An atypical antipsychotic used in:
• Treatment resistant schizophrenia (TRS)
• Patients intolerant of other antipsychotics
• Drug induced psychotic disorders occurring
during the treatment of Parkinson's disease.
• Some ‘off-license’ indications e.g. delusional
Clozapine Patient Monitoring
CPMS require that all:
• Pharmacists/technicians and pharmacy
premises supplying clozapine are registered with
• Consultants prescribing clozapine are registered
• All patients receiving clozapine treatment are
registered and monitored by them.
Clozapine Initiation I
Prior to starting Clozapine baseline monitoring should be done:
•Full Blood Count
•EEG (advised in adolescents)
•Baseline assessment of mental state
•Lying + standing blood pressure, temperature and pulse
Clozapine Initiation II
Speak with patient starting clozapine about:
• Commitment to regular blood monitoring
• Provide a CPMS handbook to the patient. This
gives information about side effects and benefits
as well as everything the patient needs to know
about Clozapine. (Handbooks are available
• Discuss possible side-effects with patient.
Patient friendly information is available from
Sussex Partnership intranet.
What are the main
• Patients should be made aware that FBC monitoring is a
prerequisite of ongoing clozapine supply.
• They should also be made aware that there are possible
potentially serious side effects:
3% Risk of developing neutropenia
Cardiac effects (myocarditis)
Constipation and chronic bowel obstruction
Seizures (higher doses & dose related)
• Doses will be titrated up slowly due to effects on BP and HR
and to prevent severe side effects.
Once it has been decided to start clozapine the patient will need
to be registered with CPMS.
Forms available on CPMS website. To be completed by a CPMS
• A second FBC should be done after 4 days and
treatment started within 10 days of the first test.
• Following registration:
– A weekly FBC must be done for the first 18
– A fortnightly FBC must be done for the rest of
the first year.
– A monthly FBC must be done thereafter.
Supply of Clozapine
• The CPMS registered Pharmacy will make a
supply depending on the patients monitoring
7 days supply (absolute
maximum 10 days)
14 days supply (absolute
maximum 21 days)
28 days supply (absolute
maximum 42 days
Blood kits and barcodes
Orange envelope for FBC
Yellow envelope for plasma level
The blood kits are the same for both tests
Each patient has their own barcodes which need to be
attached to the paperwork and the blood vial.
All non drug items, (bloodkits, envelopes, paperwork and
barcodes) are to be ordered by the ward / unit using the non
drug order form (available on the CPMS website)
FBC orange envelope- Plasma Yellow envelope
Blood results for clozapine supply
>3.5 x 10 9/L
3.0 – 3.5 x 10 9/L
<3.O x 10 9/L
>2.0 x 10 9/L
1.5 – 2.0 x 10 9/L
<1.5 x10 9/L
And or platelets
<50 x 10 9/L
Continue supply if
Extra samples will
SAMPLES TO BE
TAKEN ON NEXT
TWO DAYS AS PER
• Clozapine is gradually titrated over the first 14
days and the patient is monitored carefully
during the titration.
• This is to lessen any side effects and to ensure
that the patient can tolerate clozapine.
• Temperature, pulse and B.P is monitored and a
record is made of any of the common side
effects suffered by the patient.
SPT Inpatient Titration Chart
SPT Community titration chart
• For both inpatients and outpatients a full examination
should be undertaken each week during titration
• Nurses should inform the doctor if:
– Temperature rises above 38° C (this is common and
on its own not a good reason to stop clozapine)
– Pulse is >100 BPM
– Postural drop of >30mmHg
– Patient clearly over sedated
– Any other adverse effect is intolerable
Compliance Issues I
• If a dose is omitted, take next dose at normal
• If patient has missed >48 hours, complete retitration is necessary because tolerance to
hypotensive effects diminishes rapidly:
– Inform doctor and pharmacist immediately
– Recommended to restart at 12.5mg on first day
– However, sometimes possible to do “fast
– Ensure observations are done as before
Compliance Issues II
• If < 96 hours have been missed the blood
monitoring frequency stays the same.
• If > 96 hours has been missed the patients blood
monitoring becomes weekly again for 6 weeks
before returning to the original frequency.
• The hydrocarbons in tobacco smoke induce the production or
activity of various liver enzymes, in particular cytochrome CYP1A2,
an enzyme associated with the metabolism of several drugs,
including clozapine. This results in reduced plasma levels of such
• When a patient stops smoking the metabolism of these drugs will
decrease and plasma levels will rise. For clozapine plasma levels
may be elevated by up to 70%, leading to toxicity.
• CYP1A2 activity is affected by hydrocarbons in cigarettes and not by
nicotine. Therefore nicotine replacement therapy (NRT) will not
affect drug metabolism.
• Patients, carers and healthcare professionals should be advised to
inform the responsible medic if the patients starts or stops smoking.
• Patients should still be encouraged to stop or reduce smoking.
• If a patient decides to stop smoking– Latest clozapine levels should be reviewed and a new baseline level
taken as soon as practicable (this is not urgent as dose reduction is not
– Review side-effects history and, if possible, check against the serum
clozapine levels at which they occurred.
– Assess the risk of toxicity (ie. if level exceeds 1000ng/ml) by estimating
the non-smoking serum clozapine level using the formula below:
Serum clozapine (Non-smoker) = [1.5 x Serum clozapine (Smoker) ] + 50
eg. smoking level of 500ng/ml gives a non-smoking level of 800ng/ml
Set a target (non-smoking) serum clozapine level, taking into consideration
the patient’s current condition and clinical response to current dose / level. If
indicated, adjust the clozapine dose accordingly.
Necessary reductions in daily dose should normally be made at a rate of
approximately 10% per day.
If possible, monitor serum clozapine level at day 3 and then weekly (until
stabilised to target level).
Monitor for adverse effects – bearing in mind that some may take as long
as 2 to 3 weeks after adjustment of dose to become apparent.
On discharge or leave, reassess patient’s likelihood to recommence
smoking and the potential reduction in serum clozapine level in response. If
this occurs it is likely that the clozapine dose will have to be increased.
Post-discharge, where possible, monitor serum clozapine level once each
week, (or fortnightly if total dose change was less than 20%), until stable.
On discharge from an
• Check which registered Pharmacy will be supplying
clozapine. This is dependent on where they live.
• Make arrangements for the patient to be given access to
blood monitoring supplies. These are ordered and
supplied by the CPN
• Arrange with the registered Pharmacy where the
medication is to be collected from.
• Make sure that the patient is transferred on CPMS to the
outpatient consultant and that a current prescription has
been sent to the pharmacy. All change of detail forms are
available on CPMS website
SPT Community clozapine
• The doctor will need to supply an
outpatient clozapine prescription.
• This is:
– Current for six dispensings
– For clozapine supply only - all other
meds should be prescribed by the GP
• There are areas on the chart to
Blood test frequency
If a clozapine patient is admitted
or handed over to your team
• Check when last blood was taken and when next blood is due
- ask pharmacy
• Check how frequently blood tests are needed - ask pharmacy
• How much clozapine does the patient have? - ask the team or
• Blood tests should be done on a Monday and posted to
CPMS (Orange Envelope)
• If you miss this a local test can be done but this will cost your
• Barcodes for blood tests can be handed over from the ward
and further supplies re-ordered using the non drug order form.
• Keep Pharmacy informed of any clozapine patients
• In short anything to do with Clozapine - Pharmacy
want to know about it!