RT info:eu-repo/semantics/article
T1 Escaping the Long Shadow Cast by Agranulocytosis: Reflections on Clozapine Pharmacovigilance Focused on the United Kingdom
A1 León, José de
A1 Arrojo Romero,  Manuel
A1 Verdoux, Hélène
A1 Ruan, Can-Jun
A1 Schoretsanitis, Georgios
A1 Rohde, Christopher
A1 Cohen, Dan
A1 Schulte, Peter F. J.
A1 Kim, Se Hyun
A1 Cotes, Robert O.
A1 Leung, Jonathan G.
A1 Otsuka,  Yuji
A1 Kirilochev, Oleg O.
A1 Baptista, Trino
A1 Grover, Sandeep
A1 Every-Palmer, Susanna
A1 Clark, Scott R.
A1 McGrane, Ian R.
A1 Motuca, Mariano
A1 Olmos, Ismael
A1 Wilkowska, Alina
A1 Sagud, Marina
A1 Yağcioğlu, A Elif Anil
A1 Ristic, Dragana Ignjatovic
A1 Lazary, Judit
A1 Sanz, Emilio J.
A1 Cuevas Castresana, Carlos De Las
A2 Medicina InternaDermatología y Psiquiatría
A2 Adherencia Terapéutica
K1 lozapine/adverse effects
K1 clozapine/administration and dosage
K1 clozapine/metabolism
K1 clozapine/therapeutic use
K1 clozapine/toxicity
K1 Covid-19
K1 drug labeling
K1 infection
K1 inflammation
K1 mortality/drug effects
K1 pneumonia
K1 schizophrenia
K1 sex
K1 smoking
AB Purpose/background: A recent article in this journal presented a US perspective regarding the modernization of clozapine prescription and proposed an escape from the long shadow cast by agranulocytosis.Methods: Here, an international group of collaborators discusses a point of view complementary to the US view by focusing on worldwide outcomes of clozapine usage that may be uneven in terms of frequency of clozapine adverse drug reactions.Findings/results: Studies from the Scandinavian national registries (Finland and Denmark) did not find increased mortality in clozapine patients or any clear evidence of the alleged toxicity of clozapine. Data on clozapine-associated fatal outcomes were obtained from 2 recently published pharmacovigilance studies and from the UK pharmacovigilance database. A pharmacovigilance study focused on physician reports to assess worldwide lethality of drugs from 2010 to 2019 found 968 clozapine-associated fatal outcomes in the United Kingdom. Moreover, the United Kingdom accounted for 55% (968 of 1761) of worldwide and 90% (968 of 1073) of European fatal clozapine-associated outcomes. In a pharmacovigilance study from the UK database (from 2008 to 2017), clozapine was associated with 383 fatal outcomes/year including all reports from physicians and nonphysicians. From 2018 to 2021, UK clozapine-associated fatal outcomes increased to 440/year.Implications/conclusions: The interpretation of fatal outcomes in each country using pharmacovigilance databases is limited and only allows gross comparisons; even with those limitations, the UK data seem concerning. Pneumonia and myocarditis may be more important than agranulocytosis in explaining the uneven distribution of fatal outcomes in clozapine patients across countries.
YR 2023
FD 2023
LK http://riull.ull.es/xmlui/handle/915/39637
UL http://riull.ull.es/xmlui/handle/915/39637
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 22-dic-2024