Download Appendix 9 Shared care guidelines

Appendix 9: Shared care guidelines: Information for the GP
Clozapine Risk Management Guidelines for
Primary and Secondary Care
Name of patient treated under this guideline:
This shared care guideline has been produced to support prescribing and monitoring of
patients between secondary and primary care, and provides an information resource to
support clinicians providing care to the patient. It does not replace discussion about
sharing care on an individual patient basis.
This guideline was prepared using information available at the time of preparation, but
users should always refer to the manufacturer’s current edition of the Summary of Product
Characteristics (SPC or “data sheet”) available at www.medicines.org.uk
1.0 Status of Clozapine
Clozapine (Clozaril®) is a red drug. This means that treatment will be initiated and retained
by secondary care. However, because of the extensive adverse reactions, interactions and
monitoring of clozapine it is essential for all GPs to be fully aware which of their patients
are receiving clozapine and the relevant prescribing issues.
2.0 Indications and Dose
Clozapine is indicated for treatment-resistant schizophrenia and in schizophrenia patients who
have severe, untreatable neurological adverse reactions to other antipsychotic agents.
Treatment resistance is defined as a lack of satisfactory clinical improvement despite the use of
adequate doses of at least two different antipsychotic agents, including an atypical antipsychotic
agent, prescribed for adequate duration.
Clozapine is also indicated in psychotic disorders occurring during the course of Parkinson's
disease, in cases where standard treatment has failed.
3.0 Referral Criteria
Not applicable. Clozapine will only be initiated in secondary care.
4.0 Patient Selection
Not applicable. Clozapine will only be initiated in secondary care
5.0 Safety Issues
Clozapine (Clozaril®) is a very effective atypical antipsychotic used when other treatment
strategies have failed. Approximately 3% of patients treated with clozapine will develop
neutropenia (around 1% will progress to agranulocytosis) which makes them vulnerable to
serious infections. Detection of neutropenia is achieved by regular haematological
monitoring, through the Clozaril Patient Monitoring Service (CPMS).
All patients receiving clozapine must be registered with the CPMS and monitored for the
complete duration of therapy. In the event of an abnormal blood result the CPMS will
contact the psychiatric team immediately to request an additional blood sample if
necessary.
The patient, and if appropriate their carer, should regularly be reminded to remain vigilant
for any signs of infection, e.g. fever or sore throat, which may indicate the presence of
neutropenia. While it is unlikely that such symptoms are related to the development of
clozapine-induced neutropenia, an immediate full blood count (WBC and neutrophil counts
are required) will be necessary to exclude the possibility. Patients should be advised to
contact their GP, or hospital team, if they experience signs of infection. If neutropenia is
confirmed the patient must immediately be referred to the consultant for continued
monitoring, haematological referral if required and management of the patient’s psychiatric
condition. All clozapine supplies will be removed and withheld in the event of
agranulocytosis.
It has also been suggested that clozapine is associated with rare reports of myocarditis
and cardiomyopathy. Myocarditis seems to occur within 6-8 weeks of starting clozapine
while cardiomyopathy may occur later (median 9 months). The risk of myocarditis is
estimated to be around 1%. Patients should be monitored for symptoms such as
tachycardia, fever, flu-like symptoms, fatigue, dyspnoea and chest pains. Any signs of
heart failure should provoke the immediate discontinuation of clozapine. Successful rechallenge is possible with specialist advice.
5.1 Contra-indications (see BNF or SPC)
Hypersensitivity to the active substance or to any of the excipients.
• Patients unable to undergo regular blood tests.
• History of toxic or idiosyncratic granulocytopenia/agranulocytosis (with the exception of
granulocytopenia/agranulocytosis from previous chemotherapy).
• History of Clozaril-induced agranulocytosis.
• Impaired bone marrow function.
• Uncontrolled epilepsy.
• Alcoholic and other toxic psychoses, drug intoxication, comatose conditions.
• Circulatory collapse and/or CNS depression of any cause.
• Severe renal or cardiac disorders (e.g. myocarditis).
• Active liver disease associated with nausea, anorexia or jaundice; progressive liver
disease, hepatic failure.
• Paralytic ileus.
• Clozaril treatment must not be started concurrently with substances known to have a
substantial potential for causing agranulocytosis; concomitant use of depot antipsychotics
is to be discouraged.
5.2 Cautions (see BNF or SPC)
See general guidance or common adverse effects.
5.3 Common Side Effects (See BNF or SPC)
Clozapine is associated with a number of adverse effects, some of which are listed below.
For a complete list please refer to the BNF or www.medicines.org.uk
ADRs
Time course
Potential treatments
Sedation
Usually 4 weeks
Give a larger dose in the
evening
Hypersalivation
May persist
Hyoscine Hydrobromide
300mcgs nocte
(occasionally up to
900mcgs / day)
Constipation (which
may lead to impaction
and perforation)
Usually persists
↑ fibre, laxatives
Tachycardia
Worse first 4 weeks
Stop or Slow down
titration If persists refer to
cardiologist
Hypotension
First 4 weeks
Reduce or slow titration
Hypertension
First 4 weeks, sometimes
longer
As per hypertension
guidelines
Weight gain
First year
Dietary counselling
Nocturnal enuresis
Any time
Avoid fluids at bedtime,
altering the timing of
doses may help,
Emerging diabetes
Any time
As per diabetic guidelines
Seizures / myoclonic
jerks
Any time
Dose / dose increase
related, withhold
clozapine for 24hours,
introduce at a lower dose,
consider valproate
Management in the community is generally possible for most adverse effects by referral
to/discussion with secondary care prescribers; however those requiring immediate referral
to hospital include:
Neutropenia/agranulocytosis, persistent tachycardia, persistent or troublesome nocturnal
enuresis, chest pain, shortness of breath, severe drowsiness, seizures, severe
constipation or any other serious event.
5.4 Drug Interactions (see BNF or SPC)
All drugs which have the potential to cause neutropenia (e.g. carbamazepine,
cephalosporins, quinolones, trimethoprim, cytotoxics and long acting depot antipsychotics)
should be avoided. Clozapine is metabolised by many liver enzymes so drugs which may
alter these enzymes can either increase toxicity or increase the risk of relapse of
symptoms.
Drugs which
avoided
should
be
Drugs which may be used with
caution (extra monitoring for
clozapine
adverse
reactions
required)
Carbamazepine
Fluoxetine
Fluvoxamine
Paroxetine
Erythromycin
Sertraline
Rifampicin
Warfarin (increased INR possible)
Ciprofloxacin
Antihypertensives
Lithium
Other drugs which cause constipation
This list is not exhaustive please refer to the BNF or www.medicines.org.uk
Smoking cessation interaction
Clients who smoke usually require a higher dose than non-smokers due to the effects
cigarette smoke has on clozapine levels. When giving up smoking clozapine levels can
increase by as much as 50%, thus the dose of clozapine will need reducing. Nicotine
replacement therapy does not negate this interaction. Refer to specialist advice when a
clozapine client wishes to give up smoking.
6.0 Role of Secondary Care Team
(a) To assess the suitability of the patient for clozapine and counsel patient and carer
about implications of diagnosis and treatment.
(b) To carry out initial and on-going physical health monitoring. The GP may be asked to
conduct and interpret some of the physical health tests depending on local arrangement,
however the responsibility for ensuring monitoring is complete rests with the secondary
care team.
(c) To give the patient the appropriate drug information leaflets.
(d) To explain the possible side effects of the medication to the patient.
(e) To emphasise the need for continued compliance and the need for regular blood tests.
(f) To initiate treatment, arrange for the clozapine community card to be prescribed and
arrange ongoing supplies of clozapine through hospital pharmacy.
(g) To write to the GP informing them of the ongoing prescribing, monitoring and supply of
clozapine. This shared care guideline should be included in this correspondence.
(h) To keep the GP informed of any changes in doses, mental state or prescribing status of
clozapine.
(i) To keep the GP informed of any physical tests performed and on-going physical health
concerns regarding clozapine.
7.0 Role of GP
(a) To ensure clozapine is recorded in the GP records
(b) To notify the psychiatric team of any changes in mental state, physical state, any
suspected adverse drug reactions or changes in non-clozapine medication.
(c) To ensure all relevant staff within the practice are aware of the shared care
guidelines and the concerns surrounding clozapine
(d) To consider the precautions, interactions and adverse reactions of
clozapine when co-prescribing for patients receiving clozapine.
(e) To notify the psychiatric team when the client wishes to give up smoking and smoking
cessation advice is given.
8.0 Responsibilities of the patient / carer
a) To monitor mental state and report and deterioration in symptoms
b) Assist with adherence or discuss with the GP or secondary care team concerns with
adherence.
c) Report any side effects or physical health concerns
9.0 Cessation of treatment
Clozapine often represents the client’s best hope of recovery from enduring and treatment
resistant schizophrenia. Cessation of treatment should be avoided except in life
threatening conditions which are linked to clozapine use. Any patient wishing to
discontinue treatment should be referred back to secondary care services.
Patients who have had no clozapine for 48 hours (taken from the last dose given) should be
retitrated at 12.5mg per day, as above. The speed of the titration depends on the original
acceptance and tolerability of clozapine, however it should be noted that a slower titration is
preferable to prevent adverse reactions. Hypotension, tachycardia and seizures are particular
risks when re-starting clozapine.
Further reading
Bleakley S, Taylor D. Clozapine Handbook: Lloyd-Reinhold Communications LLP.
Warwickshire 2013.