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Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust PPT-PGN-05 Safe Prescribing of Clozapine – V03- Iss 5 Sep 2020 Part of NTW(C)38 – Pharmacological Therapy Policy
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Pharmacological Therapy Policy Practice Guidance Note
Safe Prescribing of Clozapine – V03-Dr
Version issued
Issue 1 – Apr 2019 Issue 2 – Sep 2019 Issue 3 – Nov 2020 Issue 4 – Apr 2020 Issue 5 – Sep 2020
Planned review
April 2022 PPT-PGN-05 Part of CNTW(C)38 Pharmacological Therapies Policy
Author/Designation Peter Clarke, Lead Pharmacist – South Locality
Responsible Officer / Designation
Tim Donaldson, Trust Chief Pharmacist
Contents
Section Description Page No
1 Introduction 3
2 Clozapine initiation 5
3 Clozapine maintenance and transfer of care 8
3.1 Therapeutic drug monitoring of clozapine plasma levels 9
4 Complications 10
4.1 Blood monitoring issues 10
4.2 Concordance issues 10
4.3 Discontinuation 10
4.4 Side effects 11
4.5 Smoking 13
4.6 Out of hours / transfer issues 13
Appendices, listed separate to Practice Guidance Note
Document No Description
Appendix 1 Monitoring requirements for adult patients prescribed clozapine
Appendix 2 Clozapine titration/retitration prescription
Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust PPT-PGN-05 Safe Prescribing of Clozapine – V03- Iss 5 Sep 2020 Part of NTW(C)38 – Pharmacological Therapy Policy
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Appendix 3 Clozapine initiation monitoring
Appendix 4 Clozapine clinic referral form
Appendix 5 Contact details
Appendix 6 Shared care agreement & GP letter template
Appendix 7 Clozapine clinic standard work
Appendix 8 Guide to interpretation of clozapine plasma levels
Appendix 9 RED result protocol
Appendix 10 AMBER result protocol
Appendix 11 Overdue blood results
Appendix 12 Denzapine re-challenge process
Appendix 13 Treatment break protocol
Appendix 14 Retitration by the CRHT
Appendix 15 Clozapine related constipation
Appendix 16 Clozapine related hypersalivation
Appendix 17 Clozapine related tachycardia
Appendix 18 Clozapine and smoking
Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust PPT-PGN-05 Safe Prescribing of Clozapine – V03- Iss 5 Sep 2020 Part of NTW(C)38 – Pharmacological Therapy Policy
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1 Introduction 1.1 This document outlines the process to safely initiate and maintain clozapine in
patients within CNTW services. 1.2 Clozapine is an atypical antipsychotic and is licensed for1:
Treatment resistant schizophrenia (TRS)
Severe untreatable neurological adverse reactions to other antipsychotic drugs
Psychotic disorders in Parkinson’s Disease 1.3 Clozapine is recommended by National Institute for Health and Care Excellence
(NICE) as a treatment option in TRS2,3. 1.4 To comply with the Product Licence1 of clozapine in the UK, regular monitoring of
white cell count (WCC) and a differential is mandatory. The frequency of this is weekly for the first 18 weeks, fortnightly until 1 year of clear results (as stated by the monitoring service), then 4-weekly thereafter for the total duration of treatment (and 4 weeks after stopping clozapine).
1.5 Prior to commencement on clozapine, all patients must be fully registered with the
Denzapine Monitoring Service (DMS) and have a valid blood test. DMS must be informed of all subsequent, relevant changes relating to the patient (e.g. prescriber, location, physical illness).
1.6 Any patients transferred from outside CNTW services who are registered with another
clozapine monitoring service must be re-registered with DMS. 1.7 Other indications are deemed as off license, and must be discussed with the multi-
disciplinary team (MDT) and DMS. Refer to section 9 of the Prescribing Medicines policy (UHM-PGN-02) for further guidance on off license prescribing.
1.8 RiO Clozapine documentation should be completed by all teams managing patients prescribed clozapine. These are available at: Service Specific Files > Physical Treatment > Clozapine Documentation and include:
Clozapine Pre-Treatment Checklist
Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust PPT-PGN-05 Safe Prescribing of Clozapine – V03- Iss 5 Sep 2020 Part of NTW(C)38 – Pharmacological Therapy Policy
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Clozapine Clinic Record New
Side Effect Monitoring Record
Clozapine Initiation Care Plan and Monitoring Record
Clozapine Maintenance Care Plan
1.9 Patients should be given information and education regarding:
Mandatory monitoring (its significance and consequences)
Onset of action and expected benefits
Side effects and how to combat these (The side effect monitoring record in the clozapine treatment pack and on RiO can be used as an aide memoire to support this discussion)
Missed doses
Clinic attendance
Timing of plasma levels
The effect of smoking
This discussion must be clearly documented in the clinical record 1.10 Clozapine can be initiated safely as an inpatient or in a community setting – see
section 2 for initiation guidance.
Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust PPT-PGN-05 Safe Prescribing of Clozapine – V03- Iss 5 Sep 2020 Part of NTW(C)38 – Pharmacological Therapy Policy
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2 Clozapine initiation
Decision to prescribe after considering the following: diagnosis, drug history, oral compliance, swallowing difficulties, comorbidities, client/family views, concurrent (interacting) drugs and whether a SOAD is needed (Prescriber)
On RiO, see Service Specific Files> Physical Treatment> Clozapine Documentation:
Complete Pre-Treatment Checklist including baseline bloods, ECG,
CK and physical examination by SHO/screening for faecal impaction:
(Prescriber, Nurse)
Register patient with Denzapine Monitoring Service (DMS)
(Prescriber)
Prescriber must also be registered DMS (Prescriber)
Complete Initiation Care Plan and Monitoring record on RiO
(Nurse)
Complete Side Effect Monitoring Record (at baseline / titration)
(Prescriber/Nurse/Pharmacy)
Patient Clozapine counselling, including discussion around side
effects and monitoring requirements (Pharmacy/Prescriber)
Complete core documentation care plan (Nurse)
For patients being re-initiated – see section 3 Troubleshooting
Inpatient Initiation
Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust PPT-PGN-05 Safe Prescribing of Clozapine – V03- Iss 5 Sep 2020 Part of NTW(C)38 – Pharmacological Therapy Policy
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Prescribe clozapine titration (Prescriber)
Ensure DMS is updated with blood results (Prescriber)
A valid blood result (<10 days old) is required before commencing treatment
Send valid order including titration prescription (appendix 2) to NTW
Solutions Pharmacy (Pharmacy/Nurse)
Dispense and supply appropriate quantities of clozapine on receipt of
valid DMS green blood result (Dispensing Pharmacy)
Throughout titration, physical health observations (pulse, blood
pressure, temperature) must be completed on the Clozapine Initiation
Care Plan and Monitoring Record on RiO – see also appendix 1
(Nurse)
Ensure patient has enough supplies of medication and taking into
account any weekends, bank holidays (Nurse/Pharmacy)
Community Initiation
Decision to prescribe after considering the following: diagnosis, drug history, oral compliance, swallowing difficulties, comorbidities, client/family views, concurrent (interacting) drugs and whether hospital admission is required. Ideally discussed with an NTW pharmacist based in community services (Prescriber) Complete Pre-Treatment Checklist including baseline bloods, ECG, CK
and physical examination by SHO/faecal impaction screening:
(Doctor/Prescriber/Nurse/Pharmacy)
Register patient with Denzapine Monitoring Service (DMS) (Prescriber)
Prescriber must also be registered with DMS (Prescriber)
Clozapine patient counselling including information around side effects
and explanation of monitoring requirements (Prescriber/Pharmacy)
Contact relevant blood collection centre to request routine blood
monitoring before initiation within 10 days of starting. Complete referral
form (Nurse/Pharmacy)
Contact relevant CRHT to discuss involvement over weekends if
applicable – medication supplies, physical observations, or bloods
(Prescriber/Pharmacy)
Complete core documentation care plan (Nurse)
Complete a clozapine care plan with details of arrangements,
monitoring, and physical health monitoring thresholds to report back to
designated available medic (Nurse)
For patients being re-initiated, notify relevant blood collection clinic or
GP surgery, DMS, NTW Solutions Pharmacy, Community Treatment
Team, and community Consultant Psychiatrist (Nurse/Pharmacy)
Prescribe clozapine titration on outpatient prescription and on titration chart (appendix 2). Ensure DMS is updated with blood results. Send prescription and escalation chart to NTW Solutions Pharmacy. Ensure arrangements already in place for supply to patient (Prescriber)
The initial blood result MUST be no more than 10 days old on the day the patient starts treatment
Dispense and supply appropriate quantities of clozapine on receipt of
valid green DMS blood result (Dispensing Pharmacy)
Throughout titration, physical health observations (pulse, blood pressure,
and temperature) must be completed on the Clozapine Initiation Care
Plan and Monitoring Record on RiO – see also appendix 1 (Nurse)
Ensure there is a local procedure in place for highlighting any abnormal
readings to a designated medic for nursing staff to report to
(Prescriber/Nurse)
Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust PPT-PGN-05 Safe Prescribing of Clozapine – V03- Iss 5 Sep 2020 Part of NTW(C)38 – Pharmacological Therapy Policy
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2.2 Clozapine dose titration
Clozapine should be initiated using the CNTW ‘Clozapine Titration/Re-titration
Prescription’ (see appendix 2) which is available from the Pharmacy Admin
Team. They can be contacted at [email protected] or 0191
2456606.
Intensive physical health monitoring is required initially (see appendix 1 and
Clozapine Initiation Care Plan and Monitoring Record on RiO). For patients
in the community, locally agreed arrangements should be put in place to
ensure this is carried out safely. See appendix 3 for practical guidance on
initiation monitoring.
Only clozapine labelled with the relevant patient’s name can be administered
to that patient. Out of hours, the on-call pharmacist should be contacted if
labelled medication unavailable (see section 4).
Should any dose–dependent side effects e.g. hypotension become
problematic during titration, a slower dose increase should be considered by
the prescriber. The CNTW ‘Clozapine Titration/Re-titration Prescription’ can
be used to facilitate an unambiguous dose modification.
In older patients, it is recommended to prescribe lower doses of clozapine and
titrate more slowly, starting at 12.5mg daily with maximum increments of 25mg
daily1.
In Parkinson’s disease psychosis there is evidence for very low clozapine
doses, starting at 6.25mg-12.5mg daily and increasing by no more than
12.5mg per day with a target of 25-37.5mg daily at maintenance. Doses of
50mg daily should not normally be exceeded, except in exceptional
circumstances. The maximum licensed dose is 100mg daily1,4.
Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust PPT-PGN-05 Safe Prescribing of Clozapine – V03- Iss 5 Sep 2020 Part of NTW(C)38 – Pharmacological Therapy Policy
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3 Clozapine maintenance and transfer The following chart demonstrates the process for patients who have been stabilised on treatment.
Physical health monitoring to be completed as per appendix 1 (nurse/ prescriber)
Baseline clozapine plasma level one week after dose stabilised see section 3.1 (prescriber)
On RiO, see service specific files>physical treatment>clozapine documentation: Ensure Clozapine Clinic Record New is completed for each intervention/blood monitoring episode (prescriber/nurse) Clozapine Maintenance Care Plan to be completed 3 months post initiation and annually (prescriber/nurse)
Complications– e.g. retitration, red result, side effects – see section 4
Clozapine clinic referral form (appendix 4) to be completed: -Contact community treatment team (CTT) to inform of pending discharge in order to arrange OP prescription to be sent to NTW Solutions Pharmacy (prescriber/nurse) -Contact relevant clozapine clinic to arrange appointment details (prescriber/nurse/pharmacy) see appendix 5 for contact details for each clinic. -Contact DMS (see appendix 5) to update clinic/prescriber/pharmacy details (nurse/pharmacy/clinic team) -Arrange discharge medication with ward pharmacy team (prescriber/nurse) -Forward completed referral form to clozapine clinic and scan onto RiO (prescriber/nurse/pharmacy) -Inform patient/CTT of clinic appointment details (prescriber/nurse)
If patient is unable to access a clozapine clinic, arrangements should be made with the CTT for provision of blood sampling and monitoring. In exceptional circumstances a shared care agreement may be required (see appendix 6).
Patient to attend clozapine clinic (or CTT) for mandatory monitoring -see clozapine clinic standard work (appendix 7) for process and recording requirements. (nursing/pharmacy clinic staff)
Physical health monitoring to be completed as per appendix 1 (nurse/ prescriber)
Community
maintenance
Discharge
preparation
Inpatient
maintenance
Plasma levels minimum annually (see section 3.1). (nurse/ prescriber)
Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust PPT-PGN-05 Safe Prescribing of Clozapine – V03- Iss 5 Sep 2020 Part of NTW(C)38 – Pharmacological Therapy Policy
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3.1 Therapeutic Drug Monitoring of Clozapine Plasma Levels 3.1.1 Clozapine plasma levels are useful for optimising therapy as support to the clinical
monitoring (response and adverse effects) of patients prescribed clozapine. Plasma levels should be checked and recorded at the following points:
Baseline – 7 days after target dose reached
Annually
3.1.2 In addition, as per the MHRA drug safety update8 relating to clozapine toxicity,
clozapine plasma levels should always be checked in the following circumstances:
Prescribed medicines which may interact and increase blood clozapine
levels
Patient stops/reduces smoking or switches to e-cigarettes
Suspected toxicity / overdose
Suspected poor metaboliser
Patient has pneumonia or other serious infection
3.1.3 It is also advisable to check levels in the following scenarios:
Clozapine dose change (minimum 7 days after change)
Poor compliance suspected
Poor response to treatment (after >3 months)
Increase in smoking
Suspected rapid metaboliser
Prescribed medicines which may interact and lower blood clozapine levels
3.1.4 Plasma Assay forms can be accessed from Analytical Services International (ASI) -
see appendix 5. The forms should be sent to ASI as instructed on the form. 3.1.5 Trough blood sample to be taken 10-12 (minimum 6) hours post dose (usually in the
morning before a dose is taken). 3.1.6 See appendix 8 for a guide to plasma level interpretation and clinical response. For
further advice, contact ASI (see appendix 5).
Complications– e.g. retitration, red result, side effects – see section 4
Annual review by prescriber (prescriber)
Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust PPT-PGN-05 Safe Prescribing of Clozapine – V03- Iss 5 Sep 2020 Part of NTW(C)38 – Pharmacological Therapy Policy
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3.1.7 Plasma level requests and results should be documented on RiO progress notes with a clear rationale.
3.1.8 Abnormal clozapine plasma level results should be acknowledged by clinicians on
RiO, along with documenting clear actions to be taken in response. 4 Complications 4.1 Blood monitoring issues
4.1.1 In the event of a RED result, the prescriber and ward/team are contacted by DMS
directly. Clozapine should be stopped immediately; the patient should be assessed
for any signs of infection. The relevant clozapine monitoring service must be
contacted for guidance on the management of red results. (See Appendix 9).
4.1.2 In the event of an AMBER result, arrange a retest and contact DMS. (See Appendix
10)
4.1.3 If blood monitoring becomes overdue (e.g. because patient does not attend clinic
appointment), the prescriber is responsible for ensuring alternative arrangements are
made for monitoring. A supply of clozapine can still be made for a short period (see
appendix 11). Once clozapine becomes prohibited a further supply will not be made
until a valid blood result is received.
4.1.4 If a prescriber wishes to recommence clozapine in a patient with a previous
discontinuation due to RED result (rechallenge), the process outlined in appendix 12
must be followed.
4.2 Concordance issues
4.2.1 If a dose or doses of clozapine are omitted, it can be safely continued at the patient’s
normal dose. However if there has been a break of more than 48 hours, the clozapine
will need to be retitrated. Depending on the length of the break, this may also affect
monitoring frequency and potentially require re-registration. Please see Appendix 13
for the treatment break protocol.
4.2.2 If retitration is required please follow the process outlined in the initiation section of
this document (section 2). Please see appendix 14 if CRHT involvement is required
in the retitration process.
Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust PPT-PGN-05 Safe Prescribing of Clozapine – V03- Iss 5 Sep 2020 Part of NTW(C)38 – Pharmacological Therapy Policy
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4.3 Discontinuation
4.3.1 Clozapine should usually be prescribed and monitored for at least one year in order to establish its effectiveness as a long term treatment.
4.3.2 If the decision is made to discontinue clozapine for anything other than a
haematological reason, the dose should be reduced as slowly as possible. This should take into account any clinical risk factors, the mental state of the patient and alternative treatment plan.
4.4 Side effects 4.4.1 Side effects and tolerability to treatment should be reviewed at each review and
following dose changes. More frequent monitoring of side effects may be indicated where the clinical significance of the side effect warrants this. A summary of the yearly review should be recorded in the patient’s clinical records and communicated to the GP.
4.4.2 Constipation
Severe constipation is a potentially life threatening complication of clozapine that can lead to intestinal obstruction, faecal impaction, paralytic ileus and ultimately death. To minimise the risk of serious constipation prescribers should:
Educate patients about the risk of constipation and provide written information on dietary management (this should be documented)
Be particularly vigilant for constipation in patients who are prescribed concomitant medicines with anticholinergic activity (e.g. hyoscine, tricyclic antidepressants, drugs for bladder instability)
Exercise caution in patients aged 60 years and older and patients with a history of colonic disease or lower bowel surgery.
Consider prophylactic laxative treatment when starting clozapine in patients with a history of constipation or bowel obstruction.
Monitor for signs and symptoms related to reduced bowel movements, including nausea, vomiting, bloating, abdominal pain or difficulty passing wind.
Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust PPT-PGN-05 Safe Prescribing of Clozapine – V03- Iss 5 Sep 2020 Part of NTW(C)38 – Pharmacological Therapy Policy
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If the patient is constipated, clozapine should not be initiated until this has been resolved
Use lowest effective dose of clozapine
Monitor bowel movements daily for the first 4 weeks then weekly thereafter at each clinic appointment or blood sampling.
If there is a change in bowel habits or the patient has had fewer than
three bowel movements per week an abdominal examination should
be carried out
Intervene actively when patients report constipation, ensuring that an
effective laxative regimen is prescribed promptly (e.g. senna &
docusate sodium or a polyethylene glycol-based osmotic laxative) and
that the effectiveness of this treatment is monitored closely thereafter
Refer urgently all patients who present with symptoms indicating a
potentially life-threatening gastrointestinal complication (e.g.
abdominal pain with nausea in the context of constipation), in whom
clozapine should be temporarily discontinued
Please refer to appendix 15 and the Bowel Care policy (PPT-PGN-16) for further information.
4.4.3 Tachycardia – please see appendix 17
4.4.4 Hypersalivation – please see appendix 16
4.4.5 Hypotension
Hypotension is listed as a potential adverse effect of clozapine which is most likely
during the first 4 weeks of treatment.
In the first instance patients should be advised to take time when standing up and
encouraged to increase their fluid intake to 2 litres a day.
Slowing down the rate of dose increase or a small reduction in dose could be
considered.
If hypotension persists or is severe, medical review is required.
4.4.6 Pneumonia and other infections
A robust approach should be made to ensure that Clozapine patients presenting with
symptoms of infection are monitored closely to minimise risks associated with
Clozapine toxicity. Clozapine levels should be checked and urgent consideration
Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust PPT-PGN-05 Safe Prescribing of Clozapine – V03- Iss 5 Sep 2020 Part of NTW(C)38 – Pharmacological Therapy Policy
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given by the treating clinician to reducing the Clozapine dose until the patient is fully
recovered.
An increased risk of pneumonia should be assumed for all patients taking Clozapine
for any length of time and regardless of age. Early medical intervention should be
considered where there is any doubt about the severity or type of chest infection when
reported or observed.
At each consultation, a patient receiving Clozapine must be reminded to contact the
treatment team immediately if any kind of infection begins to develop. Particular
attention should be paid to flu-like complaints such as fever or sore throat, persistent
cough and to other evidence of infection.
Many of our patients have co-morbidities such as COPD and diabetes and would
therefore fit the criteria to have influenza and pneumococcal vaccination. Clinical staff
should strongly encourage these are received.
As clozapine metabolism may be inhibited by respiratory infections, serious
respiratory infection may contribute to additional side effects thereby exacerbating
the risk of hyper salivation, sedation, aspiration and arrhythmia.
During episodes of respiratory infection or illness, there is also a likelihood that
patients may reduce smoking habits. Therefore please refer to 4.5 below.
4.5 Smoking
Patients intending to stop/start smoking, or change their smoking habit should seek advice from the clozapine clinic staff/prescriber, who will formulate a plan, to ensure their ongoing safety. Please see appendix 18 for further advice.
4.6 Out of hours / transfer issues 4.6.1 Out of area admission to CNTW ward
Contact clozapine monitoring service to confirm monitoring frequency and when
blood test is next due.
If monitored by DMS, the details should be updated and a supply can then be made
if needed.
If monitored by a different service, complete a transfer form from DMS website and
return completed form by fax.
Once received DMS will contact the previous monitoring service to transfer the
patient and information onto the DMS system.
Supply of medication made if necessary once DMS system has been updated.
4.6.2 Patient transfer /admission to acute hospital
CNTW is responsible for the supply of clozapine to local acute hospitals.
Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust PPT-PGN-05 Safe Prescribing of Clozapine – V03- Iss 5 Sep 2020 Part of NTW(C)38 – Pharmacological Therapy Policy
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When transferred from a CNTW inpatient setting, a copy of the inpatient
prescription chart and a clozapine supply should be sent with the patient.
When directly admitted from a community setting, the acute hospital should be
advised to attempt to obtain the patient’s own supply in the first instance.
If re-titrating, the clozapine titration/re-titration prescription (appendix 2) should be
completed by the prescriber and sent to the relevant CNTW pharmacy site as well
as a copy to the acute hospital for reference.
Ongoing supply of clozapine from CNTW pharmacy obtained by acute hospital ward
staff through liaison with CNTW pharmacy department.
4.6.3 Out of hours
When clozapine is newly started or a patient is admitted out of hours, the CNTW EDC pharmacist should be contacted via switchboard before obtaining a supply to ensure the patient is appropriately registered and has a valid blood result.
References
1. Summary of Product Characteristics (SPC) Denzapine 100mg tablets.
https://www.medicines.org.uk/emc/product/6120/smpc Accessed 24/01/19
2. National Institute for Health and Care Excellence (NICE). Psychosis and
schizophrenia in adults: treatment and management (CG178). Last updated
February 2014. Accessed at: https://www.nice.org.uk/guidance/CG178
3. National Institute for Health and Care Excellence (NICE). Psychosis with Co-
Existing Substance Misuse (CG120). Last updated March 2011. Accessed at
https://www.nice.org.uk/guidance/CG120
4. Taylor, David, Barnes, Thomas E., Young, Allan. The Maudsley Prescribing
Guidelines in Psychiatry. 13th Edition. 2018. pp 592
5. Medicines and Healthcare products Regulatory Agency Drug Safety Update
(26th October 2017). Clozapine: reminder of potentially fatal risk of intestinal
obstruction, faecal impaction, and paralytic ileus https://www.gov.uk/drug-
Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust PPT-PGN-05 Safe Prescribing of Clozapine – V03- Iss 5 Sep 2020 Part of NTW(C)38 – Pharmacological Therapy Policy
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safety-update/clozapine-reminder-of-potentially-fatal-risk-of-intestinal-
obstruction-faecal-impaction-and-paralytic-ileus.Accessed 30/01/20
6. US Food and Drug Administration (28th January 2020). Clozaril, Fazaclo ODT,
Versacloz (clozapine): Drug Safety Communication - FDA Strengthens Warning
That Untreated Constipation Can Lead to Serious Bowel Problems
https://www.fda.gov/safety/medical-product-safety-information/clozaril-fazaclo-
odt-versacloz-clozapine-drug-safety-communication-fda-strengthens-warning-
untreated. Accessed 30/01/20
7. Jose De Leon, Emilio J Sanz, Carlos De las Cuevas, Data From the World
Health Organization’s Pharmacovigilance Database Supports the Prominent
Role of Pneumonia in Mortality Associated With Clozapine Adverse Drug
Reactions, Schizophrenia Bulletin, Volume 46, Issue 1, January 2020, Pages
1–3, https://doi.org/10.1093/schbul/sbz093
8. Medicines and Healthcare products Regulatory Agency Drug Safety Update (26th
August 2020). Clozapine and other antipsychotics: monitoring blood concentrations
for toxicity. Accessed at https://www.gov.uk/drug-safety-update/clozapine-and-
other-antipsychotics-monitoring-blood-concentrations-for-toxicity on 02/09/20