| Name: | Description: | Size: | Format: | |
|---|---|---|---|---|
| 914.94 KB | Adobe PDF |
Authors
Advisor(s)
Abstract(s)
Introdução: Notificações espontâneas de reações adversas músculo-esqueléticas duradouras motivaram a autoridade alemã do medicamento a solicitar, em 2017, um referral procedure ao PRAC (Pharmacovigilance Risk Assessment Committee) para as formas sistémica e inaladas dos antibióticos pertencentes às quinolonas e fluoroquinolonas. A revisão levou à remoção de todas as quinolonas do mercado, e à restrição do uso das fluoroquinolonas, associada a uma DHPC (Direct Healthcare Professional Communication), em 2019, e na comissão do estudo EUPAS37856, cujos resultados levaram à emissão de uma segunda DHPC em 2023.
Objetivos: Este estudo descritivo procura explorar o efeito destas ações regulamentares no padrão global de notificações espontâneas para as fluoroquinolonas, e no padrão de notificação para as fluoroquinolonas relativo às reações adversas para as quais as DHPC alertavam.
Métodos: Notificações espontâneas de fluoroquinolonas abrangidas por ambas DHPC, nas formas sistémica e inaladas, de 1 de abril de 2014 a 30 de abril de 2024, do EEE, foram recolhidas da base de dados EudraVigilance. Notificações provenientes da literatura e relativas a outras formas farmacêuticas foram excluídas. O conjunto de notificações foi então submetido a uma análise de todas as notificações, uma análise de casos com pelo menos um PT (Preferred Term) do MedDRA (Medical Dictionary for Regulatory Activities) pertencente às SOC (System Organ Classes) “Perturbações músculo-esqueléticas e do tecido conjuntivo” e “Perturbações do sistema nervoso”, e uma análise selecionando apenas casos com PT relativos a tendinite.
Resultados: Obtivemos um total de 31681 casos de interesse. O total de notificações aumentou desde 2016, atingiu o pico em 2019 (5005) e diminuiu para um nadir em 2021 (1977). Seguiu-se um segundo pico mais fraco em 2023 (3005), que diminuiu até ao final do período de análise. Estes resultados repetiram-se nas análises subsequentes.
Conclusão: Casos aumentaram, devido a utilização incorreta, até à primeira DHPC, associada ao pico dos casos, e que levou à diminuição do uso de fluoroquinolonas ao alertar profissionais de saúde. O segundo pico pode ser atribuído à segunda DHPC, e o efeito menos dramático pode dever-se a dessensibilização e/ou efetividade parcial da primeira DHPC. As DHPC aumentarão a notificação espontânea, reforçando a sua importância.
Background: Case reports of long-lasting musculoskeletal side-effects motivated the German Medicines Authority to request, in 2017, a referral procedure to the PRAC (Pharmacovigilance Risk Assessment Committee), for systemic and inhaled quinolone and fluoroquinolone antibiotics. The review led to the removal from the market of all quinolones, and to a restriction in the use of fluoroquinolones, associated to a Direct Healthcare Professional Communication (DHPC) in 2019, and the commissioning of the study EUPAS37856, which results led the PRAC to issue a second DHPC in 2023. Objectives: This descriptive study aims to explore these regulatory actions’ effect on the overall pattern of spontaneous reports for the fluoroquinolones, as well as on the pattern of notification for the fluoroquinolones relative to the adverse reactions for which the DHPCs precautioned. Methods: Case reports of fluoroquinolones ranged by both DHPCs, in their inhaled and systemic forms, from April 1, 2014, to April 30, 2024, from the EEA, were retrieved from the EudraVigilance database. Cases from literature, and other pharmaceutical forms were excluded. The set of reports was then submitted to an analysis of all notifications, an analysis of cases with at least one MedDRA (Medical Dictionary for Regulatory Activities) PT (Preferred Term) belonging to the “Musculoskeletal and connective tissue disorders” and “Nervous system disorders” SOCs (System Organ Classes), and a third analysis for cases containing a PT relative to tendinitis. Results: A total of 31681 cases of interest were retrieved. The total number of reports for fluoroquinolones increased since 2016, peaked in 2019 (5005), and declined to a nadir in 2021 (1977). A second, weaker peak followed in 2023 (3005), which decreased until the end of the period of analysis. These results were mirrored in subsequent analyses. Conclusion: Cases increased due to undue use until the first DHPC, which, associated with the peak in reports, alerted healthcare professionals and contributed to a decrease in fluoroquinolone use. The second peak can be attributed to the second DHPC, and its less dramatic effect may be due to desensitisation and/or partial effectiveness of the first DHPC. The DHPCs may lead to spontaneous reporting increases, reinforcing their importance.
Background: Case reports of long-lasting musculoskeletal side-effects motivated the German Medicines Authority to request, in 2017, a referral procedure to the PRAC (Pharmacovigilance Risk Assessment Committee), for systemic and inhaled quinolone and fluoroquinolone antibiotics. The review led to the removal from the market of all quinolones, and to a restriction in the use of fluoroquinolones, associated to a Direct Healthcare Professional Communication (DHPC) in 2019, and the commissioning of the study EUPAS37856, which results led the PRAC to issue a second DHPC in 2023. Objectives: This descriptive study aims to explore these regulatory actions’ effect on the overall pattern of spontaneous reports for the fluoroquinolones, as well as on the pattern of notification for the fluoroquinolones relative to the adverse reactions for which the DHPCs precautioned. Methods: Case reports of fluoroquinolones ranged by both DHPCs, in their inhaled and systemic forms, from April 1, 2014, to April 30, 2024, from the EEA, were retrieved from the EudraVigilance database. Cases from literature, and other pharmaceutical forms were excluded. The set of reports was then submitted to an analysis of all notifications, an analysis of cases with at least one MedDRA (Medical Dictionary for Regulatory Activities) PT (Preferred Term) belonging to the “Musculoskeletal and connective tissue disorders” and “Nervous system disorders” SOCs (System Organ Classes), and a third analysis for cases containing a PT relative to tendinitis. Results: A total of 31681 cases of interest were retrieved. The total number of reports for fluoroquinolones increased since 2016, peaked in 2019 (5005), and declined to a nadir in 2021 (1977). A second, weaker peak followed in 2023 (3005), which decreased until the end of the period of analysis. These results were mirrored in subsequent analyses. Conclusion: Cases increased due to undue use until the first DHPC, which, associated with the peak in reports, alerted healthcare professionals and contributed to a decrease in fluoroquinolone use. The second peak can be attributed to the second DHPC, and its less dramatic effect may be due to desensitisation and/or partial effectiveness of the first DHPC. The DHPCs may lead to spontaneous reporting increases, reinforcing their importance.
Description
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2024, Universidade de Lisboa, Faculdade de Farmácia
Keywords
Fluoroquinolones EudraVigilance Risk minimization measures Pharmacovigilance DHPC Mestrado Integrado - 2024