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Canberra Hospital and Health ServicesClinical Procedure Treatment Guidelines for the Initiation, Administration and Monitoring of People on Clozapine Contents

Contents....................................................................................................................................1

Purpose.....................................................................................................................................2

Scope........................................................................................................................................ 2

Section 1 – Background.............................................................................................................2

Section 2 – Clozapine System in the ACT..................................................................................3

Section 3 – Medical Officer Registration...................................................................................3

Section 4 – Commencing a Person on Clozapine.......................................................................4

Section 5 – Ongoing Monitoring Requirements........................................................................7

Section 6 – Clozapine Prescribing..............................................................................................8

Section 7 – Pathology Results...................................................................................................8

Section 8 – Clozapine Clinics.....................................................................................................8

Section 9 – Management of Person in the AMBER Range........................................................9

Section 10 – Management of People in the RED Range............................................................9

Section 11 – Recommencing Clozapine After a Therapy Interruption.....................................10

Section 12 – Discontinuing Clozapine – Dose Reduction and Monitoring...............................10

Section 13 – Transfers within Australia and Overseas............................................................11

Section 14 – Special Dispensation of Clozapine......................................................................11

Section 15 – Important Contacts.............................................................................................12

Related Policies, Procedures, Guidelines and Legislation.......................................................12

References.............................................................................................................................. 12

Search Terms.......................................................................................................................... 12

Attachments............................................................................................................................12

Doc Number Version Issued Review Date Area Responsible PageMH:1:9:15 1 Sept 2012 July 2018 MHJHADS 1 of 14

Do not refer to a paper based copy of this policy document. The most current version can be found on the ACT Health Policy Register

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Purpose

The purpose of this Procedure is to provide a framework for service providers involved in the prescribing, dispensation, administration and monitoring of Clozapine in the ACT. Mental Health, Justice Health & Alcohol and Drug Services (MHJHADS) has a responsibility to ensure the safe use of Clozapine with adherence to the Clozapine Patient Monitoring System (CPMS) Protocol as well as local service standards, and to optimise the management and care of people receiving clozapine therapy.

Note: These treatment guidelines should be read in conjunction with the CPMS Protocol which has supplementary information but for practicality is not all repeated in this document.

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Scope

This Procedure pertains to all MHJHADS clinical staff involved in the initiation, maintenance and monitoring of people with a mental disorder or mental illness on Clozapine.


Section 1 – Background

Clozapine is an atypical antipsychotic of the dibenzodiazapine class and is licensed for treatment resistant schizophrenia in people who are unresponsive to, or intolerant of other antipsychotics. The Royal Australian and New Zealand College of Psychiatrists (RANZCP) Clinical Practice Guidelines recommend that clozapine treatment be commenced in people who have received two previous trials of antipsychotic, one being atypical, however have had limited response after uninterrupted therapy.

Neutropenia, agranulocytosis and myocarditis are adverse effects of clozapine treatment. It is a requirement of treatment that all people be registered on to the national database CPMS and attend blood monitoring of white cell and neutrophil levels whilst receiving clozapine. Attendance at clozapine clinics is also a requirement of people receiving this drug.

The preparation of clozapine currently used in the ACT is Clozaril, developed by Novartis Pharmaceuticals and is available is 25mg and 100mg oral preparations- an elixir is also available for use within the inpatient setting. Clozapine is a Schedule 100 medicine and cannot currently be prescribed by General Practitioners in the ACT. The introduction of generic products may require changes to the present arrangements for the procurement of Clozapine, blood monitoring and registration of people on the national database. This document will be reviewed if the current contract is changed in the future.



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Section 2 – Clozapine System in the ACT

There are currently two clozapine centres in the ACT – The Canberra Hospital and The Calvary Hospital. The Canberra Hospital provides clozapine to its campus, the Adult Mental Health Unit (AMHU), community mental health teams, as well as to the private sector. The Calvary Hospital provides clozapine to its campus, Ward 2n, Brian Hennessy Rehabilitation Centre, The Older Persons Mental Health Unit, and Hyson Green.

Each inpatient setting and community team has a local clozapine assistant whose responsibilities include notification to people or support workers that blood testing is due, transcribing of results onto the CPMS database, transfer of scripts to the appropriate centre pharmacy, collection and dispensation, and running of the clozapine clinics. The Clozapine assistant will also alert the prescriber of any concerns with the person and communicate dosage changes to pharmacy staff.

The Clozapine Coordinator is a senior clinician whose primary duties include overall management of the clozapine system, and whose role is to: Authorise new people registrations; Communicate registrations, discontinuations, transfers and information about people

from the centre to the CPMS office; Ensure that the centre complies with the CPMS protocol; Approval of personnel registrations including Medical Officers, Pharmacists, and

assistants, through the DoCS office Provide assistance and training to staff involved in caring for people receiving clozapine;

All adverse events or abnormal blood results must be communicated to the Clozapine Coordinator immediately


Section 3 – Medical Officer Registration

Medical Officers must have approval and be a registered prescriber on the CPMS database in order to prescribe clozapine. Medical Officers who are new to the service or require registration can contact the Clozapine Coordinator who will authorise approval through the DoCS. Medical Officers seeking registration must read and be competent in the CPMS protocol which is available from the Clozapine Coordinator or assistant. A letter of confirmation of registration must be received before prescribing is commenced.


Section 4 – Commencing a Person on Clozapine

(Also see Attachment A - How to initiate people on Clozapine)



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4.1 Relevant history Information from the person’s previous treating psychiatrist/ team/ carer(s) including past history would be considered in the preparation and planning for Clozapine treatment.

4.2 ConsentThe person should be provided with verbal and written information and the opportunity to discuss clozapine treatment. They must be aware of the need for regular blood and cardiac monitoring, benefits of treatment, possible side effects, and the initiation process. A written consent form can be obtained from the Clozapine Coordinator or assistant, signed and returned before registration can occur.

When the person has an identified carer or family member this person should also be advised of the benefits and possible side effects, the need for monitoring and how to seek assistance as need from the Clozapine coordinator and/ or psychiatrist.

4.3 Location for clozapine to be initiated:People can be commenced on clozapine as a day patient or admitted to the ward (Acute Adult Mental Health Unit, Calvary Ward 2n, Brian Hennessy Rehabilitation Centre, or the Older Persons Inpatient Unit). Clozapine can also be commenced within the Alexander Maconochie Centre. In the case of a person commencing clozapine as a day patient, the medical work-up and registration must be completed prior to admission.

4.4 CPMS Registration:The Medical Officer will inform the Clozapine Coordinator of their intention to commence the person on clozapine. Before a person can be started on clozapine, the Medical Officer must determine whether clozapine has been used before and if the person was previously discontinued from any brand of clozapine due to neutropenia or agranulocytosis, has a history of drug induced neutropenia, or bone marrow disorders. The Medical Officer must also determine if the person is unsuitable for treatment due to other reasons.

Information required for registration: Person’s initials; Date of birth; Sex; Blood group; Consent form completed; Previously treated with clozapine; History of drug induced neutropenia; History of any bone marrow disorders; Name of the initiating Medical Officer (must be registered with CPMS) Baseline / pre-treatment results

4.5 Baseline measurements/ pre-treatment results:



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Baseline full blood count and physical information is required in order to complete registration. Blood results can be no older than 10 days old to be valid for registration. Detailed medical history, including history of cardiac problems; Physical examination; Height, weight and waist measurement; Body Mass Index; Fasting blood glucose/ lipids; U&E, LFT, Prolactin and Thyroid function; Full blood count and differential; Cardiac enzymes (including Troponins and creatinine kinase); ECG ; Baseline echocardiogram may be indicated in people with a personal or family history of

cardiac conditions

Assessment of blood resultsWBC and Neutrophil count results Action

WBC >3.5 X 109/LAndNeutrophils >2.0x 109L GREEN

Clozaril therapy may be commenced subject to assessment by the treating Medical Officer and successful registration

WBC 3.0 – 3.5 X 109/LAnd/orNeutrophils 1.5 - 2.0x 109L AMBER

Repeat blood count after one week. If still within the same range, Clozaril therapy may commence subject to assessment by the treating Medical Officer and successful registration

WBC <3.0 X 109/LAnd/ orNeutrophils <1.5 x 109L RED

CLOZARIL THERAPY MUST NEVER BE STARTED

4.6 Clozapine titration guide:In most people, antipsychotic efficacy can be expected between 200 - 450mg per day. The total daily dose may be divided unevenly after initial titration, with the larger portion at bedtime. The maximum permissible dose of clozapine is 900mg per day. After the maximum therapeutic benefit has been achieved, the minimum effective dose should be used to maintain clinical remission and reduce occurrence of adverse effects.

How to initiate ClozapineDay Daily dose

1 12.5mg2 25mg3 25mg4 50mg5 50mg6 75mg



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7 100mg8 125mg9 150mg

10 150mg11 175mg12 175mg13 175mg14 200mg

Titration above 200mg per day: increase daily dose in increments of 25 – 50mg

4.7 Monitoring post initiation:Day 1 Lying and standing BP, temperature and pulse to be attended 15 minutes prior to the first dose, 15 minutes after dose and then hourly for six hours Day 7 Full blood count, Troponins, ECGDay 14 Full blood count, Troponins, ECG

4.8 Common Side effects: Below is a list of the most common side effects (not a comprehensive list) associated with clozapine use. Most side effects are dose-dependent and may be associated with the speed of titration. They also tend to be most common at the beginning of therapy.

Side effects ManagementIf the person has a raised temperature, sore throat of other infection, this may be a sign of low white cell count caused by clozapine

The Medical Officer should be informed immediately and an FBC attended. If the blood results are satisfactory and the temperature is below 38.5o C clozapine can be continued. The temperature is over 38.5oC, consider withholding the clozapine until the temperature subsides. Paracetamol may be used to treat fever.

Hypotension Clozapine must be initiated gradually. BP both lying and standing should be monitored. People should be encouraged to increase daily fluid intake and avoid dizziness by standing slowly from a sitting or lying position.

Constipation High fibre diet and adequate fluid intake. Bowel movements should be monitored and aperients prescribed if required. Constipation if untreated can lead to paralytic ilius.

Sedation Consider adjusting the dose so a higher proportion is taken at bedtime. The person should be advised not to drive if affected, or not at all during initial titration

Hypersalivation Hyoscine hydrobromide at a dose of 150mcg – 300mcg up to three times per day, or Atropine drops 1% - one drop in water before bed.

Weight gain Psychoeducation on diet and exercise at initiation is vital. Regular weighs at clozapine clinics. Liaison with GP and referral to dietician may be indicated

Dry mouth Sugar free chewing gum, citrus fruit, or low calorie



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drinks may help. Artificial mouth sprays are also available. Ongoing dry mouth may lead to poor dentition

Tachycardia Pulse should be monitored at the clozapine clinic. Referral to GP is indicated if pulse is persistently >100bpm

Headache Paracetamol can be prescribedNeuroleptic Malignant Syndrome – POTENTIALLY LIFE THREATENING. Symptoms include fever, severe muscle rigidity, with two or more of: diaphoresis, dysphagia, tremor, incontinence, tachycardia, altered BP, altered level of consciousness, raised Creatinine Kinase level

If NMS is suspected, clozapine should be stopped immediately and the person transferred to the Emergency Department for treatment. Inpatient unit staff should call a CODE BLUE

Metabolic syndrome – Impaired glucose tolerance and/ or exacerbation of diabetes mellitus. On very rare occasions, severe hyperglycaemia, sometimes leading to ketoacidosis/ hyperosmolar coma

Perform fasting plasma glucose at baseline (for non-diabetic’s) or HbA1c (for diabetics), then at one month, then six months annually. If HbA1c is raised, perform fasting plasma glucose- consider stopping clozapine or referring to GP or endocrinologist


Section 5 – Ongoing Monitoring Requirements

People receiving clozapine treatment must have a full blood count and attend the clozapine clinic for monitoring weekly for 18 weeks and then 4 weekly for the remaining period they are receiving clozapine.

Further testing requirements include: Fasting lipid studies – 6 monthly; Fasting serum glucose – 6 monthly; Troponins – 12 monthly; Clozapine level – 6 monthly or as ordered depending on individual need or compliance

monitoring; ECG - at 3 months, then 12 monthly ECHO – at 6 months, then 12 monthly


Section 6 – Clozapine Prescribing

Clozapine can be ordered on any type of script however The Canberra Hospital (TCH) prefers the use of their own generic scripts which are available from the TCH Pharmacy, the Clozapine Coordinator, or assistants.



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People subject to weekly monitoring can receive no more than 7 days’ supply of clozapine, and people subject to monthly monitoring can receive a maximum of 28 days’ supply of clozapine. Medical Officers must review the person’s blood results and confirm that they are in the GREEN or AMBER range before providing a new script. Blood results must be within 48 hours of the script being written to be valid. The clozapine assistant will facilitate the collection and delivery of the script to either The Canberra Hospital or Calvary Hospital Pharmacy.


Section 7 – Pathology Results

People may choose any one of ACT Pathology, Capital Pathology, or Symbion Laferty to attend their bloods, and will generally select the centre which is closest to their home. A Rule 3 exemption should be written on all requests for FBC as this allows the person to attend blood testing six times on the one form. Requests should be marked as ‘urgent’ and results to be received by fax. It is preferable that persons attend to blood testing early in the week, so results are available prior to the clozapine clinic. Blood results are entered onto the CPMS database by the Clozapine assistant.

Any concerns about blood test results would be discussed with the pesron/ carer prior to any further issue of a script or if Clozapine treatment needs to be ceased.


Section 8 – Clozapine Clinics

Clozapine clinics are attended within each community centre and are run by the clozapine assistant. The purpose of the clinic is to monitor the physical health of the person receiving clozapine including monitoring of side effects, weight, and providing education. Note that people also have regular appointments for ongoing assessments as well as Clozapine review appointments.

The clozapine assistant will attend and record the person’s weight, blood pressure, pulse, and girth, as well as assess for signs of infection and other side effects of clozapine treatment. Annual height will be recorded as well as three monthly blood glucose level. People presenting with signs of infection may require increased blood monitoring and will have their temperature and respirations recorded also.

Following assessment by the clozapine assistant, people will then attend review by the Medical Officer who will evaluate all of the vital signs and blood results for the person. If all results are within appropriate limits, clozapine can be dispensed. The Medical Officer is required to complete either the “Weekly clozapine form” or the “Monthly clozapine form” which is located on MHAGIC.



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Section 9 – Management of Person in the AMBER Range

People within the AMBER range can continue clozapine treatment, however clinical and blood monitoring should be increased to twice weekly until results return to the GREEN range. People can then return to weekly or monthly monitoring depending on their commencement date.


Section 10 – Management of People in the RED Range

Clozapine should be stopped immediately if blood results fall in the RED range. The Clozapine Coordinator is to be notified immediately. Alternatively, the CPMS officer should be notified if the Clozapine Coordinator is unavailable. A second full blood count is required within 24 hours of receipt of the RED result, and results provided to the Clozapine Coordinator (or CPMS).

If the second set of results are also in the RED range, full blood counts must be performed daily and the person closely monitored for symptoms of infection. Transfer to hospital may be indicated at this time. Once results have returned to the AMBER range, refer to section 9 for continued management.

If WBC or Neutrophil levels continue to fall despite clozapine cessation, management must be guided by the CPMD Haemetologist, and protective isolation may be indicated. People whose blood cell counts have fallen into the RED range (Neutropenia or Agranulocytosis) due to clozapine therapy can NEVER be rechallenged.

Eosinophilia is a further adverse effect of clozapine therapy. If Eosinophil count is >3000/mm3 clozapine should be discontinued until level falls <1000/mm3


Section 11 – Recommencing Clozapine After a Therapy Interruption

People miss doses of clozapine for a number of reasons, however taking a full dose of clozapine after a 72 hour interruption poses a great risk of potentially life threatening seizures. MHJHDAS endorses the CPMS Protocol therapy interruption retitration guide. Retitration and monitoring is dependent on the period of time since the last dose was taken.

Period of interruption (time since last dose was due)

Dosage and monitoring requirements

< 48 hours No change to dosage or monitoring> 48 hours & < 72 hours Start on 12.5mg and titrate up

No additional monitoring requirements> 72 hours & < 28 days Start on 12.5 and titrate up



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For monthly people – weekly monitoring for 6 weeks. If no abnormalities, resume monthly monitoringFor weekly people – weekly monitoring for 6 weeks and as long as needed to reach 18 weeks (whichever is greatest)

> 28 days New people registration form and pre-treatment bloodsNew pre-treatment result and monitoring as with a new person (18 weeks); no 6 hour vital sign monitoring requiredStart on 12.5mg and titrate up


Section 12 – Discontinuing Clozapine – Dose Reduction and Monitoring

Discontinuation of a person should be communicated to the Clozapine Coordinator who will formally complete the CPMS discontinuation documentation. If clozapine therapy needs to be ceased, it is recommended that the dose be gradually reduced over a period of one to two weeks where ever possible.

If abrupt cessation is necessary (likely to be in cases of people with myocarditis or blood dyscrasias), the person should be closely observed for an intense rebound of psychotic symptoms. Cholinergic symptoms may also develop, including headache, nausea, vomiting, and diarrhoea. An anticholinergic agent can be used to prevent the occurrence of these symptoms.

Post-discontinuation monitoring for weekly people:Weekly Full blood count for 4 weeks following the last dose of clozapine

Post-discontinuation monitoring for monthly people:One full blood count should be performed one month following the last dose of clozapine.

For people who are subject to increased monitoring due to infection or AMBER blood result are required to attend twice weekly full blood count until WBC is >3.5 x 109/L, neutrophils are >2.0 x 109/L and/ or symptoms of infection have resolved. Once these values have returned to the GREEN range, blood monitoring is required for a further 4 weeks.

People who have discontinued clozapine due to a RED result must attend DAILY full blood count, until WBC and Neutrophils have returned to the GREEN or AMBER range. Once back in the GREEN range, perform full blood count weekly for 4 weeks.


Section 13 – Transfers within Australia and Overseas

The Clozapine Coordinator will attend transfers to and from other areas. Many areas within Australia use alternate brands of clozapine, and require at least three days to be registered with the CPMS as their previous blood history will need to be transcribed over. The



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Clozapine Coordinator requires a minimum of three weeks’ notice to arrange clozapine dispensation for overseas travel.


Section 14 – Special Dispensation of Clozapine

Under special circumstances, CPMS may approve an extension of the blood test period and allow a dispensation of additional clozapine. Weekly people can be approved for up to two days of medication and monthly people up to two weeks. Requests for special dispensation should be communicated to the Clozapine Coordinator.




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Section 15 – Important Contacts

Clozapine Coordinator: Phone: 0418 288 614

CPMS Office: Phone: 1800 501 768(Office hours are 9am to 5pm, Monday to Friday) Fax: 1800 550 150

CPMS Consultant Haematologist (24 hour): Phone: 0404 451 327

Adverse reaction reporting: Phone: 1800 814 677Fax: 1800 650 493


Related Policies, Procedures, Guidelines and Legislation

LegislationHealth Practitioner Regulation National Law (ACT) 2009Health Records (Privacy and Access) Act 1997Human Rights Act (2004)Medicines, Poisons and Therapeutic Goods Act (ACT) 2008Mental Health Act 2015

PoliciesMedication Handling Policy

Standards National Mental Health Standards 2010ACHS EQuIP 5. Clinical 1.5.1 & Corporate 3.1.1


References

Clozapine Patient Monitoring System (CPMS) Protocol


Search Terms

Clozapine, MHJHADS, Chief PsychiatristBack to Table of Contents

Attachments

Attachment A. How to initiate a person on Clozapine



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Disclaimer: This document has been developed by ACT Health, Canberra Hospital and Health Service specifically for its own use. Use of this document and any reliance on the information contained therein by any third party is at his or her own risk and Health Directorate assumes no responsibility whatsoever.

Date Amended Section Amended Approved ByEg: 17 August 2014 Section 1 ED/CHHSPC Chair



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Attachment A. How to initiate a person on Clozapine



Person identified. Consent form, person profile completed

Pre-treatment blood sampling CPMS cross check of database

Green Amber Red

Person RegisteredCPN Issued

NO Clozaril started

Repeat in 7 days

If green, register patient

Blood sample (7 days after commencing treatment)

Green Amber Red

Weekly monitoring

Twice weekly monitoring

STOP

CONTINUE THERAPY After 18 weeks review every 28 days

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