Appendix 6: Guidelines for the management of a red clozapine result.

1) Background information:

The CPMS categorise blood results according to the following colour-coded system:

Colour alert / WBC count x 109/L / Neutrophil count x 109/L
Green / > 3.5 / > 2.0
Amber / 3.0 – 3.5 / 1.5 – 2.0
Red / <3.0 / <1.5

If a patient has an amber blood result, a full blood count must be performed twice weekly until the blood count stabilizes in this range or increases.

2) Management of a Red Alert:

If a patient’s WBC is less than 3.0 x 109 /L and/or the 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.
  • Check the patient for any signs of infection (refer to details below) and contact the CPMS as soon as possible.
  • Make arrangements to undertake confirmatory blood counts on the 2 days following the date of the red alert sample. If either of these follow up blood counts is in the red alert range then red alert status is taken to be confirmed.
  • If the red alert is confirmed, THE PATIENT MUST NOT RESTART CLOZAPINE TREAMENT.
  • Full blood counts with differential white cell counts must be performed DAILY whilst the blood counts remain in the RED range, and the patient must be observed closely for infection (e.g. sore throat, fever). The results should be reported to the CPMS as soon as they are available.
  • If antipsychotic medication is considered essential, use agents with low potential to cause neutropenia and avoid depot preparations.
  • Review all other medication. Consider stopping those agents with potential to adversely affect neutrophil counts. If necessary, introduce a more appropriate alternative.

If a patient’s neutrophil count falls to less than 1.0 x 109/L or the WBC falls to less than 2.0 x109 /L OR if the patient develops a fever, please observe the following additional recommendations:

It is extremely important to contact a specialist haematologist, or failing this, a general medical physician, regarding the most appropriate treatment for the patient. This will probably involve transferring the patient to a ward with facilities for the care of neutropenic patients. If unable to contact the hospital haematologist immediately, please refer to the guidelines below:

  • Check the patient’s temperature, blood pressure and pulse FOUR hourly.
  • Nurse patient in a single room, taking care to wash hands before and after contact with the patient, wear aprons etc.
  • Avoid salads, yoghurt, unpeeled fruit, paté or soft cheese in the patient’s diet. Give sterilised milk, water or canned drinks. Remove flowers from the patient’s room.
  • Give patient an antibacterial and antifungal mouthwash prophylactically (eg. chlorhexidine 10mls QDS and nystatin suspension 1ml QDS )

Granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony stimulating factors have been used in the management of clozapine induced agranulocytosis although this is not a licensed indication. The cost of such drugs if used will be reimbursed by CPMS.

Effect of sudden discontinuation of clozapine:

When a patient has a red alert it is essential to stop clozapine immediately. This sudden cessation of treatment can lead to physical and mental withdrawal effects which may occur within 2 – 3 days and usually within the first 2 weeks. Patients may experience a rapid deterioration in their mental state with rebound psychosis. In addition, abrupt withdrawal of clozapine has been associated with symptoms such as nausea, vomiting, diarrhoea, headache, restlessness, agitation and sweating and it has been suggested that these are a result of cholinergic rebound since clozapine has strong anticholinergic action.

SOUTHERN HEALTH NHS FOUNDATION TRUST

GUIDELINES FOR THE MANAGEMENT OF A RED CLOZAPINE RESULT

LOCAL PRACTICAL ACTION

A pharmacist is available at CPMS 24 hours a day, for the provision of patient specific pharmaceutical advice.
  • Telephone number 9am – 5pm Monday to Friday: 0845 7698269 option 2
  • Out of hours service: 01276 692504

ACTION / SIGNATURE / DATE
1. / Ensure the patient’s consultant, care coordinator and the clozapine clinic staff are aware of the red result and management implications as soon as possible and discuss and determine an individual care plan on RIO for monitoring bloods mental and physical health and review of medication. For out-patients, inform the patient’s GP.
2. / Ensure that all involved are aware of contact details and are in receipt of these guidelines.
3. / Care coordinator to ensure that adequate systems are in place so that the:
3.1 / Patient does not receive any more clozapine until advised that this can be reintroduced by the CPMS. If the patient is off clozapine for morethan 48 hours, this will need to be retitrated.
3.2 / Patient is monitored for mental state (possibility of rebound psychosis following abrupt clozapine withdrawal).
3.3 / Patient is monitored for any physical health problems including temperature as they will be less able to combat these due to the low white cell count.
ACTION / SIGNATURE / DATE
3.4 / Arrangements are in place for daily full blood count tests which will need to be analysed as soon as possible and the results phoned through to the CPMS. Doctor on call should do bloods if out of hours There will need to be at least 2 days worth of daily follow up blood tests; these will continue until advised by the CPMS that they are no longer required (at least 2 consecutive non red results).
3.5 / The team responsible for care over a weekend has available the patient’s full notes, including up to date risk assessment, details of current medication, a description of the patient and emergency contact details (eg next of kin), on-call services at group homes.
3.6 / In order to facilitate all of the above, for patients for whom admission is not appropriate or necessary and where follow-up is needed over the weekend, is likely to be the most appropriate course of action. This team will then need to liaise with the on-call duty doctor to ensure the daily blood tests occur at a suitable time and venue on each day.