Análisis de las dosis habituales, incidencia de reacciones adversas e interacciones de inmunosupresores con monitorización farmacocinética (tacrolimus y ciclosporina) en pacientes sometidos a trasplante de precursores hematopoyéticos : lugar de desarrollo Hospital del Salvador
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Archivos
Fecha
2023
Autores
Profesor/a Guía
Facultad/escuela
Idioma
es
Título de la revista
ISSN de la revista
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Editor
Universidad Andrés Bello
Nombre de Curso
Licencia CC
Licencia CC
Resumen
El trasplante de progenitores hematopoyéticos se realiza con la finalidad de
restablecer la función medular ya sea por estar defectuosa o ser ineficiente o por
neoplasias, dicho trasplante puede ser alogénico, el cual es manejado con
inmunosupresores, ya que puede provocar enfermedad injerto contra huésped. El
principal objetivo fue determinar la incidencia de efectos adversos, factores de
riesgo, interacciones y analizar dosis habituales de ciclosporina y tacrolimus con
monitorización de niveles sanguíneos en pacientes trasplantados de progenitores
hematopoyéticos en el Hospital del Salvador.
Se llevó a cabo un estudio cuantitativo observacional, descriptivo y transversal
mediante la revisión de las fichas clínicas de los pacientes y seguimiento
farmacoterapéutico donde además se analizó la evolución y resultados de
exámenes de laboratorios en pacientes sometidos a TPH alogénico desde
diciembre 2021 hasta febrero 2023.
Se logró reclutar a 70 pacientes con una mediana de 30 años de edad, en donde,
aproximadamente la mitad era de sexo femenino y la otra mitad de sexo masculino.
El traspaso de vía IV a VO de los inmunosupresores fue en promedio el día 17. Al
45.8% de los pacientes no se le modificó la dosis al momento del traspaso a vía
oral, sin embargo, 37.5% de los pacientes se le disminuyó la dosis en un promedio
de 14% al momento de cambiar de vía intravenosa a vía oral el inmunosupresor.
Además, se logró determinar la incidencia de reacciones adversas, de los 70
pacientes, el 96% presentó RAM, de ellos, el 57% presentó falla renal, el 17% de
los pacientes hipertensión arterial, el 15% temblores y el 13% de los pacientes
cefalea, siendo las más frecuentes. Sin embargo, no es posible afirmar con certeza
la causalidad de estas reacciones adversas ya que es una probabilidad de que una
reacción adversa ocurra debido al medicamento y no a otros factores.
Con respecto a las interacciones, al iniciar el uso concomitante de
inmunosupresores con fluconazol, en un 16% de los pacientes se vio un aumento
de niveles en un promedio de 62%. Por otro lado, al momento de suspender
fluconazol, se observó en un 24.49% de los pacientes una disminución de niveles
de inmunosupresores en un promedio de 29%.
De los factores que pueden alterar los niveles de inmunosupresores se encontraron
los corticoides. En un 3.08% de los pacientes se tuvo que disminuir la dosis de
inmunosupresores al momento de iniciar uso de corticoides en un promedio de 33%,
sin embargo, en un 6.15% de los pacientes se tuvo que aumentar la dosis de
inmunosupresores en promedio de 104% y en un 3.08% de los pacientes se observó
una disminución de niveles en un 25% en el uso concomitante de inmunosupresores
y corticoides.
En conclusión, en los pacientes sometidos a trasplante de progenitores
hematopoyéticos en tratamiento con ciclosoporina o tacrolimus, se vio una elevada
incidencia de EICH. El principal factor de riesgo fueron los corticoides, sin embargo, no interfieren con relevancia en los niveles de inmunosupresores. La principal
interacción con los inhibidores de la calcineurina fue el fluconazol, aunque, en un
gran porcentaje no interfieren de manera notable. Se observó una elevada
incidencia de nefrotoxicidad, hipertensión arterial y en menor medida temblores y
cefalea. Finalmente, se lograron caracterizar las pautas terapéuticas y se identificó
que la mayoría de las dosis no se aumentaron al doble debido a niveles terapéuticos
con la misma dosis IV y oral.
Hematopoietic progenitor transplantation is performed in order to restore bone marrow function either because it is defective or inefficient or due to neoplasms, said transplant can be allogeneic, which can cause graft-versus-host disease. In order to evaluate compliance with conventional immunosuppressive therapies of said transplant, according to the provisions in the literature, as well as analyze the factors associated with alterations in immunosuppressive levels, incidence of adverse effects and interactions, an observational, descriptive and cross-sectional quantitative study was carried out. The main objective was to determine the incidence of adverse effects, risk factors, interactions and analyze usual doses of cyclosporine and tacrolimus with monitoring of blood levels in patients transplanted from hematopoietic progenitors at the Hospital del Salvador. An observational, descriptive and cross-sectional quantitative study was carried out through the review of the clinical records of the patients and pharmacotherapeutic follow-up where the evolution and results of laboratory tests in patients undergoing allogeneic TPH were also analyzed from December 2021 to February 2023. In this study, a review of the clinical records of the patients was carried out, where the pharmacotherapy, evolution and results of laboratory examinations were analyzed from December 2021 to February 2022. The main objective being to determine the incidence of adverse effects, risk factors, interactions and to analyze usual doses of Cyclosporine and Tacrolimus with monitoring of blood levels in patients transplanted from hematopoietic progenitors in the Hospital of Salvador. It was possible to recruit 70 patients with a median of 30 years of age, where approximately half were female and the other half were male. The transfer from route IV to VO of immunosuppressants was on average on day 17. 45.8% of the patients did not change the dose at the time of the transfer to the oral route, however, 37.5% of the patients the dose was reduced by an average of 14% at the time of changing the immunosuppressant from intravenous to oral route. In addition, it was possible to determine the incidence of adverse reactions, of the 70 patients, 96% had adverse reactions, of which 57% had renal failure, 17% of patients had high blood pressure, 15% tremors and 13% of patients had headache, being the most frequent. However, it is not possible to affirm with certainty the causality of these adverse reactions. With respect to interactions, when starting the concomitant use of immunosuppressants with fluconazole, 16% of patients saw an increase in levels by an average of 62%. On the other hand, at the time of discontinuation of fluconazole, a decrease in immunosuppressive levels of an average of 29% was observed in 24.49% of patients. and in 4.08% an increase in levels was observed in an average of 23%. Of the factors that can alter the levels of immunosuppressants, corticosteroids were found. In 3.08% of the patients, the dose of immunosuppressants had to be reduced at the time of starting the use of corticosteroids by an average of 33%, however, in 6.15% of the patients the dose of immunosuppressants had to be increased by an average of 104% and in 3.08% of the patients a decrease in levels of 25% in the concomitant use of immunosuppressants and corticosteroids was observed. In conclusion, in patients undergoing hematopoietic progenitor transplantation treated with ciclosoporine or tacrolimus, a high incidence of GVHD was seen. The main risk factor was corticosteroids, however, they do not interfere with significant immunosuppressant levels. The main interaction with calcineurin inhibitors was fluconazole, although, in a large percentage, they do not interfere significantly. A high incidence of nephrotoxicity, high blood pressure and to a lesser extent tremors and headache were observed. Finally, it was possible to characterize the therapeutic guidelines and it was identified that most of the doses were not doubled due to therapeutic levels with the same IV and oral dose.
Hematopoietic progenitor transplantation is performed in order to restore bone marrow function either because it is defective or inefficient or due to neoplasms, said transplant can be allogeneic, which can cause graft-versus-host disease. In order to evaluate compliance with conventional immunosuppressive therapies of said transplant, according to the provisions in the literature, as well as analyze the factors associated with alterations in immunosuppressive levels, incidence of adverse effects and interactions, an observational, descriptive and cross-sectional quantitative study was carried out. The main objective was to determine the incidence of adverse effects, risk factors, interactions and analyze usual doses of cyclosporine and tacrolimus with monitoring of blood levels in patients transplanted from hematopoietic progenitors at the Hospital del Salvador. An observational, descriptive and cross-sectional quantitative study was carried out through the review of the clinical records of the patients and pharmacotherapeutic follow-up where the evolution and results of laboratory tests in patients undergoing allogeneic TPH were also analyzed from December 2021 to February 2023. In this study, a review of the clinical records of the patients was carried out, where the pharmacotherapy, evolution and results of laboratory examinations were analyzed from December 2021 to February 2022. The main objective being to determine the incidence of adverse effects, risk factors, interactions and to analyze usual doses of Cyclosporine and Tacrolimus with monitoring of blood levels in patients transplanted from hematopoietic progenitors in the Hospital of Salvador. It was possible to recruit 70 patients with a median of 30 years of age, where approximately half were female and the other half were male. The transfer from route IV to VO of immunosuppressants was on average on day 17. 45.8% of the patients did not change the dose at the time of the transfer to the oral route, however, 37.5% of the patients the dose was reduced by an average of 14% at the time of changing the immunosuppressant from intravenous to oral route. In addition, it was possible to determine the incidence of adverse reactions, of the 70 patients, 96% had adverse reactions, of which 57% had renal failure, 17% of patients had high blood pressure, 15% tremors and 13% of patients had headache, being the most frequent. However, it is not possible to affirm with certainty the causality of these adverse reactions. With respect to interactions, when starting the concomitant use of immunosuppressants with fluconazole, 16% of patients saw an increase in levels by an average of 62%. On the other hand, at the time of discontinuation of fluconazole, a decrease in immunosuppressive levels of an average of 29% was observed in 24.49% of patients. and in 4.08% an increase in levels was observed in an average of 23%. Of the factors that can alter the levels of immunosuppressants, corticosteroids were found. In 3.08% of the patients, the dose of immunosuppressants had to be reduced at the time of starting the use of corticosteroids by an average of 33%, however, in 6.15% of the patients the dose of immunosuppressants had to be increased by an average of 104% and in 3.08% of the patients a decrease in levels of 25% in the concomitant use of immunosuppressants and corticosteroids was observed. In conclusion, in patients undergoing hematopoietic progenitor transplantation treated with ciclosoporine or tacrolimus, a high incidence of GVHD was seen. The main risk factor was corticosteroids, however, they do not interfere with significant immunosuppressant levels. The main interaction with calcineurin inhibitors was fluconazole, although, in a large percentage, they do not interfere significantly. A high incidence of nephrotoxicity, high blood pressure and to a lesser extent tremors and headache were observed. Finally, it was possible to characterize the therapeutic guidelines and it was identified that most of the doses were not doubled due to therapeutic levels with the same IV and oral dose.
Notas
Seminario (Química Farmacéutica)
Palabras clave
Agentes Inmunosupresores, Efectos Adversos, Trasplante de Progenitores Hematopoyéticos, Medicamentos, Aministración y Dosificación