Neutropenia and Agranulocytosis in Patients Receiving Clozapine in the UK and Ireland

Atkin, K; Kendall, Frank M.; Gould, Donna J.; Freeman, Hugh; Liberman, Joshua N.; O'Sullivan, D

doi:10.1192/bjp.169.4.483

Cited by 262 publications

(212 citation statements)

References 9 publications

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“…This is consistent with the lack of dependence of clozapine‐associated agranulocytosis and neutropenia on dose 30, but in contrast with the dose dependency of beta‐lactam antibiotic‐mediated agranulocytosis 31. …”

Section: Discussionsupporting

confidence: 82%

Deferiprone‐induced agranulocytosis: 20 years of clinical observations

Tricta¹,

Uetrecht

Galanello

et al. 2016

American J Hematol

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Use of the iron chelator deferiprone for treatment of iron overload in thalassemia patients is associated with concerns over agranulocytosis, which requires weekly absolute neutrophil counts (ANC). Here, we analyze all episodes of agranulocytosis (n = 161) and neutropenia (n = 250) during deferiprone use in clinical trials (CT) and postmarketing surveillance programs (PMSP). Rates of agranulocytosis and neutropenia in CT were 1.5% and 5.5%, respectively. Of the agranulocytosis cases, 61% occurred during the first 6 months of therapy and 78% during the first year. These events appeared to be independent of dose, and occurred three times more often in females than males. Their duration was not significantly shortened by use of G‐CSF. No patient with baseline neutropenia (n = 12) developed agranulocytosis during treatment, which raises questions about the validity of prior neutropenia as a contraindication to use. Only 1/7 novel neutropenia cases in CT progressed to agranulocytosis with continued treatment, indicating that neutropenia does not necessarily lead to agranulocytosis. The agranulocytosis fatality rate was 0% in CT and 15/143 (11%) in PMSP. Rechallenge with deferiprone produced agranulocytosis in 75% of patients in whom the event had already occurred, and in 10% with previous neutropenia. Weekly ANC monitoring allows early detection and interruption of therapy, but does not prevent agranulocytosis from occurring. Its relevance appears to decrease after the first year of therapy, when agranulocytosis occurs less often. Based upon analysis of data collected over the past 20 years, it appears that patient education may be the key to minimizing agranulocytosis‐associated risks during deferiprone therapy. Am. J. Hematol. 91:1026–1031, 2016. © 2016 The Authors. American Journal of Hematology Published by Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 82%

Deferiprone‐induced agranulocytosis: 20 years of clinical observations

Tricta¹,

Uetrecht

Galanello

et al. 2016

American J Hematol

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“…In adults, the risk of developing neutropenia and agranulocytosis as a result of clozapine is approximately 3 and 0.8%, respectively (Alvir et al, 1993;Atkin et al, 1996;Copolov et al, 1998; Kang et al, , 2003). The risk is highest for both neutropenia and agranulocytosis within the first 6-18 weeks of treatment and most cases occur within the first 6 months (Atkin et al, 1996)-the risk of developing agranulocytosis falls to 0.08% after 1 year of treatment, that is after 1 year the risk is similar to that with chlorpromazine (chlorpromazine agranulocytosis risk up to 0.13%; King and Wager, 1998).…”

Section: Clozapine and Neutropeniamentioning

confidence: 99%

“…The risk is highest for both neutropenia and agranulocytosis within the first 6-18 weeks of treatment and most cases occur within the first 6 months (Atkin et al, 1996)-the risk of developing agranulocytosis falls to 0.08% after 1 year of treatment, that is after 1 year the risk is similar to that with chlorpromazine (chlorpromazine agranulocytosis risk up to 0.13%; King and Wager, 1998). The mortality rate due to clozapine-induced agranulocytosis has been estimated at 3-4% of identified agranulocytosis cases (Gerson, 1994).…”

Section: Clozapine and Neutropeniamentioning

confidence: 99%

Haematological toxicity of drugs used in psychiatry

Flanagan

Dunk

2007

Hum. Psychopharmacol. Clin. Exp.

187

154

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“…117,121,124 Ten studies related to the incidence of blood dyscrasias such as agranulocytosis and leucopenia. [125][126][127][128][129][130][131][132][133][134] One was a study of NMS, 135 another of venous thromboembolic complications that occurred during clozapine treatment. 136 Five were studies of epilepsy or seizure rates 122,[137][138][139][140] …”

Section: Rare or Long-term Eventsmentioning

confidence: 99%

A systematic review of atypical antipsychotic drugs in schizophrenia

Bagnall

Jones

Ginnelly

et al. 2003

Health Technol Assess

150

114

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Neutropenia and Agranulocytosis in Patients Receiving Clozapine in the UK and Ireland

Abstract: The use of a patient monitoring service kept the haematological risks associated with using clozapine within acceptable limits, particularly in view of the benefits of this medication in treatment-resistant schizophrenia.

Cited by 262 publications

References 9 publications

Deferiprone‐induced agranulocytosis: 20 years of clinical observations

Deferiprone‐induced agranulocytosis: 20 years of clinical observations

Haematological toxicity of drugs used in psychiatry

A systematic review of atypical antipsychotic drugs in schizophrenia

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