Clozapine-associated neutropenia and agranulocytosis in Argentina (2007-2012)

Autores
Balda, María Victoria; Garay, Osvaldo U.; Papale, Rosa M.; Bignone, Inés; Bologna, Viviana G.; Brandolini, Andrés; Prokopez, Cintia R.; Balasini, Juan I.; Baldessarini, Ross J.; Daray, Federico Manuel
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The risks of severe leukopenia and agranulocytosis have varied over time and among geographical regions and cultures, with little information available on South American populations. Accordingly, we reviewed and analyzed data from a 6-year experience monitored by an Argentine national registry to which reporting of adverse events reports is required. We analyzed data for 2007-2012 from the pharmacovigilance program of the Argentine drug-regulatory agency (ANMAT) using standard bivariate and multivariate statistical methods and survival analysis. We identified 378 cases of adverse hematological events over 6 years among an average of 12 305 individuals/year treated with clozapine (308±133 mg/day) to estimate the mean annualized rates of leukopenia [0.19 (95% confidence interval [CI] 0.11-0.27)], neutropenia [0.38 (95% CI 0.34-0.43)], and agranulocytosis [0.05 (95% CI 0.02-0.08)] % per year [median latency 2 (95% CI 1.3-2.1) months]; fatalities related to agranulocytosis averaged 4.2 (95% CI 0.0-9.2) per 100 000 treated individuals/year. Factors associated significantly and independently with agranulocytosis were female sex, older age, and use of other drugs in addition to clozapine. With monitoring by international standards, recent risks of clozapine-associated agranulocytosis in Argentina were lower, but fatality rates were higher than that in other regions of the world. Risk factors include the use of multiple psychotropic drugs, female sex, and older age.
Fil: Balda, María Victoria. Ministerio de Salud. Administración Nacional de Medicamentos, Alimentos y Tecnología Médica; Argentina
Fil: Garay, Osvaldo U.. Instituto de Efectividad Clinica y Sanitaria; Argentina
Fil: Papale, Rosa M.. Ministerio de Salud. Administración Nacional de Medicamentos, Alimentos y Tecnología Médica; Argentina
Fil: Bignone, Inés. Ministerio de Salud. Administración Nacional de Medicamentos, Alimentos y Tecnología Médica; Argentina
Fil: Bologna, Viviana G.. Ministerio de Salud. Administración Nacional de Medicamentos, Alimentos y Tecnología Médica; Argentina
Fil: Brandolini, Andrés. Ministerio de Salud. Administración Nacional de Medicamentos, Alimentos y Tecnología Médica; Argentina
Fil: Prokopez, Cintia R.. Ministerio de Salud. Administración Nacional de Medicamentos, Alimentos y Tecnología Médica; Argentina
Fil: Balasini, Juan I.. Ministerio de Economía y Finanzas Públicas. Secretaría de Política Económica; Argentina
Fil: Baldessarini, Ross J.. Harvard Medical School; Estados Unidos
Fil: Daray, Federico Manuel. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Agranulocytosis
Clozapine
Argentina
Pharmacovigilance
Leukopenia
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/16174
Acceder
id CONICETDig_0daf91346ce26481418438f67d94a0f6
oai_identifier_str oai:ri.conicet.gov.ar:11336/16174
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Clozapine-associated neutropenia and agranulocytosis in Argentina (2007-2012)Balda, María VictoriaGaray, Osvaldo U.Papale, Rosa M.Bignone, InésBologna, Viviana G.Brandolini, AndrésProkopez, Cintia R.Balasini, Juan I.Baldessarini, Ross J.Daray, Federico ManuelAgranulocytosisClozapineArgentinaPharmacovigilanceLeukopeniahttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3The risks of severe leukopenia and agranulocytosis have varied over time and among geographical regions and cultures, with little information available on South American populations. Accordingly, we reviewed and analyzed data from a 6-year experience monitored by an Argentine national registry to which reporting of adverse events reports is required. We analyzed data for 2007-2012 from the pharmacovigilance program of the Argentine drug-regulatory agency (ANMAT) using standard bivariate and multivariate statistical methods and survival analysis. We identified 378 cases of adverse hematological events over 6 years among an average of 12 305 individuals/year treated with clozapine (308±133 mg/day) to estimate the mean annualized rates of leukopenia [0.19 (95% confidence interval [CI] 0.11-0.27)], neutropenia [0.38 (95% CI 0.34-0.43)], and agranulocytosis [0.05 (95% CI 0.02-0.08)] % per year [median latency 2 (95% CI 1.3-2.1) months]; fatalities related to agranulocytosis averaged 4.2 (95% CI 0.0-9.2) per 100 000 treated individuals/year. Factors associated significantly and independently with agranulocytosis were female sex, older age, and use of other drugs in addition to clozapine. With monitoring by international standards, recent risks of clozapine-associated agranulocytosis in Argentina were lower, but fatality rates were higher than that in other regions of the world. Risk factors include the use of multiple psychotropic drugs, female sex, and older age.Fil: Balda, María Victoria. Ministerio de Salud. Administración Nacional de Medicamentos, Alimentos y Tecnología Médica; ArgentinaFil: Garay, Osvaldo U.. Instituto de Efectividad Clinica y Sanitaria; ArgentinaFil: Papale, Rosa M.. Ministerio de Salud. Administración Nacional de Medicamentos, Alimentos y Tecnología Médica; ArgentinaFil: Bignone, Inés. Ministerio de Salud. Administración Nacional de Medicamentos, Alimentos y Tecnología Médica; ArgentinaFil: Bologna, Viviana G.. Ministerio de Salud. Administración Nacional de Medicamentos, Alimentos y Tecnología Médica; ArgentinaFil: Brandolini, Andrés. Ministerio de Salud. Administración Nacional de Medicamentos, Alimentos y Tecnología Médica; ArgentinaFil: Prokopez, Cintia R.. Ministerio de Salud. Administración Nacional de Medicamentos, Alimentos y Tecnología Médica; ArgentinaFil: Balasini, Juan I.. Ministerio de Economía y Finanzas Públicas. Secretaría de Política Económica; ArgentinaFil: Baldessarini, Ross J.. Harvard Medical School; Estados UnidosFil: Daray, Federico Manuel. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaLippincott Williams2015-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/16174Balda, María Victoria; Garay, Osvaldo U.; Papale, Rosa M.; Bignone, Inés; Bologna, Viviana G.; et al.; Clozapine-associated neutropenia and agranulocytosis in Argentina (2007-2012); Lippincott Williams; International Clinical Psychopharmacology; 30; 2; 3-2015; 109-1140268-1315enginfo:eu-repo/semantics/altIdentifier/doi/10.1097/YIC.0000000000000060info:eu-repo/semantics/altIdentifier/url/http://journals.lww.com/intclinpsychopharm/pages/articleviewer.aspx?year=2015&issue=03000&article=00008&type=abstractinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:14:04Zoai:ri.conicet.gov.ar:11336/16174instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 12:14:04.445CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Clozapine-associated neutropenia and agranulocytosis in Argentina (2007-2012)
title Clozapine-associated neutropenia and agranulocytosis in Argentina (2007-2012)
spellingShingle Clozapine-associated neutropenia and agranulocytosis in Argentina (2007-2012)
Balda, María Victoria
Agranulocytosis
Clozapine
Argentina
Pharmacovigilance
Leukopenia
title_short Clozapine-associated neutropenia and agranulocytosis in Argentina (2007-2012)
title_full Clozapine-associated neutropenia and agranulocytosis in Argentina (2007-2012)
title_fullStr Clozapine-associated neutropenia and agranulocytosis in Argentina (2007-2012)
title_full_unstemmed Clozapine-associated neutropenia and agranulocytosis in Argentina (2007-2012)
title_sort Clozapine-associated neutropenia and agranulocytosis in Argentina (2007-2012)
dc.creator.none.fl_str_mv Balda, María Victoria
Garay, Osvaldo U.
Papale, Rosa M.
Bignone, Inés
Bologna, Viviana G.
Brandolini, Andrés
Prokopez, Cintia R.
Balasini, Juan I.
Baldessarini, Ross J.
Daray, Federico Manuel
author Balda, María Victoria
author_facet Balda, María Victoria
Garay, Osvaldo U.
Papale, Rosa M.
Bignone, Inés
Bologna, Viviana G.
Brandolini, Andrés
Prokopez, Cintia R.
Balasini, Juan I.
Baldessarini, Ross J.
Daray, Federico Manuel
author_role author
author2 Garay, Osvaldo U.
Papale, Rosa M.
Bignone, Inés
Bologna, Viviana G.
Brandolini, Andrés
Prokopez, Cintia R.
Balasini, Juan I.
Baldessarini, Ross J.
Daray, Federico Manuel
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Agranulocytosis
Clozapine
Argentina
Pharmacovigilance
Leukopenia
topic Agranulocytosis
Clozapine
Argentina
Pharmacovigilance
Leukopenia
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The risks of severe leukopenia and agranulocytosis have varied over time and among geographical regions and cultures, with little information available on South American populations. Accordingly, we reviewed and analyzed data from a 6-year experience monitored by an Argentine national registry to which reporting of adverse events reports is required. We analyzed data for 2007-2012 from the pharmacovigilance program of the Argentine drug-regulatory agency (ANMAT) using standard bivariate and multivariate statistical methods and survival analysis. We identified 378 cases of adverse hematological events over 6 years among an average of 12 305 individuals/year treated with clozapine (308±133 mg/day) to estimate the mean annualized rates of leukopenia [0.19 (95% confidence interval [CI] 0.11-0.27)], neutropenia [0.38 (95% CI 0.34-0.43)], and agranulocytosis [0.05 (95% CI 0.02-0.08)] % per year [median latency 2 (95% CI 1.3-2.1) months]; fatalities related to agranulocytosis averaged 4.2 (95% CI 0.0-9.2) per 100 000 treated individuals/year. Factors associated significantly and independently with agranulocytosis were female sex, older age, and use of other drugs in addition to clozapine. With monitoring by international standards, recent risks of clozapine-associated agranulocytosis in Argentina were lower, but fatality rates were higher than that in other regions of the world. Risk factors include the use of multiple psychotropic drugs, female sex, and older age.
Fil: Balda, María Victoria. Ministerio de Salud. Administración Nacional de Medicamentos, Alimentos y Tecnología Médica; Argentina
Fil: Garay, Osvaldo U.. Instituto de Efectividad Clinica y Sanitaria; Argentina
Fil: Papale, Rosa M.. Ministerio de Salud. Administración Nacional de Medicamentos, Alimentos y Tecnología Médica; Argentina
Fil: Bignone, Inés. Ministerio de Salud. Administración Nacional de Medicamentos, Alimentos y Tecnología Médica; Argentina
Fil: Bologna, Viviana G.. Ministerio de Salud. Administración Nacional de Medicamentos, Alimentos y Tecnología Médica; Argentina
Fil: Brandolini, Andrés. Ministerio de Salud. Administración Nacional de Medicamentos, Alimentos y Tecnología Médica; Argentina
Fil: Prokopez, Cintia R.. Ministerio de Salud. Administración Nacional de Medicamentos, Alimentos y Tecnología Médica; Argentina
Fil: Balasini, Juan I.. Ministerio de Economía y Finanzas Públicas. Secretaría de Política Económica; Argentina
Fil: Baldessarini, Ross J.. Harvard Medical School; Estados Unidos
Fil: Daray, Federico Manuel. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description The risks of severe leukopenia and agranulocytosis have varied over time and among geographical regions and cultures, with little information available on South American populations. Accordingly, we reviewed and analyzed data from a 6-year experience monitored by an Argentine national registry to which reporting of adverse events reports is required. We analyzed data for 2007-2012 from the pharmacovigilance program of the Argentine drug-regulatory agency (ANMAT) using standard bivariate and multivariate statistical methods and survival analysis. We identified 378 cases of adverse hematological events over 6 years among an average of 12 305 individuals/year treated with clozapine (308±133 mg/day) to estimate the mean annualized rates of leukopenia [0.19 (95% confidence interval [CI] 0.11-0.27)], neutropenia [0.38 (95% CI 0.34-0.43)], and agranulocytosis [0.05 (95% CI 0.02-0.08)] % per year [median latency 2 (95% CI 1.3-2.1) months]; fatalities related to agranulocytosis averaged 4.2 (95% CI 0.0-9.2) per 100 000 treated individuals/year. Factors associated significantly and independently with agranulocytosis were female sex, older age, and use of other drugs in addition to clozapine. With monitoring by international standards, recent risks of clozapine-associated agranulocytosis in Argentina were lower, but fatality rates were higher than that in other regions of the world. Risk factors include the use of multiple psychotropic drugs, female sex, and older age.
publishDate 2015
dc.date.none.fl_str_mv 2015-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/16174
Balda, María Victoria; Garay, Osvaldo U.; Papale, Rosa M.; Bignone, Inés; Bologna, Viviana G.; et al.; Clozapine-associated neutropenia and agranulocytosis in Argentina (2007-2012); Lippincott Williams; International Clinical Psychopharmacology; 30; 2; 3-2015; 109-114
0268-1315
url http://hdl.handle.net/11336/16174
identifier_str_mv Balda, María Victoria; Garay, Osvaldo U.; Papale, Rosa M.; Bignone, Inés; Bologna, Viviana G.; et al.; Clozapine-associated neutropenia and agranulocytosis in Argentina (2007-2012); Lippincott Williams; International Clinical Psychopharmacology; 30; 2; 3-2015; 109-114
0268-1315
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1097/YIC.0000000000000060
info:eu-repo/semantics/altIdentifier/url/http://journals.lww.com/intclinpsychopharm/pages/articleviewer.aspx?year=2015&issue=03000&article=00008&type=abstract
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Lippincott Williams
publisher.none.fl_str_mv Lippincott Williams
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1846782546531057664
score 12.982451

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