant complications including liver graft rejection (4.0% vs 18.7%, P = .11); de novo malignancy (0.0% vs 8.0%, P = .33); cytomegalovirus infection (4.0% vs 1.3%, P = .44); and renal impairment (20.0% vs 40.0%, P = .069) between the 2 groups. CONCLUSIONS: Successful institution of CNI monotherapy within 6 months is safe, and does not increase the risk of rejection.


Assuntos
Inibidores de Calcineurina/administração & dosagem , Transplante de Fígado , Complicações Pós-Operatórias/epidemiologia , Tacrolimo/administração & dosagem , Fatores de Tempo , Adulto , Esquema de Medicação , Quimioterapia Combinada , Feminino , Seguimentos , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/etiologia , Humanos , Hepatopatias/epidemiologia , Hepatopatias/etiologia , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Complicações Pós-Operatórias/etiologia , Insuficiência Renal/epidemiologia , Insuficiência Renal/etiologia , Estudos Retrospectivos
10.
Transplant Proc ; 51(7): 2308-2311, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31400977

RESUMO

BACKGROUND: This study aimed to determine whether de novo, prolonged-release tacrolimus- (PR-tacro) based immunosuppressive regimen affected graft and patient survival when compared to an immediate-release, twice-daily, tacrolimus- (IR-tacro) based regimen in kidney transplant recipients. We also aimed to determine the difference between the frequency of side effects, including diabetes control, in study groups. METHODS: A total of 115 standard risk kidney transplant recipients were enrolled in this single center, retrospective study. Fifty-two patients received PR-tacro and 63 patients received IR-tacro as a calcineurin inhibitor. The primary outcome measures included incidence of graft loss and delayed graft function (DGF), biopsy-proven acute rejection , graft and patient survival, and creatinine clearance. Secondary outcome measures included the incidence of non-adherence, drug-induced tremor; post-transplant diabetes mellitus diagnosis rate; and control of diabetes in pre-transplant diabetic patients. RESULTS: Baseline characteristics and mean tacrolimus trough levels were comparable between groups. Incidence of graft loss, DGF, and graft and patient survival were similar between groups (P > .05). Mean creatinine clearance level was also similar (P > .05). Mean serum levels of fasting glucose (P < .05) and A1C (P < .05) were lower in PR-tacro group when compared to IR-tacro group. Post-transplant diabetes mellitus diagnosis rate was also lower in PR-tacro group when compared to IR-tacro group (P = .040). CONCLUSION: This study suggests that there is no statistically significant difference between PR-tacro and IR-tacro in terms of patient and graft survival, DGF, and biopsy-proven acute rejection rates in kidney transplant recipients. Post-transplant diabetes mellitus frequency is lower in non-diabetic patients, and glucose metabolism control is better in diabetic patients.


Assuntos
Inibidores de Calcineurina/administração & dosagem , Rejeição de Enxerto/mortalidade , Imunossupressores/administração & dosagem , Transplante de Rim/mortalidade , Tacrolimo/administração & dosagem , Adulto , Função Retardada do Enxerto/etiologia , Feminino , Rejeição de Enxerto/tratamento farmacológico , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida
11.
Transplant Proc ; 51(8): 2633-2636, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31447192

RESUMO

INTRODUCTION: The most effective immunosuppressant protocol in kidney transplantation (KT) is the combination of a calcineurin inhibitor, steroid, and mycophenolate mofetil (MMF) until now. However, MMF withdrawal (MW) is performed for many reasons, and the clinical course of the KT recipients after MW is not clearly known. The purpose of this study was to investigate the clinical outcomes of KT after MW. MATERIALS AND METHODS: We retrospectively analyzed the medical records of 626 KT recipients between 2000 and 2016. We evaluated the incidence of biopsy-proven acute rejection (BPAR), graft and patient survival rates, and risk factors related with graft failure. RESULTS: The proportion of MW was 33.2% (208 of 626 patients). The median time between KT and MW was 6.4 months (range, 3.2-32.1 months). The common causes of MW were infection (70.7%), hematologic abnormalities (9.1%), and gastrointestinal trouble (7.7%). The incidence of BPAR was significantly higher in the MW group compared with the MMF continuation group (27.4% vs 8.9%, respectively, P < .001). Death-censored graft survival and patient survival rates were significantly lower in the MW group compared with the MMF continuation group (P < .001; P < .001, respectively). In the multivariate analysis, BPAR after MW was an independent risk factor for graft failure (hazard ratio 6.058, 95% confidence interval, 3.172-11.569, P < .001). CONCLUSIONS: The incidence of rejection, graft failure, and patient mortality in KT were high after MW. Therefore, MW should be considered carefully.


Assuntos
Rejeição de Enxerto/mortalidade , Imunossupressores/administração & dosagem , Transplante de Rim , Ácido Micofenólico/administração & dosagem , Síndrome de Abstinência a Substâncias/mortalidade , Suspensão de Tratamento , Adulto , Inibidores de Calcineurina/administração & dosagem , Quimioterapia Combinada , Feminino , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Esteroides/administração & dosagem , Síndrome de Abstinência a Substâncias/etiologia , Resultado do Tratamento
12.
Surg Today ; 49(12): 1066-1073, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31309329

RESUMO

PURPOSE: We evaluated the recent incidence of surgery and the changing surgery trends for ulcerative colitis (UC) in Japan due to the increasing use of anti-tumor necrosis factor (TNF) agents. METHODS: A questionnaire survey was performed to assess the number of surgeries, surgical indications, surgical timing, and immunosuppressive treatments before surgery between 2007 and 2017. RESULTS: A total of 3801 surgical cases were reported over 11 years. The prevalence of UC surgery decreased over the period studied. The rate of prednisolone (PSL) use did not change. The prevalence of both calcineurin inhibitors (CNIs) and anti-TNF agents increased during the period studied (p < 0.01). The prevalence of urgent/emergent surgery did not change. The most distinctive change in surgical indications was the increase in cancer/dysplasia (CAC), the prevalence of which increased from 20.2% in 2007 to 34.8%. CONCLUSION: The prevalence of UC surgery seems to be decreasing according to the increasing rate of anti-TNF agent and CNI administration. However, the indication of CAC significantly increased. Further research should evaluate whether or not long-term remission maintained with several agents can lead to increasing CAC.


Assuntos
Produtos Biológicos/administração & dosagem , Inibidores de Calcineurina/administração & dosagem , Colectomia/estatística & dados numéricos , Colectomia/tendências , Colite Ulcerativa/cirurgia , Uso de Medicamentos/estatística & dados numéricos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Estudos de Coortes , Colite Ulcerativa/epidemiologia , Humanos , Japão/epidemiologia , Prevalência , Indução de Remissão , Inquéritos e Questionários , Fatores de Tempo
13.
Expert Rev Clin Pharmacol ; 12(8): 781-790, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31242782

RESUMO

Introduction: There is a high incidence of venous thromboembolism (VTE) in solid organ transplant recipients. The safety and efficacy of direct-acting oral anticoagulants (DOAC) have been well established in clinical practice for the prevention and treatment of VTE in broad populations. However, the management of VTE in the setting of solid organ transplantation remains a challenge to clinicians due to limited evidence of DOAC usage with calcineurin inhibitors. Areas covered: The current literature available on the pharmacokinetic-pharmacodynamic interaction between DOACs and calcineurin inhibitors is presented. A comprehensive review was undertaken using PubMed, Embase, drug product labeling, and drug product review conducted by the US Food and Drug Administration using Drugs@FDA. The potential for mitigation strategies and clinical management using extant knowledge is explored. Expert opinion: Immunosuppression therapy is necessary to prevent graft rejection by the host. The sparsity of data together with the lack of well-designed prospective studies of DOAC use in solid organ transplant recipients presents a unique challenge to clinicians in determining the clinical relevance of possible drug interactions. Existing evidence suggests that with attention to concomitant drug use and renal function, the co-administration of DOACs and calcineurin inhibitors is safe and effective.


Assuntos
Anticoagulantes/administração & dosagem , Inibidores de Calcineurina/administração & dosagem , Imunossupressores/administração & dosagem , Administração Oral , Anticoagulantes/efeitos adversos , Inibidores de Calcineurina/efeitos adversos , Interações de Medicamentos , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/efeitos adversos , Transplante de Órgãos/métodos , Projetos de Pesquisa , Tromboembolia Venosa/prevenção & controle
14.
Lupus ; 28(7): 799-805, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31042129

RESUMO

Cutaneous lupus erythematosus (CLE)-a common presentation of lupus erythematosus-may exist independently or as a part of the systemic manifestations of systemic lupus erythematosus. The effects of living with and treating a chronic condition such as CLE can be debilitating to a patient's health and finances. The management of patients with CLE is made particularly challenging by poor compliance, limited therapeutic options, scarcity of evidence supporting their use, and significant differences in costs of medications. Effective management of CLE should center on prevention, individualized treatment regimens, and a mutual understanding of the challenges that patients with CLE face. This article seeks to provide an overview of the efficacy, safety, and cost of therapeutic options for CLE.


Assuntos
Custos e Análise de Custo/estatística & dados numéricos , Lúpus Eritematoso Cutâneo/economia , Lúpus Eritematoso Cutâneo/terapia , Administração Tópica , Antimaláricos/uso terapêutico , Inibidores de Calcineurina/administração & dosagem , Efeitos Psicossociais da Doença , Medicina Baseada em Evidências , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Esteroides/administração & dosagem
15.
J Cutan Med Surg ; 23(4): 442-448, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31053034

RESUMO

Pimecrolimus is a topical calcineurin inhibitor currently approved for second-line use in the management of mild-to-moderate atopic dermatitis in patients age 2 years and older. Given the safety profile and nonsteroidal mechanism of pimecrolimus, there has been significant interest in its use in the treatment of a variety of dermatological conditions. This article reviews research that has been published on the off-label uses of topical pimecrolimus, with a focus on published RCTs. Convincing evidence exists supporting pimecrolimus' efficacy in oral lichen planus and seborrheic dermatitis. For other conditions studied to date, pimecrolimus may prove to be a useful treatment alternative when conventional agents fail. Adverse events seen with its off-label use were typically application site reactions, the most common being a transient burning sensation. In summary, pimecrolimus appears to be an effective agent in the treatment of multiple dermatological conditions and may be worth considering as a pharmacologic alternative in several conditions when first-line treatment fails, or for areas that are more susceptible to the adverse effects of topical corticosteroids.


Assuntos
Inibidores de Calcineurina/uso terapêutico , Dermatopatias/tratamento farmacológico , Tacrolimo/análogos & derivados , Administração Tópica , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/efeitos adversos , Dermatite Alérgica de Contato/tratamento farmacológico , Dermatite Perioral/tratamento farmacológico , Dermatite Seborreica/tratamento farmacológico , Dermatoses da Mão/tratamento farmacológico , Humanos , Líquen Plano Bucal/tratamento farmacológico , Uso Off-Label , Psoríase/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Rosácea/tratamento farmacológico , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Tacrolimo/uso terapêutico , Vitiligo/tratamento farmacológico
16.
An Bras Dermatol ; 94(2): 164-171, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31090821

RESUMO

BACKGROUND: Tacrolimus, for its activity on modulation of collagen production and fibroblast activity, may have a role in the prevention of hypertrophic scars. OBJECTIVES: Evaluate macroscopic, microscopic, metabolic, laboratory effects and side effects of the use of topical tacrolimus ointment, in different concentrations, in the prevention of hypertrophic scars. METHODS: Twenty-two rabbits were submitted to the excision of 2 fragments of 1 cm of each ear, 4 cm apart, down to cartilage. The left ear of the animals was standardized as control and Vaseline applied twice a day. The right ear received tacrolimus ointment, at concentrations of 0.1% on the upper wound and 0.03% on the lower wound, also applied twice a day. Macroscopic, microscopic, laboratory criteria and the animals' weight were evaluated after 30 days of the experiment. RESULTS: Wounds treated with tacrolimus, at concentrations of 0.1% and 0.03%, when compared to control, showed a lower average degree of thickening (p = 0.048 and p <0.001, respectively). The average of scar thickness and lymphocyte, neutrophil and eosinophil concentrations are lower in the treated wounds compared to the control (p <0.001, p=0.022, p=0.007, p=0.044, respectively). The mean concentration of lymphocytes is lower in wounds treated with a higher concentration of the drug (p=0.01). STUDY LIMITATIONS: experiment lasted only 30 days. CONCLUSIONS: Tacrolimus at the 2 concentrations evaluated reduced the severity of inflammatory changes and positively altered the macroscopic aspect of the scar in the short term. Its use was shown to be safe, with no evidence of systemic or local adverse effects.


Assuntos
Inibidores de Calcineurina/uso terapêutico , Cicatriz Hipertrófica/prevenção & controle , Tacrolimo/uso terapêutico , Administração Tópica , Alanina Transaminase/sangue , Alanina Transaminase/efeitos dos fármacos , Animais , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/farmacologia , Cicatriz Hipertrófica/patologia , Creatinina/sangue , Modelos Animais de Doenças , Orelha Externa/patologia , Eritema/patologia , Inflamação/patologia , Inflamação/prevenção & controle , Contagem de Linfócitos , Masculino , Pomadas , Coelhos , Albumina Sérica/análise , Albumina Sérica/efeitos dos fármacos , Tacrolimo/administração & dosagem , Tacrolimo/farmacologia , Resultado do Tratamento , Ureia/sangue , Cicatrização/efeitos dos fármacos , gama-Glutamiltransferase/sangue , gama-Glutamiltransferase/efeitos dos fármacos
17.
An. bras. dermatol ; 94(2): 164-171, Mar.-Apr. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1001151

RESUMO

Abstract BACKGROUND: Tacrolimus, for its activity on modulation of collagen production and fibroblast activity, may have a role in the prevention of hypertrophic scars. OBJECTIVES: Evaluate macroscopic, microscopic, metabolic, laboratory effects and side effects of the use of topical tacrolimus ointment, in different concentrations, in the prevention of hypertrophic scars. METHODS: Twenty-two rabbits were submitted to the excision of 2 fragments of 1 cm of each ear, 4 cm apart, down to cartilage. The left ear of the animals was standardized as control and Vaseline applied twice a day. The right ear received tacrolimus ointment, at concentrations of 0.1% on the upper wound and 0.03% on the lower wound, also applied twice a day. Macroscopic, microscopic, laboratory criteria and the animals' weight were evaluated after 30 days of the experiment. RESULTS: Wounds treated with tacrolimus, at concentrations of 0.1% and 0.03%, when compared to control, showed a lower average degree of thickening (p = 0.048 and p <0.001, respectively). The average of scar thickness and lymphocyte, neutrophil and eosinophil concentrations are lower in the treated wounds compared to the control (p <0.001, p=0.022, p=0.007, p=0.044, respectively). The mean concentration of lymphocytes is lower in wounds treated with a higher concentration of the drug (p=0.01). STUDY LIMITATIONS: experiment lasted only 30 days. CONCLUSIONS: Tacrolimus at the 2 concentrations evaluated reduced the severity of inflammatory changes and positively altered the macroscopic aspect of the scar in the short term. Its use was shown to be safe, with no evidence of systemic or local adverse effects.


Assuntos
Animais , Masculino , Coelhos , Tacrolimo/uso terapêutico , Inibidores de Calcineurina/uso terapêutico , Pomadas , Ureia/sangue , Albumina Sérica/análise , Albumina Sérica/efeitos dos fármacos , Administração Tópica , Tacrolimo/administração & dosagem , Tacrolimo/farmacologia , Cicatriz Hipertrófica/patologia , Cicatriz Hipertrófica/prevenção & controle , Contagem de Linfócitos , Creatinina/sangue , Alanina Transaminase/efeitos dos fármacos , Alanina Transaminase/sangue , Modelos Animais de Doenças , Orelha Externa/patologia , Eritema/patologia , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/farmacologia , Inflamação/patologia , Inflamação/prevenção & controle
18.
Mini Rev Med Chem ; 19(13): 1049-1059, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30836913

RESUMO

AIM: The clinical management of OLP represents a considerable challenge for the oral physician. The aim of this review is to assess the main intervention used in the management of OLP and the efficacy of every type of treatment. MATERIALS AND METHODS: We searched and analyzed PubMed database for articles on OLP management. Only randomized controlled trials, comparing an active treatment with placebo, or between different active treatments, were considered in this systematic review. Only patients with symptomatic OLP were included and interventions of all types were considered (topical treatment, systemic drugs, non pharmacological intervention). RESULTS: A total of 25 randomized controlled trials were examined and included in this review. Steroids are the most frequently employed drug in the treatment of OLP and their efficacy and safety are demonstrated. Also calcineurin inhibitors and photo-dynamic therapy are used in different studies for OLP management, with positive results. CONCLUSION: Topical steroids remain the first-line treatment for symptomatic OLP, however, many different pharmacological and non-pharmacological therapies would represent a valid alternative for its management, but, nowadays they require further investigations.


Assuntos
Inibidores de Calcineurina/uso terapêutico , Líquen Plano Bucal/tratamento farmacológico , Esteroides/uso terapêutico , Administração Tópica , Calcineurina/metabolismo , Inibidores de Calcineurina/administração & dosagem , Humanos , Fotoquimioterapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Esteroides/administração & dosagem
19.
PLoS One ; 14(3): e0213913, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30897127

RESUMO

Low plasma CsA concentrations (<300-350 ng/mL) early following allogeneic hematopoietic stem cell transplantation (HSCT) is associated with an increased risk of developing acute graft-versus-host disease (aGvHD). Nevertheless, the current optimal target trough concentration for CsA following HSCT is considered to be 200-400 ng/mL. Here, we performed a retrospective analysis of a homogeneous group of 129 patients who received HSCT after non-myeloablative conditioning, and we analyzed the impact of CsA trough concentration measured during the first four weeks (CsA W1-4) on the incidence aGvHD, relapse-free survival (RFS), non-relapse mortality (NRM), overall survival (OS), and toxicity. The 180-day incidence of grade II-IV aGvHD was 25% (32/129 patients). In multivariate analysis the incidence of grade II-IV aGvHD was significantly lower among patients with a CsA W1-4 concentration ≥350 ng/mL compared to patients with a concentration <350 ng/mL (18% versus 38%, respectively; P = 0.007), with a hazard ration (HR) of 0.38 (95% CI: 0.19-0.77). In contrast, we found no correlation between CsA trough concentration and RFS, NRM, or OS. Moreover, we found an increased incidence of hypomagnesemia at higher CsA concentrations, but no difference in the incidence of acute renal toxicity, hepatic toxicity, or electrolyte imbalance. Interestingly, 30% of patients experienced hyponatremia with no apparent cause other than the use of CsA, with urinalysis suggesting SIADH as the underlying cause. Our findings suggest that a CsA trough concentration of 350-500 ng/mL might be more appropriate in the first month following non-myeloablative HSCT.


Assuntos
Inibidores de Calcineurina/sangue , Ciclosporina/sangue , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Aguda , Adulto , Idoso , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/efeitos adversos , Estudos de Coortes , Ciclosporina/administração & dosagem , Ciclosporina/efeitos adversos , Feminino , Neoplasias Hematológicas/terapia , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/sangue , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Países Baixos , Estudos Retrospectivos , Transplante Homólogo/efeitos adversos , Resultado do Tratamento , Desequilíbrio Hidroeletrolítico/etiologia , Adulto Jovem
20.
Am J Clin Dermatol ; 20(4): 515-526, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30911977

RESUMO

Vitiligo is a common acquired depigmenting skin disease characterized by a progressive loss of functional melanocytes. It may appear from the first years of life to late adulthood. Childhood vitiligo (CV), defined as vitiligo that begins before the age of 12 years, is common and may differ from post-CV in terms of epidemiology, clinical presentation, comorbidities, and treatment options. Taking into consideration the potential significant psychosocial impact of the disease on both children and their parents, all available therapeutic options must be offered to patients who desire treatment. According to the most recent guidelines, topical corticosteroids, topical calcineurin inhibitors, and narrowband ultraviolet B phototherapy are the most commonly used treatment modalities for vitiligo in children. This review presents recent data regarding the whole spectrum of CV. Differences between CV and post-CV are also discussed.


Assuntos
Doenças Autoimunes do Sistema Nervoso/epidemiologia , Fármacos Dermatológicos/administração & dosagem , Estresse Psicológico/etiologia , Terapia Ultravioleta/métodos , Vitiligo/terapia , Administração Tópica , Idade de Início , Inibidores de Calcineurina/administração & dosagem , Criança , Comportamento Infantil/psicologia , Comorbidade , Glucocorticoides/administração & dosagem , Humanos , Pais/psicologia , Prevalência , Qualidade de Vida , Estresse Psicológico/psicologia , Resultado do Tratamento , Vitiligo/epidemiologia , Vitiligo/psicologia
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