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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/16174
Ver los metadatos del registro completo
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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 Técnicas2025-09-29T10:41:29Zoai: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:34982025-09-29 10:41:29.514CONICET 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 |
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1844614445649625088 |
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13.070432 |