RT info:eu-repo/semantics/article
T1 Adverse drug reactions and their fatal outcomes in clozapine patients in VigiBase: Comparing the top four reporting countries (US, UK, Canada and Australia)
A1 Cuevas Castresana, Carlos de Las
A1 Sanz, .Emilio J-
A1 León, José de
A2 Adherencia Terapéutica
K1 Clozapine
K1 Adverse drug reaction
K1 Fatal outcome
K1 VigiBase
K1 Disproportionality analysis
AB Background: Pharmacovigilance findings and box warnings in the clozapine package inserts have marked the history of clozapine. Objective: This is the largest review of clozapine adverse drug reactions (ADRs) and their associated fatal outcomes. Reports to the World Health Organization’s global pharmacovigilance database, VigiBase™, were analyzed, extending from clozapine’s introduction to December 31, 2022. Methods: The analysis focused on the top four reporting countries: United States (US), United Kingdom (UK), Canada and Australia (83 % of fatal outcomes worldwide). Attempts were made to control for population and clozapine prescription in each country. Results: Clozapine ADRs worldwide accounted for 191,557 reports, with the highest number (53,505) in “blood and lymphatic system disorder”. Of the 22,596 fatal outcomes reported in clozapine patients, 9587 were from the US, 6567 from the UK, 3623 from Canada and 1484 from Australia. The top category worldwide in fatal outcomes was nonspecifically labeled “death” with 46 % (range 22–62 %). “Pneumonia” was second with 30 % (range 17–45 %). Agranulocytosis was numerically only the 35th top clozapine ADR associated with fatal outcomes. On average, 2.3 clozapine ADRs were reported per fatal outcome. Infections were associated with 24.2 % of the UK fatal outcomes (9.4 %–11.9 % in the 3 other countries). Conclusions: The four countries appeared to report clozapine ADRs in different ways, making comparisons difficult. We estimated higher fatal outcomes in the UK and Canada after controlling for cross-sectional estimations of population and published clozapine use. This last hypothesis is limited by the lack of precise estimation of accumulated clozapine use in each country.
SN 1573-2509
YR 2024
FD 2024
LK http://riull.ull.es/xmlui/handle/915/39625
UL http://riull.ull.es/xmlui/handle/915/39625
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 22-dic-2024