Physical Health Monitoring (Clozapine)

Due to license restrictions, mandatory blood monitoring must be undertaken in all patients prescribed clozapine. These restrictions apply because a small number of clozapine patients may develop neutropenia.

Patients prescribed clozapine will have full blood count (FBC) measurements taken to the following schedule:

Note: Patients may only progress from weekly to fortnightly or fortnightly to 4 weekly FBC if authorised by the clozapine monitoring service.

Clozapine clinics and wards must have reliable processes for ensuring clozapine FBCs are taken as scheduled.

FBCs are normally sent to the clozapine monitoring service’s laboratory for analysis. 

If samples for patients are analysed locally it is the responsibility of the ward multi-disciplinary team and community based clozapine clinics to obtain that result and communicate it to the clozapine monitoring service and pharmacy and to act on the outcome of that result.

Clozapine discontinuation FBC monitoring will be undertaken as required by the clozapine monitoring service.

Once a FBC is entered, the patient is assigned a coloured "status":

Clozapine clinics and wards should perform additional side-effect monitoring for each patient prescribed clozapine. This will include:

• Constipation – at every contact*
• Blood pressure
• Pulse
• Hypersalivation
• Sedation
• Incontinence
• Signs of neutropenia (sore throat, temperature & flu like symptoms)
• Fits, faints & funny turns

Clinical observation and the Glasgow Antipsychotic Side-effect Scale (GASS- clozapine) should be used. GASS should be undertaken every 6 months and one month after any dose changes are made. The outcome of routine side effect monitoring and 6 monthly use of GASS must be reported to the patient’s responsible medical officer (RMO). 

A template for assessing and responding to clozapine side effects is available as an EMIS template and should be used for all patients.

* Constipation must be assessed systematically at every contact with the patient. Patients will receive education about the likelihood of becoming constipated, things they can do to minimise the risk and the need to report any change in bowel habits. It is recommended that the Clozapine & Constipation fact sheet from the Choice & Medication website be given to all patients.

Tachycardia is a commonly reported dose related adverse effect of clozapine especially during the titration phase. In most cases it is benign and resolves spontaneously after 4 – 6 weeks but it can persist throughout treatment. It can be the first sign of significant life-threatening conditions e.g. myocarditis, cardiomyopathy or neuroleptic malignant syndrome. Careful assessment and follow-up is warranted. A heart rate in excess of 120bpm or an increase of more than 30bpm, especially during titration, are considered markers for clozapine-induced myocarditis. Newly occurring tachycardia in patients on stable clozapine treatment may be an indicator of cardiomyopathy.

Management:

• Exclude other conditions especially myocarditis, cardiomyopathy and
  neuroleptic malignant syndrome. Urgent further investigation is required if
  fever, hypotension and chest pain are present as this may suggest myocarditis.
  Referral to cardiology is recommended.
• Treatment with clozapine should stop if tachycardia occurs in the context of
  chest pain or heart failure
• Reduce the dose of clozapine to the last dose at which tachycardia was not
  observed. Discontinue the standard titration and increase the dose in small
  increments less frequently to suit the individual response of the patient.
• If persists, try a cardio-selective β-blocker e.g. bisoprolol. Avoid doing so in the
  first few months of clozapine treatment as this approach may mask the
  development of myocarditis and worsen orthostatic hypotension.

Orthostatic (postural) hypotension is defined as a sustained reduction of systolic blood pressure of at least 20mmHg, or in diastolic blood pressure of 10mmHg within 3 minutes of standing.

It is important to exclude other causes e.g. other drugs (benzodiazepines, antidepressants, antihistamines and opioids) and consider if their continued use is necessary. Dehydration may also be a factor.

Where patients are already receiving treatment for cardiac conditions these may have
to be adjusted to reduce the risk of hypotension.

Management:

• Address other factors if possible
• Reduce the clozapine dose and slow the rate of titration
• If this does not resolve hypotension consider use of fludrocortisone

There is a growing body of evidence to support the early use of metformin to prevent antipsychotic-induced weight gain (AIWG). Metformin should be commenced at the start of clozapine treatment unless contraindicated and titrating to recommended daily dose of 2g daily if tolerated.

All patients prescribed clozapine treatment, regardless of setting, should be offered routine monitoring for physical health problems which may arise during treatment. The table below describes the monitoring required.