Summary
An incidence of drug-induced neutropenia of 2.5% has been found in the first 1000 patients to be treated with clozapine in the UK. The majority of affected patients experienced mild neutropenia (n = 22) with only 3 patients developing agranulocytosis. Data collected from these 25 patients suggest that the mechanism of neutropenia may be multifactorial. Laboratory investigation using liquid culture systems and immunofluorocytometry has identified clozapine and its major metabolite N-desmethyl clozapine as exhibiting toxic effects against myeloid maturation and myeloid mitotic compartments, respectively. Increased susceptibility to the toxic effects of clozapine was shown in 1 patient who had previously developed clozapine-associated neutropenia. No clinical or laboratory evidence of drug-induced antineutrophil or antimyeloid precursor antibodies was found.
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Civin CL, Loken MR. Cell surface antigens on human marrow cells: dissection of haemopoietic development using monoclonal antibodies and multiparameter flow cytometry. International Journal of Cell Cloning 5: 267–288, 1987
Feit HB, Wright SD, Durie CJ, Valinsky JE, Unkeless JC. Ontogeny of Fc receptors and complement receptor (CR3) during human myeloid differentiation. Journal of Clinical Investigation 73: 516–525, 1984
Lieberman JA, Johns CA, Kare JM, Rai K, Piscotta AV, et al. Clozapine induced agranulocytosis: non-cross reactivity with other psychotropic drugs. Journal of Clinical Psychiatry 49: 271–277, 1988
Nagler A, Binet C, Mickichan M, Negrin R, Bangs C, et al. Impact of marrow cytogenetics and morphology on in vitro haema-topoiesis in the myelodysplastic syndromes: comparison between recombinant human granulocyte colony stimulating factor and granulocyte-monocyte CSF. Blood 76: 1299–1307, 1990
Veys PA, Gutteridge CN, Macey M, Ord J, Newland AC. Detection of granulocyte antibodies using flow cytometric analysis of leucocyte immunofluorescence. Vox Sanguinis 56: 42–47, 1989
Veys PA, Wilkes S, Ellis G, Hoffbrand AV. Deficiency of DAF and CD16 on PNH neutrophils. British Journal of Haematology 76: 318–319, 1990
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Clozaril®/Leponex®
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Veys, P.A., Wilkes, S., Shah, S. et al. Clinical Experience of Clozapine-Induced Neutropenia in the UK. Drug-Safety 7 (Suppl 1), 26–32 (1992). https://doi.org/10.2165/00002018-199200071-00008
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DOI: https://doi.org/10.2165/00002018-199200071-00008