SciELO - Scientific Electronic Library Online

vol.20 issue1Oxidative stress resulting from exposure to wood smoke among native women living at high altitude - 3,850 m.a.s.l.Bacterial persistence: a cellular phenotype of clinical significance in chronic and recurrent infections author indexsubject indexarticles search
Home Pagealphabetic serial listing  

Services on Demand




  • Have no cited articlesCited by SciELO

Related links

  • Have no similar articlesSimilars in SciELO


Horizonte Médico (Lima)

Print version ISSN 1727-558X


LUQUE ESPINO, Julio César  and  OSCANOA ESPINOZA, Teodoro Julio. Clozapine-induced agranulocytosis. Horiz. Med. [online]. 2020, vol.20, n.1, pp.69-76. ISSN 1727-558X.

Clozapine currently remains the gold standard for treatment-resistant schizophrenia, but only under an adequate hematological monitoring, because it is associated with agranulocytosis. Clozapine is metabolized to produce pharmacologically active N-desmethylclozapine, inactive clozapine N-oxide and reactive oxygen species (nitrenium ion). A neutrophil count < 1000 cells/mm3 corresponds to a state of neutropenia. Agranulocytosis is a severe state of neutropenia with an absolute neutrophil count < 500 cells/mm3. Clozapine is associated with agranulocytosis in approximately 0.8 % of the patients, with an increased risk in older people and women. There are two mechanisms that explain the clozapine- induced agranulocytosis: immunological (response mediated by the immune system against haptenized neutrophils) and toxic (by the action of the metabolites N-desmethylclozapine and nitrenium ion). Pharmacogenetics represents a valuable tool to achieve the so-called personalized medicine by adapting and individualizing the treatment based on the genetic markers of each patient. Several studies have shown a potential association of clozapine-induced agranulocytosis with certain HLA haplotypes (HLA-B38, DR4, DQw3 and DQB1). After a patient has presented agranulocytosis, three mechanisms of clozapine rechallenge are known: simple, with lithium and with factors that stimulate granulocyte colonies. Due to the risk of agranulocytosis, clozapine formulations are available only through a controlled distribution, with a detailed record of the patients, and with a mandatory and systematized pharmacovigilance.

Keywords : Clozapine; Antipsychotic agents; Agranulocytosis; Neutropenia; Pharmacovigilance.

        · abstract in Spanish     · text in Spanish     · Spanish ( pdf )