Background Information

Clozapine is licensed for treatment of schizophrenia in patients unresponsive to, or intolerant of, conventional antipsychotic drugs. Although clozapine reduces overall mortality in schizophrenia, it can also cause serious, life-threatening side-effects, of which agranulocytosis is the best known. This risk is managed by the approved clozapine monitoring system. The clozaril approved monitoring system, currently used in NHS Borders, is called CPMS (clozaril patient monitoring service).

Blood results are categorized according to the following colour-coded system

Neutrophil and White Blood Cell Counts

Neutrophil count less than 1.5 x 109/L or signs of infection with WBC less than 3 x 109L

If a patient’s neutrophil count is less than 1.5 x 109/L, this is known as a red alert and the following action must be taken:

  • STOP CLOZAPINE TREATMENT IMMEDIATELY
  • Contact consultant psychiatrist (or on call consultant if out of hours) to make them aware of the red result and discuss management plan
  • Arrange for daily full blood count testing
  • Identify other medications which could be contributing to a red result and consider stopping those agents
  • Full blood counts with differential white cell counts must be performed DAILY whilst the blood counts remain in the RED range
  • Check B12 / folate as alternative / contributory causes to neutropenia
  • Perform blood pressure and pulse measurements at least once daily
  • Check temperature at least once daily
  • Monitor for any signs of infection (sore throat, fever, or other flu-like symptoms) and instruct the patient to report such symptoms immediately
  • Monitor the patient for changes to mental state (possibility of rebound psychosis following abrupt  clozapine withdrawal)
  • Contact on call haematologist to discuss if granulocyte colony-stimulating factor (GCSF) treatment is appropriate if during working hours. OOH admit to BGH as below.


If the neutrophil count falls to 1.0x109 /l or less and if the patient develops a fever (>38OC) or any other signs of infection, admit to the BGH and manage as per the NHS Borders Neutropenic Sepsis Protocol

Please note granulocyte colony-stimulating factor (GCSF) has been used in the management of clozapine  induced agranulocytosis although this is not a licensed indication.

Please discuss the use of GCSF for individual patients with a Consultant Haematologist (via BGH switchboard or via email: HaematologyConsultants@borders.scot.nhs.uk)

White blood cell count less than 3.0x109 /l but neutrophils normal:

• Stop Clozapine
• Daily FBC
• Contact haematologist for further advice on other tests and management.

This is not an emergency and can wait until working hours.

Advice

It is advised that the patient is not treated with additional antipsychotics during episodes of neutropenia.  Switching to another (atypical) antipsychotic with a lower risk of neutropenia, such as Amisulpride, Aripiprazole or Haloperidol should only be considered after two consecutive green results in daily frequency

Management of a Red Clozapine result - Flowchart

Editorial Information

Last reviewed: 01/11/2023

Next review date: 30/11/2025

Author(s): Richardson-Read S.

Version: v2

Author email(s): segdae.richardson-read@nhs.scot.

Co-Author(s): Harvey K.

Approved By: Mental Health Clinical Governance Group

Reviewer name(s): Richardson-Read S.

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