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Indian Journal of Psychiatry logoLink to Indian Journal of Psychiatry
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. 2015 Oct-Dec;57(4):429–430. doi: 10.4103/0019-5545.171849

Clozapine induced eosinophilia: An often neglected important adverse effect

Pavan Kumar Kadiyala 1, Maldar A Ahmed 1, Denzil A Pinto 1, John P Mathai 1
PMCID: PMC4711251  PMID: 26816437

Sir,

Clozapine, though effective in resistant schizophrenia, needs extensive monitoring more than any drug in psychiatry. Initial concerns were mainly related to agranulocytosis, but in recent years the focus has been shifted to eosinophilia and its potentially fatal complications.[1,2]

Eosinophilia, a nondose-dependent side-effect, is seen in around 1% of clozapine-treated patients. It occurs during 1st year of treatment, mostly in the initial 4 weeks.[1,3,4] It is considered as an allergic reaction with a transient course and spontaneous remission. However, in some cases, it may predict subsequent neutropenia, myocarditis, eosinophilic colitis, pancreatitis and toxic hepatitis.[3,4] The manufacturer of clozapine recommends to interrupt its use when absolute eosinophil count >4000/cu mm until the eosinophil count falls below 3000/cu mm.[5] However, if there are no signs of end-organ damage or inflammation, clozapine continuation or rechallenge with careful monitoring may be considered.[6]

Hereby reporting a patient who developed eosinophilia with clozapine. Mr. K.B, a 45-year-old male, was admitted in November 2012 with diagnosis of schizophrenia undifferentiated. Due to inadequate response to other antipsychotics, he was put on clozapine. His leukocyte count prior to the initiation of clozapine was 10,300/cu mm with eosinophil count being 1%. However, on day 7 of initiation of clozapine, the total leukocyte count of the patient was found to be 12,300/cu mm (eosinophil count 27%). After ruling out other medical causes, eosinophilia was found to be clozapine-induced. Instead of discontinuing, clozapine was continued and escalated gradually with close monitoring of its complications. The eosinophil count started falling by the 2nd week to 22%, further reduced to 20% by 4th week and the patient got discharged.

Clozapine induced eosinophilia, leukocytosis and thrombocytopenia are generally benign events that resolves on their own.[4,7] In the above case, the eosinophil count increased during the 1st week of clozapine treatment, thereafter started resolving gradually. Eosinophilia, though considered benign and transient, needs to be monitored in view of a possible association with life-threatening conditions like myocarditis and predictor of subsequent neutropenia.

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Conflicts of interest

There are no conflicts of interest.

REFERENCES

  • 1.Chatterton R. Eosinophilia after commencement of clozapine treatment. Aust N Z J Psychiatry. 1997;31:874–6. doi: 10.3109/00048679709065515. [DOI] [PubMed] [Google Scholar]
  • 2.Layland JJ, Liew D, Prior DL. Clozapine-induced cardiotoxicity: A clinical update. Med J Aust. 2009;190:190–2. doi: 10.5694/j.1326-5377.2009.tb02345.x. [DOI] [PubMed] [Google Scholar]
  • 3.Majumder P, Chadda RK, Goyal P, Mittal A, Kumar N. Clozapine induced eosinophilia. Indian J Psychiatry. 2011;53:152–3. doi: 10.4103/0019-5545.82546. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Nielsen J, Correll CU, Manu P, Kane JM. Termination of clozapine treatment due to medical reasons: When is it warranted and how can it be avoided? J Clin Psychiatry. 2013;74:603–13. doi: 10.4088/JCP.12r08064. [DOI] [PubMed] [Google Scholar]
  • 5.Novartis Pharmaceuticals. CLOZARIL® (clozapine) Tablets, Prescribing Information (PDF). Novartis Pharmaceuticals. 2010. [Last retrieved on 2013 Nov 6]. from http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019758s062lbl.pdf .
  • 6.Roberts CE, Mortenson LY, Merrill DB, Rafizadeh N, Smith TE, Lieberman JA. Successful rechallenge with clozapine after eosinophilia. Am J Psychiatry. 2011;168:1147–51. doi: 10.1176/appi.ajp.2010.10040519. [DOI] [PubMed] [Google Scholar]
  • 7.Lambertenghi Deliliers G. Blood dyscrasias in clozapine-treated patients in Italy. Haematologica. 2000;85:233–7. [PubMed] [Google Scholar]

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