ABSTRACT
Background: The consumption of antibiotics is one of the metrics used to evaluate the impact of antimicrobial stewardship programs (ASP). The aim of this study was to determine the prevalence of antibiotic consumption in Brazilian intensive care units (ICUs) and estimate the deviation of the prescribed daily dose (PDD) from the defined daily dose (DDD). Methods: This is a multicenter, observational, point-prevalence study carried out in adult ICUs of 8 Brazilian hospitals from August 2019, to February 2020. We collected data on the patient's demographic and clinical characteristics, antibiotic therapy, classification and site of infections. The DU90 (antibiotic accounting for 90% of the volume utilized) was calculated, and the antibiotics were classified by the Anatomical Therapeutic Chemical (ATC) Index and the World Health Organization (WHO) Access, Watch, Reserve (AWaRe) groups. For the most prevalent antibiotics, the deviation of PDD from DDD was determined. Results: Three hundred thirty-two patients from 35 ICUs were analyzed. The prevalence of antibiotic use was 52.4%. The patients in use of antibiotics were predominantly over 60 years of age (81.6%) with pulmonary infections (45.8%). A predominance of empirical regimens was observed (62.6%) among antibiotic therapies. The highest frequencies of prescriptions observed were for piperacillin + tazobactam (16.1%), meropenem (13.3%), amoxicillin + clavulanate (7.2%), azithromycin (7.2%), and teicoplanin (6.1%). The watch (64.2%) and reserve (9.6%) categories of the AWaRe classification accounted for 73.8% of all antibiotics, and they were prescribed alone or in combinations. High variability of doses was observed for the most prescribed antibiotics, and large deviations of PDD from the DDD were observed for meropenem, teicoplanin, and tigecycline. Conclusions: The high prevalence of antibiotic prescription was related to a predominance of empirical regimens and antibiotics belonging to the WHO Watch classification. High variability of doses and large deviations of PDD from DDD for meropenem, teicoplanin, and tigecycline was observed, suggesting that DDD may be insufficient to monitor the consumption of these antibiotics in the ICU population. The variability of doses found for the most prescribed antibiotics suggests the need for monitoring and intervention targets for antibiotic stewardship teams.
ABSTRACT
Biological products have sparked a worldwide therapeutic revolution. However, the high cost of these products threatens health systems' sustainability. The development of copies is considered an economic alternative, but due to the products' complexity, many concepts used in generic drugs do not apply. Interchangeability between biologicals poses a regulatory challenge. This essay discusses the main regulatory challenges for establishing criteria for interchangeability between new biologicals and their copies in the scope of the Brazilian Unified National Health System (SUS), considering the guidelines adopted by the world's main drug regulatory agencies concerning interchangeability and the prevailing Brazilian regulatory framework on this issue. Concerns related to the interchangeability of biologicals include automatic substitution, nomenclature, pharmacovigilance, immunogenicity, and extrapolation of therapeutic indications and clinical data from new biologicals to their copies. While the clinical success and economic benefits of switching from new biologicals to their biosimilars have already been observed, the heterogeneity between countries in the regulatory barriers to the approval of copies of biologicals should be taken into consideration during the regulation of interchangeability of biologicals in Brazil.
Produtos biológicos revolucionaram a terapêutica mundial. O alto custo desses medicamentos, no entanto, ameaça a sustentabilidade dos sistemas de saúde. O desenvolvimento de cópias é tido como uma alternativa econômica, mas devido à complexidade desses produtos, muitos conceitos utilizados para os medicamentos genéricos não se aplicam. A intercambialidade entre produtos biológicos representa um desafio regulatório a ser superado. Este ensaio discute os principais desafios regulatórios relacionados ao estabelecimento de critérios para intercambialidade entre produtos biológicos novos e suas cópias no âmbito do Sistema Único de Saúde (SUS), considerando as diretrizes adotadas pelas principais agências reguladoras de medicamentos do mundo sobre a intercambialidade e o arcabouço regulatório vigente no Brasil para esta questão. Preocupações relacionadas à intercambialidade de produtos biológicos incluem substituição automática, nomenclatura, farmacovigilância, imunogenicidade e extrapolação das indicações terapêuticas e dos dados clínicos de produtos biológicos novos para suas cópias. Embora o sucesso clínico e os benefícios econômicos da alternância entre alguns produtos biológicos novos e seus biossimilares já tenham sido observados, a heterogeneidade das barreiras regulatórias para aprovação das cópias de produtos biológicos entre diferentes países deve ser considerada para a regulamentação da intercambialidade de produtos biológicos no Brasil.
Los productos biológicos revolucionaron la terapéutica mundial. El alto coste de estos medicamentos, no obstante, amenaza la sostenibilidad de los sistemas de salud. El desarrollo de copias se considera como una alternativa económica, pero debido a la complejidad de estos productos, muchos conceptos utilizados para los medicamentos genéricos no se aplican a los mismos. La intercambiabilidad entre productos biológicos representa un desafío regulatorio que se debe superar. Este trabajo discute los principales desafíos regulatorios, relacionados con el establecimiento de criterios para la intercambiabilidad entre productos biológicos nuevos y sus copias en el ámbito del Sistema Único de Salud (SUS), considerando las directrices adoptadas por las principales agencias regulatorias de medicamentos del mundo sobre la intercambiabilidad y el armazón regulatorio vigente en Brasil para esta cuestión. Las preocupaciones relacionadas con la intercambiabilidad de productos biológicos incluyen la sustitución automática, nomenclatura, farmacovigilancia, inmunogenicidad y extrapolación de las indicaciones terapéuticas, así como de los datos clínicos de productos biológicos nuevos para sus copias. A pesar de que el éxito clínico y los beneficios económicos de la alternancia entre algunos productos biológicos nuevos y sus biosimilares, ya se han observados, la heterogeneidad de las barreras regulatorias para la aprobación de las copias de productos biológicos entre los diferentes países debe ser considerada para la regulación de la intercambiabilidad de productos biológicos en Brasil.
Subject(s)
Biological Products , Biosimilar Pharmaceuticals , Legislation, Drug , Brazil , Drug Approval , Drugs, Generic , Humans , Legislation, Pharmacy , National Health Programs , Pharmacovigilance , Therapeutic EquivalencyABSTRACT
Resumo: Produtos biológicos revolucionaram a terapêutica mundial. O alto custo desses medicamentos, no entanto, ameaça a sustentabilidade dos sistemas de saúde. O desenvolvimento de cópias é tido como uma alternativa econômica, mas devido à complexidade desses produtos, muitos conceitos utilizados para os medicamentos genéricos não se aplicam. A intercambialidade entre produtos biológicos representa um desafio regulatório a ser superado. Este ensaio discute os principais desafios regulatórios relacionados ao estabelecimento de critérios para intercambialidade entre produtos biológicos novos e suas cópias no âmbito do Sistema Único de Saúde (SUS), considerando as diretrizes adotadas pelas principais agências reguladoras de medicamentos do mundo sobre a intercambialidade e o arcabouço regulatório vigente no Brasil para esta questão. Preocupações relacionadas à intercambialidade de produtos biológicos incluem substituição automática, nomenclatura, farmacovigilância, imunogenicidade e extrapolação das indicações terapêuticas e dos dados clínicos de produtos biológicos novos para suas cópias. Embora o sucesso clínico e os benefícios econômicos da alternância entre alguns produtos biológicos novos e seus biossimilares já tenham sido observados, a heterogeneidade das barreiras regulatórias para aprovação das cópias de produtos biológicos entre diferentes países deve ser considerada para a regulamentação da intercambialidade de produtos biológicos no Brasil.
Abstract: Biological products have sparked a worldwide therapeutic revolution. However, the high cost of these products threatens health systems' sustainability. The development of copies is considered an economic alternative, but due to the products' complexity, many concepts used in generic drugs do not apply. Interchangeability between biologicals poses a regulatory challenge. This essay discusses the main regulatory challenges for establishing criteria for interchangeability between new biologicals and their copies in the scope of the Brazilian Unified National Health System (SUS), considering the guidelines adopted by the world's main drug regulatory agencies concerning interchangeability and the prevailing Brazilian regulatory framework on this issue. Concerns related to the interchangeability of biologicals include automatic substitution, nomenclature, pharmacovigilance, immunogenicity, and extrapolation of therapeutic indications and clinical data from new biologicals to their copies. While the clinical success and economic benefits of switching from new biologicals to their biosimilars have already been observed, the heterogeneity between countries in the regulatory barriers to the approval of copies of biologicals should be taken into consideration during the regulation of interchangeability of biologicals in Brazil.
Resumen: Los productos biológicos revolucionaron la terapéutica mundial. El alto coste de estos medicamentos, no obstante, amenaza la sostenibilidad de los sistemas de salud. El desarrollo de copias se considera como una alternativa económica, pero debido a la complejidad de estos productos, muchos conceptos utilizados para los medicamentos genéricos no se aplican a los mismos. La intercambiabilidad entre productos biológicos representa un desafío regulatorio que se debe superar. Este trabajo discute los principales desafíos regulatorios, relacionados con el establecimiento de criterios para la intercambiabilidad entre productos biológicos nuevos y sus copias en el ámbito del Sistema Único de Salud (SUS), considerando las directrices adoptadas por las principales agencias regulatorias de medicamentos del mundo sobre la intercambiabilidad y el armazón regulatorio vigente en Brasil para esta cuestión. Las preocupaciones relacionadas con la intercambiabilidad de productos biológicos incluyen la sustitución automática, nomenclatura, farmacovigilancia, inmunogenicidad y extrapolación de las indicaciones terapéuticas, así como de los datos clínicos de productos biológicos nuevos para sus copias. A pesar de que el éxito clínico y los beneficios económicos de la alternancia entre algunos productos biológicos nuevos y sus biosimilares, ya se han observados, la heterogeneidad de las barreras regulatorias para la aprobación de las copias de productos biológicos entre los diferentes países debe ser considerada para la regulación de la intercambiabilidad de productos biológicos en Brasil.
Subject(s)
Humans , Biological Products , Biosimilar Pharmaceuticals , Legislation, Drug , Brazil , Therapeutic Equivalency , Drugs, Generic , Drug Approval , Pharmacovigilance , Legislation, Pharmacy , National Health ProgramsABSTRACT
No presente estudo, são relatadas as intervenções realizadas pelo serviço de farmácia junto ao corpo clínico de uma instituição pública federal, referência nacional para cirurgias de alta complexidade em ortopedia no Rio de Janeiro. Realizou-se estudo retrospectivo no qual foram analisadas as intervenções farmacêuticas realizadas entre junho de 2004 e junho de 2005. O serviço de farmácia atendeu 13,6% dos 5476 pacientes internados neste período. Dos pacientes atendidos, 30,4% necessitaram de pelo menos uma intervenção deste profissional junto ao corpo clínico em algum momento da sua internação, perfazendo um total de 227 intervenções. Os médicos foram os profissionais mais contatados (71,1%), seguidos dos enfermeiros (16,9%) e auxiliares de enfermagem (4,6%). Dos problemas detectados, 84,1% correspondiam a erros, dos quais 49,5% foram prevenidos com as intervenções. A análise dos erros encontrados nos permite sugerir alguns dos principais problemas relacionados a medicamentos apresentados pelos pacientes da instituição. Das intervenções realizadas, 70% foram aceitas, sendo este percentual de 60% para as intervenções relacionadas à prescrição. Os resultados sugerem que as intervenções farmacêuticas foram ferramentas efetivas para a prevenção de eventos adversos, reforçando a importância da assistência farmacêutica para a qualidade da assistência hospitalar.
In the present study, we describe the pharmaceutical interventions performed by the pharmacy service of a publicorthopaedic hospital at Rio de Janeiro, Brazil. In a retrospective study, we analysed the pharmaceutical interventions performed during a year (from june 2004 to june 2005). The pharmacy service assisted 13.6% of the5476 patients that were submitted to internation. In 30.4 % of the patients that were directly assisted by the pharmacist was identified the necessity of pharmaceutical interventions, reaching 227 interventions during the period of the study. The physicians were the most requested professionals (71.1%), followed by nurses 16.9%. Eighty four percent of the problems that were detected were related to potential medication errors. Forty nine percent of these errors were prevented by the pharmacists. It was possible to predict some of the potential drug related problems that could be related to these patients as well. Seventy percent of the pharmaceutical interventions were accepted by the professionals. For the interventions related to prescription,sixty percent were accepted. The results suggest that pharmaceutical interventions were effective to prevent drug adverse events, reinforcing the important role of pharmacists in hospital assistance.
Subject(s)
Dosage/analysis , Pharmaceutical Services , Pharmacy Service, Hospital , Pharmaceutical Preparations/standardsABSTRACT
ATP and ADP induce retinal cell proliferation through activation of PKC and extracellular signal-regulated kinases (ERKs). Here, we characterized the effect of purinergic agonists on the turnover of phosphoinositides and activation of ERKs during development of the chick embryo retina. When intact retinas were incubated with ATP, ADP or UTP, a dose-dependent accumulation of [(3)H]-phosphoinositides was observed (% of control, EC(50): 548+/-20.5%, 0.18 mM; 314+/-53.8%, 0.51 mM; 704+/-139.9%, 0.018 mM, respectively). Only the response promoted by ADP was completely inhibited by the P2 receptor antagonists, PPADS and suramin. All the responses decreased with the progression of retinal development. Western blot assays revealed that ATP, ADP and UTP stimulated the phosphorylation of ERKs in the chick embryo retina very early during development (% of control: 174+/-16; 199+/-16.4 and 206+/-37, respectively). The responses to ADP and UTP were transient and dose-dependent, showing EC(50) values of 0.12 mM and 0.009 mM. The response to ADP was inhibited by the antagonists PPADS and suramin and by U73122 and chelerythrine chloride, which block PLC and PKC, respectively. Conversely, chelerythrine chloride did not block the response induced by UTP. Immunohistochemical analysis revealed that ATP and ADP induced the phosphorylation of ERKs in cells of the neuroblastic layer of retinas from embryos at E8. Our data showed that ATP, ADP and UTP stimulate the turnover of InsPs and promoted the activation of ERKs in the chick embryo retina. ADP, through activation of P2Y(1) receptors, activated ERK pathway through PLC and PKC and UTP, via P2Y(4)-like receptors, induced the phosphorylation of ERKs through a pathway that did not involve PKC.
