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Antieméticos , Aprepitant , Gastrectomía , Laparoscopía , Obesidad Mórbida , Náusea y Vómito Posoperatorios , Humanos , Aprepitant/uso terapéutico , Náusea y Vómito Posoperatorios/prevención & control , Antieméticos/uso terapéutico , Gastrectomía/efectos adversos , Obesidad Mórbida/cirugía , Morfolinas/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como AsuntoAsunto(s)
Antieméticos , Aprepitant , Gastrectomía , Laparoscopía , Obesidad Mórbida , Náusea y Vómito Posoperatorios , Humanos , Aprepitant/uso terapéutico , Náusea y Vómito Posoperatorios/prevención & control , Antieméticos/uso terapéutico , Gastrectomía/efectos adversos , Obesidad Mórbida/cirugía , Morfolinas/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) is associated with postoperative nausea and vomiting (PONV). We aimed to compare the effects of aprepitant on the incidence of PONV after LSG. METHODS: In this double-blind, randomized controlled trial, the case group received the standard care regimen for PONV (dexamethasone 10 mg, ondansetron 4 mg, and metoclopramide 10 mg) plus prophylactic oral aprepitant 80 mg 1 h preoperatively. The control group received standard care plus a placebo. Comparative analyses using the Rhodes index were performed at 0, 6, 12, and 24 h postoperatively. RESULTS: A total of 400 patients (201 in the aprepitant group and 199 in the placebo group) underwent LSG. The groups were homogeneous. The aprepitant group experienced less PONV: early, 69 (34.3%) vs. 103 (51.7%), p ≤ 0.001; 6 h, 67 (33.3%) vs. 131 (65.8%), p ≤ 0.001; 12 h, 41 (20.4%) vs. 115 (57.8%), p ≤ 0.001; and 24 h, 22 (10.9%) vs. 67 (33.7%), p ≤ 0.001. Fewer patients in the aprepitant group vomited: early, 3 (1.5%) vs. 5 (2.5%), p = 0.020; 6 h, 6 (3%) vs. 18 (9%), p = 0.020; 12 h, 2 (1%) vs. 17 (8.5%), p = 0.006; and 24 h, 1 (0.5%) vs. 6 (3%), p = 0.040. Patients in the aprepitant group required less additional PONV medication: early, 61 (30.3%) vs. 86 (43.2), p = 0.008; 6 h, 7 (3.5%) vs. 34 (17%), p = 0.001; 12 h, 6 (3%) vs. 31 (15.6%), p ≤ 0.001; and 24 h, 5 (2.5%) vs. 11 (5.5%), p ≤ 0.001. CONCLUSIONS: Prophylactic aprepitant improved PONV between 0 h (early) and 24 h postoperatively in patients undergoing LSG.
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Antieméticos , Laparoscopía , Obesidad Mórbida , Humanos , Aprepitant , Antieméticos/uso terapéutico , Náusea y Vómito Posoperatorios/tratamiento farmacológico , Obesidad Mórbida/cirugía , Gastrectomía , Método Doble CiegoRESUMEN
ABSTRACT Introduction: This study was performed to evaluate the degree of 3-day chemotherapy-induced nausea and vomiting (CINV) in children with cancer who received highly emetogenic chemotherapy (HEC) to ascertain the efficacy of aprepitant single-dose on dayL 1 plus granisetron and dexamethasone (DEX). Methods: This clinical trial study was conducted on 120 patients in the age range of 5 to 18 years old who received chemotherapy. Patients were divided into two groups; Group A received aprepitant at 125 mg/kg on day 1 orally, followed by 80 mg/kg daily on days 2 and 3 and Group B received a single dose of aprepitant 125 mg/kg on day 1 orally and placebo on days 2 and 3. All groups received granisetron 3 mg/m2 on day 1 and DEX on days 1 to 3. The primary and secondary endpoints were to evaluate the proportion of patients with acute, delayed and overall CINV within each group. Results: There were no significant differences between the two groups for vomiting, nausea or the use of rescue therapy. The number of patients without vomiting on day 1 was similar in both groups (96.5% vs. 98.3%, respectively; p = 0.848). Conclusion: According to the results of this study, a single dose of aprepitant 125 mg/kg was as effective as administering three doses of aprepitant on 3 days. Therefore, the use of a single dose of aprepitant in combination with other standard treatment regimens to prevent CINV in children who received HEC was safe and efficacious and can be beneficial.
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Humanos , Preescolar , Niño , Adolescente , Vómitos , Dexametasona , Granisetrón , Aprepitant , NáuseaRESUMEN
PURPOSE: The present study explored the role and mechanism involved in aprepitant-induced cardioprotective effects in rat model of ischemia-reperfusion injury. METHODS: The isolated hearts of Wistar male albino rats were subjected to ischemia-reperfusion injury on Langendorff apparatus. The extent of myocardial injury was assessed by measuring lactate dehydrogenase 1 and CK-MB release in the coronary effluent. The rats were treated with aprepitant (5, 10 and 20 mg/kg) before isolating hearts. After injury, the levels of HIF-1α, p-AkT, p-GSK-3ß/GSK-3ß were measured in heart homogenates. LY294002 was employed as PI3K inhibitor. RESULTS: Ischemia-reperfusion led to significant myocardial injury and decreased the levels of HIF-1α, p-AkT and ratio of p-GSK-3ß/GSK-3ß. Aprepitant attenuated myocardial injury and restored the biochemical changes in a dose-dependent manner. Pre-treatment with LY294002 (10 and 20 mg/kg) abolished aprepitant-mediated cardioprotective effects and restored the biochemical parameters in the heart homogenate. CONCLUSIONS: Aprepitant may be effective in preventing ischemia-reperfusion-induced myocardial injury, which may be due to activation of PI3K-AkT-GSK-3ß and HIF-1α signaling pathway.
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Daño por Reperfusión Miocárdica , Proteínas Proto-Oncogénicas c-akt , Animales , Ratas , Masculino , Proteínas Proto-Oncogénicas c-akt/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Aprepitant/farmacología , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/prevención & control , Daño por Reperfusión Miocárdica/metabolismo , Ratas Wistar , Transducción de Señal , IsquemiaRESUMEN
PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) is a very common side effect of pediatric cancer therapy. High-quality, evidence-based, pediatric-specific guidelines for prophylaxis and treatment of CINV are available. At many centers, guideline-concordant care is uncommon. We formed a multidisciplinary quality improvement team to implement guideline-concordant care for CINV prophylaxis at our center. We present the results following the first year of our interventions. METHODS: We planned and implemented a multipronged approach in three key phases: (1) developing and publishing an acute CINV prophylaxis pathway, (2) education of providers, and (3) updating the computerized provider order entry system. We used iterative, sequential Plan-Do-Study-Act cycles and behavioral economic strategies to improve adherence to guideline-concordant CINV prophylaxis. We focused on aprepitant usage as a key area for improvement. RESULTS: At the beginning of the study period, < 50% of patients were receiving guideline-concordant CINV prophylaxis and < 15% of eligible patients were receiving aprepitant. After 1 year, more than 60% of patients were receiving guideline-concordant care and 50% of eligible patients were receiving aprepitant. CONCLUSION: We describe the development and implementation of a standardized pathway for prevention of acute CINV in pediatric oncology patients. With a multidisciplinary, multifaceted approach, we demonstrate significant improvements to guideline-congruent CINV prophylaxis.
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Antieméticos , Antineoplásicos , Neoplasias , Antieméticos/farmacología , Antieméticos/uso terapéutico , Aprepitant/efectos adversos , Niño , Humanos , Náusea/inducido químicamente , Náusea/tratamiento farmacológico , Náusea/prevención & control , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Vómitos/inducido químicamente , Vómitos/tratamiento farmacológico , Vómitos/prevención & controlRESUMEN
Refractory pruritus can be a symptom difficult to manage. We describe a case of a 37-year-old female patient with an oncological diagnosis of high-grade mesenchymal osteosarcoma in the left sacrum, hospitalized for urinary tract infection and polymicrobial bacteremia. During hospitalization, she presented pruritus of unknown cause, refractory to multiple treatments. Given the severity of symptoms and refractoriness, we administered aprepitant obtaining a complete resolution of the pruritus. With these findings, we raise the possibility of using aprepitant as a treatment for refractory pruritus.
El prurito refractario puede ser un síntoma de difícil manejo. Se presenta un reporte de caso de una paciente femenina de 37 años con diagnóstico oncológico de osteosarcoma mesenquimal de alto grado en sacro izquierdo, hospitalizada por infección de vías urinarias y bacteriemia polimicrobiana, quien presentó prurito de causa desconocida, refractario a múltiples manejos antipruriginosos. Dada la severidad de los síntomas y refractariedad, se administró aprepitant, obteniendo resolución completa del cuadro. Con estos hallazgos se plantea la posibilidad del empleo de aprepitant como tratamiento para el prurito refractario.
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Humanos , Femenino , Adulto , Prurito/tratamiento farmacológico , Antagonistas del Receptor de Neuroquinina-1 , Aprepitant/uso terapéutico , Antipruriginosos/uso terapéuticoRESUMEN
Purpose: The present study explored the role and mechanism involved in aprepitant-induced cardioprotective effects in rat model of ischemia-reperfusion injury. Methods: The isolated hearts of Wistar male albino rats were subjected to ischemia-reperfusion injury on Langendorff apparatus. The extent of myocardial injury was assessed by measuring lactate dehydrogenase 1 and CK-MB release in the coronary effluent. The rats were treated with aprepitant (5, 10 and 20 mg/kg) before isolating hearts. After injury, the levels of HIF-1α, p-AkT, p-GSK-3ß/GSK-3ß were measured in heart homogenates. LY294002 was employed as PI3K inhibitor. Results: Ischemia-reperfusion led to significant myocardial injury and decreased the levels of HIF-1α, p-AkT and ratio of p-GSK-3ß/GSK-3ß. Aprepitant attenuated myocardial injury and restored the biochemical changes in a dose-dependent manner. Pre-treatment with LY294002 (10 and 20 mg/kg) abolished aprepitant-mediated cardioprotective effects and restored the biochemical parameters in the heart homogenate. Conclusions: Aprepitant may be effective in preventing ischemia-reperfusion-induced myocardial injury, which may be due to activation of PI3K-AkT-GSK-3ß and HIF-1α signaling pathway.
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Animales , Ratas , Cardiotónicos , Daño por Reperfusión , Aprepitant/administración & dosificación , IsquemiaRESUMEN
Faunipollenites Bharadwaj is considered a junior synonym of Protohaploxypinus Samoilovich emend. Morbey. However, Indian workers claim it is a valid genus due to a poorly defined corpus and absence of folds in distal attachment. In India, a standard method is applied including the oxidization with HNO3 more than 48 hours (+10' of KOH). We analyze the effects of that treatment on the morphology of pollen grains of both genera in samples from the Permian of India and Brazil. The same samples are also processed with HCl, HF, two hours of HNO3 and 2' of KOH and slides are mounted after each step. Our analysis reveals that distinct or indistinct central body and presence/absence of folds in distal attachment do not change in contrast to the indistinct central body and mostly absence of folds from samples that underwent a longer period of oxidization (24-48 hours and KOH 10'). The synonymization of Faunipollenites to Protohaploxypinus is confirmed. Species of Faunipollenites are reassigned to the revised species of Protohaploxypinus. The usage of the latter genus and its species in Permian biostratigraphic studies of India will improve Gondwanan correlations and paleobiogeographic reconstructions in future studies.
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Polen , Aprepitant , Brasil , Humanos , IndiaRESUMEN
OBJECTIVES: To evaluate the addition of a fourth antiemetic intervention in patients at high risk for postoperative nausea and vomiting (PONV). METHODS: High-risk patients (Apfel score 3 or 4) scheduled for unilateral mastectomy were randomly allocated in one of two groups, oral aprepitant (oral aprepitant 80 mg, intravenous dexamethasone 8 mg, and palonosetron 0.075 mg) and oral placebo (oral placebo, intravenous dexamethasone 4 mg, and palonosetron 0.075 mg). Patients and caregivers were blinded to the group assignments. The primary efficacy endpoints included the incidence of nausea and vomiting, and the secondary endpoints included use of rescue antiemetics during a 48-hour postoperative period. ClinicalTrials.gov: NCT02431286. RESULTS: One hundred patients were enrolled in this study and 91 were analyzed, 48 in group A and 43 in group P. No patient presented with nausea or vomiting in the first 2 hours after surgery. From the 2nd to the 6th hour, the incidence of PONV was 8.33% in group A and 9.30% in group P. In the first 24 hours, the incidence of PONV was 27.08% in the group A and 20.93% in group P. From the 24th to the 48th hour, the incidence of PONV was 8.33% in group A and 13.95% in group P. There were no statistically significant differences in PONV between groups. CONCLUSION: The addition of aprepitant as a third antiemetic resulted in no significant reduction in the incidence of PONV in this population. However, the incidence of PONV was reduced in relation to the general population.
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Neoplasias de la Mama , Palonosetrón , Aprepitant , Neoplasias de la Mama/cirugía , Método Doble Ciego , Humanos , Mastectomía , Náusea y Vómito Posoperatorios/prevención & controlRESUMEN
OBJECTIVES: To evaluate the addition of a fourth antiemetic intervention in patients at high risk for postoperative nausea and vomiting (PONV). METHODS: High-risk patients (Apfel score 3 or 4) scheduled for unilateral mastectomy were randomly allocated in one of two groups, oral aprepitant (oral aprepitant 80 mg, intravenous dexamethasone 8 mg, and palonosetron 0.075 mg) and oral placebo (oral placebo, intravenous dexamethasone 4 mg, and palonosetron 0.075 mg). Patients and caregivers were blinded to the group assignments. The primary efficacy endpoints included the incidence of nausea and vomiting, and the secondary endpoints included use of rescue antiemetics during a 48-hour postoperative period. ClinicalTrials.gov: NCT02431286. RESULTS: One hundred patients were enrolled in this study and 91 were analyzed, 48 in group A and 43 in group P. No patient presented with nausea or vomiting in the first 2 hours after surgery. From the 2nd to the 6th hour, the incidence of PONV was 8.33% in group A and 9.30% in group P. In the first 24 hours, the incidence of PONV was 27.08% in the group A and 20.93% in group P. From the 24th to the 48th hour, the incidence of PONV was 8.33% in group A and 13.95% in group P. There were no statistically significant differences in PONV between groups. CONCLUSION: The addition of aprepitant as a third antiemetic resulted in no significant reduction in the incidence of PONV in this population. However, the incidence of PONV was reduced in relation to the general population.
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Humanos , Neoplasias de la Mama/cirugía , Palonosetrón , Método Doble Ciego , Náusea y Vómito Posoperatorios/prevención & control , Aprepitant , MastectomíaRESUMEN
An eight-year long case series follow-up study with pediatric bone cancer patients was conducted to compare the occurrence of adverse events associated with aprepitant with official sources of drug information (manufacturer's leaflet, clinical trials, and European Medicines Agency leaflet). All patients admitted were analyzed, representing 192 aprepitant cycles. Anorexia, febrile neutropenia, and headache were observed in frequencies over 43.8 per 100 patients, which was higher than previous estimates. Adverse events were classified as probable or possible, by using Naranjo score. The increased rates of adverse events, especially on the risk febrile neutropenia, warrant further safety studies on this population.
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Antieméticos/efectos adversos , Aprepitant/efectos adversos , Neoplasias Óseas/tratamiento farmacológico , Antagonistas del Receptor de Neuroquinina-1/efectos adversos , Niño , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: Post-operative nausea and vomiting (PONV) is one of the most important causes of patient discomfort after laparoscopic surgeries despite the use of a multimodal pharmacological approach. This study assessed whether the addition of aprepitant to a multimodal regimen would further decrease the incidence of PONV in high-risk patients. METHODS: Apfel-score three or four patients, scheduled for laparoscopic procedures to treat abdominal or pelvic cancer, were randomized to receive oral starch (control group) or 80 mg of oral aprepitant (treatment group) before induction of anaesthesia in a double-blind study. All patients received 4-8 mg of intravenous dexamethasone (at induction) and 4-8 mg of ondansetron (at the end) and a standardized total intravenous anaesthesia (TIVA) technique combined with neuraxial blockade. PONV was defined as any episode of nausea, vomiting or retching in the first 24 h after anaesthesia. RESULTS: Sixty-six patients completed the study. Vomiting occurred in 13/32 (40.6%) patients in the control group and in 1/34 (2.9%) patients in the treatment group (P = 0.0002, 95%CI: 18-54%) in the first 24 h after anaesthesia. Severe nausea occurred in two (6.3%) patients, and severe vomiting occurred in four (12.5%) patients in the control group. One patient presented with severe vomiting in the treatment group in the first 24 post-operative hours. CONCLUSION: Eighty milligrams of aprepitant added to a three-drug multimodal prophylaxis strategy can bring benefits to a high-risk population by reducing PONV episodes and rescue antiemetic requirements. This study was registered in the ClinicalTrials.gov (NCT 02357693) database.
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Antieméticos/uso terapéutico , Aprepitant/uso terapéutico , Náusea y Vómito Posoperatorios/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Aprepitant/administración & dosificación , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Náusea y Vómito Posoperatorios/epidemiologíaRESUMEN
AIMS: To review the efficacy and safety of aprepitant in combination with ondansetron and dexamethasone (triple therapy) in children and adolescents on moderate to highly emetogenic chemotherapy. METHODS: Medline, Embase, Scielo, Lilacs, Cochrane and congress abstracts published until September 2016 were used as data sources. Two reviewers independently selected manuscripts and extracted data. A third reviewer solved discrepancies in study selection and data extraction. The primary outcome was overall complete response (no vomiting from 0 to 120 h). Secondary outcomes were: response in acute phase, delayed phase and reported toxicities. Each study was considered a unit of analysis. Summarized relative risks were recalculated based on reported data. All meta-analyses used a random-effects model and heterogeneity was reported using the I2 method. RESULTS: From 1004 studies, we screened 288 titles and abstracts and included three trials for data extraction. The population comprised 451 patients. Most patients were males, ranging from 6 months to 19 years of age, and weighing from 6 to 134 kg. Bone cancer was the most incident (≥50%) neoplasm, followed by rhabdomyosarcoma and Hodgkin's lymphoma. Triple therapy was associated with a reduced risk of developing chemotherapy-induced vomiting (CIV) (RR = 0.48; 95% CI 0.34-0.67). There were no differences in incidence of febrile neutropenia between groups (RR = 1.02; 95% CI 0.66-1.58). CONCLUSIONS: Triple therapy decreased CIV risk, without increasing the occurrence of febrile neutropenia. However, this review could not address which subpopulations would most benefit from using this strategy. Future studies should focus on assessing risk factors for nausea and vomiting, as many patients did not achieve a complete antiemetic response.
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Antieméticos/administración & dosificación , Morfolinas/administración & dosificación , Vómitos/prevención & control , Adolescente , Antieméticos/efectos adversos , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Aprepitant , Niño , Preescolar , Dexametasona/administración & dosificación , Dexametasona/efectos adversos , Quimioterapia Combinada , Humanos , Lactante , Morfolinas/efectos adversos , Náusea/inducido químicamente , Náusea/prevención & control , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Ondansetrón/administración & dosificación , Ondansetrón/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Vómitos/inducido químicamente , Adulto JovenRESUMEN
INTRODUCCIÓN: El análisis de costo-efectividad de ondansetrón, alizaprida, domperidona, granisetrón, aprepitant, propofol, dexametasona, dimenhidrinato, metoclopramida y haloperidol para la profilaxis y/o tratamiento de pacientes con náusea y vómito en Colombia, se desarrolla en el marco del mecanismo técnico-científico para la ampliación progresiva del plan de beneficios y la definición de la lista de exclusiones, establecido en el artículo 15 de la Ley 1751 de 2015. Estas tecnologías fueron seleccionadas por la Dirección de Beneficios, Costos y Tarifas del Aseguramiento en Salud del Ministerio de Salud y Protección Social (MSPS), y remitidas al Instituto de Evaluación Tecnológica en Salud (IETS) para su evaluación. La náusea es una sensación desagradable, de asco intenso a los alimentos, o de vómito inminente, y está asociada a la disminución de la actividad motora gástrica, el incremento del tono de la pared duodenal y reflujo de su contenido al estómago, lo que causa su distensión. Ésta, se acompaña de manifestaciones del sistema nervioso autónomo como hiper-salivación, palidez, sudación, taquicardia y taquipnea El vómito, por su parte, es la expulsión fo
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Humanos , Vómitos/tratamiento farmacológico , Dexametasona/uso terapéutico , Propofol/uso terapéutico , Ondansetrón/uso terapéutico , Granisetrón/uso terapéutico , Dimenhidrinato/uso terapéutico , Domperidona/uso terapéutico , Aprepitant/uso terapéutico , Haloperidol/uso terapéutico , Metoclopramida/uso terapéutico , Náusea/tratamiento farmacológico , Evaluación en Salud/economía , Eficacia , ColombiaRESUMEN
BACKGROUND: The addition of neurokinin-1 receptor (NK1R) antagonists to antiemetic regimens has substantially reduced chemotherapy-induced nausea and vomiting (CINV). We sought to systematically review the overall impact of NK1R antagonists on CINV prevention. METHODS: We systematically searched the MEDLINE, EMBASE, and CENTRAL databases, and meeting proceedings for randomized controlled trials (RCTs) that evaluated NK1R antagonists plus standard antiemetic therapy for CINV prevention. Complete response (CR) to therapy was defined as the absence of emesis and the absence of rescue therapy. The endpoints were defined as CR in the overall phase (during the first 120 hours of chemotherapy), CR in the acute phase (first 24 hours), and the delayed phase (24-120 hours) after chemotherapy, nausea, and toxicity. Subgroup analyses evaluated the type of NK1R antagonist used, the emetogenic potential of the chemotherapy regimen, and prolonged use of 5-HT3 (serotonin) receptor antagonists, a class of standard antiemetic agents. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Statistical tests for heterogeneity were one-sided; statistical tests for effect estimates and publication bias were two-sided. RESULTS: Seventeen trials (8740 patients) were included in this analysis. NK1R antagonists increased the CR rate in the overall phase from 54% to 72% (OR = 0.51, 95% CI = 0.46 to 0.57, P < .001). CR and nausea were improved in all phases and subgroups. The expected side effects from NK1R antagonists did not statistically significantly differ from previous reports; however, this analysis suggests that the incidence of severe infection increased from 2% to 6% in the NK1R antagonist group (three RCTs with a total of 1480 patients; OR = 3.10; 95% CI = 1.69 to 5.67, P < .001). CONCLUSIONS: NK1R antagonists increased CINV control in the acute, delayed, and overall phases. They are effective for both moderately and highly emetogenic chemotherapy regimens. Their use might be associated with increased infection rates; however, additional appraisal of specific data from RCTs is needed.