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Western Australia

Clinical policies and procedures for the


use of methadone and buprenorphine
in the treatment of opioid dependence

Drug & Alcohol Office


October 2007

Acknowledgements
The Drug and Alcohol Office and Department of Health are grateful for the contribution to the
development of this manual from the following sources.
The Australian Government Department of Health and Ageing National Clinical Guidelines and
Procedures for the Use of Buprenorphine/Methadone in the Treatment of Opioid Dependence,
from which much of the material is directly drawn.
The NSW Department of Health NSW Clinical guidelines for methadone and buprenorphine treatment of opioid dependence, from which the chapter summaries are adapted.
The Opioid Pharmacotherapy Advisory Committee (OPAC) and the clinicians at Next Step Drug and
Alcohol Services who have provided invaluable comments during the consultation process which
has preceded the development of many of the WA specific policies.

Prepared by
The Drug and Alcohol Office, Community Clinical Programs, in consultation with the
Community Program for Opioid Pharmacotherapy Management Committee
For further information, or to obtain copies of the documents, please contact:
Next Step Drug and Alcohol Services - Community Clinical Programs
Drug and Alcohol Office
PO Box 126, Mt Lawley WA 6929
Telephone (08) 9219 1919

ISBN: 978-1-876684-20-4
Drug and Alcohol Office (WAADA) 2006

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Foreword
The Western Australia clinical policies and procedures for the use of methadone and
buprenorphine in the treatment of opioid dependence have been adapted from the national
guidelines to include the legislative and administrative requirements for W.A.
Compliance with the policies, procedures and clinical practices set out in this document is a
condition of authorisation for prescribers and dispensers of methadone and buprenorphine to
opioid dependent patients.
On occasions, clinicians may need to vary their clinical practice from that recommended in this
document according to patient requirements. In these circumstances clinicians should clearly
document the reasons for any variations and any advice received from the Clinical Advisory
Service. There should be no variation from the legislative or administrative requirements set out
in section 1 of this document.
The provision of methadone and buprenorphine treatment for opioid dependence in Western
Australia is managed jointly by the Department of Health (DOH) and the Drug and Alcohol Office
(DAO).

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

TABLE OF CONTENTS
INTRODUCTION

1.0
LEGISLATIVE AND ADMINISTRATIVE REQUIREMENTS

1.1 LEGISLATIVE REQUIREMENTS

Authorisation as a methadone/buprenorphine prescriber in Western Australia

Authorisation as a methadone/buprenorphine dispenser in Western Australia

Authority to Prescribe

Conditions Associated with the Authority to Prescribe Opioid Pharmacotherapy

1.2
INFORMED CONSENT AND PATIENT INFORMATION.

Appeals/Complaints Process

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2.0
CLINICAL PHARMACOLOGY

2.1
GENERAL INFORMATION

What is Methadone?

Pharmacokinetics

Drug Interactions

Safety

Withdrawal from methadone

What is buprenorphine?

Pharmacokinetics

Drug Interactions

Safety

Withdrawal from buprenorphine

Buprenorphine-naloxone combination product (Suboxone)

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3.0
CLINICAL MANAGEMENT FOR MAINTENANCE TREATMENT 

3.1
ENTRY INTO METHADONE/BUPRENORPHINE MAINTENANCE TREATMENT

Indications

1. Opioid dependence

2. Patient must be at least 16 years of age (see section 5.10)

3. Patient must have 100 points of ID (see Appendix 3 and section 3.10)

4. Patients must be able to give informed consent (see section 1.2)

Contraindications

Precautions

3.2
SELECTING MAINTENANCE PHARMACOTHERAPIES

3.3
ASSESSMENT FOR MAINTENANCE TREATMENT

3.4 COMMENCING MAINTENANCE TREATMENT

3.5
INDUCTION TO METHADONE TREATMENT

Commencing methadone from heroin use

Size of the first dose

Stabilisation

Monitoring during the first two weeks.

Dose titration

Methadone dose levels

Changing dose level

Split dosing of methadone

Transfer from other pharmacotherapies

From buprenorphine

From oral naltrexone

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Clinical policies and procedures for the use of methadone


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3.6









3.7

3.8

3.9

3.10











3.11







3.12







INDUCTION TO BUPRENORPHINE TREATMENT


Commencing buprenorphine from heroin use
Stabilisation
Monitoring during the first two weeks
Dose levels
Changing dose level
Split dosing
Frequency of dosing: alternate-day and three-times-a-week dosing regimes
Transferring from methadone maintenance treatment
MONITORING DRUG USE
COORDINATED CARE
ADJUNCT TREATMENT
COMMUNITY PHARMACY DISPENSING AND ADMINISTRATION
Approved Methadone/Buprenorphine Dispensing Pharmacies
Storage
Commencing new patients
Prescriptions
Patient identification
Pharmacotherapy administration
Changes to dosing location
Changes to dose
Dual dispensing locations
Dispensing fees
TRANSFER OF TREATMENT PROVIDER
Transfers within Western Australia
Transferring to a new prescriber
Patients requesting prescriber transfers
Prescribers requesting patient transfers
Interstate transfers
International travel
CESSATION OF METHADONE/BUPRENORPHINE MAINTENANCE TREATMENT
Voluntary withdrawal
Management of withdrawal from maintenance treatment
The use of buprenorphine to assist withdrawal from
methadone maintenance programs
Involuntary withdrawal
Risk of relapse
Transfer to naltrexone from buprenorphine maintenance treatment
Transfer to Naltrexone from Methadone

4.0
TAKEAWAY AND MISSED DOSES

4.1
TAKEAWAY DOSES

Indications of stability

Contraindications

Authorisation of takeaway doses of methadone/

buprenorphine outside this schedule

Frequency of takeaway doses

Schedule for takeaway doses

Size of the takeaway doses

Dispensing of takeaway doses

Labelling and containers
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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

4.2

MISSED DOSES AND REINTRODUCTION

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5.0
COMMON MANAGEMENT ISSUES

5.1
SIDE EFFECTS/ADVERSE DRUG REACTIONS

5.2
OVERDOSE

Methadone

Buprenorphine

5.3
DOSING INTOXICATED PATIENTS

5.4
VOMITED DOSES

5.5
INCORRECT DOSE ADMINISTERED

Methadone

Buprenorphine

5.6 CONTINUED HIGH RISK DRUG USE & POLYDRUG USE

Benzodiazepines

5.7
TREATING HOSPITALISED PATIENTS

5.8
ANALGESIA AND ANAESTHESIA

Analgesic requirements for inpatients on methadone

Analgesic requirements for patients on buprenorphine

5.9
DIVERSION OF METHADONE/BUPRENORPHINE

5.10 PATIENTS LESS THAN 18 YEARS OLD

5.11 PREGNANCY AND LACTATION

The patient who becomes pregnant while in buprenorphine treatment

Principles in managing pregnancy in opioid dependent women

Dose reductions or detoxification during pregnancy

Breastfeeding

Neonatal Withdrawal Syndrome

5.12 HIV

5.13 HEPATITIS B & C

5.14 PSYCHIATRIC COMORBIDITY

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6.0
CLINICAL MANAGEMENT OF HEROIN WITHDRAWAL

6.1
HEROIN WITHDRAWAL IN CONTEXT

6.2
NON-PHARMACOLOGICAL ASPECTS IN MANAGING HEROIN WITHDRAWAL

The optimal setting for withdrawal

Getting organised for withdrawal

Supportive care

Monitoring

Scales for assessing opiate withdrawal

6.3
OVERVIEW OF BUPRENORPHINE IN THE MANAGEMENT OF HEROIN WITHDRAWAL

Efficacy of buprenorphine compared to other withdrawal medication regimes

Use of ancillary medications in conjunction with buprenorphine

Continued use of heroin and other drugs

Gateway model of treatment with buprenorphine

6.4
BUPRENORPHINE REGIMENS IN OUTPATIENT WITHDRAWAL SETTINGS

Flexible dosages

6.5
BUPRENORPHINE FOR HEROIN WITHDRAWAL IN RESIDENTIAL SETTINGS

6.6
TRANSITION TO POST-WITHDRAWAL TREATMENT

Transition to buprenorphine maintenance treatment.

Transition to methadone maintenance treatment

Commencing naltrexone treatment after short

duration buprenorphine withdrawal

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

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APPENDIX 1

POSSIBLE DRUG INTERACTIONS WITH METHADONE

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APPENDIX 2

MEDICATIONS METABOLISED BY CYTOCHROME P450 3A4

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APPENDIX 3 PATIENT IDENTIFICATION

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APPENDIX 4 URINALYSIS

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APPENDIX 5 RESOURCES FOR HEALTH PROFESSIONALS

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APPENDIX 6 RESOURCES FOR PATIENTS

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APPENDIX 7 ASSESSMENT OF ACUTE INTOXICATION

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APPENDIX 8 DIVERSION

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APPENDIX 9 NEONATAL WITHDRAWAL SCORING INSTRUMENT

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APPENDIX 10 OPIATE WITHDRAWAL SCALES

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APPENDIX 11 WITHDRAWAL STATES FROM COMMONLY USED DRUGS

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APPENDIX 12 FURTHER READING AND REFERENCES

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APPENDIX 13 FORM TEMPLATES

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APPENDIX 14 DRUGS OF DEPENDANCE RECORDING REQUIREMENTS

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LIST OF TABLES
Table 1 Effects of Methadone
Table 2 Effects of mono (Subutex) and combination (Suboxone) preparations
Table 3 Diagnostic Definition of Opioid Dependence (DSM IV)
Table 4 Key features of the assessment
Table 5 Key factors affecting precipitated withdrawal
Table 6 Common Side Effects with Methadone/Buprenorphine
Table 7 Signs and Symptoms of Methadone Overdose
Table 8 Clinical features of the Heroin Withdrawal Syndrome
Table 9 Criteria for residential withdrawal services

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LIST OF FIGURES
Figure 1 Program Structure
Figure 2 Treatment Pathways for dependent heroin users
Figure 3 Plasma levels of Methadone during First 3 days of Dosing
Figure 4 Gateway Model of treatment with Buprenorphine

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Section Summaries
The following pages contain the quick read summaries of each section. The reference to source
the full information is also provided.

Introduction
Summary

See page

Illicit opioid use has significant health, social and economic


costs for individuals and Australian society

There is extensive research evidence demonstrating the effectiveness


of methadone and buprenorphine treatment of opioid dependence

Treatment is delivered in W.A. via:



Next Step Drug and Alcohol Services

Community GPs and pharmacies

Prisons

The benefits of treatment are optimised when programs are readily


accessible, entry into treatment is prompt and retention in treatment is high.
Outcomes improve as time in treatment increases.

A range of treatments for opioid dependence, other than methadone


or buprenorphine, are available that may suit different individuals:

Withdrawal management (detoxification)

Naltrexone

Psycho-social interventions (counselling etc).

The aims of the opioid treatment program are to:



Reduce or eliminate heroin and other illicit drug use by those in treatment

Improve the health, psychological functioning and well-being of individuals

and families

Facilitate the social rehabilitation of those in treatment

Reduce the spread of blood-borne diseases associated with injecting drug use

Reduce the risk of overdoses and deaths associated with opioid use

Reduce the level of involvement in crime associated with opioid use

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Chapter 1

Chapter 1 Legislative and Administrative Requirements


Summary

viii

See page

Medical practitioners who prescribe buprenorphine and methadone for the


treatment of opioid dependence must be authorised by the Department of Health. (DOH)
To become an authorised prescriber a medical practitioner must:

Make an application to the DOH

Successfully complete an approved training program and assessment

Agree to comply with the clinical policies and procedures of the CPOP
An initial period of probationary authorisation will apply until the prescriber has been
approved for at least a twelve month period and managed a minimum of 20 patients.
Authorisation will be for a period of three years and may be renewed for further periods,
following a review process.
Prescribers wishing to cease prescribing methadone and/or buprenorphine must notify
the Clinical Advisory Service (CAS) to ensure patients can be transferred to other
treatment providers without disruption.

Authorised medical practitioners must apply for an authority to prescribe


for every patient commencing on treatment using the Authority to
Prescribe Opioid Pharmacotherapies form and faxing it to CAS.
This form must be signed by the client and forms the basis of client consent to treatment
(see below).
A patient must not be given methadone or buprenorphine until an authority number has
been provided by DOH via CAS.
An authority to prescribe is valid for a maximum of 2 years. At the end of this period a
Patient Authority Renewal will be sent to the prescriber. This form must be completed
and returned by fax to DOH.
When a patient ceases to be prescribed methadone/buprenorphine the prescriber must
send a completed Notification of termination of Methadone/Buprenorphine treatment
form to CAS.

A medical practitioner can prescribe methadone or buprenorphine to a


maximum total number of 150 patients. Application can be made to DoH to increase this
number to 200.

Maximum dose limits of 120 mg of methadone or 24 mg of buprenorphine apply.


To exceed this amount a prescriber must complete an Exceeding the maximum dose
form and fax to CAS.

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Takeaway doses can only be prescribed in accordance with the


takeaway policy set out in section 4.

Patients under the age of 18 years must be referred to Next Step Youth Service for
assessment. A copy of the assessment report must be attached to the Application for
Authority to Prescribe Pharmacotherapies to an Opioid Dependent Person.
Patients under the age of 16 will require special approval from the Department of
Health, Chief Executive Officer.

See page

Chapter 1

Summary

The patient must be able to give informed consent before the treatment begins.
This includes:

Explanation of treatment options, aims, policies and expectations
Warning not to drive or operate machinery during the first 10 days of treatment,
34 days after a dose increase or when taking other drugs (e.g. other CNS
depressants)

Written information about treatment
Signing of the consent to treatment form on the Authority to Prescribe
Pharmacotherapies form.

Documentation of a treatment plan.
Asking a patient to sign a release of information form for HIC data can help prevent
doctor shopping.

Confidentiality/Privacy legislation
Due to legislative requirements patients do need to sign appropriate consent forms to
allow the sharing of information between service providers and ensure appropriate
management. This is done when the patient signs the patient declaration form on the
application form.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Section 2 Clinical Pharmacology

Chapter 2

Summary
Methadone pharmacology:

Onset of effects: 30 minutes

Peak effects: about 3-4 hours

Half-life: 1347 hours (mean 24 hours)

Blood levels continue to rise during the first week of daily dosing

Time to stabilise methadone in the body: 510 days

Side effects as for heroin
Methadone withdrawal onset: 3648 hours, peak intensity within 57 days.

13

Methadone drug interactions:


Combination of methadone and other sedative drugs (opioids, alcohol,
benzodiazepines, tricyclic antidepressants, major tranquillisers and sedating
antihistamines) can be fatal.

Effects of methadone are reversed or inhibited by naltrexone and naloxone
People who are taking 40mg or more of methadone each day are likely to
experience withdrawal symptoms if given a dose of buprenorphine.

Methadone is metabolised by the cytochrome P450 3A enzyme system.
Drugs which induce or inhibit this system can increase or slow the metabolism of
methadone respectively.

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Methadone does not cause damage to any of the major organs or systems of the body.
The major hazard is the risk of overdose, particularly at the time of induction to
treatment and when methadone is used in combination with sedative drugs. Slow onset
of action and long half life of methadone mean that toxic effects may become life
threatening many hours after ingestion. Clinical vigilance is most important in the first
14 days of treatment.

Buprenorphine pharmacology:

Onset of effects: 3060 minutes

Peak effects: 14 hours

Half life: 2072 hours (mean 34 hours)

Time to stabilise buprenorphine levels in the body: 710 days

Side effects as for heroin
Buprenorphine withdrawal onset 25 days, symptoms
generally milder than withdrawal from other opioids.

See Page

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Summary

See Page
16

Buprenorphine is safer in overdose than pure opioid receptor agonists.


Respiratory depression from buprenorphine overdose is less likely, but intravenous
use of buprenorphine can be fatal.

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The buprenorphine-naloxone combinationation product Suboxone has been developed


to limit the abuse potential of the mono product. Use of the combination product
will apply to most buprenorphine patients from May 1st 2006.

Chapter 2

Buprenorphine drug interactions:


Combination of buprenorphine and sedative drugs (opioids, alcohol,
benzodiazepines, tricyclic antidepressants, major tranquillisers and sedating
antihistamines) can be dangerous.
Buprenorphine has a higher affinity for opioid receptors than naltrexone or
naloxone. Very high doses of naloxone (10 35 mg) are required to reverse
an overdose of buprenorphine.
Bupreorphine can produce withdrawal in people dependent on another opioid
drug. Buprenoprphine can interfere with the effectiveness of other opioids given for
analgesia.
Buprenorphine is metabolised by the cytochrome P450 3A4 enzyme system,
but current evidence suggests that other medications that induce or inhibit
this system have minimal impact on buprenophines effects.

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Clinical policies and procedures for the use of methadone


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Section 3 Clinical Management for Maintenance Treatment


Summary

See page

Methadone or buprenorphine maintenance treatment is indicated for people who are


neuroadapted to opioids. For some patients with a history of opioid dependence and a
high risk of returning to opioid use, it is reasonable to offer methadone or buprenorphine
maintenance even when neuroadaptation is not currently evident.

Chapter 3

Opioid




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dependence is identified by:


History taking (typical day history will identify some features of opioid
dependence)
Physical examination (injecting sites, signs of opioid intoxication or withdrawal)
Corroborative evidence from other sources
Urine test for opioids

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Contraindications:

Severe hepatic or respiratory insufficiency

Known hypersensitivity to the proposed drug formulation

Inability to give informed consent

Buprenorphine is not recommended in pregnancy and breastfeeding

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Precautions:

High risk polydrug use or co-ocurring alcohol dependence

Acute or unstable psychiatric illness

Chronic pain

Concomittant medical problems

Cardiac vigilance required with methadone doses greater than 150mg

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Selecting maintenance treatment.


The relative merits of methadone and buprenorphine are:

More clinical experience with methadone
Buprenorphine is safer in overdose, may need to be taken less often and may be
easier to withdraw from than methadone

Buprenorphine takes longer to administer (must dissolve under the tongue)
Buprenorphine can be more easily diverted to improper use because it is in
tablet form. The buprenorphine-naloxone combination may discourage diversion
to injecting drug use.

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Aims of initial assessment:



Establish an effective therapeutic relationship and begin harm reduction

Determine the patients suitability for the opioid treatment program

Enable the patient to make an informed decision about treatment

Provide advice and resources to facilitate harm reduction

Meet legislative requirements for the CPOP

Document an initial treatment plan

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Summary

See page
27

All eligible patients merit prompt admission to treatment, but this is especially
important for:

Pregnant women

People with HIV and their opioid using partners

Hepatitis B carriers and their opioid using partners

People being released from correctional institutions

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Chapter 3

Key features of the initial assessment:


Opioid use ( detailed history, periods of abstinence, overdoses, current use)
Other drug use (alcohol and other drugs, prescribed medications)
Assessment of dependence and tolerance
Health status
Psychosocial status
Risk behaviours, risk of deliberate self-harm or suicide
Dependent children
Past treatment
Motivation for treatment
Physical examination
Investigations (if indicated: urine screening, HIV, HBV, HCV)
Domestic violence screening

Commencing treatment:
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Patients need to begin methadone or buprenorphine treatment in a well supervised
setting to ensure frequent monitoring. Special attention needs to be given to patients
with the precautions listed above.
Safety is achieved by:

Establishing a therapeutic relationship that fosters good communication between
patient and doctor

Cautious initial dosing

Caution with concurrent prescribing of sedative medication

Caution when concomittant medical conditions are present

Repeated observation of the patient during the first week

Careful explanation of intoxicating effects and withdrawal during the induction and
maintenance phases of treatment

The treatment plan outlined at the initial assessment is developed during the first week of
treatment in collaboration between the patient, the prescriber and other members of the
treatment team. The plan should be reviewed at least every six months.

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Chapter 3

Summary

xiv

See page

When deciding starting dose consider:



Severity of dependence and current level of tolerance

Where dosing is to occur

Time since last opioid use

Concomitant use of benzodiazepines, alcohol, or any other sedative

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Starting dose methadone. Starting dose of 20-25mg and increase by 5mg every 2-3 days
subject to assessment. Caution: deaths in the first two weeks have been associated with
methadone doses in the range 25 100 mg/day. A dose of 20 mg for a 70kg patient with
low tolerance can be presumed safe.

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Starting dose buprenorphine. The first dose of buprenorphine should not be given
until at least 6 12 hours after the patients last dose of heroin and at least 24 36
hours after the last dose of methadone to avoid precipitated withdrawal.
A starting dose of 4 8 mg of buprenorphine will be tolerated by most patients and will
lead to rapid stabilisation. Aim for dose of 12 - 16 mg by day 3 or 4.
Some patients may select slow increases in dose (perhaps fearing increased dependence
or side effects) but this may result in continuing withdrawal symptoms and low retention
rates.

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Precipitated withdrawal with buprenorphine


Buprenorphines higher infinity for opioid receptors and lower intrinsic opioid activity
can cause withdrawal if other opioids are still active. This typically occurs 1 4 hours
after the buprenorphine dose and lasts for up to 12 hours. Symptomatic withdrawal
medication may be required.

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Stabilisation is about titrating the dose against the needs of the (methadone)
individual patient. Dose changes should only be made after the (buprenorphine)
patient is assessed by the prescriber.
Assessment should include:
 Features of intoxication or withdrawal over the preceding 24 hours (patients
self-report, examination)

Patients perception of dose adequacy and satisfaction with treatment

Patients adherence to dosing regimen

Other drug use (patients self-report, urine testing)

Side effects and adverse events (including intoxication and overdoses).

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Summary

See page
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Titrating buprenorphine dose


Decrease the dose if there are features of intoxication at the time of peak effects
(1 4 hours after dosing) or if there are severe or intolerable side effects.
From day 3 onwards dose increases can be as much as 8 mg per day.
The maximum daily dose at the end of the first week should be no more than 24 mg.
There is rarely a reason to prescribe more than 24 mg/day of buprenorphine to any
patient. To prescribe in excess of 24 mg approval must be sought by faxing an
Exceeding the maximum Dose of Opioid Pharmacotherapy.

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Dose adjustment is an ongoing part of treatment. Maximum weekly increases:


Methadone: 10 mg
Buprenorphine: between 2 - 8 mg per day
When changing the dose of methadone or buprenorphine a prescription must reach
the pharmacy prior to the change in dose being affected.

Dose levels: Methadone


Daily methadone doses of 60 mg or more are associated with better treatment
outcomes in terms of reducing illicit opioid use, criminal activity and HIV risk-taking
behaviour and improving retention in treatment. In general the upper limit for
methadone doses is 120 mg/day. Prescribing more than 120 mg/day requires approval
of the Clinical Advisory Service and the Department of Health.
Split (twice daily) methadone dosing may be required for a few patients who
are rapid methadone metabolisers and (for a short period) by patients who are
experiencing nausea at the time of peak effects.

Chapter 3

Titrating methadone dose


Decrease dose if there are features of intoxication 3 4 hours after dosing or if there
are severe intolerable side effects
Do not increase dose for at least the first 3 days of treatment unless there are clear
signs of withdrawal 3 4 hours after dose.
Consider dose increments of 5 10 mg every 3 days, subject to assessment. Total
weekly increase should not exceed 20 mg.
Maximum dose at the end of the first week should typically be no more than 40 mg.
Warn patients not to drive or operate machinery during periods of dose adjustments.

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Chapter 3

Summary

See page

Dose levels: Buprenorphine


Effective buprenorphine dose range for most patients is 12 16 mg/day. Some patients
can be satisfactorily maintained on 8 mg/day. In general the upper limit for
buprenorphine doses is 32 mg/day. Prescribing more than 24 mg/day requires the
approval of the Clinical Advisory Service and the Department of Health. Daily dosing is
recommended for initial stabilisation of the patient, but many patients can be
maintained on alternate-day dosing or even less frequent dosing regimens. Patients on
second or third daily dosing can be prescribed doses of up to 32 mg without special
approval from CAS/DOH.

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Frequency of buprenorphine dosing


The characteristics of buprenorphine allow a wide range of dosing regimes,from daily
to once every two or three days.
Patients should first be stabilised on daily dosing
The dose dispensed for a 48 hour period is initially double the normal 24 hour dose
(to a max of 32mg)

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Transferring between treatments:


 Appropriate methadone dose before transferring to buprenorphine is less than
40 mg/day Patients should have been on this dose for at least one week before
commencing buprenorphine and the last methadone dose should be at least 2
4 hours before the first dose of buprenorphine.
 Appropriate buprenorphine dose before transferring to methadone is less than
16 mg/day. The first dose of methadone can be taken 24 hours after the last
dose of buprenorphine and should not exceed 40 mg. Patients transferring from
lower doses of buprenorphine should receive lower doses of methadone.
 Patients taking naltrexone rapidly lose tolerance to opioids. Patients transferring
from naltrexone to opioid treatment should not receive methadone or
buprenorphine until at least 72 hours after the last dose of naltrexone. Starting
doses should be no greater than 20 mg of methadone or 4 mg of buprenorphine.

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Review all patients regularly, including those who appear to be progressing well
(at least 4 times per year). A review is a comprehensive reassessment of the patient and
progress in treatment. Patients should remain in treatment until they achieve their
agreed treatment goals. There is no optimal duration of treatment.

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Coordinated care
People with opioid dependence usually have complex psychosocial and health problems.
Opioid treatment programs can provide a framework for enhanced care, involving
comprehensive assessment and treatment planning. Psychosocial interventions can add
to the effectiveness of pharmacotherapy programs and should be freely available to
all patients (not compulsory).

42

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Community dispensing
Pharmacies must be approved to dispense pharmacotherapies to opioid dependent
people. Contact the Community Clinical program on 9219 1907 or 9219 1913 to locate
pharmacies. The prescriber must notify the CAS of any changes in dosing location prior
to the change occurring.
Pharmacies do charge dispensing fees for administering each dose. These fees are
set by individual pharmacies.
Administration
Methadone and buprenorphine can only be dispenpensed in accordance with a valid
prescription. Before administration the pharmacist should check that the prescription
is valid, confirm the identity of the patient and assess that the patient is not
intoxicated. Methadone and buprenorphine doses must be stored, dispensed and
recorded in accordance with the legislative requirements.

See page
43

46

International travel
Taking methadone or buprenorphine overseas requires careful consideration of the
stability of the patient and the rules and customs of the country being visited.
Advice should be sought from Community Clinical Programs 9219 1907/9219 1913.

49

Transferring to a new dispensers


Prescribers must provide a current endorsed photograph of the patient attached to
the ID form and a prescription to the patient to give to the new pharmacy. The
prescriber must also fax a completed Pharmacy Transfer Notification form to the
current pharmacy, the new pharmacy and the Community Clinical Programs
9219 1907/9219 1913 before the transfer takes effect. This avoids the potential for
double dosing the patient.

48

Transferring to a new prescriber


Should either the patient or prescriber wish to transfer the patient to a new prescriber
the Community Clinical Programs 9219 1907/9219 1913 should be contacted to assist
in the arrangement.

48

Cessation of treatment
Outcomes of methadone and buprenorphine maintenance improve with increasing
time in treatment. It is recommended that patients be encouraged to remain in
treatment for at least 12 months to achieve enduring lifestyle changes.

Elements of successful withdrawal from therapy are:

Planning and collaboration between patient, prescriber and other staff

Flexible and slow dose reduction. Planned withdrawal can take months.
Psychosocial support such as supportive counselling, information and skills
training, close monitoring, residential rehabilitation, family involvement.
Aftercare: continuing counselling and involvement of the case manager,
careful handover to the patients general practitioner.

49

Chapter 3

Summary

xvii

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Summary

See page

Sleep disturbance is common among people who withdraw from methadone.


Provide information about withdrawal related symptoms and offer training in nonpharmacological strategies to cope with disturbed sleep. Other psychotropic medication
(in particular hypnotics and sedatives) is not recommended, except where indicated for
patients with diagnosed psychiatric comorbidity. If sedative/hypnotic medication is
prescribed it should be at a low dose for a specified short duration (3 5 days) Provide
supervision in all cases and restrict the quantity of tablets to 1 2 days requirements
for safety.
Summary

84

Return to other drug use

52

Chapter 3

The clinician should remain vigilant to the possibility that alcohol or other drug use may
increase to hazardous or harmful levels during and after cessation of treatment.

Recommended withdrawal regimen


Methadone
Dose > 45 mg Reduce by 5 mg per week until dose reaches 45 mg then reduce by
2.5 mg per week
Dose < 45 mg Reduce dose by 2.5 mg per week
Abrupt cessation of methadone can be considered from 20 40 mg/day in conjunction
with clonidine and symptomatic medications to manage withdrawal. Patients experiencing
difficulty to withdraw from methadone may wish to convert to buprenorphine and then
withdraw from that drug

50

51

Buprenorphine
Dose > 16 mg 4 mg per week or fortnight
Dose 8 16 mg 2 4 mg per week or fortnight
Dose < 8 mg 2 mg per week or fortnight

xviii

Involuntary withdrawal
Patients may be removed from treatment for:

Violence or threat of violence against staff or other patients

Drug dealing on or near the clinic or dosing location

Diversion of dose

Unacceptable disruption to the local amenity
Dose reduction should be gradual. Rapid dose reduction or abrupt cessation of
treatment is warranted only in cases of violence, assault or threatened assault,
or repeated dose diversion.

51

Relapse
When relapse occurs after leaving treatment and the patient seeks readmission to
treatment this should be offered expeditiously and without recrimination.

51

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

52

Chapter 3

Naltrexone
Administering naltrexone to a patient who is physically dependent on opioids will
precipitate severe withdrawals. Patients transferring to naltrexone should withdraw
completely from methadone and buprenorphine before commencing naltrexone in
accordance with the timelines below:
Last dose
Commence Naltrexone
Methadone
14 days after the last dose
Buprenorphine
< 2 mg
4 5 days
> 2 mg
7 days

xix
ixx

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Section 4 Takeaway and Missed Doses


Summary

See page

Takeaway doses
Supervised dosing is an essential component of methadone/buprenorphine treatment.

54

Providing takeaway doses has both risks and benefits.


Providing takeaway doses requires the prescribing doctor to be satisfied that the patient
is reliable and stable, indicated by:

No hazardous use of opioids and other drugs (including alcohol)

Improved social functioning

Compliance with program requirements

A prior history of responsible use of takeaway doses

Able to provide adequate storage arrangements for takeaway doses

Understanding of the potential risks to children of accidental ingestion.

Chapter 4

Absolute contraindications to takeaway doses:



Repeated intoxication on presentation for dosing

Being intoxicated on presentation to collect takeaway doses

Diversion of doses within the last 3 months

Habitual injection of takeaway doses

Current chaotic and unpredictable behaviour

Current hazardous use of drugs (including benzodiazepines and alcohol)
The patient has a child or children and there are concerns that the child/children
may be at risk of harm.

Schedule of permitted frequency of takeaway doses


Methadone
First 6 months of treatment none
6 12 months one per week
1 2 years maximum of two per week
More than 2 years maximum of three per week only two of which are consecutive.
Buprenorphine (combination preparation suboxone only)
Patients on buprenorphine can be dosed on alternate day, or third daily dosing regimens
to reduce the need for takeaway doses.
First 6 months of treatment none
6 - 24 months in treatment or dosing third daily maximum of 1 per week
More than 24 months in treatment and dosing daily or second daily maximum of 2 per
week
Takeaway doses should be the same dosage as those consumed under supervision.

xx

56

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Summary

See page

Process for prescribing takeaways


Prescribers must complete a Takeaway dose application form and require the patient
to sign the patient declaration.
This form should then be placed in the patients medical records.
The prescribing doctor is to provide the pharmacy with authorisation in the
prescribers own handwriting and signed. This must be attached to or incorporated in
the current prescription and must specify the date (or if regular takeaway doses are
provided the days of the week) on which the patient is to receive takeaway doses.
Takeaway doses are to be given to the patient on the day before the scheduled
absence from the usual dosing site.
Patients must be advised of the dangers of misusing the takeaway dose, the
hazards of using it in combination with other drugs and its toxic potential if taken
by a child or anyone not tolerant to opioids.

55

Prescribing outside of the schedule or takeaway doses of Subutex


To respond to individual special circumstances prescribers can apply for authorisation
to prescribe takeaway doses, in the short or longer term, outside of the schedule or
for takeaway doses of Subutex. In these cases the application form must be faxed to
the Clinical Advisory Service and approval obtained prior to writing the prescription
for the takeaway doses.

55

Lost or stolen doses


Lost or stolen doses are not to be replaced unless there is a medical indication to do
so (such as prevalent withdrawal in pregnant patients). If medically indicated
replacement doses are not usually full doses and should be carefully titrated against
the observed clinical condition to ensure that the patient is not overdosed.
Regular loss of takeaway doses (for any reason) should result in a return to on-site
dosing.

58

Chapter 4

Regular takeaway doses


Where takeaway doses are prescribed on a regular basis the prescriber must be
satisfied at each review that the patient continues to meet the stability criteria.
Takeaway doses should be stopped it the patients circumstances have changed and
they are no longer considered stable.

58

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Summary

See page

Missed doses and reintroduction


Patients presenting for treatment after missing dose/s are at increased risk of
overdose. Assess the patient for signs of intoxication and withdrawal. Reintroduce
according to the following schedules:
Methadone
1 2 doses missed
3 4 doses missed



5 or more doses missed

No signs of intoxication dose as usual.


Pharmacist must consult with prescriber or CAS prior to
dosing. Approval to recommence dosing can be given
over the phone. <40 mg reduce dose by 5 10 mg
> 40 mg reduce dose by half.
Patient must see prescriber for re-induction.

Summary
Buprenorphine
Days missed*
1 - 4
If no evidence of intoxication dose as usual.
5 6
Consult prescriber.
> 7
Patient must see prescriber for re-induction.
* refers to days equivalent, if clients not dosing on a daily basis. E.g. a patient dosing
second daily only misses 2 doses to achieve 4 missed days.

Chapter 4

Schedule for recommencing buprenorphine


Usual 24 hour dose Recommencement dose
> 8 mg

6 8 mg
2 4 mg

8
4
6
2

mg if < 7 days with no dose


- 8 mg if > 7 days with no dose
8 mg
4 mg

If required, patients can be brought up to their usual maintenance doses over


subsequent days using the dosing increments discussed earlier.
A missed dose is not a medical emergency and it is generally not appropriate to
prescribe methadone or buprenorphine in the emergency department.

xxii

59

59

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Section 5 Common Management Issues


Summary

See page

Side effects
Methadone and buprenorphine have similar side effects to other opioids. Manage
according to nature and severity.

61

Overdose
Naloxone (Narcan) given intravenously, intramuscularly or subcutaneously is the
treatment of choice for an opioid overdose, since it leads to immediate reversal of
the overdose. Admission to hospital should always be recommended as the effect of
naloxone does not last as long as the effect of heroin or methadone.

62

Buprenorphine overdose:
The risk of lethal overdose on buprenorphine in an opioid dependent person is
less than that associated with methadone.
However the effects of buprenorphine are not reversed by the usual doses of
naloxone. Doses of 10 35 mg/70kg (10 30 times the dose used to reverse
heroin overdose) may be required to reverse the effects of buprenorphine
toxicity.
Consider the long duration of action of buprenorphine when treating the
effects of an overdose.

63

Intoxicated presentations
Patients should be assessed for intoxication prior to being dosed. Intoxicated patients
should not be dosed or be given takeaway doses and patients need to be made aware
of this at the commencement of treatment.
Signs of intoxication are set out in Appendix 7. Prescribers may give a reduced dose
if after reviewing the patient intoxication is assessed as mild.

64

Chapter 5

Methadone overdose:
 Naloxone should be given as a prolonged infusion when treating methadone
overdose. Patients who are thought to have taken a methadone overdose
require prolonged observation
Methadone overdose is usually associated with the use of other drugs and
usually occurs within the first few days of induction to treatment. Patients
should be warned of these risks.
Deaths often occur at home during sleep. Dosing in the morning reduces the
risk. Family members should be warned that deep snoring during induction to
treatment could be a sign of dangerous respiratory depression and should be
reported to the prescriber.
Concomittant medical problems.

xxiii

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Summary

See page

Vomited doses
Methadone
Vomiting more than 20 minutes after a methadone dose: reassure the patient that the
dose will have been adequately absorbed.
Vomiting less than 20 minutes after a methadone dose:
If a patient who has been in treatment for more than 2 weeks has been observed
by dispensing staff to vomit immediately after dosing a half dose may be
administered.
If a patient has been in treatment less than 2 weeks or there is uncertainty about
the event, review the patient 4 6 hours after dosing. If at this time the patient
appears to be experiencing withdrawal a dose supplementation of up to half the
patients usual dose can be given.
Monitor pregnant patients who vomit their methadone dose closely and give a
supplementary dose if necessary to avoid withdrawal, which distresses the foetus.

64

Chapter 5

Buprenorphine
Buprenorphine doses are absorbed sub-lingually within 2 7 minutes. Vomiting after
this time makes no difference to the absorbed dose.

xxiv

Incorrect methadone (over) dose administered


Patients in the first two weeks of treatment
An overdose of any size requires observation for 4 hours (longer if signs of
intoxication develop).
Patients who have been in treatment for longer than 2 weeks
If the overdose is less than 50% of the usual dose the dispenser can warn the
patient about risks of extra drug use, risks of driving or using machinery, signs and
symptoms of overdose and advise him or her to go to a hospital emergency
department if any symptoms develop. The dispenser must advise the prescriber
of the dosing error and record the event.
If the overdose is more than 50% of the usual dose the dispenser should contact
the prescribing doctor or CAS immediately. If it is decided that the patient
requires hospitalisation he or she should be accompanied to the hospital to ensure
admitting staff receive clear information on the circumstances. If the patient has
left before the mistake is realised, every attempt must be made to contact him
or her.

Patients who have been on a dose greater than 40 mg /day consistently
for 2 months can generally tolerate a single double dose without significant
symptoms. For a dose greater than double the usual daily dose the patient
will require observation for at least 4 hours (longer if signs of intoxication
develop).

Patients for whom the level of tolerance is uncertain (dose less than
40 mg/day or in treatment for less than 2 months or receiving takeaway
doses) require observation for at least 4 hours if they are given a dose
50% higher than their usual dose (longer if signs of intoxication develop).

65

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Summary
Incorrect buprenorphine (over) dose administered
Warn the patient of possible overdose effects, risks associated with extra drug use
and against driving or operating machinery

See page
67

Monitor the patient for at least 6 hours if any of the following apply:
-
The patient develops symptoms of overdose
-
The patient has commenced treatment in the last 2 weeks
-
The dose is 16mg and has been given to a patient whose normal dose is 4mg
-
A dose 64 mg or more was administered
The prescriber should review the patient before the next dose

67

Chapter 5

Managing polydrug use 


Polydrug use is common among opioid users. Many patients seeking methadone or
buprenorphine treatment are likely to be dependent on benzodiazepines, alcohol or
other drugs as well as opioids. Many are likely to be using other drugs at hazardous or
harmful levels.
Continued high risk drug use is evidenced by frequent presentations when intoxicated,
overdoses, chaotic drug using behaviour and deteriorating medical or mental states
due to drug use. Every effort should be made to therapeutically engage patients who
continue polydrug use:
Continue a courteous demeanour toward the patient even when faced with
difficult or confronting behaviour
Set clear boundaries around dosing, appropriate behaviour and the expectations
of participants in treatment programs. Provided that the prescriber considers
it safe, an increase in dose, a change from buprenorphine to methadone or a
change in the frequency of dosing may be helpful.
Invite patients to discuss concerns they may have about their recurrent
intoxicated or debilitated presentation and clearly convey the concerns that
staff have regarding their risky drug use
Offer to support patients in other challenging or difficult areas of their life
Screen for specific circumstances (eg living with other drug users) or conditions
(e.g. depression) that may be exacerbating hazardous or polydrug use.
Consider possible coexisting mental health disorder (anxiety, depression or
paranoia) or organic cognitive impairment and offer treatment or appropriate
referral when indicated
Provide patients with documentation of concerns and suggested or agreed
solutions
Wherever possible invite patients into a collaborative discussion before
notifying them of significant treatment changes
A motivational interviewing approach may work for patients who are unsure
whether they wish to change their polydrug use
If possible, document an action plan in collaboration with the patient for
reducing polydrug use.

xxv

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Summary

See page

Weigh the risks of combining methadone or buprenorphine with other drug use against
the benefits in reducing harms, improving health and improving social functioning. If the
disadvantages predominate and the patient appears unwilling or unable to change it may
be necessary to arrange the patients gradual withdrawal from treatment.
Patients who are currently using other opioids, benzodiazepines or alcohol in large doses
should not have takeaway doses.

Benzodiazepines
Prescribing benzodiazepines to patients who are dependent on benzodiazepines as well
as opioids may be necessary but caution must be exercised. Benzodiazepine injection is
associated with vascular damage and death. Injection of the gel capsule formulation of
temazepam has been reported to lead to limb amputations. This formulation should not
be prescribed.

68

Where possible benzodiazepines should be dosed daily with the patients methadone or
buprenorphine. More stable patients can be considered for less frequent dispensing of
benzodiazepines.

Chapter 5

Diversion of dose
The risk of diversion can be reduced by ensuring appropriate procedures and supervision
of on site dosing, and careful selection of patients for takeaway doses
On the first occasion patients who have diverted or attempted to divert their dose:
Should not be given any further takeaway doses for at least 6 months and
If it was a supervised dose of buprenorphine, should be transferred to methadone
for at least 6 months (if they do not want methadone they should be detoxed off
maintenance treatment)
Diverted their supervised dose of methadone should have their doses made up to
200ml with water or cordial and be administered in 50 ml aliquots.

xxvi

On subsequent occasions within a 3 year period


Further diversion or attempted diversion should result in compulsory detoxification.
Patients will not be considered for reentry into treatment for a period of 3 months.
This should be recorded in the patients clinical notes and the Clinical Advisory
Service (CAS) should be notified.

70

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

See page

Treating hospitalised patients


In general methadone or buprenorphine treatment should continue in hospital.
The hospital doctor managing the patient should consult with the prescribing
doctor. When a prescribing doctor or a staff member at a dosing location is
contacted regarding inpatient treatment of a person receiving methadone or
buprenorphine they should provide all possible assistance to the hospital doctor
(information about the legal requirements for prescribing opioid treatment,
patient history, and the significance of the patients current dosing regimen).
The pharmacist at the dosing location should document that the patient has
become an inpatient and is being dosed elsewhere. To avoid double dosing the
pharmacist should confirm that the patient has been discharged and confirm
the date on which the patient received a dose before recommencing dosing.
When a prescribing doctor is contacted regarding treatment he/she must ensure
that the dosing location has been notified.
Opioid dependent people who are not on methadone or buprenorphine
maintenance treatment may experience withdrawal if admitted to hospital.
Methadone or buprenorphine may be used to treat withdrawal symptoms if
the patients premature self-discharge before completion of therapy would
prejudice optimum management. In these circumstances consultation should
occur with the CAS.

68

Analgesia and anaesthesia


Inpatients
Patients on methadone or buprenorphine treatment who are experiencing acute pain
in hospital often have their pain under treated. Because of their tolerance of opioids
they may require larger doses of analgesia for adequate pain relief.

69

Primary care setting patients


Patients on methadone or buprenorphine who need acute pain management can be
managed as for patients who are not opioid dependent, although doses of analgesic
drugs may need to be higher. Buprenorphine binds strongly to opioid receptors and
can interfere with the effectiveness of other opioids prescribed for pain relief. Consult
the Clinical Advisory Service (CAS) for advice.
Patients on methadone or buprenorphine who experience chronic pain may require
specialist management.

Chapter 5

Summary

xxvii
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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Chapter 5

Summary

xxviii

See page

Pregnancy and breastfeeding


Pregnant women who use opioid drugs such as heroin are at an increased risk of
developing serious complications in pregnancy.
The newborn from these pregnancies are at risk of neonatal abstinence syndrome and
sudden infant death syndrome.
Opioid withdrawal during pregnancy carries particular risks and requires specialist care.
Opioid treatment during pregnancy:

Helps stabilise drug use and lifestyle
Reduces or eliminates illicit opioid drug use and can help stabilise the in utero
environment

Facilitates access to comprehensive antenatal and postnatal care

Does not increase the risk of congenital abnormalities in the foetus.

74

Buprenorphine is not recommended for pregnant or breastfeeding women.

75

Methadone maintenance in pregnancy


Pregnant women should be maintained on an adequate dose of methadone to achieve
stability and prevent relapse or continued illicit drug use. Women already in methadone
treatment who become pregnant can continue in treatment.
The bioavailability of methadone is decreased in the later stages of pregnancy. It may be
necessary to divide the daily dose and possibly to increase the dose in the third trimester
of pregnancy to avoid withdrawal symptoms and minimise additional drug use.Antenatal
and postnatal care should be managed in collaboration with a specialist obstetric service
experienced in the management of drug dependency during pregnancy. Dose reductions or
withdrawal, if requested by the patient, are best carried out in the second trimester of
pregnancy. Breastfeeding should be encouraged.

74

Neonatal abstinence syndrome


All babies born to opioid dependent mothers should be observed by experienced staff
for the development of withdrawal signs.
Supportive treatment of neonatal withdrawal involves minimising environmental stimuli
and enhancing the babys comfort. It is recommended that neonatal care be managed in
collaboration with a specialist obstetric or paediatric service in the management of
babies born to drug dependent mothers.

Child protection
On initial assessment, at treatment review and when assessing eligibility for takeaway
doses it is important to consider the safety and well being of any children in the
patients care. A parents enrolment in an opioid treatment program alone is not a
reason to make a report to the Department of Child Protection.

76

77

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

See page

Patients with HIV


Both methadone and buprenorphine have interactions with HIV medications.
See appendix 1 & 2

78

Patients with hepatitis B or C


Refer patients who are acutely infected or who are chronic carriers of
hepatitis B to a gastroenterologist for special assessment and follow up.
Recommend hepatitis B vaccinations to all patients who are found to have no
immunity to the hepatitis B virus
A high percentage of patients entering treatment programs will be hepatitis C
antibody positive and eligible for treatment with interferon and riboviron.
Abrupt changes in liver function might necessitate substantial dose adjustments.

78

Patients with coexisting mental health problems


The prevalence of mental health problems is higher among opioid users than
in the general population
Assessing mental health status should be an integral part of the care of
patients in an opioid treatment program. Checking for suicidal thoughts should
be routine.
Methadone or buprenorphine maintenance can reduce levels of psychiatric
distress with improvement apparent within weeks of commencement of
treatment. Screen mental health status again after stabilisation on treatment.
Psychotherapy as an adjunct to methadone or buprenorphine treatment may
benefit patients with medium and high levels of psychiatric problems.
Evidence of effectiveness of antidepressants as adjuncts to methadone of
buprenorphine treatment is equivocal. Tricyclic antidepressants have been
associated with an increased risk of overdose. The selective serotonin
reuptake inhibitors are preferred.

79

Chapter 5

Summary

ixxx
1

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Chapter 6 Clinical management of heroin withdrawal


Summary

See page

Features of heroin withdrawal


Sweating, lacrimation, rhinorrhoea.
Diarrhoea, abdominal cramps, nausea, vomiting.
Muscle spasm leading to headaches, backache, leg cramps, twitching, arthralgia.
Piloerection, pupillary dilation, elevated blood pressure, tachycardia.
Anxiety, irritability, dysphoria, disturbed sleep, increased cravings for opioids.

80

Chapter 6

Physical symptoms generally commence 6 24 hours after last use and peak in severity
during days two to four, generally subsiding by day seven.

xxx
2

Set realistic withdrawal objectives


Heroin users present to withdrawal services for a range of reasons. Many patients, family
members, friends and health and welfare professionals have unrealistic expectations of
the outcome of withdrawal treatment. It is important to set realistic withdrawal
objectives such as:

To alleviate distress

To prevent severe withdrawal sequelae

To break a pattern of heavy and regular drug use

To support patients access to help with other problems

80

Non pharmacological aspects


In addition to the use of medication the delivery of withdrawal services entails:

Assessment

Treatment matching

Planning for withdrawal

Supportive care

Follow up

81

Optimal setting for withdrawal


Most heroin withdrawal attempts can occur in an outpatient setting usually with the
assistance of a general practitioner, alcohol or other drug worker, or other health
professional.Commencing outpatient withdrawal requires planning and mobilisation of
the necessary resources and services, including a safe environment in which to proceed.
Criteria for intensive residential setting (inpatient withdrawal unit)
Unstable medical/psychiatric condition
Polydrug dependence and withdrawal from multiple drugs
Unclear medical, psychiatric or drug use histories requiring close monitoring
in a supervised environment

82

Criteria for supported residential setting (community withdrawal unit)


Unsupportive home environment, such as with other drug users or without anyone
reliable to supervise and support the patient
Repeated failure at outpatient withdrawal

83

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Summary

See page

Supportive care
Patients need information regarding

The nature and duration of withdrawal symptoms

Strategies for coping with symptoms and cravings

Strategies to deal with high-risk situations

The role of medication

83

Monitoring
An important part of withdrawal treatment is regular and frequent monitoring to check:

General progress

Drug use

Response to medication

Severity of withdrawal symptoms (see Appendix 10 for withdrawal scales)

Complications or difficulties

Ongoing motivation levels

84

Buprenorphine in the management of heroin withdrawal


Buprenorphine can be used effectively to manage heroin withdrawal as it provides
general relief of withdrawal symptoms so that other symptomatic medications are not
routinely required. Treatment regimens are set out in sections 6.4 and 6.5

85

Patients should not receive the first dose of buprenorphine whilst they are still
experiencing heroin effects. It is preferable to withhold the first dose until the patient
is beginning to experience the early features of withdrawal.

Induction
Induction onto buprenorphine for the purposes of detoxification should follow the
same principles as for buprenorphine maintenance.

86

Review
Review by a trained health professional is recommended on a daily basis during the
first few days of the withdrawal regime. This is important so that doses can be
adjusted, if necessary, and any difficulties being experienced on the medication can
be addressed.

88

Chapter 6

Buprenorphine doses should be titrated against severity of withdrawal features and


cravings for heroin use, actual use of heroin or other drugs and occurrence of side
effects.
A fixed daily dose can be prescribed or alternatively prescribe a flexible regimen with
upper and lower limits and instructions for the pharmacist (e.g. Day 1: 6mg,
Day 2: 6 10 mg, Day s: 8 12 mg etc)

xxxi
3

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Summary
Transition to post withdrawal treatment
To buprenorphine maintenance: continue with an upward titration to optimal dose
To methadone maintenance: induct as per section 3.4 waiting at least 24 hours after
the last dose of buprenorphine before administering the first dose of methadone.

Chapter 6

To naltrexone: a number of procedures can be used, all patients need supervision and
access to the prescriber

xxxii
4

See page
90

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Chapter 1

INTRODUCTION
Opioid dependence can result in a range of problems for the user, their family and friends and
for the wider community. These problems include health and social costs, the risk of overdose,
spread of blood borne viruses, the family breakdown; economic costs associated with morbidity,
mortality and absenteeism related to illicit drug use; and the cost of law enforcement for
drug related crime. Opioid replacement pharmacotherapy treatment is an effective strategy
for reducing the demand for drugs and the associated harms, by stabilising the lives of drug
dependent persons and reducing drug use and crime.
In Western Australia, opioid replacement treatment is available through the Community Program
for Opioid Pharmacotherapies (CPOP) a partnership program between government and community
service providers. The program adopts a shared care approach, with opioid treatment for
most people being provided by general practitioners and pharmacists in primary health care
settings. Next Step Specialist Drug and Alcohol Services provides support through education and
training, clinical consultancy and client referral as required. Next Step also provides services
directly to patients with more complex needs. The regulatory functions are provided through the
Pharmaceutical Services Branch within the Department of Health. The Drug and Alcohol Office
coordinates program management and policy development. Additionally, the Department of
Justice provides pharmacotherapy services for clients in custodial care.
Two pharmacotherapy medications are available, methadone and buprenorphine. Methadone
maintenance is now widely accepted as an effective treatment for opioid dependence. It
has been shown to achieve improvements in a number of areas, such as personal health and
social integration, reduction of criminal activity and reduced blood borne virus transmission.
Clinical trials have indicated that buprenorphine also has tremendous potential benefit as a
pharmacotherapy for the treatment of opioid addiction. Buprenorphine offers advantages in
terms of safety, the relative ease of withdrawal, the need for less frequent administration, and
flexibility with transition to other treatments. Methadone and buprenorphine as treatments for
opioid dependence are endorsed as a key strategies under the National Drug Strategy within the
framework of harm reduction.

PROGRAM STRUCTURE
The CPOP management structure is as follows:
Figure 1
Poisons Act 1964
& Regulations

Delegate of the
Department of Health

CPOP Management
Committee

Opioid Pharmacotherapy
Advisory Committee
(OPAC)

Mortality Review
Committee

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Chapter 1

CPOP Management Committee (CPOPMC)


The role of the CPOP Management Committee is to provide strategic direction and manage the
operation of the CPOP in Western Australia. The Committee oversees the development and
implementation of relevant policies, procedures and clinical guidelines and ensures delivery
of appropriate training programs for prescribers and dispensers of methadone/buprenorphine.
Membership is comprised of relevant staff from the Drug and Alcohol Office/Next Step Drug and
Alcohol Service and the Department of Health.

Opioid Pharmacotherapy Advisory Committee (OPAC)


OPAC is a group of key stakeholders who support the operation of CPOP by representing
stakeholder interests and providing stakeholder feedback on policy and program initiatives.
The group also has a role in identifying issues of concern regarding the delivery of methadone/
buprenorphine and making recommendations to the CPOP Management Committee. Membership
comprises of representatives from GPs, pharmacies, consumer groups, the Drug and Alcohol
Office, Next Step and the Department of Health.

Mortality Review Committee


The role of the committee is to monitor mortality associated with methadone/buprenorphine and
provide regular reports on trends and findings to the CPOP Management Committee.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Chapter 1

Range of Treatments for Opioid Dependence


Treatment selection is a synthesis of:
- assessment of the patient;
- examination of the available treatment options and likely outcomes; and
- negotiation with the patient around a suitable treatment plan.
In considering possible modalities, it is important to remember that many people come for
treatment with misconceptions and/or inadequate information about the two major options
available. The treatment pathways for dependent opioid users are set out in Figure 2. The
benefits of treatment are optimised when programs are readily accessible, entry into treatment
is prompt and retention in treatment is high. Outcomes improve as time increases.

Figure 2

TREATMENT PATHWAYS FOR DEPENDENT HEROIN USERS


Dependent
Heroin Use

Substitution
maintenance
treatment

Withdrawal

Methadone
Buprenorphine

Withdrawal from
substitution treatment

Postwithdrawal Interventions
Psychosocial interventions +/- naltrexone

Withdrawal Treatment
In general, withdrawal treatment is appropriate for those who are considering abstinenceoriented, post-withdrawal treatment (such as naltrexone, residential rehabilitation programs,
counselling or 12-step programs) or for those who are not interested in longer-term treatment,
and merely want a break from dependent heroin use. Buprenorphine can also be used to assist
the withdrawal process (see Section 6).

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Chapter 1

Substitution Maintenance Treatment


Substitution maintenance treatment with methadone or buprenorphine may be more appropriate
for those with significant opioid dependence and who are not wanting to enter residential
rehabilitation or naltrexone treatment, but nevertheless who want to stop or reduce their illicit
opioid use. Clinical decision-making should have an evidentiary basis, and patients should be
presented with the relative evidence, i.e. the merits and the limitations of treatment outcomes
associated with each approach. Within such a framework, there is widespread evidence
suggesting that maintenance substitution remains the gold standard treatment for most people
with chronic heroin dependence, by virtue of its success in keeping patients in treatment, and
reducing drug-related harms.
The objectives of substitution maintenance treatment with methadone or buprenorphine are to:
reduce illicit use of opioid drugs
reduce the risk behaviours associated with contracting and transmitting infectious
diseases;
reduce the incidence of death in associated with illicit opioid use;
improve the health, well-being and social functioning of patients;
reduce drug related crime
reduce other social costs of illicit opioid use.
motivate and support patients to achieve their positive lifestyle goals.
While the achievement of an opioid-free state is a long-term goal of maintenance treatment, it
must be recognised that this may not be the initial objective of the patient, nor, in some cases,
may it be appropriate. It is reasonable to expect, however, that methadone and buprenorphine
treatment will encourage patients to develop the motivation to become opioid free.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Chapter 1

1.0 Legislative and Administrative Requirements


1.1 Legislative requirements
The legislative framework for the Community Program for Opioid Pharmacotherapy is contained
in the Poisons Regulations 1965.
Medical Practitioners require prior authorisation from the Department of Health Chief Executive
Officer to prescribe methadone and buprenorphine for the treatment of dependence and
in addition the authorised prescriber must obtain an individual patient authority from the
Department of Health Chief Executive Officer, before prescribing methadone of buprenorphine to
a drug dependent person.
The Drugs of Addiction Notification Regulations 1980 also require a medical practitioner who in
the course of her/his practice becomes aware of or suspects a person of being addicted to drugs,
to inform the Executive Director Public Health.
The following legislative requirements apply:

Authorisation as a Methadone/Buprenorphine Prescriber in Western Australia


Medical practitioners who provide methadone and/or buprenorphine treatment for opioid
dependence must be authorised by the Department of Health Chief Executive Officer under
Regulation 51C of the Poisons Regulations 1965.
Prescriber completes an Application to become an approved methadone/buprenorphine
prescriber.
The medical practitioner is required to satisfactorily complete a training and assessment
package delivered by the Drug and Alcohol Office (DAO) and make a commitment to
comply with clinical policies and procedures, codes of practice and administrative
instructions of the program.
The Drug and Alcohol Office will notify the Department of Health that the prescriber has
satisfactorily completed the training and assessment requirements.

Authorisation as a methadone/buprenorphine dispenser in Western Australia


Pharmacies participating in the dispensing of methadone/buprenorphine for opioid dependence
must be authorised by the Department of Health Chief Executive Officer.
The pharmacy proprietor is required to complete an Application to Participate in
Methadone/Buprenorphine Dispensing. The proprietor must agree that all pharmacists
participating in the CPOP have successfully completed the training and assessment
package and that the minimum standards for the dispensing of methadone/
buprenorphine have been implemented in the pharmacy.
The Department of Health issues an authorisation for the pharmacy for participation in
the dispensing of methadone/buprenorphine and notifies the nominated wholesaler that
the pharmacy is participating in the CPOP and eligible for methadone/buprenorphine
free of charge (recording fee still applies).

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Chapter 1

Authority to Prescribe
Authorised methadone/buprenorphine prescribers must obtain from the Department of Health
Chief Executive Officer an individual patient authority for each patient being commenced on
treatment under Regulation 51C of the Poisons Regulations 1965.
An application for Authority to Prescribe opioid Pharmacotherapy form is completed by
the prescriber. The patient must also sign the application to indicate that they
acknowledge that the information will be forwarded to the Department of Health and
used for the management of the program.
The completed application for Authority to Prescribe opioid Pharmacotherapy form is
forwarded to the Clinical Advisory Service and the authorisation is issued by the
Department of Health. Specialist prescribers at Next Step may make direct application
to the Department of Health although they may consult the Clinical Advisory Service if
the need arises.
An authorisation number must be obtained prior to the writing of a prescription for
methadone or buprenorphine.
Authorisation is for a maximum maintenance dose of 120 mg of methadone or 24 mg of
buprenorphine.
The number of takeaways authorised on a prescription must be in accordance with the
policy on takeaway doses as set out in chapter 4 of this manual.
On completion the application form and record of the authority number should be filed
with the patients records.
Please note: An Authority to Prescribe opioid Pharmacotherapy application is required when
initiating prescribing for a patient transferring from another prescriber or for a patient that has
previously been treated by the same prescriber where the previous authorisation has expired or
been terminated.

Conditions Associated with the Authority to Prescribe Opioid Pharmacotherapy


The authorisation for a medical practitioner to prescribe methadone or buprenophine is subject
to the following conditions.
Legal responsibility
The prescriber is legally responsible for the treatment of a patient until treatment is transferred
or terminated.
Patient numbers policy
The prescriber must not exceed the maximum number of patients set out below.
Patient numbers per approved prescriber
When approved as a methadone or buprenorphine treatment prescriber a medical
practitioner will be authorized to prescribe for a maximum of 150 clients at any one
time. To exceed this number a prescriber may apply in writing to the Pharmaceutical
Services Branch of the Department of Health. The DoH will forward the application to the
CPOP Management Committee for review. The CPOP Management Committee will make a
recommendation to the Department of Health Chief Executive Officer whether to increase
the prescribers patient numbers to a maximum of 200. In assessing the application, the
CPOP Management Committee will consider the record of the prescriber in complying with
the policies and procedures of the Community Program for Opioid Pharmacotherapies, the
ability of the prescriber to maintain appropriate levels of client care for managing more
than 150 clients, available support services and any other information considered to be
relevant.
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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Chapter 1

In exceptional circumstances authority may be provided by the Department of Health Chief


Executive Officer for an approved prescriber to temporarily exceed their maximum patient
numbers in order to ensure continuation of care for existing patients.
In the event of concerns emerging about public amenity due to a large number of clients
attending a particular medical centre or general practice, the matter may be considered by
the CPOP Management Committee which may require changes to the maximum number of
clients who can be treated at the service.
Patient numbers per approved pharmacy
The maximum number of clients to whom pharmacies are authorised to dispense as part of
the program is the equivalent of 50 clients per day. To exceed this number a pharmacy may
apply in writing to the Pharmaceutical Services Branch of the Department of Health. The
DoH will forward the application to the CPOP Management Committee for review. Following
a review of the pharmacy to determine capacity to manage more patients, the CPOP
Management Committee will make a recommendation to the Department of Health Chief
Executive Officer to increase the pharmacys patient numbers. In assessing the application,
the CPOP Management Committee will consider the record of the pharmacy in complying
with the policies and procedures of the Community Program for Opioid Pharmacotherapy,
the ability of the pharmacy to maintain appropriate levels of client care for managing more
than 50 clients and any other information considered to be relevant.
In the event of concerns emerging about public amenity due to a large number of clients
attending a particular pharmacy, the matter may be considered by the CPOP Management
Committee who may require changes to the maximum number of clients.

Maximum Dose
Approval must be obtained from the Department of Health to prescribe above a dose of 120mg
of methadone or 24 mg of buprenorphine. A completed Exceeding the Maximum Dose form is to
be completed and sent to the Clinical Advisory Service (CAS) for endorsement prior to forwarding
to the Department of Health. If approved an authorisation is issued by the Department of Health.

Takeaway Doses Policy


Authorised prescribers must comply with the schedule of takeaway doses of methadone and
buprenorphine as set out in the Takeaway Policy (Section 4). This schedule has been developed
to balance the benefits of providing takeaway doses with the serious potential for misuse and the
risks this presents.
Approval must be obtained from the Department of Health to prescribe more than the number of
takeaways set out in the schedule or to prescribe takeaway doses of Subutex. A Takeaway Doses
of Opioid Pharmacotherapy form must be completed by the prescriber and sent to the Clinical
Advisory Service (CAS) with relevant supporting evidence for endorsement prior to forwarding to
the Department of Health. If approved an authorisation is issued by the Department of Health.

Prescriptions
A patient participating in the CPOP should only be prescribed one dose (excluding split doses) of
methadone or buprenorphine per day. In order to reduce the potential for dosing at multiple sites
to occur, when multiple prescriptions are written for a patient, the authorised prescriber must
ensure that the additional prescriptions do not authorise additional doses to be obtained from
another pharmacy on the same day.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Chapter 1

Renewal of authority to prescribe


The Department of Health will forward to the prescriber an Application for Renewal of an
Authorisation to Prescribe Methadone/Buprenorphine for an Opioid Dependent Person form
during the month prior to expiration of a patients authorisation. The prescriber must renew the
authority by completing the form and returning it to the Department.

Patients under the age of 18 years


Methadone is only registered for use in patients aged 18 or over. Buprenorphine has been
registered for administration to people aged 16 and over. Caution should be exercised in
prescribing a drug of dependence for anyone under 18 years of age. However, positive results
have been reported from the combination of buprenorphine with behavioural interventions
for the treatment of opioid-dependent adolescents. Potential medico-legal implications
of prescribing methadone or buprenorphine outside of the product information should be
considered.
Patients under 18 years of age must be referred to Next Step Youth Service for a comprehensive,
multi-disciplinary assessment. Applications for authority to prescribe for patients under 16 years
of age will require special approval from the Department of Health Chief Executive Officer.
Next Step Youth Service is able to instigate treatment and stabilise the patient before referring
them back to the prescriber. Next Step Youth Services are also able to offer ongoing consultation
for medical practitioners treating young patients. In cases where the prescriber, for reason of
their location in a remote area, cannot access Next Step Youth Services the Clinical Advisory
Service should be contacted to discuss alternative assessment options.

Assessment criteria
Suitability for maintenance treatment for patients under the age of 18 and the type of
pharmacotherapy prescribed will be determined by:
the history of AOD use
the physical and psychological assessment
evidence of opioid dependency and current physical dependence
prior treatment history and current reasons for seeking treatment
parental or family support
a comprehensive risk assessment (self harm/suicide, accommodation arrangements,
ongoing chaotic drug use, etc)
capacity to give informed consent to treatment. On assessment the young person must
be deemed mature enough to understand the risks and consequences of the treatment.
Copies of the relevant forms can be downloaded from the Department of Healths website
at: www.health.wa.gov.au/cpop or can be obtained by contacting Pharmaceutical Services
Branch at Department of Health on 08 9388 4980.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Chapter 1

1.2 Informed consent and patient information.


Obtain informed consent to methadone/buprenorphine treatment in writing from the patient
before commencing treatment. For patients to make a fully informed decision, they should be
provided with written information about:
the nature of methadone/buprenorphine treatment
other treatment options
program policies and expectations
consequences of breaches of program rules
recommended duration of treatment
side effects and risks associated with taking methadone/buprenorphine
risks of other drug use
the potential impact of methadone/buprenorphine on their capacity to drive or operate
machinery.
the availability of further information about treatment.
Methadone/buprenorphine may affect the capacity of patients to drive or operate
machinery during the early stages of treatment, after an increase in dose, or when
patients are also taking other drugs. Warn patients about this effect before entry into
treatment, when the dose is increased, or when the use of other drugs is suspected.
Patients should be provided with the general information booklet and the WA specific booklet
relevant to their treatment choice (i.e. methadone, Subutex or Suboxone). Patients should also
sign a consent to treatment form, a copy of which should be retained in the patients file (see
Appendix 12 for a template consent form).

Confidentiality/Privacy Legislation
The Commonwealth Privacy Act 1988 applies rules known as Information Privacy Principles and
National Privacy Principles to acts and practices engaged in by agencies and organisations in
relation to access, collection, use and disclosure of personal information, including a persons
health information.
The National Privacy Principles apply to private health services and medical
practitioners and pharmacists in private practice, and do not apply to State government
agencies such as the Department of Health or the Drug and Alcohol Office/Next Step.
However, as a matter of best practice, the CPOP will endeavour to uphold the National
Privacy Principles in relation to personal health information.
The patient has the right to:
know why personal information is being collected and how it will be used
know which organisations are being given their details and how this information will be
used by those organisations
find out what information an organisation holds about them and how it is managed
ask for access to their own medical records and be able to correct any inaccurate
information that has been recorded

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Chapter 1

know when information will be provided without their permission e.g. in the case of
notification for the Register of Drug Dependent People or mandatory reporting of
notifiable sexually transmitted diseases
to refuse permission for the release of information without prejudicing future treatment
- permission must then be sought from the patient before information is released to
another party
Freedom of information legislation also provides patients with the right to access their medical
records held by public health services and correct any inaccuracies.
In signing the application for authority at the commencement of treatment patients provide
consent to GPs, pharmacists, Department of Health and Next Step to share information regarding
their pharmacotherapy treatment.

Appeals/Complaints Process
Patients have a right to appeal the decisions made about their treatment. The following
principles apply to patient appeals:
Patients have the right of access to procedures intended to resolve conflict between
themselves and those responsible for their treatment. Formal mechanisms are necessary
to ensure that complaints by patients receive attention.
Patients should be informed of their rights to register a complaint and the procedures
for doing so at the time of admission into methadone/buprenorphine treatment.
Patients who cannot read should be read their rights and obligations.
Where possible, patients should be retained in current treatment pending the resolution
of the complaint.

Making a complaint
Initially patients should be encouraged to discuss their concerns with the treatment provider
involved or the Coordinator of Client Management, Community Clinical Programs at Next Step 08
9219 1907.
If this does not adequately resolve the issue patients should contact the Manager, Community
Clinical Programs at Next Step on 08 9219 1919 to discuss the matter and explore options for
resolving the problem.
Where the above fails to achieve a satisfactory resolution, complaints can also be made to the
following agencies:
For concerns about breaches of privacy:
Contact the Privacy Commissioner on 1300 363 992
For concerns about discrimination:
Equal Opportunities Commission 9216 3900 or 1800 198 149 (country callers only)
For concerns about professional conduct of the treatment provider or any other matter:
Office of Health Review (08) 9323 0600 or 1800 813 583

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Chapter 1

Patients wanting assistance in making a complaint can contact:


Opioid Replacement Pharmacotherapy Advocacy and Complaints Service (ORPACS) on
(08) 9321 2877
Health Consumers Council on (08) 9221 3422
Office of Health Review on (08) 9323 0600 or 1800 813 583 (country callers only)

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

2.0 Clinical Pharmacology


2.1 General Information
What is Methadone?

Chapter 2

Methadone is a potent synthetic opioid agonist, which is well absorbed orally and has a long
plasma half-life. Two preparations are available for methadone maintenance treatment in
Australia:
Methadone Syrup from Glaxo Smith Kline. This formulation contains 5 mg/ml methadone
hydrochloride, sorbitol, glycerol, ethanol (4.75%), caramel, flavouring, and sodium benzoate.
Biodone Forte from McGaw Biomed. This formulation contains 5mg/ml methadone hydrochloride
and permicol-red colouring.
Table 1: Effects of Methadone
Actions
Analgesia
Sedation
Respiratory depression
Euphoria (oral methadone causes less euphoria
than intravenous heroin)
Other Actions
Decreased blood pressure
Constriction of the pupils
Antitussive
Gastrointestinal tract actions
Reduced gastric emptying
Reduced motility
Elevated pyloric sphincter tone
Elevated tone of Sphincter of Oddi can
result in biliary spasm
Skin actions
Histamine release

Endocrine actions including


Reduced Follicle Stimulating Hormone
Reduced Luteinising Hormone
Elevated Prolactin
Reduced Adrenocorticotrophic Hormone
Reduced testosterone (Endocrine
function may return to normal after 2-10
months on methadone)
Elevated Anti Diuretic Hormone
Side Effects
Sleep disturbances
Nausea and vomiting
Constipation
Dry mouth
Increased sweating
Vasodilation and itching
Menstrual irregularities in women
Sexual dysfunction including impotence in men
Fluid retention and weight gain

The effects of methadone are qualitatively similar to morphine and other opioids. Most people
who have used heroin will experience few side effects from methadone. Once on a stable
dose, tolerance develops until cognitive skills and attention are not impaired. Symptoms of
constipation, sexual dysfunction and occasionally increased sweating can continue to be troubling
for the duration of methadone maintenance treatment.
See chapter 5 for more information on side effects.
Because of its good oral bioavailability and long half-life, methadone is taken in an oral daily
dose.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Methadone is fat soluble and binds to a range of body tissues including the lungs, kidneys, liver
and spleen such that the concentration of methadone in these organs is much higher than in
blood. There is then a fairly slow transfer of methadone between these stores and the blood.
Methadone is primarily broken down in the liver via the cytochrome P450 enzyme system.
Approximately 10% of methadone administered orally is eliminated unchanged. The rest is
metabolised and the (mainly inactive) metabolites are eliminated in the urine and faeces.
Methadone is also secreted in sweat and saliva.

Chapter 2

Pharmacokinetics
There is wide individual variability in the pharmacokinetics of methadone but in general, blood
levels rise for about 3-4 hours following ingestion of oral methadone and then begin to fall.
Onset of effects occurs approximately 30 minutes after ingestion. The half-life of a single first
dose is 12 18 hours with a mean of 15 hours. With ongoing dosing, the half-life of methadone
is extended to between 13 and 47 hours with a mean of 24 hours. This prolonged half-life
contributes to the fact that methadone blood levels continue to rise during the first week of daily
dosing and fall relatively slowly between doses.
FIGURE 3

Typical relative plasma


concentration of methadone

PLASMA LEVELS OF METHADONE DURING FIRST 3 DAYS OF DOSING*

*Preston A (1999) The New Zealand Methadone Briefing.


Methadone reaches steady state in the body (where drug elimination equals the rate of drug
administration) after a period equivalent to 4-5 half lives or approximately 3-10 days. Once
stabilisation has been achieved, variations in blood concentration levels are relatively small and
good suppression of withdrawal is achieved. For some, however, fluctuations in methadone
concentrations may lead to withdrawal in the latter part of the inter-dosing interval. If dose
increases or multiple dosing within a twenty four hour period do not prevent this, other agonist
replacement treatment approaches such as buprenorphine should be considered.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Onset of effects

30 minutes

Peak effects

Approx 3 hours

Half life (in maintenance treatment)

13 47 hours (mean 24 hours)

Time to reach stabilisation

3-10 days

Drug Interactions
Chapter 2

Toxicity and death have resulted from interactions between methadone and other drugs. Some
psychotropic drugs may increase the actions of methadone because they have overlapping,
additive effects (e.g. benzodiazepines and alcohol add to the respiratory depressant effects of
methadone). Other drugs interact with methadone by influencing (increasing or decreasing)
metabolism (See Appendix 1). Drugs which induce the metabolism of methadone, can cause a
withdrawal syndrome if administered to patients maintained on methadone. These drugs should
be avoided in methadone patients if possible. If a cytochrome P450 inducing drug is clinically
indicated for the treatment of another condition seek specialist advice. Cytochrome P450-3A
inhibitors can decrease the metabolism of methadone and cause overdose.

A full list of drugs which interact with methadone appears at Appendix 1


Safety
Methadone taken orally in controlled doses has few long term side effects. Methadone does not
cause damage to any of the major organs or systems of the body and those side effects, which do
occur, are considerably less harmful than the risks of alcohol, tobacco and illicit opiate use (see
Section 5.1).
The major hazard associated with methadone is the risk of overdose. This risk is particularly
high at the time of induction and when methadone is used in combination with other sedative
drugs. The relatively slow onset of action and long half-life mean that methadone overdose may
not be obvious and may only become life threatening many hours after ingestion. (See Section
5.2). Because methadone levels rise progressively with successive doses during induction into
treatment, most deaths in this period have occurred on the second or third day of treatment.

The major hazard associated with methadone is the risk of overdose


Cardiac vigilance recommended for methadone
There are risks of QT prolongation and torsades de pointes with methadone, particularly high
doses. It is recommended that ECG monitoring should be undertaken in patients prescribed
methadone > 150 mg/day and in those with risk factors for QT prolongation or symptoms that
may be attributable to arrhythmia.

Withdrawal from methadone


The duration of methadone withdrawal is longer (5 to 21 days). This initial or acute, phase of
withdrawal may then be followed by a period of protracted withdrawal syndrome. The protracted
syndrome is characterised by a general feeling of reduced well being. During this period, strong
cravings for opioids may be experienced.

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Clinical policies and procedures for the use of methadone


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Untreated methadone withdrawal symptoms may be perceived as more unpleasant than heroin
withdrawal, reflecting the more prolonged nature of methadone withdrawal. Factors that have
been identified as having the potential to influence the severity of withdrawal include the
duration of opioid use, general physical health, and psychological factors, such as the reasons for
undertaking withdrawal and fear of withdrawal.

What is buprenorphine?

Chapter 2

Buprenorphine is a derivative of the morphine alkaloid, thebaine, and is a partial opioid agonist
at the mu opioid receptors in the nervous system. Although buprenorphine is a potent mu
receptor agonist at low doses, there is a ceiling on its maximal opioid activity (Walsh et al
1994; Walsh et al 1995). Buprenorphine diminishes cravings for heroin, and prevents or alleviates
opioid withdrawal in dependent heroin users. Buprenorphine has a higher affinity for mu opioid
receptors than full opioid agonists. Because of this, buprenorphine can block the effects of
other opioid agonists in a dose-dependent fashion. By its dual effects of reducing craving and
attenuating the response to administered heroin, buprenorphine reduces the self-administration
of heroin. Methadone, a full opioid agonist, also reduces the impact of additional heroin, but
the effect of methadone is primarily due to the induction of cross-tolerance which is dose
dependent. In contrast buprenorphine achieves its effect primarily by prolonged occupancy of a
high proportion of opioid receptors, blocking the action of heroin.
Unlike methadone, the effect of buprenorphine on respiratory depression reaches a ceiling,
with higher doses not increasing respiratory depression to a significant degree. However, if
buprenorphine is used in combination with other central nervous system depressants, such as
benzodiazepines, the combined effect on respiration can be life threatening.
Buprenorphine also exhibits antagonist effects at the kappa opioid receptor. The role of these
receptors in humans is still poorly understood.
Two buprenorphine products are currently registered in Australia for the treatment of opiate
dependence within a framework of medical, social and psychological treatment: the mono
product (Subutex) is a sublingual tablet containing buprenorphine hydrochloride in 0.4, 2,
and 8mg strengths; the combination product (*Suboxone) is a sublingual tablet containing
buprenorphine hydrochloride and naloxone hydrochloride in a ratio of 4:1. Suboxone is available
in two dosage strengths: 2mg buprenorphine and 0.5mg naloxone, and 8mg buprenorphine and
2mg naloxone. Buprenorphine is also registered in Australia as Temgesic sublingual tablets and
ampoules for intramuscular or subcutaneous injection, for short-term (not more than one week)
relief of moderate to severe pain, including post-operative and terminal and chronic pain. A low
dose buprenorphine patch for transdermal administration is now available in Australia for pain
relief.
Sublingual buprenorphine tablets have approximately 30-35% of the bioavailability of intravenous
buprenorphine preparations. The bioavailability of sublingual buprenorphine is largely dependent
on the time the drug is in contact with the oral mucosa and appears to improve as individuals
practice taking their medication.

Buprenorphine may induce rapid opioid withdrawal


The side effects of buprenorphine are similar to those of other opioids. Many patients report
less sedation on buprenorphine than on methadone. See chapter 5 for more information on side
effects.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Under certain circumstances, buprenorphine may precipitate opioid withdrawal symptoms 1 - 4


hours after the first dose. It has a higher affinity and lower intrinsic activity than agonists such
as methadone, morphine or heroin. Consequently, buprenorphine displaces agonists from opioid
receptors and, in the short term, may not produce sufficient agonist effects to compensate for
the displaced methadone or heroin, producing opioid withdrawal as the buprenorphine reaches its
peak effects (approx. 1 - 4 hours after initial administration). The phenomenon of precipitated
withdrawal has particular clinical relevance during the induction of heroin users and methadone
patients to buprenorphine (see Section 3.6).

Chapter 2

Pharmacokinetics
Peak plasma concentrations are achieved one to two hours after sublingual administration.
Buprenorphine undergoes extensive first pass metabolism when taken orally. The major
metabolite, norbuprenorphine, has some opioid activity but the extent of its contribution to the
effects of buprenorphine is unknown.
Buprenorphine is principally metabolised by two hepatic pathways: conjugation with glucuronic
acid and N-dealkylation, mediated by the cytochrome P450 3A4 isozyme. The metabolites are
excreted in the biliary system, with enterohepatic cycling of buprenorphine and its metabolites.
Most of the drug is excreted in the faeces and, to a lesser extent, in the urine.
Buprenorphine is a long-acting drug with a terminal elimination half-life of 24 to 37 hours. Peak
clinical effects occur one to four hours after sublingual administration. Typically effects will
continue to be experienced for up to 12 hours at low doses (2 mg), but as long as 48 to 72 hours
at higher doses (16 or 32 mg). The prolonged duration of effect at high doses enables alternateday, and even 3-days-a-week dispensing regimes.
Onset of effects

30 - 60 minutes

Peak clinical effects

1 - 4 hours

Duration of effects

8 - 12 hours at low dose (e.g. < 4 mg)


24 - 72 hours at high dose (e.g. >16 mg)

Time to reach stabilisation

7 10 days

Drug Interactions
The principal drug interactions of buprenorphine relate to its opioid activity.
Sedatives. Buprenorphine exerts additive sedative effects when used in conjunction with
other sedating medications. These include other opioids, benzodiazepines, alcohol,
tricyclic antidepressants, sedating anti-histamines, and major tranquillisers. The
combination of buprenorphine with benzodiazepines, alcohol and other sedatives has
been associated with fatal overdoses.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Chapter 2

Opioid Antagonists (naloxone and naltrexone). Buprenorphine has affinity for mu opioid
receptors similar to the opioid antagonists. In the event of overdose of buprenorphine,
very high doses of naloxone are required to reverse its effects Cases have been reported
in which naloxone in doses of 10 to 35mg was required, while in other cases doses of
2mg or less were reported to be effective in reducing respiratory depression (Boyd et al
2003). Because of the uncertain response to naloxone, prolonged ventilatory support
may be required in overdoses involving buprenorphine. Naltrexone can precipitate a
withdrawal reaction in patients on buprenorphine, although the effect may be delayed
(2 to 4 hours, occasionally up to 8 hours).
Opioid Agonists. Buprenorphine exerts a degree of blockade to the effects of full
agonist opioids, which may complicate the use of additional opioids for analgesia. The
initial dose of buprenorphine can precipitate opioid withdrawal in patients who have
recently used an opioid drug.
Hepatic Enzyme Inducers and Inhibitors. Buprenorphine metabolism can be influenced
by the presence of drugs and other compounds that are also metabolised by or affect
the activity of the cytochrome system (see Appendix 2). Patients who are concurrently
prescribed or using inhibitors of cytochrome P450 3A4 may have increased buprenorphine
blood concentrations, and those taking inducers may have decreased blood
concentrations. Such interactions are probably seldom of clinical significance.

Safety
High doses: Dose response studies show that, because of its ceiling effects, high doses (16 mg
daily or more) do not result in substantially greater peak opioid effects than lower doses (8 or
12 mg). Doses many times greater than normal therapeutic doses appear to be well-tolerated,
and rarely result in clinically-significant respiratory depression, except in individuals who are not
opioid tolerant. However, even low doses of buprenorphine can be toxic when combined with
sedatives such as benzodiazepines and alcohol (Faroqui et al 1983; Forrest 1983; Papworth 1983;
Sekar & Mimpriss 1987).

Buprenorphine is safer in high doses than full opioid agonists


Combined with other drugs: The safety of buprenorphine mixed with high doses of other sedative
drugs, such as alcohol or benzodiazepines and antipsychotics, is still unclear, with several
deaths having been reported. Naloxone may be of limited use in resuscitating individuals who
have overdosed on high doses of buprenorphine (See section 5.2 on management of overdose).
For the majority of fatalities reported to date involving buprenorphine and benzodiazepines,
patients were injecting buprenorphine along with benzodiazepines or taking large amounts
of buprenorphine outside of a doctors care. Legitimate and appropriate prescription of
these therapeutics coupled with responsible use by patients is unlikely to lead to adverse
consequences.

Not safe mixed with high doses of other sedatives


Precaution should be exercised when buprenorphine is administered concomitantly with
CYP3A4 inhibitors (eg protease inhibitors, some drugs in the class of azole antimycotics such as
ketoconazole, calcium channel antagonists such as nifedipine, and macrolide antibiotics) as this
may lead to increased plasma concentrations of buprenorphine.

21
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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Withdrawal from buprenorphine


The partial agonist properties of buprenorphine, along with its slow dissociation from opioid
receptors result in a withdrawal syndrome that is delayed and may be milder than withdrawal
from heroin, morphine and methadone (Cami et al1991; Horgan 1989; Jasinski et al 1982; Mello &
Mendelson 1980; Mudric et al 1998; Sam et al 1991; San et al 1992). Research evidence regarding
the nature and severity of withdrawal following cessation of buprenorphine maintenance
treatment remains limited.

Chapter 2

Furthermore, many of the early studies of buprenorphine withdrawal relied of observers


assessments of objective withdrawal signs, which can produce a significantly different view to
subjective assessments by patients of withdrawal severity (Kosten et al 1985).Typically, the
withdrawal syndrome following the abrupt cessation of long-term buprenorphine emerges within
three to five days of the last dose and mild withdrawal features continue for up to several weeks.

Withdrawal from buprenorphine is milder and transfers


to alternate treatments are more rapid
Buprenorphine-naloxone combination product (Suboxone)
The buprenorphine-naloxone combination product was developed to limit the abuse of
buprenorphine by reducing the potential for injection, especially by opioid dependent users
who are not in treatment. At this time there is little evidence to determine the extent to which
this will be achieved, although there have been few reports of significant abuse or diversion of
Suboxone in the three years since it was adopted for clinical use in the USA (Stanton et al 2005).
The different sublingual and parenteral potency profiles of buprenorphine and naloxone is the
rationale for the combination product. When buprenorphine is used sublingually, bioavailability is
somewhere between 30 and 55% while the bioavailability of naloxone via this route is less than 10%.
Consequently, when Suboxone is taken sublingually, it will act as if it was buprenorphine alone,
with no apparent effect from the naloxone. Addition of naloxone does not reduce bioavailability
of buprenorphine (Chiang & Hawks 2003). In fact there is some evidence that the bioavailability of
chronically administered buprenorphine-naloxone may be higher than buprenorphine alone (Strain
et al 2004). However, if the combined preparation is injected, the naloxone will have a substantial
effect and is likely to attenuate the effects of the buprenorphine in the short-term and is also
likely to precipitate withdrawal in individuals dependent on full opioid agonists (Stoller et al 2001).
In Western Australia Suboxone is the standard preparation to be used for treatment of patients
with opioid dependency. Subutex is only to be used where the following special circumstances
apply:
Pregnant or breast feeding women
Patients with a known allergy to Naloxone or Suboxone
Patients on less than 6mg buprenorphine who are reducing their dose in increments of
less than 2mg.
The special circumstances should be fully specified on the Application for authority to prescribe
form. Adverse reaction forms must accompany the application form for patients with an allergy.
Where application is made for breastfeeding women or patients on less than 6mg and reducing,
authorisations will be limited to a six month period and require renewal at the end of this period
or transfer to Suboxone if the special circumstance no longer applies.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

TABLE 2

EFFECTS OF MONO (SUBUTEX) AND COMBINATION (SUBOXONE) PREPARATIONS


OF BUPRENORPHINE IN VARIOUS SITUATIONS

Population

Combination product (Suboxone)


Sublingual (poor
bioavailability of
naloxone)

Dependent heroin user




Heroin 1 hr ago
Withdrawal precipitated
by buprenorphine

Heroin >12 hrs ago

Non-dependent heroin
user

Opiate-nave

Subutex maintenance

Methadone maintenance
(dose <24 hrs ago)


Agonist effects

Agonist effects

Agonist effects
(reduced if swallowed)

Agonist effect

Precipitated withdrawal

i.v. (high bioavailability


of naloxone)

Chapter 2

Note: Research and clinical experience in different populations of opioid users of the effects
of buprenorphine, alone and in combination with naloxone, are limited. This table summarises
current expert opinion of the likely immediate effects of buprenorphine, in doses of 8 to 32mg,
in different situations.
Mono product
(Subutex)
Sublingual or i.v.


Severe withdrawal due
to naloxone and
buprenorphine

May be mild withdrawal

Attenuated agonist effect


Precipitated withdrawal


Agonist effect initially
attenuated

Agonist effect may
initially be attenuated

Severe withdrawal
due to naloxone and
buprenorphine


Agonist effects (reduced
effects if swallowed)

Agonist effects


Agonist effects

Agonist effects


Precipitated withdrawal

All opioids have abuse potential, but as indicated in the table above, people who are frequent
users of heroin, methadone, or other opioid agonists that bind less tightly to opioid receptors
than buprenorphine, are unlikely to abuse buprenorphine. The effect of buprenorphine (taken
sublingually or by intravenous injection) in people in naltrexone maintenance treatment remains
unclear. Administration of buprenorphine to this population may result in an attenuated agonist
effect, particularly with low doses of naltrexone, as is generally the case with implanted
preparations of naltrexone.
as with all opioid drugs, the prescription of the buprenorphine-naloxone combination as a
takeaway medication for unsupervised administration needs to be based on a careful assessment
of the risk of injection of the preparation by the person for whom it was intended as well as the
potential for diversion for unauthorised use.
From Table 2 it will be apparent that the group most likely to inject the combination product
will be people on buprenorphine maintenance programs. In particular there is a risk that people
prescribed unsupervised doses of the combination product may inject their own medication.
Injection of drugs designed for sublingual administration is a health risk, and doctors have an
obligation to monitor patients closely. Specifically, patients receiving doses for unsupervised
administration should be monitored for signs of fresh injecting sites, and takeaway doses should
not be supplied to people with evidence of continued, recent injecting. (See also Section 4.)

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

3.0 Clinical Management for Maintenance Treatment


3.1 Entry into Methadone/Buprenorphine Maintenance Treatment
Substitution Maintenance Treatment
Substitution maintenance treatment with methadone or buprenorphine may be more appropriate
for those with significant opioid dependence and who are not wanting to enter residential
rehabilitation or naltrexone treatment, but nevertheless who want to stop or reduce their illicit
opioid use. Clinical decision-making should have an evidentiary basis, and patients should be
presented with the relative evidence, i.e. the merits and the limitations of treatment outcomes
associated with each approach. Within such a framework, there is widespread evidence
suggesting that maintenance substitution remains the gold standard treatment for most people
with chronic heroin dependence, by virtue of its success in keeping patients in treatment, and
reducing drug-related harms.

Chapter 3

The objectives of substitution maintenance treatment with methadone or buprenorphine are to:
reduce illicit use of opioid drugs
reduce the risk behaviours associated with contracting and transmitting infectious
diseases;
reduce the incidence of death in associated with illicit opioid use;
improve the health, well-being and social functioning of patients;
reduce drug related crime
reduce other social costs of illicit opioid use.
motivate and support patients to achieve their positive lifestyle goals.
While the achievement of an opioid-free state is a long-term goal of maintenance treatment, it
must be recognised that this may not be the initial objective of the patient, nor, in some cases,
may it be appropriate. It is reasonable to expect, however, that methadone and buprenorphine
treatment will encourage patients to develop the motivation to become opioid free.

Indications
1. Opioid dependence
Methadone/buprenorphine maintenance treatment is indicated for those who are dependent
on opioids and who have had an extended period of regular opioid use. The diagnosis of opioid
dependence should be made by eliciting the features of opioid dependence in a clinical interview
(See Section 3.3 Assessment for maintenance treatment with methadone/buprenorphine). The
definitional criteria of The diagnostic and statistical manual of mental disorders, 4th edition
(DSM-IV) are useful to diagnose dependence.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Table 3: Diagnostic Definition of Opioid Dependence (DSM IV)


Dependence is defined as A maladaptive pattern of substance use leading to clinically significant
impairment or distress as manifested by three or more of the following occurring at any time in
the same 12 month period.
Tolerance as defined by either of the following:

A need for markedly increased amounts of opioids to achieve intoxication or desired effect;

Markedly diminished effect with continued use of the same amount of opioids.
Withdrawal as manifested by either of the following:

The characteristic withdrawal syndrome for opioids (see Appendix 11).

Opioids or a closely related substance are taken to relieve or avoid withdrawal symptoms.
Impaired control over use: Opioids are often taken in larger amounts or over a longer period
than was intended.
Wish to quit: There is a persistent desire or unsuccessful attempts to cut down or control
opioid use.

Chapter 3

Time factor: A great deal of time is spent in activities necessary to obtain opioids, use
opioids, or recover from their effects.
Life style changes: Important social, occupational, or recreational activities are given up or
reduced because of opioid use.
Continued use despite awareness it causing harm: The opioid use is continued despite
knowledge of having a persistent or recurrent physical or psychological problem that is likely
to have been caused or exacerbated by opioids.
Note: Neuroadaptation is not a prerequisite for the diagnosis of drug-dependence. However, in
the absence of neuroadaptation, the prescribing medical practitioner must clearly demonstrate
potential benefits to the individuals health and well-being that outweigh the potential
disadvantages of methadone or buprenorphine treatment, and alternative treatment options
should be carefully considered.
2. Patient must be at least 16 years of age (see section 5.10)
3. Patient must have 100 points of ID (see Appendix 3 and section 3.10)
4. Patients must be able to give informed consent (see section 1.2)

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Contraindications

Chapter 3

The following patients are not suitable for treatment with either methadone or buprenorphine
respectively:
Methadone

Buprenorphine

Patients with severe hepatic impairment


(decompensated liver disease) as methadone
may precipitate hepatic encephalopathy.

Severe respiratory or hepatic insufficiency.

Patients who are hypersensitive to


methadone or other ingredients in the
formulation.

Anyone with known hypersensitivity and/or


severe side-effects from previous exposure to
buprenorphine or other ingredients in either
the mono or combined formulation

Other contraindications identified by the


manufacturers of methadone include severe
respiratory depression, acute asthma,
acute alcoholism, head injury and raised
intracranial pressure, ulcerative colitis,
biliary and renal tract spasm, and patients
receiving monoamine oxidase inhibitors or
within 14 days of stopping such treatment.

Pregnancy and breast-feeding are listed


as contra-indications for the use of
buprenorphine in Australia, principally due
to the fact that there is a lack of robust
data on the safety and effectiveness of
buprenorphine.

It is recommended that specialist advice be sought from the Clinical Advisory Service in these
cases.

Precautions
Particular caution should be exercised by prescribers when assessing individuals with the
following clinical conditions as to their suitability and safety for treatment with methadone/
buprenorphine. Concomitant medical and psychiatric problems and other drug use increase the
complexity of management of patients on methadone/buprenorphine and may also increase the
risk of overdose and death. The prescribing doctor should seek specialist advice or assistance in
such cases.
High risk poly drug use: methadone/buprenorphine treatments should be approached with
caution in individuals using other drugs, particularly those likely to cause sedation such as
alcohol, as well as benzodiazepines, antipsychotics and antidepressants in doses outside
the normal therapeutic range. Particular attention should be given to assessing the level of
neuroadaptation to opioids, the likehood of continued use of other drugs and overdose risk.
(See Sections 5.2 and 5.6).
Co-occurring alcohol dependence: due to the significant management problems presented by
this group, consideration should be given to concurrent acamprosate or disulfiram therapy. If
acamprosate or disulfiram are used, a methadone liquid formulation that does not contain
alcohol should be considered to reduce the risk of reactions.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Low or uncertain levels of neuroadaptation to opiates. Commencing methadone or


buprenorphine in someone who is opioid dependent but not currently tolerant to opioids is
justified in some circumstances where that person is likely to develop a tolerance in the near
future or whose use of opioids is likely to cause them harm, these circumstances commonly
exist in people recently released from prison. At other times, the degree of neuroadaptation to
opioids may be uncertain. Even low doses of methadone or buprenorphine can cause sedation and
respiratory depression in these circumstances. The use of concomitant sedating medications such
as benzodiazepines, neuroleptics and trycyclic antidepressants further increase this risk.
Chronic pain refer for specialist assessment first (see section 5.8)

Chapter 3

Psychiatric illness (see also Section 5.14):


People whose mental state impairs their capacity to provide informed consent (e.g.
those with an acute psychotic illness, cognitive impairment or a severe adjustment
disorder) should receive adequate treatment for the psychiatric condition so that informed
consent can be obtained before initiation of treatment. (Note: at entry to treatment most
patients exhibit some degree of depression which usually resolves quickly with methadone/
buprenorphine treatment. Most of these patients do not require antidepressant treatment
before commencement of methadone/buprenorphine).
High risk of self-harm Individuals at moderate or high risk of suicide should not be
commenced on methadone or buprenorphine in an unsupervised environment and specialist
consultation should be sought.
Poor compliance: patients who exhibit poor compliance with treatment for major intercurrent
illness such as asthma or diabetes pose a particular challenge in methadone/buprenorphine
treatment.
Transfer from another treatment for drug dependence (see section 3.5 and 3.6)
Concomitant medical problems
A significant proportion of methadone related deaths have involved individuals who were in
poor health and had other diseases (particularly hepatitis, HIV and other infections) which may
have contributed to their death. This emphasises the importance of giving consideration to
concomitant medical problems for both methadone and buprenorphine. Particularly:
Head injury and increased intracranial pressure: This is generally seen only in the
hospital emergency setting.
Compromised respiratory function. Methadone and buprenorphine, like other opioids,
should be used with caution in patients with a sustained decrease in respiratory reserve,
pre-existing respiratory depression, hypoxia, or hypercapnia such as chronic obstructive
airways disease or cor pulmonale, or sleep apnoea. In such patients, even normal
therapeutic doses of opioids may decrease respiratory drive.
Acute abdominal conditions.
Severe hepatic disease. Caution needs to be taken in considering methadone or
buprenorphine treatment for people with clinically significant liver disease (i.e. acute
hepatitis or Childs B/C cirrhosis) a severe hepatic disease may alter hepatic
metabolism. However, the presence of elevated enzyme levels on liver function testing,
in the absence of clinical evidence of liver failure, does not exclude someone from
treatment.
Severe renal disease

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Prostatic hypertrophy or urethral stricture


Diabetes mellitus, hypopituitarism, adrenocortical insufficiency, hypothyroidism,
phaeochromocytoma
Advanced age or debilitation

EXERCISE CAUTION with patients in any of the following categories:


high risk polydrug use
co-occurring alcohol dependence
history of reduction in opioid tolerance
psychiatric illness
Cardiac vigilance recommended for methadone
There are risks of QT prolongation and torsades de pointes with methadone, particularly high
doses. It is recommended that ECG monitoring should be undertaken in patients prescribed
methadone > 150 mg/day and in those with risk factors for QT prolongation or symptoms that
may be attributable to arrhythmia.

Chapter 3

3.2 Selecting maintenance pharmacotherapies


Patients commonly present for treatment at a time when they are in crisis. It may be that
heroin use has escalated to a point of being out of control or, sometimes, a change in their
circumstances, such as an ultimatum from family, or being charged with a criminal offence, may
be the precipitant to entering treatment. In these crisis situations, patients are often resolved
to cease drug use and change their lifestyle. They often seek short-term treatment, without
necessarily having considered all their treatment options, simply hoping that an attempt at
withdrawal will be sufficient to stop heroin use.
Clinical experience and research have repeatedly demonstrated that motivation to remain
abstinent is often short-lived. There is strong evidence that longer-term treatment is associated
with a greater likelihood of long-term abstinence from heroin than are shorter periods of
treatment. Stability and consequent improvements in drug use and psychosocial stability gained
as a result of opioid replacement therapy tend to become significant after three months of
treatment, with the majority of benefit gained after one year (benefits may be sustained beyond
this point with continued treatment). However, this is seldom what patients or their families
wish to hear at the time of entering treatment. This is particularly an issue with patients
requesting buprenorphine treatment, since many are seeking short-term treatment rather than
maintenance. In contrast, in recent years in Australia, most patients requesting methadone are
seeking maintenance treatment.
All eligible patients merit prompt admission to treatment but this is especially important for
pregnant women, people with HIV and/or Hepatitis B carriers and their opioid using partners, and
people being released from correctional institutions.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Buprenorphine is particularly useful in managing heroin withdrawal, in that it is not only effective
during the withdrawal period, but also facilitates links to post-withdrawal treatment. The use
of buprenorphine for several days generally alleviates withdrawal symptoms without significant
sedation, thereby allowing patients and clinicians to examine post-withdrawal issues relatively
early on in the withdrawal episode. (Many other withdrawal medications, such as benzodiazepines
or clonidine, cause patients to be either psychologically distressed or heavily sedated such that
this would not be possible.) A formal review of treatment plans should be structured several days
into the withdrawal episode, at which time treatment can be tailored accordingly.
Patients who are not interested in ongoing pharmacotherapy treatment can cease after a short
course of buprenorphine with minimal rebound discomfort. Alternatively, those patients who
want to extend the duration of their withdrawal program, or have reconsidered the role of a
maintenance treatment program, can continue buprenorphine treatment over a longer period of
time. Another benefit of buprenorphine is that naltrexone can be initiated after buprenorphine
administration with less delay and less severe withdrawal than is the case following methadone
maintenance treatment. These treatment pathways are shown in Figure 4.

Chapter 3

FIGURE 4. GATEWAY MODEL OF TREATMENT WITH BUPRENORPHINE


Naltrexone treatment for
relapse prevention
Commenced during or
after buprenorphine
cessation

Dependent heroin user


entering treatment

Withdrawal episode
Buprenorphine regime
for 4 - 8 days with
exploration of post
withdrawal treatment
plans

Substitution
maintenance treatment
Buprenorphine or
methadone

No ongoing
pharmacotherapy
Psychosocial
interventions

It is increasingly common for clinicians to be confronted with people requesting repeated, shortterm episodes of buprenorphine treatment, perhaps three or four episodes of detoxification
within a year. In this situation, where people are continually failing and relapsing, it may be
more useful to recommend methadone rather than another short-term episode of buprenorphine
treatment.

Choosing a maintenance pharmacotherapy


Current evidence suggests that key treatment outcomes for maintenance buprenorphine and
methadone treatment are comparable under optimal treatment conditions. Patients or clinicians
may however develop personal preferences. These might reflect:
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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Response to treatment
Ultimately, the continued use of a medication should depend on its ability to meet the aims and
objectives of treatment. This requires the identification of treatment goals by the patient and
decisions about how the treatment outcomes will be assessed.
Where these goals are not being met, a review of treatment strategies should
occur, including:
- the role of psychosocial interventions
- levels of supervision, monitoring and review
- dose of the pharmacotherapy
- the role of adjuvant interventions
- a review of alternative opioid pharmacotherapies. For example, patients who cannot
stabilise their continued use of heroin, even on high doses of buprenorphine, may be
better suited to high doses of a full agonist (methadone).

Individual variation in absorption, metabolism and clearance

Chapter 3

There may be considerable pharmacokinetic and pharmacodynamic differences between


individuals in their response to methadone or buprenorphine.

Adverse events
Individuals experiencing significant side-effects from one opioid medication may benefit from
treatment with an alternative medication. In particular, buprenorphine may be preferred by
individuals complaining of continued sedation under methadone.

Logistics of participating in treatment


Including issues such as; ease of access for participants, frequency of dispensing, convenient
location of treatment services and the costs to patients, service providers and funding bodies.
Once stabilised on a daily dosing regime, some patients on buprenorphine will be able to switch
to an alternate-day, or three-times-a-week dosing regime. This should be more convenient for
patients and reduce the need for takeaway doses.

Ease of withdrawal from maintenance buprenorphine treatment.


A limiting factor for many patients considering maintenance treatment is the problem of
dependence on the maintenance opioid. As it is only a partial agonist and dissociates slowly from
receptors, buprenorphine appears to have a milder withdrawal syndrome than methadone. It is
not clear if this translates into greater success for patients discontinuing maintenance treatment.

Patient (and clinician) expectations.


Expectations of any medication may impact seriously on its perceived outcomes. The introduction
of new treatments for heroin dependence may give rise to unrealistic expectations in patients,
their families, and even service providers.

Ease of transfer between pharmacotherapies


Transferring from buprenorphine to methadone is relatively straight forward. However, patients
on more than 30mg methadone will get precipitated withdrawal symptoms when transferring to
buprenorphine.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

3.3 Assessment for Maintenance Treatment


Initial assessment procedures are similar for all opioid users seeking treatment. A comprehensive
assessment of the patients drug use, medical, psychological, and social conditions, previous
treatment history and current treatment goals must be conducted and documented. Specific
attention should be given to assessment of dependence and tolerance, state of intoxication or
withdrawal and the indications, contraindications, and precautions for maintenance treatment.
Obtain corroborative evidence of identity and aspects of the history relating to drug use, medical
and psychiatric conditions to clarify any inconsistencies between physical examination findings
and reported history. Accuracy of clinical assessment may be improved by using corroborating
evidence such as urine tests and examination of veins for evidence of injecting drug use.
Corroborative evidence of dependence should also be obtained. The best evidence is observed
signs of opioid withdrawal, or a verifiable history of previous treatment for opioid dependence
(detoxification or maintenance).

Table 4: Key features of the assessment

Chapter 3

Drug use and treatment


Heroin and other opioid use
quantity and frequency (amount, cost, number of times used per day)
duration
route of administration (injected/non-injected)
when last used
features and severity of dependence
Use of other drugs (including benzodiazepines, alcohol, cannabis, psychostimulants) and
assessment of degree of dependence on each drug class.
History of prior attempts at withdrawal, maintenance and other treatment - what has
worked and not worked before.
Risk factors
Presence of risk behaviours, particularly overdoses, self-injury, or polydrug intoxication.
Medical and psychiatric history, with particular attention to unstable or active conditions
which might potentially complicate treatment.
Pregnancy and contraception.
Social circumstances
Home environment, social supports, employment, and barriers to change.
Motivations and goals for treatment. Finding the right approach requires an
understanding of the reasons for seeking treatment and of patient goals and
expectations.
Examination
Vital signs (blood pressure, pulse, respiratory rate).
Evidence of intoxication or withdrawal from heroin or other drugs.
Evidence of complications of injecting drug use, including injection site problems,
hepatic disease, lymphadenopathy, systemic infections.
Evidence of injection marks consistent with the stated history.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Investigations
Urinary drug screens can be helpful in clarifying or confirming an unclear drug use
history. While delays in getting the results of routine urine tests often limit their
usefulness at initial assessment, conducting a urine drug screen prior to the
commencement of opioid substitution therapy provides supportive evidence of opioid use
that can otherwise be difficult to obtain.
Tests of viral serology (HIV, Hepatitis B and C) should be considered at some stage with
appropriate pre- and post-test counselling. (This is advisable after stabilisation, when
the patient is better able to understand the significance and consequences of testing).
Liver function tests are recommended at the commencement of treatment to establish
a baseline. Periodic monitoring of liver function is also recommended.
The initial assessment will enable a case formulation and an initial management plan to be
developed, which can be implemented directly. However, extra information will also need to be
gathered at subsequent reviews so that more comprehensive treatment plans can be developed.

3.4 Commencing maintenance treatment


Chapter 3

Objectives during induction to methadone/buprenorphine are to retain individuals in treatment


by reducing the signs and symptoms of withdrawal and to ensure their safety. This can be
achieved by careful explanation regarding intoxicating effects and withdrawal during the
induction and maintenance phases of treatment, establishment of a therapeutic relationship, safe
dosing and repeated observation of patients.
It is particularly important to clearly explain that it takes time to complete induction onto
treatment and that patients will experience increasing drug effects over the first few days of
treatment even if the dose is not increased.

There is a need to achieve a balance between adequate relief of withdrawal


symptoms and the avoidance of toxicity and death during the induction
phase. The aim is to minimise the symptoms and signs of withdrawal while
simultaneously minimising the risks of sedation and toxicity.

3.5 Induction to methadone treatment


Commencing methadone from heroin use
While doses of methadone which are too high can result in toxicity and death, inadequate
commencement doses may cause patients experiencing withdrawal symptoms to top up the
prescribed dose of methadone with heroin, benzodiazepines or illicit methadone. This can have
potentially lethal consequences. It is particularly important to clearly explain that it takes time
to complete induction onto methadone and that patients will experience increasing effects from
methadone over the first few days of treatment even if the dose is not increased.

For most patients withdrawal symptoms will be alleviated but


not entirely eliminated by doses less than 30mg.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Deaths during the induction phase of methadone treatment have been related to:
concomitant use of other drugs (particularly sedatives such as alcohol, benzodiazepines,
other sedatives and psychiatric medications)
inadequate assessment of tolerance
commencement on doses that are too high for the level of tolerance
lack of understanding of the cumulative effect of methadone
inadequate observation and supervision of dosing
individual variation in metabolism of methadone
concomitant medical conditions.

Size of the first dose


The first dose of methadone should be determined for each patient based on the severity of
dependence and level of tolerance to opioids.

Chapter 3

The history of quantity, frequency and route of administration of opioids, findings on


examination, corroborative history and urine testing together provide an indication of the level of
tolerance a patient has to opioids, but do not predict it with certainty.
A defined period of observation for signs and symptoms of opioid toxicity and withdrawal is a
more accurate method of assessing opioid tolerance than history alone. In circumstances where
there is doubt about the degree of tolerance, a review of the patient at a time when withdrawal
symptoms are being experienced may help to resolve uncertainty about a safe starting dose.
Prescribers should make every effort to communicate with other practitioners who may have seen
the patient previously in order to corroborate significant elements of the patients history and to
assist in decision making about commencing treatment.
New patients should be dosed with caution. Deaths in the first two weeks have been associated
with doses in the range 25-100 mg/day, with most occurring at doses of 40-60 mg/day.
If at all possible, patients should be observed 3-4 hours after the first dose (i.e. at the time of
peak effect) for signs of toxicity or withdrawal. (See Appendix 7 and 11)
- If the patient is experiencing persistent withdrawal symptoms at 4 hours, a
supplementary dose of 5mg can be considered.
When deciding on the commencing dose, also consider:
Where dosing is to occur.
Are staff and facilities available for observation and assessment of the patient before
and after dosing?
Who will assess withdrawal/intoxication prior to dosing? (See Section 5.3)
Time since last opioid use.
Concomitant use of benzodiazepines or alcohol. (See also Sections 5.2 & 5.6)
The risk of overdose increases markedly when other central nervous system depressants
are also used.
If the patient shows signs of intoxication with benzodiazepines or alcohol, the dose
should be withheld or reduced.

Induct morphine, codeine and oxycodone users with the same caution as if they were
heroin users.
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29

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

5mg of methadone is equal to 1ml methadone.


A dose of less than or equal to 20mg for a 70kg patient can be presumed
to be safe, even in opioid-nave patients as this is the lowest dose at which
toxicity has been observed.
Caution should be exercised for starting doses of 25mg or more.
Exercise extreme caution if an initial dose of methadone exceeding 40mg
is considered necessary. CAS consultation is required.
Stabilisation
During the first two weeks of methadone maintenance treatment the aim is to stabilise the
patient so that they are not oscillating between intoxication and withdrawal. This does not
necessarily mean that the patient will reach an optimum maintenance dose in that time and
further dose adjustments may be required after the patient has been initially stabilised.

Dose titration
Stabilisation is about titrating the dose against needs of the individual patient.

Chapter 3

Do not increase the methadone dose for at least the first 3 days of treatment unless there are
clear signs of withdrawal at the time of peak effect (i.e. 3-4 hours after dose) as the patient will
experience increasing effects from the methadone each day.
Consider dose increments of 5mg every 2-3 days subject to assessment.
Total weekly increase should not exceed 20mg.
The maximum dose at the end of the first week should typically be no more than 40mg.
Consultation with the Clinical Advisory Service is required where a more rapid induction to
methadone is considered necessary.
Patients should be warned not to drive or operate machinery during periods of dose adjustments.

Monitoring during the first two weeks.


Patients should be observed daily prior to dosing and an assessment made of intoxication.
This generally involves the pharmacist at the dosing pharmacy. If there are any concerns
they should be seen by their doctor before the dose is administered.
It is desirable that patients are reviewed at least once, preferably twice, by the
prescribing doctor in the first week.
Do not increase the methadone dose for at least the first 3 days of treatment unless
there are clear signs of withdrawal at the time of peak effect (i.e. 3-4 hours after dose) as
the patient will experience increasing effects from the methadone each day (see Section 2,
figure 3).
Extra caution is required where there is a history of polydrug use.It is reasonable to
consider specialist referral for polydrug users commencing methadone treatment.

30
34

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

An appropriate pattern of review by the treating doctor is as follows:


the day of the first dose
every 2 - 4 days until stabilisation
every week during the following 4 - 6 weeks
every 2 weeks during the following 4 - 6 weeks
monthly reviews thereafter
Individuals with continuing high-risk patterns of drug use or concominant medical, psychiatric or
social problems may require more frequent review.

Methadone dose levels


Doses should be determined for individual patients but generally a higher dose of methadone is
required for maintenance than is required for initial stabilisation. Typically effective methadone
maintenance doses are in the range of 60-100 mg per day.

Chapter 3

There is a dose response relationship between maintenance doses of methadone, retention in


treatment and continued use of heroin. Methadone doses in excess of 60 mg/day are associated
with higher retention rates and less heroin use. This has been demonstrated in both randomised
controlled trials and cohort studies.
Cross tolerance to heroin increases as a function of increasing methadone dose and results in
blockade of the euphoric effect of concurrent heroin use. A daily methadone dose of 60mg or greater
should be sufficient to ensure a substantial level of tolerance to effects of heroin in the majority of
individuals.

Doses for effective methadone maintenance treatement are typically


60-100 mg/day.
Doses in excess of 100mg/day may be necessary to achieve successful maintenance with patients
who have a fast methadone metabolism. There is no evidence from treatment outcome studies to
suggest that routine dosing at levels in excess of 100mg/day results in any additional benefit for
the majority of patients. An Application for Exceeding the maximum dose form is required to be
faxed to the Clinical Advisory Service for approval before patients can be prescribed more than
120mg of methadone.

Approval is required to prescribe more than 120 mg of methadone


Changing dose level
Patient input to treatment decisions, including determination of dosing levels, promotes a good
therapeutic relationship by enhancing patient trust and responsibility. When making decisions
about changes in dosage the following should be taken into consideration:
concurrent use of illicit opioids and continued injecting use may indicate the need for a
higher dose
individual variation in methadone metabolism
use of other medications (See Appendix 1)
pregnancy (See Section 5.11)
polydrug use (See Section 5.6).

35
31

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Daily administration of methadone is recommended to ensure that plasma methadone levels


are maintained and to avoid withdrawal symptoms. If plasma levels are not maintained, cross
tolerance to heroin will be lessened, reducing the capacity of methadone to moderate the
euphoric effect of heroin. Reduced compliance is therefore associated with an increased risk of
relapse to heroin use.

Split dosing of methadone


Research indicates that some individuals metabolise methadone rapidly so whilst their dose level
may be adequate they do not maintain the levels long enough. These patients may require their
dose to be split and administered twice, rather than once, a day. Split dosing may be used in the
short term for clients suffering nausea, either as a result of pregnancy or in the early stages of
treatment. The schedule of takeaway doses applies to split dosing so contact the Clinical Advisory
Service for authorisation if you wish to provide the split doses as a takeaway dose.

Transfer from other pharmacotherapies

Chapter 3

Prescribers may need to seek specialist advice when prescribing for


patients who are transferring from other pharmacotherapies with which
they are unfamiliar.
From buprenorphine
Consideration should be given to transferring a patient from buprenorphine to methadone under
the following circumstances:
patient experiencing intolerable side effects from buprenorphine
inadequate response with buprenorphine treatment
transferring to a service where buprenorphine is not available
problems with supervision of buprenorphine dosing.
Patients should be stabilised on daily doses of buprenorphine and their buprenorphine dose
reduced to 16mg or less for several days prior to transfer.
Methadone can be commenced 24 hours after the last dose of buprenorphine.
The initial methadone dose should not exceed 40mg.
Patients transferring from lower doses of buprenorphine (4 mg or less) should be commenced on
lower doses of methadone.
Care should be taken not to increase the dose of methadone too quickly.

From naltrexone
Patients who have relapsed to opioid use following cessation of naltrexone (oral, implant) can
be considered for treatment with an opioid pharmacotherapy. Because of its safety profile during
induction buprenorphine is the drug of choice in this situation.
Patients who have been taking naltrexone lose tolerance to opioids. Consequently, patients
transferring from naltrexone should be treated as if they were nave to opioids and non tolerant to
their effects unless the clinical circumstances clearly indicate a return to regular, heavy heroin use.
Extreme caution should be exercised if commencing methadone, and the starting dose should be
no greater than 20mg. The first dose of methadone should not be given until at least 72 hours
after the last dose of naltrexone.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

3.6 Induction to buprenorphine treatment

Research evidence indicates that the mono buprenorphine product (Subutex) and the
buprenorphine/naloxone combination (Suboxone) formulation are largely interchangeable.
There are some circumstances, eg. pregnancy, naloxone allergy, or the induction period for
patients with high levels of neuroadaption, when the mono product will be preferred.
In W.A. all patients are required to be treated with Suboxone unless evidence supports the use of
Subutex in the following special circumstances:
pregnant & breastfeeding women (patients must sign a consent form see Appendix 13)
clients with known allergies to Suboxone (prescribers must complete an adverse reaction
form)
patients on a low dose (<6mg) withdrawal regimen. (to be completed within 6 months)

Commencing buprenorphine from heroin use

Chapter 3

The aim should be to stabilise patients on an effective dose of buprenorphine as soon as possible.
More rapid dose induction (ie. 12 to 16mg by day 3) may be associated with better retention in
treatment (Doran et al 2005). However, this needs to be weighed against individual reactions to
initial dosing and safety considerations.
Rapid dose induction is most easily achieved with an initial dose in the range of 4 to 8mg. Higher
initial doses will facilitate rapid dose induction but increase the risk of precipitated withdrawal
(if the patient has recently used opioids) or sedation (if the patient has a lower level of opioid
dependence or also consumes other sedatives such as benzodiazepines).
Patients should ideally be observed for a few hours after the first dose, and a further dose
administered on the same day if there are no signs of sedation. An appropriate dose to achieve on
the first day is 6 to 8mg. This may be given as a single dose or, if resources permit, in two doses
of 3 or 4mg, four hours apart to reduce the risk of precipitated withdrawal and adverse effects.

Prescribers should aim to achieve 12 to 16 mg/day by day 3.


Prescriptions may be written as a fixed, increasing dose regime over the first week (eg. 8mg day
1, 12mg day 2, 16mg day 3).
Due to manufacturing methods and regulatory requirements it is not recommended that
buprenorphine tablets be broken to create smaller dose sizes. Doses should only be expressed in
multiples of 2 or 8 mg for Suboxone and 0.4, 2 and 8 mg for Subutex.
The following factors must be taken into consideration when deciding the initial dose of
buprenorphine:
Time since last opioid use, and whether long-acting opioids such as methadone, have
been taken in the last one to two days.
The perceived likelihood of concurrent drug abuse, including alcohol consumption, use
of prescription sedative drugs (particularly benzodiazepines), or illicit drug use. In such
instances, lower doses of buprenorphine should be prescribed, with frequent reviews.
Concurrent medical conditions (particularly severely impaired hepatic function and
interactions with other medications) warrant the use of lower initial doses of buprenorphine
with regular monitoring (see Section 2 Clinical pharmacology, Precautions).

37
33

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

The first dose of buprenorphine should be administered when the patient


is experiencing early features of opioid withdrawal, at least six, and
preferably 12 hours after last heroin use.
Scales for assessing opioid withdrawal, such as the Subjective and Objective Withdrawal Scales (see
Appendix 10) can be useful for confirming the presence of opioid withdrawal prior to administration
of the first dose of buprenorphine. Opioid withdrawal will generally become apparent within six
hours of heroin use. Particular care should be taken not to administer buprenorphine to a patient
who is intoxicated on opioids.
Patients administered buprenorphine soon after heroin use may experience opioid withdrawal, as
the buprenorphine displaces heroin from the opioid receptors (Clark et al 2002; Gourarier et al
1996; Jacobs & Bickel 1999; Johnson et al 2003). With delayed administration of the first dose of
buprenorphine, as outlined above, the occurrence of withdrawal precipitated by buprenorphine
will be relatively rare.

Chapter 3

Buprenorphine precipitated withdrawal typically begins one to four hours after the first
buprenorphine dose, is generally mild to moderate in severity, and lasts for up to 12 hours. If
this happens, patients may require symptomatic withdrawal medication, and should be directed
to see their doctor. Administration of the first dose of buprenorphine early in the day provides an
opportunity to manage precipitated withdrawal if it occurs.
If precipitated withdrawal occurs following the initial buprenorphine dose, subsequent doses of
buprenorphine (taken the following day) should result in minimal withdrawal discomfort if the
patient has not used heroin during the intervening period. Patients who continue to use heroin
between their first and second doses of buprenorphine may have difficulty stabilising on the
treatment, with ongoing features of opioid withdrawal. They should be advised to cease heroin
use at least six hours prior to the next dose of buprenorphine.

34
38

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

TABLE 5: KEY FACTORS AFFECTING PRECIPITATED WITHDRAWAL


Discussion

Recommended strategy

Dose of methadone
when transferring to
buprenorphine

Doses greater than 30 mg of methadone


are more often associated with
precipitated withdrawal. In general, the
higher the methadone dose, the more
severe the withdrawal experienced.

Attempt transfer from low dose


of methadone (e.g. <30 mg where
possible).

Time between last


methadone dose and
first buprenorphine
dose

Buprenorphine should not be taken


within 24 hours of last methadone dose.
Increasing the interval between last
dose of methadone and first dose of
buprenorphine reduces the incidence and
severity of precipitated withdrawal.

Cease methadone and delay


first dose of buprenorphine
until patient is experiencing
features of methadone
withdrawal

Dose of
buprenorphine

Very low doses of buprenorphine (e.g.


2 mg) are generally inadequate to
substitute for methadone for 24 hours
(unless the methadone dose is very low).
High first doses of buprenorphine
(e.g. 8 mg or more) are more likely
to precipitate withdrawal, as there is
greater displacement of methadone from
the receptors. This is a common mistake
by inexperienced prescribers.

First dose of buprenorphine


should generally be 4 mg,
with review of the patient 2
- 4 hours later (or early the
following day)

Patient expectancy

Patients who are not prepared for the


possibility of precipitated withdrawal
are more likely to be distressed and
confused by its onset, with potential
negative consequences (e.g. treatment
drop-out, abuse of other medications).

Inform patients fully (and


carers where relevant).
Provide written information.
Prepare a contingency
management plan for severe
symptoms.

Use of other
medications

Symptomatic medication (eg clonidine)


can be useful in relieving any
precipitated withdrawal.

Prescribe and dispense


in accordance with a
management plan

Chapter 3

Factor

Stabilisation
The optimal maintenance dose needs to be individualised according to the patients response to
buprenorphine. However, typically a maintenance dose will be in the range of 12 to 16mg/day.
Peoples responses vary considerably, according to the following factors:
1. rates of absorption or metabolism of buprenorphine. The duration of contact with the oral
mucosa is a significant factor for the absorption of buprenorphine. Hence, instructing patients
in the technique of administering buprenorphine is important.
2. experience of side-effects;
3. continued use of other drugs.

39
35

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

These variations require the clinician to titrate the buprenorphine dose to optimise treatment
objectives.

TO ACHIEVE STABILISATION OF BUPRENORPHINE DOSE:


Regular patient reviews for first few weeks
adequacy of dose; withdrawal symptoms, side-effects, any additional drug use
(see below for minimal schedule of prescriber reviews).
Increase dose only as indicated by reviews
(see below for guidance on titration of doses)
Stabilisation by the end of the first week, reported symptoms of both withdrawal and
intoxication should be minimal. The optimal dose for the patient is one which is sufficient to
diminish or abate the discomfort of withdrawal for the full interdosing interval, and to support
a significant reduction in or cessation of other opiate use without inducing significant toxicity or
side effects. Typically optimal doses at the end of the first week would be in the range of 12 to
24mg/day.

Chapter 3

Monitoring during the first two weeks


Frequent reviews by the prescriber, or delegated staff, are required in the first few weeks to:
establish adequacy of dose;
inquire about withdrawal symptoms or side-effects; and
monitor any additional drug use.
make a more comprehensive overall assessment of the patient; and
further discuss treatment plans.
An appropriate pattern of review by the treating doctor, or a suitably trained nurse or
pharmacist, is as follows:
The day, or the day after, of the first dose of buprenorphine.
Every two to four days until stabilisation.
Every week during the following four to six weeks.
Every two weeks during the following six to eight weeks.
Monthly reviews thereafter, although the prescriber may wish to extend reviews to up to
three months for stable patients.
Individuals with continuing high-risk patterns of drug use, or concomitant medical, psychiatric or
social problems, may require more frequent review.

Dose levels
The optimal maintenance dose needs to be individualised according to the patients response to
buprenorphine. Peoples responses vary considerably, according to the following factors:
1.
2.
3.
4.

36
40

rates of absorption or metabolism of buprenorphine


levels of opioid neuroadaptation and dependence
experience of side-effects
continued use of other drugs.

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Due to manufacturing methods and regulatory requirements it is not recommended that


buprenorphine tablets be broken to create smaller dose sizes. Doses should only be expressed in
multiples of 2 or 8 mg for Suboxone and 0.4, 2 and 8 mg for Subutex.
Effective maintenance doses, resulting in reduced heroin use and improved treatment retention,
may be achieved with buprenorphine doses in the range of 8 to 24mg per day. A dose of 32mg
would typically only be prescribed to patients on alternate-day or four-times-a-week dosing
regimes. Special permission is required to prescribe a 7 days a week dose of more than 24mg.
This can be obtained by completing the Exceeding the maximum dose form and faxing to CAS.
Doses of 4mg or less will not be as effective in retaining patients in treatment or reducing heroin
use (evidence suggests that such doses produce outcomes that are similar to, or worse than, the
outcomes associated with methadone doses of 20mg). Most patients will require at least 12mg
daily for effective buprenorphine maintenance treatment, and most patients will be able to be
maintained on a dose of around 16mg/day.

Chapter 3

People wishing to reduce their use of heroin, or other opioids, can do so with increases in the
dose of buprenorphine, as higher doses of buprenorphine produce more effective blockade of
the effects of additional heroin. However, this only succeeds up to a point. Continued heroin
use despite adequate daily doses of buprenorphine may indicate that the patient needs more
intensive psychosocial interventions, and/or an alternative opioid substitution (e.g. methadone).

Approval is required to prescribe a 7 days a week dose of more than 24mg.


Changing dose level
If daily reviews by the prescriber or a suitably trained nurse or pharmacist can be organised,
daily increases can be accommodated. Practically, however, most prescribers may not be able
to review the patient more than every two or three days (e.g. because of sessional practice
or weekends). A period of two to three days on a specific dose allows the patient time to get
a feel for their current dose, and the opportunity to modify behaviour appropriately prior to
further dose changes. The buprenorphine dose may be decreased where there are concerns
regarding the patients safety (e.g. where there are reports of intoxication or overdose).

Doses can be increased or decreased by between 2 and 8mg/day


The following should guide prescribers in determining changes in the buprenorphine dose.

41
37

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

INDICATORS OF NEED FOR DOSE ADJUSTMENT


Increase dose if:
Features of withdrawal over preceding 24
hours, increasing in the period immediately
prior to the next dose (ie. not due to
precipitated withdrawal)

Decrease dose if:


Features of intoxication to buprenorphine
(e.g. sedation) particularly at peak effect
times (1 to 4 hours after dosing)

No features of intoxication to buprenorphine,


particularly at peak effect times (1 to 4 hrs
after dosing)
Heroin use or craving

Chapter 3

Nil or mild and tolerable side effects.

Severe or intolerable side effects (including


severe precipitated withdrawal)

Split dosing
Buprenorphine does not need to be provided more frequently than once a day for those on a
maintenance regimen. Therefore split dosing is not necessary.

Frequency of dosing: alternate-day and three-times-a-week dosing regimes


The characteristics of buprenorphine allow a wide range of dosing regimes, from daily to
once every two or three days. The availability of the combination product, with potentially a
lower risk of diversion, allows for the possibility of unsupervised dosing, which patients can be
expected to manage.
Patients should first be stabilised on daily dosing. When stabilised, consideration can be given to
a switch to alternate day dosing for a trial period. If the trial is unsuccessful, the patient should
be returned to daily dosing. If the trial is successful, after a further period of stabilisation,
further reductions in the frequency of dosing could be considered.
The main reasons for considering reduced-frequency dosing are convenience for patients, and
reduced staffing requirements for supervised dose administration.
Patients suitable for a trial of reduced-frequency dosing are those:
on a stable dose of buprenorphine for one to two weeks;
with no high-risk drug use (ie. frequent abuse of other sedatives including alcohol,
benzodiazepines, heroin or other opioids, intoxicated presentations to the pharmacy or
medical practitioner, or recent history of overdose).
It is recommended that suitable patients initially be tried for two weeks on an alternate-day
dosing regime of buprenorphine. If this is successful, the patient can then be tried on a threetimes-a-week regime. If a patient cannot be stabilised on such dosing regimes due to the onset
of withdrawal, cravings, side-effects or features of intoxication, they should be returned to a
more frequent dosing regime. It is expected that less than half of patients will prefer supervised
alternate day dispensing to daily supervised dispensing.

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42

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Alternate-day or four-times-a-week regime: This involves attending the pharmacy for dosing on
alternate days (i.e. a dose every 48 hours), or attending four times a week (with 3 x 48 hour
doses and 1 x 24 hour dose each week (e.g. Mon; Tues; Thurs; Sat)). The advantage of the latter
approach (4 times a week) is that the patient is on a regular attendance each week, with less
likelihood of attendance errors on the patients part and dosing errors by the pharmacist.
The dose dispensed for a 48-hour period is initially double the normal daily (24 hour)
buprenorphine dose (to a maximum of 32mg at a time). While doses higher than 32mg have been
used, the registration of buprenorphine in Australia specifies a maximum dose of 32mg. More
regular supervision is needed when patients are switched to less frequent dosing.
The patient should be reviewed following the first or second 48-hour dose. Dose adequacy can be
inferred if patients report:
being as comfortable on the second day as on the first;
sleeping as well on the second night as on the day of dosing; and
no more cravings on the second day than on the first.

Chapter 3

If the patient reports onset of withdrawal or cravings, or sleep difficulties in the second day
then the 48-hour buprenorphine dose should be increased. If the patient reports features of
intoxication from the dose of buprenorphine during its peak effects (normally at about four
hours), the 48-hour dose should be reduced.
Patients on low doses of buprenorphine may find that double the dose does not last for 48 hours.
Patients on reducing doses of buprenorphine may need to switch to daily dosing as the dose
becomes lower (i.e. below 4mg). Some patients are not comfortable with double dose when
switched to less than daily dosing.
Three-times-a-week regime: Some patients may tolerate three-times-a-week dosing with
buprenorphine, reducing the inconvenience and costs of treatment further. This should be
attempted once a two-week trial on four-days-a-week dosing has been shown to be successful.
The recommended regime for a three-day dose is:
3-day dose = three times the normal 24 hour dose if 24 hour buprenorphine dose < 12 mg
3-day dose = 32 mg when 24 hour buprenorphine dose 12 mg.

As with alternate day regimes the dose should be titrated against symptoms
with frequent review following transfer to the regime. If a patient cannot
be stabilised on a three-times-a-week dosing regime, the four-times-a-week
dosing regime should be considered.
Some patients attempting alternate-day dosing may benefit from doses greater than 32mg,
however, there is limited evidence regarding the safety of higher doses, and buprenorphine is
registered in Australia with a maximum recommended dose of 32mg. Practitioners should be
aware of the medico-legal implications of off-label prescribing before they prescribe doses of
greater than 32 mg.

Frequent clinical and hepatic monitoring is recommended


under such circumstances.

43
39

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Transferring from methadone maintenance treatment


Transfer from methadone to buprenorphine may be appropriate when:
side effects of methadone are intolerable;
the patient wishes to change, perhaps in anticipation of using buprenorphine as a
transitional detoxification agent, or to enable a reduced frequency dosing schedule;
the patient has not done well on methadone;
there are concerns over polydrug use.
There is a risk that previously stable patients may be destabilised when transferring from
methadone to buprenorphine. Careful monitoring and support should be provided to any patient
transferring from methadone and particularly those either reducing their methadone dose prior
to transfer to buprenorphine or patients transferring from higher doses of methadone to avoid
precipitating a return to illicit drug use. Transfers should be planned, considered and monitored.
If they result in destabilisation, return to methadone treatment may be the best option.

Chapter 3

When methadone patients take a dose of buprenorphine, the methadone is displaced from the
mu opioid receptors by buprenorphine. Patients on low doses of methadone (e.g. less than 30 mg)
generally tolerate this transition with minimal discomfort. Patients on higher doses of methadone
may find the replacement of methadone with buprenorphine causes significant discomfort.
However, the occurrence of precipitated withdrawal can be greatly minimised by careful initial
dosing and rapid titration to an appropriate maintenance dose of buprenorphine.

Wherever possible, patients in methadone treatment should have


their methadone dose reduced and should be stabilised on this lower dose
prior to transferring to buprenorphine.
Wherever possible, patients should be on a methadone dose of less than 40mg for at least
one week prior to receiving their first dose of buprenorphine. For many patients, the optimal
methadone dose prior to transferring to buprenorphine may be below 30mg/day.
It is preferable for patients to be experiencing a mild degree of methadone withdrawal prior
to converting to buprenorphine. This would typically occur at least 24 hours after the last dose
of methadone (or at least 12 hours after the last dose of slow-release oral morphine) and is an
indication that sufficient time has elapsed for there to be minimal risk that the first dose of
buprenorphine will precipitate significant withdrawal. Mild withdrawal would equate to a score
no greater than 8 on the Clinical Opiate Withdrawal Scale (see Appendix 10).
An initial dose of buprenorphine 4mg (2mg for those transferring from methadone doses above
30mg) should be given and the patient observed for one hour. If withdrawal symptoms improve,
the patient can be administered an additional 4mg dose. If withdrawal symptoms do not improve
or worsen, a second dose of 2-4mg should be administered and the patient observed for another
hour. If comfortable, the patient can be administered a further 4mg dose. The prescribing doctor
should make arrangements to contact the patient later in the day to assess the response to
dosing.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

This approach of repeated small doses is to be preferred. Once the


buprenorphine is on the opioid receptors, the risk of precipitated withdrawal
is reduced. If resources are not available for onsite dosing and regular
reviews as outlined above, or for patients wishing to transfer from 40mg
methadone or more should be referred to a specialist service.
The likelihood of precipitating withdrawal on commencing buprenorphine is reduced as the time
interval between the last methadone dose and the first buprenorphine dose increases. The risk of
precipitated withdrawal may be reduced by ensuring the last dose of methadone is taken early in
the morning, and the first dose of buprenorphine is taken late the following day.

The first dose of buprenorphine should be administered when the


patient is experiencing early features of opioid withdrawal, at least
24 hours after the last methadone dose.

Chapter 3

Features of a precipitated withdrawal following the first dose of buprenorphine are typically
mild to moderate in severity, and may distress the unprepared patient. Symptoms commence
one to four hours after the first buprenorphine dose and last for up to 12 hours before subsiding.
Patients experiencing discomfort may re-present to the prescribing doctor later in the day and
require symptomatic withdrawal medication (eg clonidine 0.1mg, 3 to 4 hourly). Subsequent
doses of buprenorphine (the following day) are less likely to precipitate withdrawal symptoms.

There is a lack of research evidence, but the mono preparation is the preferred
formulation to administer following methadone to avoid any risk of withdrawal
that might be precipitated by the small amounts of naloxone that might be
absorbed from the combination product. Once induction with the mono product
is completed, the patient can be switched directly to the combination product.
Transferring from higher doses of methadone (>40mg)
This is associated with a significant risk of precipitated withdrawal and hence is difficult in
an outpatient setting. Transfer from higher doses of methadone can be safely undertaken in
inpatient settings (eg. detoxification units) where supervised clonidine and diazepam can be used
to manage withdrawal symptoms (Clark et al 2005). The critical issue in making such transfers
is to wait until the patient has signs of opioid withdrawal before administering the first dose of
buprenorphine. This may involve a delay of 72 hours after the last dose of methadone.
Buprenorphine can be commenced at low doses given frequently, i.e. 2mg bd increasing to 4mg
bd and then 8mg bd, titrating as necessary.
Due to the concerns for patient safety, transfers from doses of methadone > 40mg require a
completed patient consent form (see Appendix 13) to be attached to the application for authority
to prescribe. The patient is considered to be a transfer if it is less than 7 days since methadone
dosing ceased. If it is 7 days or more since the last methadone dose the patient is treated as a
new induction and patient consent is not required.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

3.7 Monitoring Drug Use


Concurrent use of other drugs with methadone or buprenorphine treatment may threaten
patients safety. Consequently it is important to monitor patients use of other drugs on an
ongoing basis. Monitoring drug use can also provide a basis for program evaluation. There is little
evidence to support the use of drug monitoring as a deterrent against unsanctioned drug use.
Self report, urine testing and clinical observation are currently available monitoring approaches.
Pathology laboratories do not routinely test for buprenorphine in the urine and it will not be
detected as an opioid. Hair analysis and saliva analysis can also be an option.

Self report
Self report can be a reliable guide to drug use in settings where no negative consequences result
from disclosure. However, in the clinical situation there are always contingencies which patients
may perceive as punitive. Consequently, caution should be exercised when making clinical
decisions based solely on self-reported drug use. The best information is usually obtained from a
combination of self-report and urinalysis.

Urine testing
Chapter 3

Urine drug screening may be useful in the following circumstances:


Patients in the early stages of treatment.
Where clarity of drug use is required for diagnostic purposes.
Provision of information about drug use of patients where poly substance
use is of concern.
Urinalysis is an objective measure of drug use. However, urinalysis may not be a reliable
indication of drug use if collection is not observed. Observed urines are demeaning to
both patients and staff. Reliability of unobserved urines may be increased by checking the
temperature of the urine sample.
Urinalysis will only detect recent drug use. The actual time frame varies depending on the drug
being measured and will also depend on the threshold level set by the testing laboratory. The
table at Appendix 4 can be used as a guide. False positives and false negatives do occur.
Urine testing is an expensive investigation and should be conducted only if the results are likely
to be important. Medicare allows for a maximum of 21 urinalysis tests per patient per year. It is
expected that the average number of tests will be significantly lower than this maximum and will
decrease the longer a patient has been in treatment

3.8 Coordinated Care


The relationship between the prescriber and dispenser of methadone/buprenorphine treatment
requires ongoing communication to ensure consistency in the overall treatment program. The
prescriber and dispenser and other members of the therapeutic team have a duty of care to the
patient that may necessitate sharing of information despite professional obligations to maintain
patient confidentiality.
The dispenser is legally required to assess whether a dose of methadone/buprenorphine is
appropriate and can withhold treatment if necessary. This may occur if the patient is intoxicated
of if there are concerns about dose diversion.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

At least six monthly, a comprehensive review of treatment progress should be undertaken. If the
patient has at least two health professionals involved in their care (eg. Pharmacist, counsellor
or other specialist) a Coordinated Care Plan can be developed. Contact your local Division of
General Practice for more information on Care Plans.

3.9 Adjunct Treatment


People with a background of heroin dependence often have a range of social problems (e.g.
financial, employment, parenting, legal, accommodation) and psychological difficulties (e.g.
depression, anxiety). The stability afforded by long-term substitution treatment provides an
opportunity for these issues to be addressed. It is one of the key roles of treating clinicians to
assist in this process, either as direct service providers, or as case managers referring the patient
on to other appropriate services.
There has been considerable debate over the role of counselling in maintenance substitution
programs. The evidence from methadone treatment studies suggests that counselling should be
available to all patients, and that patients should be actively encouraged to avail themselves of
counselling services. See Appendix 6 for a list of patient resources.

Chapter 3

Once opioid use is stabilised, prescribing doctors need to monitor for the presence of, or
emergence of, other concurrent problems, particularly mental health issues. Such monitoring and
documentation of response to treatment is a critical part of effective treatment.

3.10 Community Pharmacy Dispensing and Administration


Most patients participating in the Community Program for Opioid Pharmacotherapy will attend
a community pharmacy for dose dispensing. Methadone and buprenorphine must be consumed
under the direct supervision of the pharmacist except where dispensed as an authorised
takeaway dose. Buprenorphine tablets must be crushed (to coffee granule consistency) prior to
administration in order to reduce the potential for dose diversion.

Approved Methadone/Buprenorphine Dispensing Pharmacies


Pharmacies are required to submit an application, undergo required training and be approved by
the Department of Health before they are able to dispense methadone or buprenorphine. The
number of patients pharmacies can dispense to is also limited. The Clinical Advisory Service can
be contacted to provide names of the approved methadone/buprenorphine pharmacies in your
area.
When a pharmacy changes ownership and/or wishes to change the number of days open each
week, alter trading hours or no longer be involved in the program they should notify the Clinical
Advisory Service of this intention 30 days before the changes take effect.
It is also the responsibility of the pharmacy to advise patients dosing at the pharmacy and
provide 30 days notice of the changes, to allow sufficient time for the appropriate dosing
arrangements to be made
These may include
The patient finding a new pharmacy for dosing and a new prescription obtained from the
prescriber
The patient locating a new pharmacy for Sundays and public holidays(if the pharmacy is
reducing the number of trading days) and obtaining new prescriptions to reflect the
change in dosing sites. This applies when patients are not eligible for takeaways or are
currently receiving the maximum takeaways allowed.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

The patient obtains a new prescription from their prescriber to reflect the the increase
in takeaways if appropriate (dependent on patient stability and in some cases CAS
approval)

Storage
Methadone and buprenorphine must be stored in accordance with Regulations 56, 56A, 56E
and Appendix M (and other relevant sections) of the Poisons Regulations 1965. Methadone and
buprenorphine must be stored in a locked safe. If a pharmacist is on the premises then they can
be stored in a locked cupboard or drawer and the key kept in the possession of the pharmacist.
It is important that methadone and buprenorphine are securely stored immediately after dosing a
patient.

Role of the pharmacist


Pharmacists play a key role in the delivery of methadone and buprenorphine treatment. The
pharmacists role includes:

Chapter 3

Checking that the prescription satisfies the legal requirements, i.e is endorsed with a
DoH authorisation number and is valid
Ensure positive identification of the patient before administration of the dose
Checking the prescribers instructions (use of a daybook or diary is recommended)
Explaining any side effects of medication when appropriate
Assessing the patient for intoxication and contacting the prescriber if necessary
Ensure the dose is correct
Supervising the consumption of each dose
Dispensing any take away doses according to requirements
Maintaining contact with the prescriber and providing any relevant information
concerning the patients progress, including with regard to any missed doses, intoxicated
presentations etc.
Supporting the patient and encouraging a healthy lifestyle
Ensuring that patient information is kept confidential
Ensuring all pharmacy staff (including locum pharmacists) are appropriately trained and
informed of the CPOP requirements
Ensure that methadone and buprenorphine are stored in compliance with the Poisons
Regulations and that records are maintained as required (See Appendix 14 for recording
requirements).

Commencing new patients


Pharmacies are under no obligation to accept any patient for dispensing. It is recommended
that the pharmacist interview the proposed patient before agreeing to act as their dispenser. If
the pharmacist agrees to accept the patient it is recommended that the patient sign a contract
that outlines the conditions under which dispensing is to occur. See Appendix 13 for a template
contract for use by CPOP pharmacies. The patient should be given a copy of the contract for
their information.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Prescription for methadone and buprenorphine


The prescriber must contact the proposed pharmacy to confirm that the patient may attend
for dispensing. The prescription for methadone or buprenorphine must satisfy the usual legal
requirements for a Schedule 8 drug.
A prescription which includes:
the patients full name, address and date of birth
date of prescription
the patients DOH authorisation number
the drug to be administered*
the date of administration of first dose*
the finish date*
the daily dose expressed in milligrams, written in both numbers and words*
any variations to daily dosing to be written in milligrams and words*
number of takeaway doses*

Chapter 3

the pharmacy/dispensing point at which the script is valid*


the signature of the prescriber*
the name and address of the prescriber.
* To be in the authorised prescribers own handwriting.

Patient identification
a recent photo of the patient endorsed by the prescribing doctor; or
a Next Step identity form.
This information must arrive at the pharmacy prior to the patient receiving the first dose of
methadone/buprenorphine. A prescriber may authorise the patient to deliver the original
prescription/documentation to a pharmacy. In this case faxed copies must also be sent to the
pharmacy.
Supply of methadone or buprenorphine can only be in accordance with the instructions on the
prescription. Amounts in excess of the total quantity ordered on the prescription, for a longer
period than that specified or after the expiry date must not be made. Missed doses cannot be
administered at a later date.
Takeaway doses must only be supplied in accordance with a prescription or instructions in writing
from the authorised prescriber.
Lost or stolen takeaway doses (see section 4) or vomited doses (see section 5.4) should not be
replaced without a written authorisation from the prescriber.

Other prescriptions
There is an increasing incidence of benzodiazepine abuse and dependence often
associated with opioid abuse.
A combination of opioid (that is, methadone and buprenorphine) and sedative drugs may
be potentially hazardous and requires close cooperation between the prescriber and the
dispenser.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

If the patient presents a prescription from another prescriber for a drug that may be
abused, the prescriber should be advised that the patient is receiving pharmacotherapy
treatment.
Pharmacists must use their professional discretion in deciding if they should dispense any
prescription.
Pharmacists retain the right to refuse to dispense a legal prescription if an opinion is formed that
such a supply could compromise the well-being and overall health of the patient.

Pharmacotherapy administration
The duty pharmacist is to be satisfied that the administration of each dose is to the correct
person. If photographic identity cannot be established then administration should not occur.
Check that the prescription is valid. Check that the patient has not missed any doses prior to this
presentation (refer to Chapter 4 for instructions on management of missed doses).

Chapter 3

Assess the patient for intoxication (see Appendix 7 for indicators of intoxication). If the patient
appears intoxicated the prescriber should be contacted before administration occurs.
Administer the dose in a discreet manner to protect the confidentiality of the patient. Do not
allow paperwork to be viewed by persons not entitled to have access. The use of drop folders is
recommended.
Do not permit patients to enter the dispensary, to be aware of the number of patients attending
the pharmacy, the delivery arrangements for stock or of security arrangements.

REFER TO THE PRESCRIBER WHEN


The patient presents to the nominated pharmacy for a dose and appears intoxicated.
The patient has missed doses as per the policy set out in chapter 4.
The patients prescription has expired.

Methadone administration
Conical measures are not accurate for measuring methadone. The use of syringes or suitably sized
cylindrical measures is recommended.
Supervise the consumption of the dose and follow-up with a drink of water or cordial. Cordial
assists in masking the bitter taste of methadone. Engage in a short conversation with the patient
after the administration to ensure that the complete dose has been swallowed by the patient.
Patients are not permitted to provide their own drink container. This is to prevent the dose being
spat back into the container and then being diverted or abused.
Rinse empty methadone bottles with water and deface the label before discarding.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Buprenorphine administration
When buprenorphine is to be administered some water or liquid should be given before hand to
pre-moisten the mouth to aid dissolution of the dose. The patient must not be allowed to handle
the tablets.
The dose should be crumbled in a commercial crusher to the consistency of large coffee
granules (if it is crushed to a powder it is harder to get under the tongue and keep it there long
enough for proper absorption) and handed to the patient in a clean container to place under the
tongue.
Correct dosing technique is important to ensure the patient receives the full benefit of their
dose. Patients should be advised to keep the dose under their tongue until fully dissolved and not
to talk.
The patient should be supervised for at least two minutes or until the dose completely dissolves.
Patients are not permitted to provide their own drink container. This is to prevent the dose being
spat back into the container and then being diverted or abused.

Chapter 3

Minimum time between doses.


In instances where extended trading hours permit a patient to attend late at night for dosing
on one day and then attend early the following morning for that days dose pharmacists should
ensure that there is a gap of at least 8, and preferably 12 hours, between pharmacotherapy
doses.

Changes to dosing location


The prescriber must notify the Clinical Advisory Service of a change in dosing location prior to
the change occurring. Assistance with locating an alternative dispensing location can be provided
by the Clinical Advisory Service.

CANCELLINGOLDPRESCRIPTIONS
Where there is a possibility of a current prescription existing at a pharmacy, other than
the pharmacy nominated on the new script, it is essential that the prescriber contact
the pharmacy to cancel the earlier prescription.This avoids the possibility of the
patient dosing at two sites concurrently.

Changes to dose
When changing the dose of methadone/buprenorphine a prescription must reach the pharmacist
prior to the change in dose being affected.

Dual dispensing locations


In some circumstances where a patient, for work or family reasons, needs to regularly spend
time away from home, then the prescribing doctor may, in consultation with the Clinical Advisory
Service, arrange for the methadone/buprenorphine to be dispensed from dual dispensing locations.
In such cases, the prescribing doctor must ensure that each dispensing location is provided with
prescriptions that clearly specify on what days the patient is to attend each location.

Dispensing fees
Community pharmacies commonly charge patients a fee to cover the professional costs of
dispensing methadone and buprenorphine. Pharmacies are free to set fees at appropriate levels,
and the Pharmacy Guild of Australia (Western Australian Branch) provides advice on this matter.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

3.11 Transfer of treatment provider


Patients may need a temporary or permanent transfer to another prescriber or dispensing
location for work, holiday or social reasons. the Community Clinical Program (ccp) team at Next
Step (see appendix 5 for contact numbers) should be contacted for assistance in coordinating the
transfer. To avoid the risk of double-dosing good communication between the new and existing
treatment providers is essential.
Where there is a risk of a current prescription existing at the old pharmacy it is essential that the
prescriber contact the pharmacy to cancel the earlier prescription. This avoids the possibility of
the patient dosing at two sites concurrently.

Transfers within Western Australia


Transferring to a new dispensing site
When a patient is transferring to a different dispensing site, the prescribing doctor must:

Chapter 3

Provide a current endorsed photograph of the patient attached to the patient ID form
and a prescription to the patient to give to the new dispensing pharmacy
Fax the completed Pharmacy Transfer Notification form to the current pharmacy, new
pharmacy and CAS as a matter of priority.
The pharmacy must receive the information prior to the patient being transferred.

The Clinical Advisory Service must be advised of transfers and can


provide assistance to arrange or locate a new dispensing pharmacy.
Transferring to a new prescriber
Patients requesting prescriber transfers
Patients can request to be transferred to a new prescriber. This can be arranged through the CCP
team (see Appendix 5). The new prescriber must apply for a new authorisation number.
Prescribers requesting patient transfers
Patients with complex clinical, behavioural and other problems should be discussed with the
Clinical Advisory Service. Transfer of the patient to a Drug & Alcohol Clinic (DAC) or another
prescriber can be arranged if appropriate.
Interstate transfers
The transfer of patients from one state to another must be arranged in accordance with the
policies and procedures of each jurisdictional authority.
The Community Clinical Program (CCP) coordinates interstate transfers. The patient should be
advised to contact the CCP to make arrangements for a new prescriber and dispensing location.
The prescriber should provide the patient with:
a referral letter giving any relevant clinical details
photo ID of the patient.
Up to four weeks notice is advised to enable the necessary arrangements to be made with
interstate authorities and to find and notify an appropriately located prescriber and pharmacist.

Scripts for S8 medication written in WA are not valid in other jurisdictions.


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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

International Travel
Prescribing doctors should contact the Clinical Advisory Service for inquiries regarding
international travel, as arrangements vary depending on the country to be visited. Some prohibit
the import of methadone and/or buprenorphine and do not have methadone/buprenorphine
maintenance programs.
NB: Always express methadone doses in milligrams as concentrations per millilitre vary in other
countries.

3.12 Cessation of methadone/buprenorphine maintenance treatment


Voluntary withdrawal
Factors that motivate patients to consider detoxification include family, work and lifestyle
issues, personal rewards from being opioid free and perceptions and attitudes directed towards
methadone/buprenorphine treatment.
Evidence from methadone research suggests that long-term outcomes of treatment are
enhanced by:

Chapter 3

Longer treatment episodes. Evidence from methadone research suggests that long-term
outcomes are enhanced by treatment episodes of more than 12 months.
A more stable and supportive lifestyle. The longer treatment episode allows the opportunity
for the patient to establish a lifestyle away from heroin and other drug use prior to withdrawing
from methadone treatment. Premature withdrawal from pharmacotherapy (before the patient
has achieved a degree of stability in social circumstances and drug use) is more likely to be
associated with a relapse into dependent heroin use.
The likelihood of premature withdrawal from maintenance treatment is reduced if patients are
well-informed about how treatment works. A patient may wish to withdraw from maintenance
treatment for a range of reasons, (i.e. the need for interstate travel, concerns about side-effects
or about remaining in treatment too long). The clinician should discuss issues regarding the
duration of treatment and withdrawal early in the treatment program and provide information
regarding the process of withdrawal. Patient literature is now available regarding withdrawal
from methadone/buprenorphine treatment. Despite withdrawal from buprenorphine being
frequently described as milder than from other opioids, patients should be informed of the likely
duration of withdrawal symptoms.

Management of withdrawal from maintenance treatment


Before commencing a reduction in pharmacotherapy dose, the prescriber should assess the
patient and determine their motivation, psychosocial stability, current alcohol and other drug
use, expectations, source of support, concerns and after care plans. A treatment plan for
withdrawal should be developed, including the frequency of dose reduction, and preparation
for withdrawal (e.g. removing paraphernalia, informing significant others, avoiding stressors
etc). Information should also be provided to the patient about the nature and severity of the
withdrawal symptoms from their medication.
Contraindications to dose reduction and withdrawal include:
Irregular attendance at the dispensing site for dose pick-up;
Non attendance at review appointments

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Significant current psychological problems or social instability or distress (e.g. acute


mental health problem, bereavement, homelessness)
Significant current opiate or other substance use (as indicated by self report or drug
testing)
When abstinence is an immediate goal, withdrawal from maintenance can generally be achieved
in periods of two to eight weeks, depending on starting dose and the rate of dose reduction.
Most dose reductions can take place safely and effectively within the community.
Dose reduction regimes can be planned to address variables such as starting dose, duration
of time on maintenance, the timeframe and circumstances of the patient with an overall aim
of minimising discomfort and maximising the chance of the patient achieving their aims. The
patient should be assured that the rate of reduction can be changed if the patient experiences
difficulties, e.g. intolerable withdrawal, stressors, or resumption of regular opiate use.

Chapter 3

Dose reductions should be made in consultation with the patient. Patients should be aware of
their dose, except where an agreement has been reached between patient and service provider
to the administration of a blind dose. Continued reduction in the face of distress is usually
counterproductive. It may be appropriate to maintain a patient at a reduced dose for a prolonged
period until the patient feels comfortable recommencing the reduction regime.
During this phase the aim of treatment is to ensure that the withdrawal process is completed
with safety and comfort. Increased supportive counselling, as well as information and education,
should be available for patients withdrawing from methadone/buprenorphine. There may be a
role for other medication for symptomatic relief (clonidine). Caution should be applied regarding
the use of potential drugs of abuse (e.g. benzodiazepines).

Withdrawal regime for methadone


When a regime of reducing doses of methadone is used typically signs and symptoms of opioid
withdrawal will begin to increase as the methadone dose falls below 20mg/day, with peak
symptoms occurring two to three days after cessation of methadone. Subsidence of the symptoms
is slow with studies reporting withdrawal scores not falling below baseline until 10 to 20 days
after the cessation of methadone, depending on the duration of the methadone taper.
Clonidine offers no benefit as an adjunct to a regime of reducing doses of methadone,
primarily because of a high incidence of hypotensive side effects when clonidine is used in this
way. However, clonidine can be given after cessation of methadone.

Voluntary Withdrawal Schedule


Recommend reducing dose by 5mg/week to a level of 45mg/day, then 2.5mg/week.
Rates of reduction should be negotiated with patients, and dose changes should occur
no more frequently than once a week.
Abrupt cessation of methadone can be considered from 20 - 40mg/day in conjunction
with clonidine and symptomatic medications to manage withdrawal signs and symptoms.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

The use of buprenorphine to assist withdrawal from methadone


maintenance programs
Many patients on long-term methadone maintenance programs experience considerable
difficulties in conventional approaches to withdrawing from methadone, including a prolonged
period of withdrawal discomfort with risk of relapse to heroin use. Consequently, there is
considerable interest in finding alternative methods of withdrawing from methadone maintenance
programs.
Two approaches have been recently proposed:
1. the use of opioid antagonists (rapid opioid withdrawal techniques), and
2. transfer to buprenorphine when the dose of methadone is less than 30 mg.
The latter approach entails a reduction in the dose of methadone, transfer to buprenorphine, and
subsequent withdrawal from buprenorphine.

Withdrawal regime for buprenorphine

Chapter 3

Graduated reduction over weeks results in better outcomes (less relapse to heroin use) than rapid
reductions. The following rates of dose-reduction are proposed, although reductions can occur
more rapidly or more slowly:

RATES OF DOSE REDUCTION


Dose of buprenorphine

Reduction rate

Above 16 mg

4 mg per week or fortnight

8 - 16 mg

2 - 4 mg per week or fortnight

Below 8 mg

< 2 mg per week or fortnight

An increase in heroin or other drug use, or a worsening of the patients physical, psychological or
social well-being, may warrant a temporary cessation or slowing-down of the reduction rate.
Some patients will request dose reductions of less than 2mg. Reductions of 0.4mg or 0.8mg may
then be appropriate, especially for those coming off longer term treatment.
As 0.4mg tablets are not available in Suboxone, patients wanting to reduce in increments of
less than 2mg will be required to transfer to Subutex. Patients must be on a dose of 6mg or
less in order to qualify for Subutex for this purpose. Prescribers must complete an Application
for authority to prescribe and receive a new Department of Health authority number before
prescribing Subutex. A special 6 month limited authority will be granted in these situations,
prescribers should ensure that the patients withdrawal plan is managed within the 6 month time
frame.

Involuntary withdrawal
It is sometimes necessary to discharge a patient from treatment for the safety or well being of
the patient, other patients or staff. This may be the result of
violence or threat of violence against staff or other patients
diversion of methadone/buprenorphine
illegal activities such as, theft, property damage or drug dealing in or near the service

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

poor compliance with treatment


continued high risk poly drug use.
Interruption to treatment may also occur as the result of a change in the patients situation such
that they are no longer able to access a dispensing site.
Patients being discharged must be warned about the risks of illicit drug use and informed of other
treatment options

Chapter 3

Circumstances

Methadone

Buprenorphine

Serious threat to safety of


other patients or staff

Abrupt cessation of
methadone or rapid dose
reduction

Can be abruptly terminated


without a graduated dose
reduction

Less serious breaches or other


reasons

Withdraw according to the


above voluntary withdrawal
schedule with reductions
every 5 7 days

Faster reduction schedule


of up to 4 - 8 mg reductions
every 3 - 4 days).

Cases where the prescriber is considering an involuntary withdrawal


of treatment should be discussed with the Clinical Advisory Service.
Risk of relapse
A longer duration and greater intensity of pre treatment opioid use is associated with an
increased probability of relapse to opioid use after leaving treatment.
The likelihood of a patient maintaining abstinence after leaving treatment is increased in people
who have established drug-free social supports, are in stable family situations, employed, and
with good psychological strengths.
There is evidence from randomised controlled trials that structured after care (compared with
assistance on request) reduces the risk of relapse, self reported crime and helps unemployed
patients find work.

Supportive care should be offered for at least 6 months following


cessation of pharmacotherapy.
For recently discharged patients an automatic fast track for readmission
to pharmacotherapy treatment should be available if needed.
Transfer to naltrexone from buprenorphine maintenance treatment
To minimise the risk of withdrawal symptoms, naltrexone should be delayed for 5-7 days after
the last buprenorphine dose. Doses of naltrexone taken earlier than this are likely to induce
some withdrawal symptoms depending on the buprenorphine doses in the last few weeks and
the timing of the first naltrexone dose (Eissenberg et al 1996; Kosten et al 1991; Rosen &
Kosten 1995; Umbricht et al 1999). Naltrexone (12.5mg) taken within one to three days of the
last buprenorphine dose (2mg or more) may induce a severe withdrawal syndrome (Clark et al
2005a). If transfer to naltrexone is required in less than five days advice should be sought from a
specialist service.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

The following procedures are recommended.


Where the maintenance dose of buprenorphine is less than 6mg for at least a week, the
first dose of naltrexone can be commenced within 24 hours of cessation of
buprenorphine in an inpatient setting capable of managing severe withdrawal symptoms
including dehydration and delirium. Outside of this setting, or if the maintenance dose is
greater than 6mg, the use of naltrexone is not recommended within seven days as it
may induce severe withdrawal features.
The initial dose of naltrexone (12.5 mg orally) should be administered in the morning.
The patient should be monitored for up to 3 hours after the first dose of naltrexone for
features of opioid withdrawal.
Symptomatic withdrawal medication should be available for the patient to use in the 12
hours after the first dose of naltrexone, including clonidine (0.1-0.15mg, 3-4 hourly),
benzodiazepines (e.g. diazepam up to 5-10 mg every 3-4 hours as needed),
metoclopramide, hyoscine butylbromide and NSAIDS.

Chapter 3

Subsequent doses of naltrexone at 25mg for a further 2-3 days and then 50mg per day is
usually recommended. Clinical guidelines regarding the use of naltrexone should be
consulted (Bell et al. 2003).
Given the potential for patients to use heroin or other opioids following the cessation of
buprenorphine and prior to the commencement of naltrexone, some objective test should be
conducted prior to commencing naltrexone in order to exclude recent opioid use. The naloxone
challenge test or appropriate urine drug screening are recommended. However, a naloxone
challenge test is difficult to interpret if conducted within three days of buprenorphine use.

Transfer to Naltrexone from Methadone


Administration of naltrexone to a patient who is physically dependent on opioids will precipitate
a severe withdrawal syndrome. Methadone maintenance patients being transferred to naltrexone
should undergo methadone detoxification (see managing methadone withdrawal) followed by a 14
day drug free period to allow stored methadone to be eliminated from the body. Seek specialist
advice from the Clinical Advisory Service if it is not possible to follow this regime.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

4.0 Takeaway and Missed Doses


4.1 Takeaway doses
Supervised dispensing is an essential component of methadone/buprenorphine treatment.
In general, doses should be consumed under direct supervision at a pharmacy. There are
circumstances where the prescribing doctor may appropriately authorise either a one off or
regular takeaway doses.
There are, however, significant risks associated with providing takeaway doses. These include:
accidental overdose or death of the patient or of a third person
dose diversion and involvement in drug trafficking
self administration by injection resulting in toxicity, bacterial infection or spread of
blood borne viruses.

Where there is concern about possible misuse of takeaway


doses these should not be provided.
The provision of takeaway doses can have a number of potential benefits including:
reduced inconvenience of regular attendance at a pharmacy and reduced costs for the
patient thereby enhancing retention.
rewarding the achievement of treatment goals
encouraging patients to take responsibility for their own treatment
reinforcing a trusting relationship between the prescriber and the patient

Chapter 4

enhancement of integration into the community, through reduction of time and


associated travel costs for the patient.
Studies have indicated that programs which have takeaway policies have better retention rates
than programs which restrict takeaway doses.
Takeaway doses can be prescribed when:
the patient is assessed as stable and there are no contraindications to takeaway doses
the reasons for the patients request for takeaway doses have been carefully assessed
and documented and the benefits of an exception to supervised dose administration
established and recorded
the patients progress in treatment and past performance with takeaway doses has been
reviewed and is considered favourable
the prescribing doctor has documented reassurances given by the patient to concerns
raised about the proper care and consumption of takeaway doses.
The long duration of action of buprenorphine means that some patients only need to be dosed
every second or third day. These longer interval dosing options should be used as an alternative
to providing one off takeaway doses and make regular takeaway doses only necessary for
buprenorphine patients who cannot tolerate second daily dosing schedules.

From 1 May 2006 takeaway doses of Subutex will no longer be allowed


other than in very exceptional circumstances.
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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Indications of stability include the following:


Evidence that the patient is not engaging in continuing hazardous use of opioids;
benzodiazepines, alcohol or psychostimulants. Evidence of hazardous use should be
based on history, self report, examination of injection sites, observation for signs of
intoxication, and feedback from others involved in the patients care.
Regular and reliable contact with prescriber and community pharmacy
Suitable accommodation (stable, adequate storage facilities)
Functional social behaviour (e.g. no violence or threats to staff or other patients, stable
employment/education)
Prior history of responsible use of takeaway doses, where the patient has previously
been given them
The assessment of contraindications should be recorded.

Contraindications include the following:


Diversion or attempted diversion in the last 6 months
Recent injection of illicit drugs
Unstable or acute psychiatric illness
Irregular contact with prescriber, pharmacist or other relevant worker
Current hazardous use of alcohol, benzodiazepines or other drugs
Child protection concerns
Homelessness

Chapter 4

Patients who are found to have diverted their takeaway dose should not be given any further
takeaway doses and the Clinical Advisory Service should be notified of this event.
(see section 5.9)

Authorisation of takeaway doses of methadone/buprenorphine (Suboxone)


Prescribers may authorise takeaway doses of methadone/buprenorphine (Suboxone) in accordance
with the schedule of frequency outlined on the next page, when:
The prescribing doctor is satisfied that the patient is stable.
The patient has signed a completed Takeaway Application form. The completed form
should be filed with the patients records.

It is advisable to ask the patient to sign the agreement at the bottom of


the form since it ensures that the patient is aware of the dangers of
misuse of takeaway doses and serves as a useful medicolegal record should
such misuse result in mortality
Authorisation of takeaway doses of methadone/buprenorphine outside of
the schedules or for takeaway doses of Subutex
Where the prescriber decides that exceptional circumstances exist that warrant the prescribing
of additional takeaway doses outside of this schedule, or for takeaway doses of Subutex, the
completed Takeaway Dose Application Form must be sent to the Clinical Advisory Service, with
evidence to support the exceptional circumstances.

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and buprenorphine in the treatment of opioid dependence

The prescription must not be written until approval has been obtained from CAS.
Frequency of takeaway doses
It is important that takeaway doses do not place the patient or others at risk of harm.
Consequently the frequency of takeaway doses is restricted to the schedules set out below. It
is important the patients are seen by a dispenser (pharmacist or nurse) at least once per week.
To ensure this the frequency of takeaway doses is different for patients on less than daily dosing
with buprenorphine.
Patients transferring between prescribers (including interstate transfers to WA), where there is
no break in treatment, can continue to be prescribed takeaway doses if stability criteria with
the previous prescriber is confirmed and the new prescriber is satisfied that the patient remains
stable.
Time on methadone or buprenorphine treatment in prison does not count towards the length of
time in treatment for the purposes of calculating eligibility for takeaway doses.
The takeaway week should be defined (e.g. Monday to Sunday) to avoid any confusion.

Schedule for takeaway doses


First 6 months* of treatment
Except in exceptional circumstances no takeaway doses of methadone or buprenorphine should
be prescribed until the patient has been in continuous treatment for 6 months. Wherever possible
the patients should be placed with a seven day pharmacy to enable daily dosing. Alternatively
a second dispensing point may be used on the seventh day if the patient attends a six day
pharmacy.

Chapter 4

Where the prescriber decides that exceptional circumstances exist and supervised daily
dispensing arrangements cannot be made, an Application for Authorisation to Prescribe
Takeaway Doses form must be sent to the Clinical Advisory Service. The prescription must not be
written until approval has been obtained from CAS.

Methadone
Length of time in
treatment*

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60

Number of takeaway doses permitted

6 - 12 months

After six months of continuous treatment and where the patient is


assessed as stable and is working towards achieving treatment goals,
they may be eligible for one takeaway dose of methadone per week.

12 - 24 months

After 12 months of continuous treatment and where the patient has


demonstrated stability with one takeaway dose per week they may be
eligible for two non-consecutive takeaway doses per week.

More than 24 months

After 2 years of continuous treatment and where the patient has


demonstrated stability with two takeaway doses per week they may
be eligible for 3 takeaway doses of methadone per week. Only two of
these may be consecutive.

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Buprenorphine (Suboxone)
Buprenorphine has a long half life (24 36H) and many patients can be dosed every second or
third day thus minimizing the need for takeaway doses. The long half life of buprenorphine can
also mean that takeaway doses are more easily diverted as missing part or all of a days dose
does not result in severe opiate withdrawal. For this reason no more than one takeaway dose per
week is permitted for patients prescribed buprenorphine until they have been on the program for
24 months
Length of time
In treatment*

Daily Dosing

Dosing every
second day

Dosing every
third day

Nil

Nil

Nil

6 - 24 months

1 per week

1 per week

1 per week

More than 24 months

2 per week

2 per week

1 per week

Less than 6 months

*NB: Duration refers to continuous period of dosing with either methadone or buprenorphine.
It does not refer to continuity with the same service provider.

Size of the takeaway doses


The takeaway dose must not exceed the normal supervised daily dose.

Dispensing of takeaway doses

Chapter 4

Takeaway doses can only be dispensed in accordance with instructions on a prescription. If a


prescriber authorises a takeaway dose verbally, the prescriber should dispatch confirmation of
verbal instructions within 24 hours.
Pharmacists should advise patients to store their takeaway doses in a secure place (not in the
refrigerator) out of the reach of children.
The takeaway dose(s) must be given to the patient on the day before the scheduled day(s) of
absence from the usual dispensing location.
Patients are responsible for the care and proper consumption of each takeaway dose once they
have taken possession of it.

Labelling and containers for takeaway doses


Takeaway doses must be dispensed in accordance with the following instructions:
Methadone
Takeaway doses of methadone are to be made up to 100ml with water
Individually dispense each days takeaway dose in an opaque plastic container with a child
resistant cap, ensuring that the label contains the following information:

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Keep Out of Reach of Children


Methadone Hydrochloride
This bottle contains _____ mg of methadone hydrochloride diluted to 100ml with water.
Take the contents of this bottle as a single dose on (date to be consumed) (name of patient)
(Rx No 00000)

(Date of dispensing)

Pharmacy name and address


Attach an Appendix K label.
Buprenorphine
Takeaway doses of buprenorphine must be dispensed without being crushed in their original
blister pack. Each days dose (may include more than one strength) should be retained in its
original packaging and individually dispensed in a box or bottle labelled to include the following:
Keep Out of Reach of Children
Buprenorphine Sublingual tablets
This container contains _____ mg of buprenorphine hydrochloride.
Take the contents of this container as a single dose dissolved under the tongue
on (date to be consumed) (name of patient)
(Rx No 00000)

(Date of dispensing)

Chapter 4

Pharmacy name and address

Alternatively, if the tablets are removed from the original blister packaging then they must be
packed in a container with a child resistant closure.
Attach an Appendix K label.

In the event that a patient reports that takeaway doses have been lost,
stolen or damaged, they should not be replaced*.
* Consideration should be given to the particular clinical situation of the patient in this situation
Prescribing regular takeaway doses
Where takeaway doses are prescribed on a regular or ongoing basis the prescriber should be
satisfied at each review that the patient continues to meet the stability criteria. Should the
patients situation become unstable or if contraindications are present the prescriber should
withdraw or reduce the number of takeaway doses prescribed.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

4.2 Missed doses and reintroduction


When patients miss pharmacotherapy doses they go into opioid withdrawal and their tolerance
to opioids may be reduced. Patients may use other opioid drugs or other central nervous system
depressants such as alcohol or benzodiazepines. This places them at increased risk of overdose
if the pharmacotherapy is reintroduced. Missing doses also compromises the rehabilitation gains
made. To reduce these risks the following procedures are recommended:
Before recommencing dosing the prescriber should take into consideration:
the reasons for failure to attend
drug use during this period
symptoms of opioid withdrawal; and
physical examination for evidence of withdrawal or intoxication.
Due to the different safety profiles of methadone and buprenorphine different procedures apply
for resumption after missed doses.
In general the following schedules can be presumed to be safe and effective:

Recommencing methadone after missed doses


Doses missed
One

Response
If no evidence of intoxication dose as usual

Three
Four

Pharmacists must consult with prescriber or CAS prior to dosing.


Approval to commence treatment can be given over the phone.
<40 mg reduce dose by 5 10 mg
>40mg reduce dose by half

Five or more

Patient must be seen by the prescriber for reinduction

Chapter 4

Two

Review the patient the following day and adjust the dose accordingly.

Recommencing buprenorphine after missed doses


Days missed*
1-4

Response
If no evidence of intoxication dose as usual

5-6

Consult prescriber (or CAS if prescriber is unavailable)

7 or more

Patient must see the prescriber for reinduction

* refers to days equivalent if client is not dosing on a daily basis e.g. a client dosing second daily
only misses 2 doses to achieve 4 missed days

Missed doses are not a medical emergency


Missed doses are not a medical emergency and it is generally not appropriate to prescribe
methadone or buprenorphine in the emergency department.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Attendance on non dosing days (buprenorphine)


Sometimes a patient prescribed buprenorphine who is on an alternate-day or four-times-a-week
regime misses a dosing day, attending the pharmacy on the following (non-dosing) day. When
this happens, a lower dose of buprenorphine can be prescribed and dispensed in order to
tide the patient over until the next scheduled dose.
The following procedures should be followed:

Chapter 4

The pharmacist should contact the prescriber. The buprenorphine dose prescribed should
be sufficient to last until the next scheduled dose (if this is 24 hours, then prescribe a
24-hour dose; if 48 hours - a 48-hr dose).
In circumstances where the pharmacist cannot contact the prescribing doctor, no
buprenorphine can be dispensed (as there is no valid prescription). However, this
increases the risk that the patient will drop out of treatment. To prevent this
happening, the prescriber can issue a prescription of buprenorphine to be administered
by the pharmacist as a one-off dose, for use if the patient on a three- or four-times-aweek regime misses the scheduled dosing day and presents on a non-scheduled day. This
prescription must not be greater than the usual 24-hour dose. The prescriber may
wish to limit the maximum level of such an emergency dose to a lower than usual dose
in order to discourage such occurrences.
Patients who repeatedly miss doses under these circumstances should be reviewed by
their prescribing doctor to find out why and whether these issues can be addressed.
Alternatively, consideration might be given to a more feasible dosing regime.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

5.0 Common Management Issues


5.1 Side effects/Adverse drug reactions
Adverse drug reactions may be predictable (on the basis of the drugs known actions) or
unpredictable (eg allergic drug responses, idiosyncratic drug reactions). Management of the
side-effects, which will depend on their nature and severity, should be negotiated between
patient and clinician. Conventional strategies should be adopted to manage opioid-related side
effects (eg constipation). The following table details the common side effects with methadone/
buprenorphine and strategies to manage these effects.

TABLE 6: COMMON SIDE EFFECTS WITH METHADONE/BUPRENORPHINE


Common causes
Dose too high
Other drug use (legal or illegal)

Things that you can do


Lower the maintenance dose and
review other medications the patient
is taking.
Review use of sedative and other
drugs affecting cognition.

Withdrawal
symptoms
maximal before
next dose

Dose too low


Changes in legal/illegal drugs that patient is
using.

Raise maintenance dose or review


other drugs patient is taking.

Withdrawal
precipitated by
buprenorphine
dose

Occurs early in treatment (or after absence


from treatment) when buprenorphine dose
administered soon after opioid use (eg heroin,
methadone, morphine)

Aim to prevent by patient education.


Delay buprenorphine dose until
patient experiencing opioid
withdrawal.

Headache

Common in first week of buprenorphine


treatment.
Other causes of headache

Side effect is transient and


generally mild. Consider aspirin or
paracetamol. Exclude other causes.

Nausea

Common early in treatment, particularly if the


dose is too high.
Usually mild and transient.

Side-effect usually transient (days).


Avoid rapid dose increases. Consider
dose-reduction if persistent.

Constipation

All opioids do this. Will be made worse by lack


of dietary fibre, fluid intake or exercise

Encourage fibre intake (fruit,


cereals), fluids, and regular exercise.

Weight gain,
particularly for
women

Fluid retention caused by opioids - more likely


on high doses
Eating more while in treatment; high salt intake

Lower dose

Poor sleep

Dose too low and causing withdrawal at night;


Dose too late at night, causing stimulation at
time of peak effects
Other drugs (particularly stimulants in the
evening, e.g. coffee, nicotine, amphetamines)
General anxiety or irregular sleep pattern

Review maintenance dose and review


other medications

Amenorrhoea or
oligomenorrhoea

All opioids can do this


May be related to lifestyle stressors, poor diet,
and general poor health

Periods may return after cessation of


heroin use, or following withdrawal
from opioids.
Address other causes.

Lowered sex
drive

More common with a high dose


Can be many other psychological factors (such
as anxiety, poor relationship with partner etc...)

Review dose. Check LH, FSH,


prolactin and testosterone levels.

Dental problems

All opioids reduce saliva flow


Poor diet, dental hygiene

Encourage dental hygiene and use of


sugar free gum. Reduce sugary drinks
and sweet food.

Lowered bone
density

Some evidence of lowered bone density in


patients on long term opioids
Often multiple risk factors present

Test bone density and treat as


required.
Address other causes.

Reduce fat and salt in diet, exercise.

Chapter 5

Side effect
Feeling drowsy
after taking dose

Follow sleep hygiene


recommendations.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Many patients report less sedation on buprenorphine than on methadone. Research evidence
suggests that buprenorphine has minimal effect on psychomotor performance (Lenne et al 2003;
Mintzer et al 2004), and less effect than methadone (Soyka et al 2005) or slow release oral
morphine (Giacomuzzi et al 2005). Any effect is likely to be greatest during the early stages
of treatment or following dose increases. At such times patients should be advised to exercise
caution in driving or operating machinery.
Buprenorphine appears to have minimal impact on hepatic function, although there have been
some reports of acute hepatitis following very high doses (>32mg iv).

Precipitated withdrawal with buprenorphine


Under certain circumstances, buprenorphine may precipitate opioid withdrawal symptoms
one to four hours after the first dose. It has a higher affinity and lower intrinsic activity than
full agonists such as methadone, morphine or heroin. Consequently, buprenorphine displaces
agonists from opioid receptors and, in the short term, may not produce sufficient agonist effects
to compensate for the displaced methadone or heroin, producing opioid withdrawal as the
buprenorphine reaches its peak effects (approx. one to four hours after initial administration).
The phenomenon of precipitated withdrawal has particular clinical relevance during the induction
of heroin users and methadone patients. It can largely be avoided by using appropriate dose
induction procedures (see Section 3.6).

5.2 Overdose
Table 7: Signs and Symptoms of Opioid Overdose
Pinpoint pupils
Nausea
Dizziness
Feeling intoxicated
Sedation/nodding off
Unsteady gait, slurred speech
Snoring
Hypotension

Chapter 5

Slow pulse (bradycardia)


Shallow breathing (hypoventilation)
Frothing at the mouth (Pulmonary Oedema)
Coma
NOTE: Symptoms may last for 24 hours or more. Death generally occurs from respiratory
depression

Methadone
In Australia, more than 90% of deaths during stabilisation on methadone involved concurrent use
of other drugs, in particular, alcohol, benzodiazepines and antidepressants. Patients should be
warned of the risks associated with using other drugs when taking methadone. (See also Sections
5.3 and 5.6).

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Death following methadone induction often occurs at home during sleep, many hours after peak
blood methadone concentrations have occurred. Typically overdose occurs around the third or
fourth day of methadone induction.
Given that many deaths occur during sleep, administration of methadone in the morning will
ensure peak methadone concentrations occur when patients are normally awake and other people
may be around if overdose should occur. Family members should be warned that deep snoring
during induction to treatment could be a sign of dangerous respiratory depression and should be
reported to the prescriber. Heavy snoring during maintenance treatment may be associated with
sleep apnoea and should also be reported.
Additional caution should be exercised with patients who:
Have concomitant medical conditions especially those that impact on respiratory drive
Have unstable mental health problems
Are on other sedative medications such as benzodiazepines and psychiatric medications.
Naloxone, which promptly reverses opioid induced coma, should be given as a prolonged infusion
when treating methadone overdose. A single dose of naloxone will wear off within one hour
leaving patients at risk of relapse into coma due to the long lasting effects of methadone.
Patients who are thought to have taken a methadone overdose require prolonged observation.

Buprenorphine
The risk of lethal overdose on buprenorphine in an opioid-tolerant individual is less than that
associated with the use of other opioid medications, such as methadone. This is due to the
ceiling dose response effects of buprenorphine. The poor bioavailability of buprenorphine when
taken orally reduces the risk of accidental overdose by children.
An opioid-nave individual may overdose with a high dose of buprenorphine. All patients should
be commenced on low doses (2 - 8mg), and even lower doses (2 or 4 mg) should be considered
where there is some doubt regarding the degree of neuroadaptation prior to commencing
treatment. Even low doses of buprenorphine can cause sedation in opioid naive individuals if
taken in combination with other sedative drugs.
While overdose on buprenorphine is relatively uncommon, there is a greater risk when it is
combined with other sedative drugs, such as alcohol, benzodiazepines, barbiturates, tricyclic
antidepressants and major tranquillisers. Several such deaths have been reported.

Chapter 5

Buprenorphine has a high affinity for mu opioid receptors, and is not easily displaced by
the antagonist, naloxone. Doses of 10 - 30 times the normal naloxone doses used to reverse
heroin overdose (up to 10 - 35 mg/70 kg) may be required to partially reverse the effects of
buprenorphine toxicity. However cases have also been reported where much smaller doses (2
4mg) of naloxone have been effective in reversing the effects of buprenorphine.

In the event of depression of respiratory or cardiac function:


Establish a clear airway
Begin assisted or controlled ventilation with oxygen.
intravenous fluids and other supportive measures should be employed as
indicated.
The long duration of action of buprenorphine should be taken into
consideration when determining the length of treatment needed to reverse
the effects of an overdose.
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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

5.3 Dosing Intoxicated Patients


Patient safety is the key consideration in responding to those who present for methadone/
buprenorphine dosing while intoxicated with opioids, alcohol, benzodiazepines or other drugs.

Intoxicated patients should not be dosed and patients should be


made aware of this prior to the commencement of treatment
Prior to dosing:
Patients should always be assessed for intoxication by the person dispensing the dose (nurse
or pharmacist) before the dose is given. The assessment should ensure that the patient is not
showing evidence of intoxication due to opioids, alcohol, benzodiazepines or other drugs.
(See Appendix 7 Assessment of Intoxication)
Patients who appear intoxicated with CNS depressant drugs should not be given their usual
methadone/buprenorphine dose or a takeaway dose at that time. The patient can be asked to represent later when they are no longer intoxicated.
If intoxication is evident but appears mild the patient may be given a reduced dose but only after
being reviewed by a medical practitioner.

Repeated intoxicated presentations


Patients with a history of repeated intoxicated presentations should be reviewed by the
prescribing doctor and the treatment plan reconsidered. (Intoxicated presentations are a
contraindication to prescribing takeaway doses of methadone and buprenorphine, see section 4
for more details.)

5.4 Vomited doses


Buprenorphine
Buprenorphine is absorbed sub-lingually after 2 7 minutes. Vomiting after this time makes no
difference to the absorption of the dose.

Methadone

Chapter 5

Vomiting after a dose of methadone creates uncertainty regarding the absorption of the dose.
The following procedures are recommended.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Situation

Response

Patient vomits 20 minutes or more after the


dose

Reassure patient that all the dose has been


absorbed

Patient who has been in treatment for more


than two weeks is observed by dispensing staff
to vomit within 20 minutes of the dose.

A half dose may be administered.

Patient is in the first two weeks of treatment


or there is uncertainty about the event.

Review the patient 4 6 hours after initial


dosing when plasma levels will be at their
peak. If withdrawal signs evident a dose
supplement up to half the patients usual
dose may be given.

Patient is pregnant

As withdrawal symptoms can produce foetal


distress, review the patient 4 6 hours after
initial dosing to ensure no signs of withdrawal.
If dosing appears inadequate a further small
dose may be considered

5.5 Incorrect dose administered


It is essential to the safety and effective working of the CPOP that all pharmacists, including
locums and part time staff, are familiar with the CPOP requirements. All prescriptions, patient
identification records and other information should be readily accessible. It is recommended the
following procedures be adopted to reduce the possibility of administering the incorrect dose:
Use a day book or diary to record and communicate important information to other
pharmacists who practice at the premises. This book should be inspected by staff daily.
All patients must have a photograph signed by the prescriber attached to their record
card.
Do not confuse millilitres (ml) with milligrams (mg) of methadone as this may result in a
fivefold error. Prescriptions for methadone should only be written in milligrams. If the
dose is written in millilitres check the dose with the prescriber.

Chapter 5

Take extra care to elicit information from a new patient regarding the effect of the
dose so as to monitor the toxicity of the dose being administered.
If there is more than one patient with the same surname attach a cautionary note to the
patients record card alerting staff to this.
Check telephone contact details for patients are kept up-to-date.

Methadone
A patient who receives a methadone dose in excess of that prescribed, is at risk of overdose. To
prevent accidental methadone overdose procedures should be established for easy and accurate
identification of patients to minimise the risk of inappropriate dosing. Patients should be
informed of the risks and signs and symptoms of overdose.
Patients in the first 2 weeks who receive an overdose of any magnitude require observation for 4
hours. If signs of intoxication continue, more prolonged observation is required. This may require
sending the patient to an Emergency Department.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Patients who have been on a dose of methadone >40mg/day consistently for two months will
generally tolerate a dose double their usual dose, without significant symptoms. For an overdose
with greater than double the usual daily dose the patient will require observation for at least 4
hours. If signs of intoxication are observed, more prolonged observation must be maintained.
If patients are receiving regular takeaway doses, or if they do not attend daily, it cannot safely
be assumed that they have been taking their daily dose and have a known level of tolerance.
Therefore, such patients require observation in the event of overdose of >50% of their usual dose.
Patients in whom the level of tolerance is uncertain (dose <40mg/day, or in treatment for <2
months) require observation for at least 4 hours if they are given a dose >50% higher than their
usual dose.

In the case of an accidental overdose the critical issues which determine


how clinicians should respond are the patients level of tolerance and the
amount of methadone given in error.
In all cases of dosing error the following procedures should be followed:
Overdose up to 50% of the normal dose:
Advise the patient of the mistake and carefully explain the possible consequences.
Inform the patient about signs and symptoms of overdose and advise him/her to go to a hospital
Emergency Department if any symptoms develop.
The dispenser must advise the prescribing doctor of the dosing error and record the event.
Overdose greater than 50% of the normal dose:
Advise the patient of the mistake and carefully explain the possible seriousness of the
consequences.
The dispenser must contact the prescribing doctor immediately. If the prescriber is unable to be
contacted consult the Clinical Advisory Service.
If it is decided by the prescriber or drug and alcohol specialist that the patient requires
hospitalisation, the reasons should be explained to the patient and they should be accompanied
to the hospital to ensure admitting staff receive clear information on the circumstances.

Chapter 5

If the patient has left before the mistake is realised, every attempt must be made to contact the
patient.
Caution regarding inducing vomiting:
Inducing vomiting may be dangerous and is contraindicated if the patient has any signs of CNS
depression. Emesis more than ten minutes after dosing is an unsatisfactory means of dealing with
methadone overdose as it is impossible to determine if the entire dose has been eliminated. In
circumstances where medical help is not readily available or the patient refuses medical care,
induction of vomiting (by mechanical stimulation of the pharynx) within 5-10 minutes of ingesting
the dose may be appropriate as a first aid measure only. Ipecac syrup is contraindicated as its
action may be delayed.

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Buprenorphine
The risks associated with an incorrect dose of buprenorphine are not as severe as with other
opioid medications.
In the event of an incorrect dose being administered:
the dispensing pharmacist (or nursing staff) should immediately notify the patient and
prescriber of the error
the patient should be warned of the likely consequences (increased sedation/drowsiness
may occur for several hours afterwards), and warned against any additional drug use,
and driving or operating machinery, for the rest of the day
if any of the following circumstances apply the patient should be monitored for at least
6 hours after an incorrect dose by trained health professionals or in the Accident &
Emergency Department of a hospital,
the patient is sedated following the dose (for any reason)
the patient is new to substitution treatment (within the first 2 weeks of treatment)
a buprenorphine dose of 64 mg was incorrectly administered (regardless of routine
daily dose).
It may be that a lower dose, or no dose, is required the following day (in effect, a two-day dose
has been administered).

5.6 Continued high risk drug use & polydrug use


Polydrug use is prevalent among opioid users. One in five patients seeking methadone
maintenance treatment are likely also to be dependent on benzodiazepines and 5% are likely to
be alcohol dependent. A high percentage of patients are likely to be using benzodiazepines or
alcohol at hazardous or harmful levels.
Continued high risk & polydrug use is evidenced by:
frequent presentations when intoxicated or with signs of benzodiazepine or alcohol
withdrawal
overdoses
chaotic drug using behaviour

Chapter 5

deteriorating medical or mental state due to drug use.

It is recommended that specialist advice be sought when treating patients


at high risk from polydrug use especially where sedatives are involved
Continued drug use can affect patient stability and treatment progress and place the patient
at risk of:
relationship, social and employment problems
contracting infectious diseases
involvement in crime
overdose and death.

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and buprenorphine in the treatment of opioid dependence

Attempts to stabilise such patients should include a review of:


psychosocial interventions and supports
precipitants to continued drug use
the risks of combining methadone/buprenorphine with other drug use against the
benefits of continued treatment
if the patients safety is not at risk from ongoing drug use it will generally be in the
patients interest to persist with treatment
if the risks of combining methadone/buprenorphine with other drug use outweigh the
benefits to the patient of maintenance treatment arrange the patients gradual
withdrawal treatment
medication regimes
increases in methadone/buprenorphine dose may be helpful if this is considered safe by
the prescriber.
S8 Doctor shopping
The Department of Health will notify a prescriber if one of their pharmacotherapy patients
attends another prescriber and obtains a prescription for an S8 medication. In this circumstance
the phamacotherapy presciber should review the adequacy of the patient's current dose of
methadone or buprenorphine and give consideration to the appropriatness of any takeaways that
have been approved.

Benzodiazepines
Benzodiazepine users exhibit overall patterns of increased risk and poorer psychological
functioning than other patients. Benzodiazepine injection is associated with vascular damage
as well as mortality. Injection of the gel capsule formulation of temazepam can lead to limb
amputations. This formulation should not be prescribed.
Patients should be advised about the interactions of benzodiazepines and methadone/
buprenorphine.

Chapter 5

Caution should be exercised in prescribing benzodiazepines in maintenance treatment. The


clinical supervision of patients receiving maintenance benzodiazepines must be of the same high
standard as for methadone/buprenorphine maintenance treatment. Use of patient contracts
(see Appendix 13) should be considered to reduce capacity for obtaining medications from
multiple sources. Good communication between prescribers and dispensers regarding use of other
prescription medications is also encouraged.

5.7 Treating hospitalised patients


Patients on pharmacotherapy treatment
In general methadone or buprenorphine treatment should continue when patients are admitted
to hospital. The hospital doctor managing the patient should consult with the prescribing doctor.
When a prescribing doctor or a staff member at a dosing location is contacted regarding inpatient
treatment of a person receiving methadone or buprenorphine they should provide all possible
assistance to the hospital doctor (information about the legal requirements for prescribing opioid
treatment, patient history, and the significance of the patients current dosing regimen).

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The pharmacist at the dosing location should document that the patient has become an inpatient
and is being dosed elsewhere. To avoid double dosing the pharmacist should confirm that the
patient has been discharged and confirm the date on which the patient received a dose before
recommencing dosing. When a prescribing doctor is contacted regarding treatment he/she must
ensure that the dosing location has been notified.
Opioid dependent patients who are not on pharmacotherapy treatment
Opioid dependent people who are not on methadone or buprenorphine maintenance treatment
may experience withdrawal if admitted to hospital. Methadone or buprenorphine may be used to
treat withdrawal symptoms if withdrawal symptoms could be reasonably be expected to interfere
with the optimum medical management of the patient or if the patient is suffering from a serious
or life-threatening illness and the patients premature self-discharge before completion of
therapy would prejudice optimum management. In these circumstances consultation should occur
with the CAS.

5.8 Analgesia and anaesthesia


Analgesic requirements for inpatients on methadone
Patients on methadone who are experiencing acute pain in hospital often receive inadequate
doses of opiates for serious pain. Analgesia should be provided to patients on methadone in
the same way as for other patients. This includes the use of injectable and patient controlled
analgesia.
There is evidence of cross tolerance between methadone and anaesthetic agents. Patients on
methadone may require higher doses of anaesthetic agents in the event of dental or surgical
procedures.
Management of acute pain in hospital
Patients on methadone or buprenorphine who need acute pain management in the hospital
setting can be managed as for patients who are not opioid dependent, although doses of
analgesic drugs may need to be higher.
Due to tolerance to opioids, patients taking methadone frequently require larger doses of opioid
analgesia for adequate pain relief. Partial agonists such as buprenorphine should be avoided as
they may precipitate withdrawal symptoms.

Chapter 5

Management of acute pain in primary care settings


Patients on methadone or buprenorphine who need acute pain management can be administered
Schedule 8 drugs in the surgery but due to regulatory requirements cannot be prescribed
Schedule 8 medications.
Consider non-opioid analgesics (NSAIDs or paracetamol). Where parenteral analgesia is required,
consider ketorolac (Toradol), or tramadol (Tramal).
Consult the Clinical Advisory Service (CAS) for advice on clinical management of these patients.
The Department of Health Pharmaceutical Services Branch (08 9388 4980) should be contacted to
clarify any regulatory issues.

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and buprenorphine in the treatment of opioid dependence

Analgesic requirements for patients on buprenorphine


Patients maintained on buprenorphine will have a diminished response to opioids prescribed for
analgesia. This is because of the opioid blocking effect of the buprenorphine. Consequently,
patients on buprenorphine who suffer severe or chronic pain will require considerably higher
doses of opioid analgesia than individuals not in buprenorphine treatment.
Use simple analgesics where possible (such as aspirin, NSAIDS, paracetamol, tramadol).
Where additional opioid analgesia is required:
Increasing the buprenorphine dose by 25% can have a limited effect, particularly when
the dose is less than 4mg daily (limited effect above 16mg).
In the hospital setting, regional anaesthesia if appropriate ketamine infusion alone or in
combination with other opiates
Failing this, cease buprenorphine and transfer to a full opioid agonist. In the community,
use methadone. In the hospital setting, using shorter acting opioids will facilitate
transfer back to buprenorphine. Transfer back to buprenorphine is usually possible when
pain has settled down. To recommence buprenorphine, first cease all other opiates,
then recommence buprenorphine when early withdrawal symptoms begin to occur
(usually 24 hours after the last dose of morphine).

Patients requiring surgery


Patients being admitted for major surgery should indicate to their doctors that they are taking
methadone or buprenorphine and discuss pain management options for the post operative period
prior to surgery.

Management of patients with chronic pain


Patients needing methadone for ongoing management of chronic pain need a comprehensive
management plan. Patients on buprenorphine who have chronic pain may need to transfer to
methadone. It is recommended that specialist advice be sought regarding such patients.

5.9 Diversion of methadone/buprenorphine


Anecdotal and other evidence indicates that diversion of supervised doses and takeaway doses of
both methadone and buprenorphine does occur in Western Australia. Whilst most patients do not
divert their medication the potential for some patients to attempt to divert their medications,
for a range of reasons, always remains a risk.

Chapter 5

Unfortunately the use of diverted medications can have serious and potentially fatal
consequences. In addition, such activities undermine the therapeutic benefits of the program for
the individual patient and damage the reputation of the program as a whole.
This needs to be balanced against the value of keeping patients in treatment when considering
the management options where diversion does occur.

Minimising the risk of diversion


To minimize the risk of diversion it is important that patients are carefully assessed for risk of
diversion, dosing is appropriately supervised (see Appendix 8), takeaway doses are supplied only
in accordance with the programs policy and procedures and patients found to be diverting are
appropriately managed.

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and buprenorphine in the treatment of opioid dependence

Concerns about suspicion of diversion may arise from observations of patient behaviour or
information from other sources, such as other service providers, friends or family members of
the patient. The service provider will need to make a judgment as to the credibility of third
party reports. See Appendix 8 for a list of possible behavioural indicators of diversion and
recommended supervised dosing strategies to minimize the risk of diversion.

All patients should be informed about the consequences of diversion or


attempted diversion of their medication at the commencement of treatment.
Service providers may wish to seek advice from the Clinical Advisory Service (CAS) or enlist the
Opioid Replacement Program Advocacy and Complaints Service (ORPACS) (ph: 08 9321 2877) to
assist in communicating with patients to positively resolve any problems before further action is
required.

Responding to diversion or attempted diversion


In all situations discussion should occur with the patient regarding their behaviour and full
consideration given to the appropriate course of action before any changes to treatment are
applied.

Chapter 5

Confirmed incidents of diversion or attempted diversion


Where there is a direct observation by pharmacy staff or other conclusive evidence of diversion
or diversion attempts the prescriber and CAS should be advised and the patient should be
referred back to the prescriber. The following action should be implemented.

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and buprenorphine in the treatment of opioid dependence

Recommended action*

For the first incident

Diversion of takeaway dose/s

Immediate cessation of takeaway doses and


no further takeaway dose/s for 6 months

Diversion of supervised buprenorphine dose

Transfer to methadone and no takeaway


doses for a minimum period of 6 months or
involuntary detox off buprenorphine.

Diversion of supervised methadone dose

Doses should be made up to 200ml with


water or cordial and the dose should be
administered in 50ml aliquots and no
takeaway doses for a minimum period of 6
months.

For subsequent incidents within a 3 year period


Treatment will be terminated and the patient will undergo an involuntary detoxification. The
patient will not be considered eligible for methadone or buprenorphine maintenance treatment
for a further 3 months from the date of termination.
All action should be recorded in the patients clinical notes and CAS must be notified.
* Consideration should be given to the particular clinical situation of the patient (e.g. pregnancy)
when deciding on the appropriateness of any action to change methadone or buprenorphine
medication.

Suspected diversion
Where the pharmacist suspects the patient is diverting or attempting to divert their
medication, the pharmacist should discuss the concerns with the patient. This may clarify any
misunderstandings regarding the dosing requirements. If required a formal first warning should
then be given to the patient by the pharmacist outlining the concerns and consequences of
further diversion attempts. The prescriber and CAS should also be notified.
Further indications or evidence of subsequent diversion incidents should result in the pharmacist
referring the patient back to the prescriber where the above actions are recommended as per
confirmed diversion.

Chapter 5

Patient complaints mechanism


Patients who do not agree with decisions made by pharmacists or prescribers under this policy
should make a complaint using the mechanism appropriate to their service provider.

Diversion of Suboxone
There are no Australian data to support the suggestion that the mono and combination products
differ significantly in abuse liability, and no information on how different drug-using populations
will respond to the introduction of the combination product. However, following the release of
the combination product in Australia, a post-marketing surveillance study will be undertaken by
the National Drug and Alcohol Research Centre. This study will assess relative rates of diversion
of the mono and combination products, as well as the relative efficacy of these tablets in the
usual practice setting.

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5.10 Patients less than 18 years old


Methadone/buprenorphine maintenance is unlikely to be an appropriate treatment choice for
young people (particularly those under 16 years of age) because they are unlikely to have:
a history of long term opioid use
significant tolerance
opioid using problems that are not amenable to other forms of help and treatment.
Young users tend to be poly-drug abusers and often have a history of erratic drug and alcohol
use. Longer term dependence on opioids is uncommon. Methadone/buprenorphine should not be
prescribed if opioids are only one of a number of drugs a young person is taking and there is no
evidence to suggest they are physically dependent on opioids. For younger users it is important
that counselling and rehabilitation options be encouraged. Those treatments that pose least risk
to the patient should be given preference.
Methadone is only registered for use in patients aged 18 or over. Buprenorphine has been
registered for administration to people aged 16 and over. Caution should be exercised in
prescribing a drug of dependence for anyone under 18 years of age. However, positive results
have been reported from the combination of buprenorphine with behavioural interventions for
the treatment of opioid-dependent adolescents (Marsch et al 2005). Potential medico-legal
implications of prescribing methadone or buprenorphine outside of the product information
should be considered.

Patients under 18 years of age must be referred to Next Step Youth


Service for a comprehensive, multi-disciplinary assessment.
Applications for authority for patients under 16 years of age will require
special approval from the Chief Executive Office of the Department of Health.
Next Step Youth Service is able to instigate treatment and stabilise the patient before referring
them back to the prescriber. Next Step Youth Services are also able to offer ongoing consultation
for medical practitioners treating young patients. In cases where the prescriber, for reason of
their location in a remote area, cannot access Next Step Youth Services the Clinical Advisory
Service should be contacted to discuss alternative assessment options.

Assessment criteria
Chapter 5

Suitability for maintenance treatment and the type of pharmacotherapy prescribed will be
determined by:
the history of AOD use
the physical and psychological assessment
evidence of opioid dependency and current physical dependence
prior treatment history and current reasons for seeking treatment
parental or family support
a comprehensive risk assessment (self harm/suicide, accommodation arrangements,
ongoing chaotic drug use, etc)
capacity to give informed consent to treatment. On assessment the young person must
be deemed mature enough to understand the risks and consequences of the treatment.
treatment history

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5.11 Pregnancy and lactation


Pregnant women who are dependent on opioids are at high risk of experiencing complications,
generally as a result of:
inadequate antenatal care
lifestyle factors including smoking, poor nutrition, high levels of stress and deprivation
repeated cycles of intoxication and withdrawal which can harm the foetus or precipitate
premature labour or miscarriage.
Substitution treatment is the preferred approach for opioid dependent pregnant women due to
its capacity to reduce these risks.
There is a lack of adequate research on safety and effectiveness of buprenorphine during
pregnancy and lactation in humans. This contrasts with methadone, where a significant body of
data has been reported over three decades. For this reason, buprenorphine treatment is contraindicated for both pregnant and lactating women and methadone maintenance is the treatment
of choice.

Methadone is the first line treatment for opiate dependence in pregnancy


However, research to date has not demonstrated areas of significant concern in animal models,
observational human studies or controlled studies for the use of buprenorphine in pregnancy.
Over 400 cases of babies being born exposed to buprenorphine (as the mono product, ie.
Subutex) have been reported with no severe adverse events clearly linked to buprenorphine
exposure. The neonatal abstinence syndrome associated with buprenorphine may be less severe
and of shorter duration than that seen in methadone-exposed babies, however this has not yet
been clearly established. As yet there has been little clinical experience of the effects of the
combination product (Suboxone) in pregnancy. Most experience with naloxone in pregnancy is
with short-term use, eg in reversal of overdose. Given the lack of knowledge of the effects on
the foetus of chronic exposure to naloxone during pregnancy, use of the combination product in
pregnancy is not recommended.

Chapter 5

Buprenorphine is a Category C drug, which has implications for pregnancy. ADEC states that this
group of drugs has caused, or may be suspected of causing, harmful effects on the human fetus
or neonate without causing malformations. These effects may be reversible. Opioid analgesics
are capable of causing respiratory depression in the neonate, and withdrawal symptoms have
been reported in cases of prolonged use.
Methadone is also classed as a Category C drug because of the potential risk of respiratory
depression in the neonate and the likelihood of neonatal withdrawal syndrome.
Respiratory depression is not a significant problem in babies born to opioid dependent mothers
receiving methadone maintenance treatment. Babies born to mothers on methadone maintenance
treatment may experience a withdrawal syndrome. Available evidence gives little support to
the existence of a relationship between the severity of the neonatal withdrawal syndrome
and maternal methadone dose at delivery and its occurrence is unpredictable. The benefits of
methadone maintenance treatment for both the mother and the baby outweigh any risks from
the neonatal withdrawal syndrome.
Any woman patient seeking maintenance treatment who might become pregnant should be
counselled on the potential risks of buprenorphine during pregnancy, with this information being
reinforced and presented to them in writing.
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and buprenorphine in the treatment of opioid dependence

Women wanting to become pregnant are better advised to consider


methadone maintenance for the management of their heroin dependence.
Reliable forms of contraception should be recommended to women not wanting to become
pregnant.

The patient who becomes pregnant while in buprenorphine treatment.


The risks and benefits of transfer to methadone or continued buprenorphine maintenance
should be discussed. As buprenorphine is contra-indicated, transfer to methadone maintenance
is advised due to greater knowledge regarding safety. Admission to hospital for transfer to
methadone should be considered as this allows for close observation of both mother and foetus,
for evidence of withdrawal or distress.
It is possible that a woman already maintained on buprenorphine will become pregnant and
refuse transfer to methadone despite the greater information known on the safety of methadone
during pregnancy.

The key issue for women who want to remain on buprenorphine during
pregnancy or breastfeeding is that they understand that the safety and
effectiveness of buprenorphine has not yet been fully evaluated
In addition women who have been stabilised on buprenorphine and who have been able to cease
heroin use may risk a return to regular heroin use as a result of being destabilised during the
transfer to methadone. For these reasons, it may be preferable for pregnant women who do
not wish to transfer to methadone to be maintained on buprenorphine. In this situation, advice
should be sought from an obstetrician and an addiction medicine specialist. Counselling must be
provided regarding treatment options to ensure that the woman is fully informed of the risks and
benefits of buprenorphine during pregnancy and breastfeeding. The mono preparation, Subutex
consent form signed by patient should be used in these situations (see Appendix 13 for template
form).

Termination of pregnancy
Women wishing to terminate the pregnancy should be referred to appropriate services.

Principles in managing pregnancy in opioid dependent women


Chapter 5

Opioid using pregnant women not already in treatment should be given high priority for
assessment.
Naloxone challenge should not be used in pregnant women because this may precipitate
miscarriage or premature labour. Pregnant women should be maintained on an adequate dose of
methadone to achieve stability and prevent relapse or continued illicit opioid drug use.
Women already in methadone treatment who become pregnant can safely be maintained on
their current dose. Transfer to buphrenorphine is not advised because of the risk of precipitated
withdrawal.
The bioavailability of methadone is decreased in the later stages of pregnancy due to increased
plasma volume, an increase in plasma proteins that bind methadone and placental metabolism
of methadone. It may be necessary to divide the daily dose and possibly to increase the dose in
the third trimester of pregnancy to avoid withdrawal symptoms and minimise additional drug use.
The dose should be reviewed after birth and adjusted according to:
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and buprenorphine in the treatment of opioid dependence

Signs of withdrawal
or
Risk of reverting to illicit drug use.

Antenatal and postnatal care should be managed in collaboration with


The Women and Newborn Drug and Alcohol Service at KEMH. This clinic is
experienced in the management of drug dependency during pregnancy.
Dose reductions or detoxification during pregnancy
Opioid withdrawal in the first trimester of pregnancy is thought to be associated with an
increased risk of miscarriage. Opioid withdrawal in the third trimester of pregnancy may be
associated with foetal distress and death. Therefore, it is important that pregnant women are not
exposed to withdrawal during the first and third trimesters.
If dose reductions or detoxification are to be undertaken during pregnancy these should be
implemented in the second trimester and in consideration of the following:
dose reductions should only occur if the pregnancy is stable
the magnitude and rate of reduction needs to be flexible and responsive to the
symptoms experienced by the woman concerned
withdrawal symptoms should be avoided as much as possible as they cause considerable
distress to the foetus
careful monitoring of the pregnancy and foetus should be undertaken during dose
reduction
in most instances, dose reductions of 2.5mg -5 mg per week are considered safe.

Breastfeeding
Breast milk contains only small amounts of methadone and mothers can be encouraged
to breastfeed regardless of methadone dose provided that they are not using other drugs.
Breastfeeding may reduce the severity of the neonatal withdrawal syndrome. Women receiving
high doses of methadone should be advised to wean their babies slowly to avoid withdrawal in
the infant.

Chapter 5

It is known that only small amounts of buprenorphine and buprenorphine-naloxone pass into
breast milk. Given that the infant swallows the milk, absorption of buprenorphine from breast
milk would be expected to be minimal. However, there is a lack of research evidence regarding
the safety and effects on development of breast fed babies exposed to buprenorphine. In the
absence of adequate information of the effects of buprenorphine and buprenorphine/naloxone
on breastfeeding infants, breastfeeding should be approached with some caution. However,
the potential risks of buprenorphine should be balanced with the overall positive effects of
breastfeeding. Consultation with a specialist paediatric unit with substance use expertise is
advised.

Neonatal Withdrawal Syndrome


The occurrence and severity of neonatal withdrawal is very unpredictable. Severity of withdrawal
is probably ameliorated if neonates can be kept with their mothers rather than in the neonatal
intensive care nursery, which may be stressful and overstimulating. However, this is not always
possible.

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and buprenorphine in the treatment of opioid dependence

All babies born to opioid dependent mothers should be observed by experienced staff for the
development of withdrawal signs. It is recommended that a validated scale be used to assess the
presence and severity of the neonatal withdrawal syndrome (see Appendix 9).
Common signs include
Irritability and sleep disturbances
Sneezing
Fist sucking
A shrill cry
Watery stools
General hyperactivity
Ineffectual sucking
Poor weight gain
Dislike of bright lights
Tremors
Increased respiration rate

Less common signs include


Yawning
Vomiting
Increased mucus production
Increased response to sound
Convulsions (rare)

Withdrawal symptoms usually start within 48 hours of delivery but may be delayed for 7-14 days
in a small number of cases. Experience in the US suggests that in cases where withdrawal is
delayed it may be because methadone was being used in conjunction with illicit benzodiazepines
and the infant is withdrawing from the benzodiazepines.
Supportive treatment involves minimising environmental stimuli and enhancing the babys
comfort and may include:
soothing by holding close to the body or swaddling
keeping nostrils and mouth clear of secretions
use of a dummy to relieve increased sucking urge
frequent small feeds.

Chapter 5

Treatment should be based on the severity of the withdrawal signs. Use the Finnegan or modified
Finnegan (Appendix 9) to assess withdrawal severity. Treatment should be commenced when the
score averages 8 or more on three consecutive scores or 12 or more on two consecutive scores
when assessed by an experienced scorer. Improvement should be monitored using scores on the
screening tool.
Advice on current treatment options should be obtained from the Neonatal Intensive Care Unit at
King Edward Memorial Hospital.

Child protection
The Department of Health Guidelines for Responding to Child Abuse and Neglect and the
Impact of Family and Domestic Violence (2004) states that Department of Health and all
Health Workers are to take an active approach in their response to concerns about the care and
protection of children. A childs best interests must come first where there is a risk of child
abuse and neglect.

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Children are deemed to be in need of protection if:


A child has suffered or is likely to suffer harm as a result of physical abuse, sexual
abuse, emotional abuse, psychological abuse and/or neglect.
The childs parents are unable to provide or arrange for adequate care and/or the
provision of effective medical or other remedial treatment for the child.
A child has been abandoned by his or her parents or the childs parents are dead or
incapacitated and no suitable adult relative or other person can be found who is willing
and able to care for the child.
A child is living in a household where there are incidents of family and domestic
violence.
(Department of Health 2004)
On initial assessment, at treatment review and when assessing eligibility for takeaway doses
it is important to consider the safety and well being of any children in the patients care. A
parents enrolment in an opioid treatment program alone is not a reason to make a report to the
Department of Child Protection.

5.12 HIV
Treatment programs should ensure that HIV positive patients have access to specialist HIV
medical care so that the patients overall health may be monitored and appropriate treatment
provided as required. In general, patients who are HIV positive are able to comply with the
requirements and conditions of the methadone/buprenorphine maintenance program, however,
the medical, psychological and social implications of HIV infection may necessitate the provision
of additional services.
Methadone/buprenorphine doses must be monitored due to the potential for interactions with
HIV medications and the effects of related illnesses.
Higher doses may be necessary if HIV medications increase methadone /buprenorphine
metabolism (see also Appendix 1 & 2).
Flexibility in dosing arrangements may be needed if patients are unable to attend for daily dosing
due to illness. Discuss options with CAS.

Chapter 5

In the terminal stages of HIV-AIDS, service providers may need to work with hospice services in
managing methadone/buprenorphine treatment and AIDS conditions.

5.13 Hepatitis B & C


Hepatitis B
Hepatitis B vaccination is recommended for all patients on the methadone/buprenorphine
treatment program who are found to have no immunity to the hepatitis B virus.
Patients who are acutely infected or who are chronic carriers of hepatitis B should be referred to
a gastroenterologist for specialist assessment and follow-up.

Hepatitis C
A high percentage of patients entering methadone/buprenorphine programs will be hepatitis C
antibody positive. Patients should be treated in accordance with national and state guidelines.

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and buprenorphine in the treatment of opioid dependence

Patients who are hepatitis C antibody positive but who have 3 normal serum aminotransferases
(ALT and AST) over 6 months should have liver function tests repeated at 6 monthly intervals and
a Hepatitis C polymerase chain reaction test at 12 months.
If the patient has 3 abnormal serum aminotransferases over 6 months referral to a
gastroenterologist or liver clinic for specialist assessment and shared care is indicated.
The Hepatitis C Council is able to offer support and counselling (see Appendix 6)

Impaired liver function


Patients with chronic liver disease on long term methadone/buprenorphine treatment generally
do not need dose alterations but abrupt changes in liver function might necessitate substantial
dose adjustments.

5.14 Psychiatric comorbidity


Many opioid users exhibit symptoms of anxiety and depression at the time of presentation for
treatment. Most, but not all studies, link psychiatric distress to poorer treatment outcome.
Studies have indicated that pharmacotherapy maintenance treatment can reduce levels of
psychiatric distress with improvement apparent within weeks of commencement of treatment.
After stabilisation a careful and detailed mental state examination can be undertaken.
Psychotherapy as an adjunct may benefit some patients.

Chapter 5

Depression has been found to predict poor psycho-social functioning and to increase the risk of
relapse to heroin use. Evidence of the effectiveness of antidepressants as adjuncts is equivocal
with only a few studies demonstrating favourable effects on mood. The SSRIs are the preferred
antidepressants.

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and buprenorphine in the treatment of opioid dependence

6.0 Clinical Management of Heroin Withdrawal


6.1 Heroin withdrawal in context
Drug withdrawal is a substance-specific syndrome following the cessation or reduction in the use
of the drug. The syndrome can cause significant physical distress and impairment in social and
occupational functioning and require medical treatment. The characteristic features of heroin
withdrawal are shown in the following table.

TABLE 8: CLINICAL FEATURES OF THE HEROIN WITHDRAWAL SYNDROME


Increased sweating, lacrimation, rhinorrhoea, urinary frequency.
Diarrhoea, abdominal cramps, nausea, vomiting.
Muscle spasm leading to headaches, back aches, e.g. cramps, twitching, arthralgia
Piloerection, pupillary dilatation, elevated blood pressure, tachycardia.
Anxiety, irritability, dysphoria, disturbed sleep, increased cravings for opioids
Physical symptoms generally commence 6 - 24 hours after last use, peak in severity during days
two to four, and generally subside by day seven, while the psychological features of dysphoria,
anxiety, sleep disturbances and increased cravings may continue for weeks or even months.
Heroin withdrawal is unpleasant, though rarely, if ever, life-threatening. It can, however,
significantly complicate concomitant medical or psychiatric conditions.
Heroin users present for withdrawal services for a range of reasons and motivations and the goals
of individual patients may vary considerably. Withdrawal services should not be seen as a standalone treatment resulting in prolonged periods of abstinence. Indeed, research suggests that
withdrawal treatment alone has little, if any, long-term impact on levels of drug use1 - 4.
Unfortunately, many patients, families, friends, and health and welfare professionals hold
unrealistic expectations regarding the outcomes of withdrawal services. Many are disappointed
when people in these programs either cannot give up their heroin use in the first place, or
recommence regular heroin use soon after a withdrawal attempt.

It helps to set sensible withdrawal objectives


A realistic set of objectives for withdrawal treatment are:
1. To alleviate distress. Palliation of the discomfort of heroin withdrawal symptoms is an
important reason for patients presenting for treatment and one of the primary aims of
withdrawal services.
2. To prevent severe withdrawal sequelae. Although heroin withdrawal on its own is almost
never life-threatening, withdrawal can present various serious problems:
1 - 4 Mattick, R,P., & Hall, W. (1996). Are detoxification programmes effective?. Lancet 1996; 347: 97-100.

Chapter 6

Hubbard, R.L., Marsden, M.E., Rachal, J.V., Harwood, H.J., Cavanaugh, E.R., & Ginzburg, H.M. (1989). Drug
abuse treatment a national study of effectiveness. University of North Carolina Press: North Carolina.
Vaillant , G.E. (1988). What does long term follow up teach us about relapse and prevention of relapse in
addiction. British Journal of Addiction, 83, 1143-57.
Simpson, D.D. & Sells, S.B. (1982). Effectiveness of treatment for drug abuse: An overview of the DARP research
program. Advances in Alcohol and Substance Abuse, 2, 7-29.

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and buprenorphine in the treatment of opioid dependence

Complication of concomitant medical or psychiatric conditions e.g. precipitation of an


acute psychotic episode in a patient with schizophrenia in remission or dehydration in an
individual with poor baseline nutritional status.
Increased risk of overdose following withdrawal. This can occur with resumption of
heroin use following the reduction in opioid tolerance that accompanies withdrawal, and
due to the combined sedative effects of heroin use and medications used for the
management of heroin withdrawal (e.g. benzodiazepines).
3. To break a pattern of heavy and regular drug use. Many patients want treatment to end their
heroin use and intend to stay off heroin afterwards. However, giving up entirely is not the
goal of every patient. Many see withdrawal as a means of reducing levels of heroin use, the
severity of their dependence and some of its associated harms. So, although the cessation of
heroin use is an optimal outcome, a reduction in heroin use during a withdrawal attempt may
still represent a very positive outcome for some patients.
4. To provide linkages to, and enable engagement in ongoing treatment. Withdrawal services
are essentially acute services with short-term outcomes, whereas heroin dependence is a
chronic relapsing condition, and positive long-term outcomes are more often associated with
longer participation in treatment. Consequently, an important role of withdrawal services
is to provide links with post-withdrawal services for those with other physical problems,
psychological or social needs. Optimally, they should have automatic access to drug treatment
services, such as drug-free counselling; naltrexone treatment; residential therapeutic
communities; self-help programs; or substitution maintenance programs with methadone or
buprenorphine.
5. To help with other problems. While some people will be unwilling or unable to continue in
ongoing drug treatment programs, they may need - and be grateful for - contacts with welfare
services (e.g. accommodation); general support and case management services (e.g. outreach
workers); or primary or specialist health services.

6.2 Non-pharmacological aspects in managing heroin withdrawal


As well as the use of medication the delivery of withdrawal services entails:
assessment
treatment-matching
planning for withdrawal
supportive care
follow up.
The assessment of patients presenting for treatment was discussed in Section 3.3. Once it is
established that withdrawal is to be attempted, consideration must be given to the services
needed to achieve the best outcome. An optimal setting and adequate supports should be found
for each patient and monitoring arranged for their personal requirements and medication needs.

Chapter 6

Treatment Selection
Treatment selection is a synthesis of:
Assessment of the patient
Examination of the available treatment options and likely outcomes; and
Negotiation with the patient around a suitable pathway.

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and buprenorphine in the treatment of opioid dependence

In considering possible modalities, it is important to remember that many people come for
treatment with misconceptions and/or inadequate information about the two major options
available.
In general, withdrawal treatment is appropriate for those who are considering abstinenceoriented post-withdrawal treatment (such as naltrexone, residential rehabilitation programs,
counseling or 12 step programs) or for those who are not interested in longer-term treatment and
merely want a break from dependent heroin use.
However, maintenance substitution treatment (with methadone or buprenorphine) may be
more appropriate for those with significant opioid dependence who will not accept residential
rehabilitation or naltrexone treatment, but nevertheless want to stop or permanently reduce
their heroin use and all the damage it is causing them.
Clinical decision making should have an evidentiary basis and patients should be presented with
the relative merits and the limitations of treatment outcomes associated with each approach.
Within such a framework there is widespread evidence suggesting that maintenance substitution
remains the gold standard treatment for most people with chronic heroin dependence by virtue
of its success in keeping patients in treatment and reducing drug-related harm.
Once it is established that withdrawal is to be attempted, consideration must be given to
the services needed to achieve the best outcome. An optimal setting and adequate supports
should be found for each patient and monitoring arranged for their personal requirements and
medication needs.

The optimal setting for withdrawal


Withdrawal can occur in a continuum of settings, ranging from intensive residential (e.g.
inpatient withdrawal unit or hospital) to outpatient (e.g. ambulatory or home-based withdrawal
services). Most heroin withdrawal attempts can occur in outpatient settings, usually with the
assistance of a general practitioner, alcohol and drug worker, or other health professional.
However, there are circumstances where a residential setting is indicated (see Table 9).

Chapter 6

Some patients may wish to persevere with an outpatient withdrawal, despite unsuitable home
environments or having repeatedly failed as outpatients before. Such attempts at outpatient
withdrawal may still be appropriate if its what the patient wants. However, clinicians should
first negotiate with their patient some mutually agreed criterion of failure (e.g. no significant
progress within a week) at which point a switch will be made to an alternative treatment
pathway.

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and buprenorphine in the treatment of opioid dependence

Table 9: Criteria for residential withdrawal services


Criteria for intensive residential settings (e.g. inpatient withdrawal unit)
Unstable medical/psychiatric condition
Polydrug dependence and withdrawal from multiple drugs
Unclear medical, psychiatric or drug-use histories requiring close monitoring in a
supervised environment
Criteria for supported residential setting (e.g. community withdrawal unit)
Unsupportive home environment, such as with other drug users, or without anyone
reliable to supervise and support the patient
Repeated failure at outpatient withdrawal

Getting organised for withdrawal


Residential withdrawal settings generally provide the full range of services needed for a
withdrawal episode. They set out to be drug-free, with support available from staff and fellow
patients, and the capacity for continuous monitoring. They usually have access to medical staff
and medications. Unfortunately, such inpatient services often have waiting-lists and the patient
may need short-term support in the interim.
Commencing an outpatient withdrawal requires planning, and the mobilisation of the necessary
supports and services. Patients should prepare themselves and their environment in advance, to
maximise their chance of success. For example, it is very hard to get through withdrawal in the
company of others still using heroin.
A safe place should be organized at the beginning of the withdrawal episode. A 'safe' place is one
where there wont be any drugs easily accessible, and where patients will not be confronted by
other drug users. It is important to have caring people to support a patient during withdrawal,
and these support people themselves need guidance and information about the process, and
suggestions as to what they can reasonably do to help.

For help in locating appropriate support services contact


ADIS on 9442 5000 or toll free 1800 198 024
Supportive care
Patients need information regarding:
the nature and duration of withdrawal symptoms
strategies for coping with symptoms and cravings
strategies to remove high-risk situations
the role of medication.

Chapter 6

Patients often have limited concentration during withdrawal and information may have to be
repeated, perhaps even re-phrased, to be fully understood and absorbed. Written information is
valuable in these circumstances, and is also recommended for support people. Such information
can be provided by ADIS (see above).

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and buprenorphine in the treatment of opioid dependence

Counselling during the withdrawal episode should be aimed specifically at supporting the patient
through problems associated with withdrawal and in facilitating post-withdrawal links. Many
patients will want to deal with a range of personal, emotional or relationship problems during
the withdrawal episode, but they should be persuaded to defer all this until later. Attempting
to work through such issues will almost certainly be emotionally painful and anxiety-provoking,
which can intensify cravings and place the whole withdrawal program in jeopardy.
Patients in withdrawal tend to be irritable, agitated, tired and run-down; they can suffer from
mood swings and poor sleep patterns, as well as difficulty in concentrating. This is definitely not
the optimal frame of mind in which to try to solve significant, long-standing life problems. Assure
your patients that you understand that they have many important issues to work through to get
their lives together again, but it is best to take one step at a time. There will be opportunities
for these wider problems to be addressed as part of their ongoing rehabilitation after they get
through withdrawal. On the other hand, crisis intervention may be required during a withdrawal
episode to ensure adequate accommodation, food or other urgent welfare issues.
In addition to supportive counselling from health professionals and the support of family, friends
and peer workers, heroin users may also benefit from 24-hour telephone counselling services for
help when others are unavailable. ADIS can provide this service and can also put patients in touch
with other such services available.

Monitoring
An important part of withdrawal service is regular and frequent monitoring, to check:
general progress
drug use
response to the medication(s)
severity of withdrawal symptoms (which can be facilitated by the use of withdrawal
scales)
complications or difficulties
ongoing motivation levels.
Doses of medication can then be adjusted according to the patients progress. It is recommended
that patients undergoing outpatient withdrawal be reviewed by a health professional (eg alcohol
and drug worker, general practitioner, or experienced pharmacist) at least daily during the first
few days of treatment.

Scales for assessing opioid withdrawal

Chapter 6

There are various opioid withdrawal scales available to refer to. Subjective scales are far more
sensitive to changes in withdrawal severity, and are better predictors of patient outcomes.
Objective scales are not only less sensitive, but usually need to be administered by a health
professional. They may nevertheless be useful in corroborating subjective ratings, particularly
in individuals who are thought to be over- or under- rating their withdrawal severity. Copies of
the Subjective Opioid Withdrawal Scale and Objective Opioid Withdrawal Scale are provided in
Appendix 10.

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

6.3 Overview of buprenorphine in the management of


heroin withdrawal
Efficacy of buprenorphine compared to other withdrawal medication regimes
The efficacy of buprenorphine in the management of heroin withdrawal has been compared to
other withdrawal approaches in several randomised controlled trials conducted in inpatient(1- 3)
and outpatient settings(4 - 6).
In general, these studies have demonstrated buprenorphine to be:
more effective than symptomatic medications and clonidine in reducing withdrawal
symptoms(1, 2, 3, 5, 6),
more effective in retaining patients through the withdrawal episode and in postwithdrawal treatment(6); and
more effective in reducing heroin use in outpatient settings(6).
Readers are referred to the Cochrane Review on Buprenorphine for Opiate Withdrawal.
In the medically ill. Controlled trials comparing buprenorphine with other withdrawal
medications for the management of heroin withdrawal in medically-ill patients have not been
conducted. There is one study in a hospital ward. Nevertheless, uncontrolled studies have
reported favourably on the use of buprenorphine in these circumstances. Furthermore, the
sublingual preparation is well suited to individuals who cannot tolerate oral medications. Caution
should be used in using buprenorphine or other opioids in individuals with certain medical
conditions (see Section 2.2).

The role of buprenorphine in withdrawal


The clinician should discuss patients expectations of the medication with them and address any
misconceptions.
In particular, the following principles regarding doses should be understood by the patient:
buprenorphine doses that are too high can result in increased rebound withdrawal,
prolonged duration of symptoms, increased side-effects, and increased cost of the
medication
use of doses that are too low can result in unnecessary withdrawal discomfort,
continued heroin use and treatment drop-out
continued heroin use or cravings may not be due to inadequate doses of medication. For
example, patients who continue to associate with other heroin users and are present
when others are acquiring or using heroin can expect to have cravings regardless of their
dose of buprenorphine
buprenorphine will not reduce symptoms of withdrawal, or cravings, related to the use
of non-opioid drugs.

Chapter 6

1 Cheskin LJ, Fudala PJ, & Johnson RE (1994). A controlled comparison of buprenorphine and clonidine for acute
detoxification from opioids. Drug and Alcohol Dependence, 36(2), 115-21;
2 Nigam AK, Ray R, & Tripathi M. (1993). Buprenorphine in opiate withdrawal: A comparison with clonidine.
Journal of Substance Abuse Treatment, 10, 391-394;
3 OConnor PG, Carroll KM, Shi J, Schottenfeld RS, et al (1997). Three methods of opioid detoxification in a
primary care setting. Annals of Internal Medicine 127(7) 526-530;
4 Bickel WK, Stitzer ML, Bigelow GE, Liebson IA, et al (1988). A clinical trial of buprenorphine: Comparison with
methadone in the detoxification of heroin addicts. Clinical Pharmacology & Therapeutics, 247, 47-53;
5 Schneider U ;
6 Lintzeris N, Bell J, Bammer G, Rushworth L et al (2000) A radomised controlled trial of buprenorphine for the
management of outpatient heroin withdrawal. paper presented at the November 2000 National Methadone
Conference, Melbourne, Australia.

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and buprenorphine in the treatment of opioid dependence

The aim of medication in withdrawal is the reduction of withdrawal


symptoms and cravings not the complete removal of all symptoms
or the intoxication of the patient.
Patients should not receive the first dose of buprenorphine if they are experiencing heroin
effects. In practice, it is recommended that patients wait at least 6 hours after their last use
of heroin prior to receiving their first buprenorphine dose. It is preferable to withhold the
first dose until the patient is beginning to experience the early features of withdrawal. If there
are doubts or concerns, the patient should be asked to come back for dosing later in the day,
or alternatively, a lower initial dose can be dispensed (e.g. 2 or 4 mg) as it is less likely to
precipitate withdrawal than a high initial dose.

Buprenorphine can precipitate opioid withdrawal in someone who has recently


used heroin (within the past 6 hours) or methadone (See Section 3.5).
Preventing precipitated withdrawal on commencing buprenorphine
No heroin for at least 6 hours: severe discomfort may need palliation.
No methadone for at least 24 hours.
No buprenorphine if there are obvious heroin effects: wait for withdrawal signs or ask
patient to return the next day.

Use of ancillary medications in conjunction with buprenorphine


Buprenorphine provides general relief of withdrawal symptoms, so that other symptomatic
medications for opioid withdrawal are not routinely required. An exception is when patients
experience difficulty sleeping during withdrawal and may benefit from the limited use of
benzodiazepines as a hypnotic. However, benzodiazepines should not be used routinely from the
outset of the withdrawal episode, but rather should be added, as required, following clinical
review of the patient. Where sleep is a problem, it is safer to increase the dose of buprenorphine
than to prescribe benzodiazepines, with non-pharmacological approaches being encouraged (sleep
hygiene strategies). Non-pharmacological methods may not have an instant effect on sleep, but if
continued for days to weeks such strategies will help establish normal sleep patterns.
If considered necessary, low doses of a hypnotic (e.g. temazepam tablets 10-20 mg noct) should
be used with daily dispensing from the pharmacy (or supervised by a responsible adult). Under
normal circumstances, benzodiazepines should not be continued beyond several days.

Continued use of heroin and other drugs


Patients who keep on using heroin during buprenorphine treatment may have difficulty stabilising
on the medication and may continue to experience features of precipitated withdrawal after
each dose.
Persistent features of precipitated withdrawal discomfort may be grounds for transfer to
methadone or other withdrawal medications.

Chapter 6

The unsupervised use of other sedative drugs, such as benzodiazepines,


alcohol, other opioids, and tricyclic antidepressants in combination
with buprenorphine can be extremely dangerous, resulting in respiratory
depression, coma and death.

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and buprenorphine in the treatment of opioid dependence

All patients should be informed verbally and in writing of these risks and the advice documented
in the clinical records. Intoxicated patients should not be dosed with buprenorphine or sedative
medications.

Gateway model of treatment with buprenorphine


Buprenorphine is particularly useful in managing heroin withdrawal, in that it is not only effective
during the withdrawal period, but also facilitates links to post-withdrawal treatment. Many
patients entering withdrawal treatment do so without necessarily having considered all their
treatment options, simply hoping that an attempt at withdrawal will be sufficient to stop heroin
use.
The use of buprenorphine for several days generally alleviates withdrawal symptoms without
significant sedation, thereby allowing patients and clinicians to examine post-withdrawal issues
relatively early on in the withdrawal episode. (On many other withdrawal medications, such
as benzodiazepines or clonidine, patients are either so psychologically distressed or so heavily
sedated that this would not be possible.) A formal review of treatment plans should be structured
several days into the withdrawal episode, at which time treatment can be tailored accordingly.
For those patients who have successfully refrained from heroin use during withdrawal, and who
are considering longer-term naltrexone treatment, naltrexone can be initiated either during
buprenorphine administration or after a short course is ceased.
Patients who are not interested in ongoing pharmacotherapy treatment can cease a short course
of buprenorphine with minimal rebound discomfort. Alternatively, those patients who want to
extend the duration of their withdrawal program, or have reconsidered the role of a maintenance
treatment program, can continue buprenorphine treatment over a longer period of time. Care
should be exercised in transferring patients with short histories of heroin dependence from shortterm withdrawal programs on to long-term substitution maintenance programs. These treatment
pathways are shown in Figure 4.

Figure 4: Gateway model of treatment with buprenorphine


Naltrexone treatment
for relapse prevention
Commenced during or
soon after buprenorphine

Dependent heroin user


entering treatment

Buprenorphine regime
for 4 - 8 days with
exploration of post
withdrawal treatment
plans

Substitution
maintenance treatment
Buprenorphine or
methadone

Chapter 6

Withdrawal episode

No ongoing
pharmacotherapy
Psychosocial interventions

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

6.4 Buprenorphine regimens in outpatient withdrawal settings


Buprenorphine is long-acting so is well suited to outpatient withdrawal settings, allowing for
once-a-day supervised dosing.

Takeaway doses are not to be provided during the initial treatment period
(See section 4).
Patients unable to attend an authorised pharmacy daily for supervised dispensing should consider
alternative withdrawal medications.
There is no conclusive evidence of an optimal buprenorphine dosing regime for heroin
withdrawal. In general, daily buprenorphine doses of 4 to 16 mg appear to be most effective in
reducing withdrawal severity and heroin use (Gowing et al. 2006).
Induction onto buprenorphine for the purposes of detoxification should follow the same principles
as for buprenorphine maintenance. Once a stable dose is achieved, the rate of dose reductions
should be determined in consultation with the patient.
Some flexibility is allowable in doses to accommodate a range of factors, such as amount
of heroin use and psychological condition, impacting on each patients individual dosing
requirements and withdrawal severity.
Review by a trained health professional is recommended on a daily basis during the first few
days of the withdrawal regime. This is important so that doses can be adjusted, if necessary,
and any difficulties being experienced on the medication can be addressed. It is also needed to
ensure provision of appropriate support care and monitoring.

Buprenorphine doses should be titrated against severity of


withdrawal features and cravings for heroin use, actual use of heroin or
other drugs, and occurrence of side-effects.
Flexible dosages
Doctors may choose to prescribe a fixed daily dose (e.g. Day 1: 6 mg, Day 2: 8 mg, Day 3: 10 mg
etc) or, alternatively, prescribe a flexible regime with upper and lower limits on any particular
day and instructions for the home withdrawal sevice nurse regarding dose titration (e.g. Day 1: 6
mg, Day 2: 6-10 mg; Day 3: 8-12 mg etc).
It is a good idea to attempt a short-term regime (4 - 5 days), and schedule a formal review of
progress within a few days. At this review the clinician and patient can together consider the
available post-withdrawal treatment options (see section 5.6). Longer-term reduction regimes
(over 2 to 3 weeks) may also be effective and permit more time for relapse prevention and aftercare planning.

Chapter 6

Those patients who remain ambivalent about long-term post-withdrawal treatment and have not
been able to cease their heroin use, may need referral to an inpatient supervised withdrawal
program. Alternatively, an extension of the withdrawal regime over several weeks may be
warranted.

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and buprenorphine in the treatment of opioid dependence

However, there are good reasons for not prolonging buprenorphine treatment:
Administration of buprenorphine for more than several days commonly produces rebound
withdrawal when ceased, typically starting 1 - 3 days after the last dose of buprenorphine,
peaking 2 - 5 days after the last dose, and with some symptoms persisting several weeks.
Prolonged, probably unsuccessful, attempts at withdrawal can be demoralising for the patient,
resulting in lowered capability, self-esteem, and/or confidence in the treatment provider. For
this reason, a limit on the time spent on a gradual reduction regime should be discussed with the
patient early in the program.
Longer-term maintenance substitution treatment (with buprenorphine or methadone) should be
recommended to patients who:
cannot stop, or markedly reduce, their heroin use during the withdrawal episode;
relapse into regular heroin use as the dose of buprenorphine is reduced or ceased;
do not feel confident about maintaining abstinence but do not want to relapse to
dependent heroin use and the associated harms.
It is recommended that such patients stabilise on a maintenance substitution medication for
a longer period of time before coming off their maintenance treatment, to give them the
opportunity to first distance themselves from heroin use and possibly to address any problematic
psychological and social issues which may be distressing them.

6.5 Buprenorphine for heroin withdrawal in residential settings


Buprenorphine is well suited to use in inpatient withdrawal settings, given its ability to alleviate
the discomfort of withdrawal symptoms without significantly prolonging their duration.

It is recommended that an interval of at least 2 - 3 days be available from


the time of the last buprenorphine dose to the time of planned discharge.
Duration of dosing will be determined by the length of admission available. e.g. in a 7-day
admission, treatment will be limited to the first 4 - 5 days.
Approaches to dispensing in inpatient settings will depend on the level of supervision and
staffing available. Titration regimes generally require nursing staff who can administer
withdrawal scales and S8 medications, so places with limited access to nursing staff may be
better suited to fixed regimes with the option of additional rescue doses as required.
The additional rescue doses should only be administered:
at least 4 hours after the earlier dose and
if the patient is experiencing moderate or severe withdrawal discomfort.
Buprenorphine doses in inpatient settings can generally be lower as:
outpatient regimes must accommodate higher cravings and exert blockade effects;

Chapter 6

outpatient regimes are generally limited to once-a-day dosing.


An evening dose (between 5 PM and 10 PM) is recommended, to allow relief of withdrawal
symptoms until the morning. N.B Buprenorphine should not be administered if there are any
features of intoxication or sedation.

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and buprenorphine in the treatment of opioid dependence

The following regime is recommended for an admission time of approximately one week, and can
be tailored accordingly:

PROPOSED INPATIENT WITHDRAWAL REGIME


Day
Day 1
Day
Day
Day
Day
Day
Day

2
3
4
5
6
7

Buprenorphine S/L tablet regime

Total daily dose

4 mg at onset of withdrawal, & additional 2 to 4 mg evening dose


prn
4 mg mane, with additional 2 to 4 mg evening dose prn
4 mg mane, with additional 2 mg evening dose prn
2 mg mane prn; 2 mg evening prn
2 mg prn
no dose
no dose

4 to 8 mg
4
4
0
0

to
to
to
to

8
6
4
2

mg
mg
mg
mg

Total proposed dose = 12 to 28 mg

This regime serves as a guide only, and considerable individual variation in withdrawal severity
and medication requirements should be expected.
Post-withdrawal options should be explored prior to discharge.
Naltrexone: Patients commencing naltrexone treatment should do so during their admission.
Buprenorphine: Patients wishing to commence buprenorphine maintenance treatment should
continue their buprenorphine as inpatients until transfer to a community-based provider can be
organised.

6.6 Transition to post-withdrawal treatment


Transition to buprenorphine maintenance treatment.
Transition to a buprenorphine maintenance treatment program simply requires the continuation
of treatment, often with upward titration of the dose to achieve optimal maintenance dose levels
(e.g. 12 - 16 mg per day) (see section 3.6).

Transition to methadone maintenance treatment


The transition to methadone maintenance treatment requires the cessation of buprenorphine,
with the first dose of methadone given at least 24 hours later (see section 3.5).

Commencing naltrexone treatment after short duration buprenorphine withdrawal


This section considers commencement of naltrexone after a short period of use of buprenorphine
(less than 10 days) to manage withdrawal from heroin. Commencement of naltrexone after
cessation of buprenorphine maintenance treatment is discussed in section 3.12. Refer to the
clinical guidelines on the use of naltrexone (Bell et al. 2003) for treatment of opioid dependence
for information on patient selection, and management once on naltrexone.

Chapter 6

The simplest approach is to wait seven days after last dose of buprenorphine before commencing
naltrexone. Precipitation of withdrawal by naltrexone is unlikely following a 7-day opioidfree period (Bell et al. 2003). However, the pharmacology of buprenorphine does enable the
commencement of naltrexone earlier than this (Umbricht et al 1999). Naltrexone commenced
early in the course of heroin withdrawal managed with buprenorphine (day 2 or 3 after

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and buprenorphine in the treatment of opioid dependence

cessation of heroin while buprenorphine still being prescribed) will result in increased severity
of withdrawal on the day of the first dose of naltrexone, but may reduce the duration of
withdrawal. This approach is best undertaken in an inpatient or intensive day-care setting that is
able to respond to serious withdrawal symptoms if they occur.
A third option is to commence naltrexone 2 to 5 days after cessation of a brief course of
buprenorphine for management of heroin withdrawal. This is likely to be associated with mild to
moderate precipitated withdrawal. It is best undertaken in an inpatient or day care setting with
the ability to respond to severe withdrawal if it were to occur.
Administration of naltrexone within five days of stopping buprenorphine use is likely to result in
opioid withdrawal following the first dose of naltrexone. This typically commences 90 minutes to
4 hours after the first naltrexone dose, peaks around 3 to 6 hours after the naltrexone dose, and
generally subsides in severity within 12 to 24 hours. The withdrawal is frequently experienced as
moderate to severe at its peak. Subsequent doses of naltrexone produce considerably less severe
withdrawal discomfort.
Most patients undergoing this procedure request symptomatic medication, and clonidine (0.10.15 mg every 3 to 4 hours as required) and a benzodiazepine (eg diazepam 5mg, 3 to 4 hourly,
maximum of 30 mg in a day, as required) should be prescribed.

Chapter 6

PREPARE THE PATIENT IN ADVANCE


for the increase in withdrawal severity, the role of medications,
and the risks of using heroin to overcome the withdrawal symptom

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Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Appendix 1 Possible Drug Interactions with Methadone


Drug

Effect

Mechanism

Alcohol

Clinically important

Increased sedation,
increased respiratory
depression. Combination
may also have increased
hepatotoxic potential.

Additive central nervous


system depression.

Barbiturates

Clinically important

Reduced Methadone
levels. Increased
sedation. Additive CNS
depression.

Barbiturates stimulate
hepatic enzymes
involved in methadone
maintenance.

Benzodiazepines

Clinically important

Enhanced sedative
effect.

Additive CNS depression

Buprenorphine

Clinically important

Antagonist effect or
enhanced sedative and
respiratory depression.

Buprenorphine is a
partial agonist of opiate
receptors.

Carbamazepine

Clinically important

Reduced methadone
levels.

Carbamazepine
stimulates hepatic
enzymes involved in
methadone metabolism.

Chloral Hydrate

Clinically important

Enhanced sedative effect

Additive CNS depression

Chlormethiazole

Clinically important

Enhanced sedative effect

Additive CNS depression

Cimetidine

Two cases have been


reported in patients
taking methadone as
analgesia

Possible increase in
Cimetidine inhibits
methadone plasma levels. hepatic enzymes involved
in methadone metabolism

Ciprofloxacin

Case in a patient taking


methadone

Enhanced sedative
effect and respiratory
depression requiring
naloxone.

Probably by inhibiting
hepatic enzymes
involved in methadone
metabolism.

Cisapride
Domperidone
Metoclopramide

Theoretical

Theoretically might
increase the speed of
onset of methadone
absorption but not the
extent.

Possibly by reversing the


delayed gastric emptying
associated with opioids.

Cyclazine and
other sedating
anti-histamines.

Clinically important

Anecdotal reports of
injection of cyclazine
with opioids causing
hallucinations.
Reports of injections
of high doses of
dephenhydramine to
achieve buzz.

Additive psychoactive
effects. Anti muscarinic
effects at high doses.

(cyclazine is
not available in
Australia)

92
96

Status of Interaction

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Drug

Status of Interaction

Effect

Mechanism

Desipramine

Clinically important

Raised desipramine levels


by up to a factor of two.

Unknown mechanism not


seen with other tricyclic
antidepressants.

Other tricyclic
antidepressants

Theoretical

Enhanced sedative effect


which is dose dependent

Additive CNS depression.

Disulfiram

Avoid in combination with Very unpleasant reaction


methadone formulations
to alcohol which can be
containing alcohol (check dangerous.
with manufacturer)

Disulfiram inhibits
metabolism of alcohol
allowing metabolites to
build up.

Erythromycin

In theory should interact


but combination has not
been studied.

Increase in methadone
levels

Decreased methadone
metabolism.

Fluconazole

In theory the same as


ketoconazole

Fluoxetine
Sertraline

Clinically important

Raised methadone levels


but not as significant as
for fluvoxamine

Decreased methadone
metabolism

Fluvoxamine

Clinically important

Raised plasma methadone


levels

Decreased methadone
metabolism

Other SSRIs

Theoretical

Grapefruit juice

Should interact in theory


and there have been
several anecdotal reports

Raised methadone levels

Decreased methadone
metabolism

Indinavir

Clinically important

Raised methadone levels

Decreased methadone
metabolism

Ketoconazole

Clinically important

Raised methadone levels

Decreased methadone
metabolism

MAOI (including
selegiline and
moclobemide)

Severe with pethidine


though unlikely with
methadone and has never
been described

CNS excitation,
delirium, hyperpyrexia,
convulsions, hypotension
or respiratory depression.

Unclear, avoid the


combination if possible

Meprobamate

Clinically important

Enhanced sedative and


respiratory depressant
effect

Additive CNS depression

Naltrexone

Clinically important

Blocks effect of
methadone (long acting)

Opioid antagonist
competes for opiate
receptors.

Naloxone

Clinically important

Blocks effects of
methadone (short acting)
but may be needed if
overdose suspected.

Opioid antagonist
competes for opiate
receptors.

Nevirapine

Clinically important

Decreased methadone
levels

Increased methadone
metabolism

97
93

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Drug

Status of Interaction

Nifedipine

Has been demonstrated


in vitro only.

Increased nifedipine
levels. No effect on
methadone levels.

Methadone increases
metabolism of nifedipine.

Omeprazole

To date demonstrated
only in animals

Increased methadone
levels

Possibly an effect on
methadone absorption
from the gut.

Antagonist effect or
enhanced sedative and
respiratory depression

Pentazocine is a partial
agonist of opiate
receptors with weak
antagonist effect.
Phenytoin stimulates
hepatic enzymes involved
in methadone metabolism

Pentazocine

94
98

Effect

Mechanism

Phenobarbitone

See barbiturates above

Phenytoin

Clinically important

Reduced methadone
levels

Propanolol

To date demonstrated
only in animals.
Significance in humans
is not known. Exercise
caution when coadministering.

Enhanced lethality of
toxic doses of opioids

Rifampicin

Very important. Most


patients are likely to be
affected.

Reduced methadone
levels

Rifampicin stimulates
hepatic enzymes involved
in methadone metabolism

Rifabutin

Occasionally clinically
important

Decreased methadone
levels

Increased methadone
metabolism.

Ritonavir

Clinically important

Ritonavir may decrease


plasma methadone levels

Increased methadone
metabolism.

Thioridazine

Clinically important

Enhanced sedative effect


which is dose dependent

Enhanced CNS
depression.

Other protease
inhibitors

Theoretical

May raise or lower


Inhibits methadone
methadone plasma levels. metabolism.

Urine acidifiers
e.g. ascorbic
acid vitamin C

Clinically important

Reduced plasma
methadone levels

Increased urinary
excretion of methadone

Urine alkalisers
e.g. sodium
bicarbonate

Clinically important

Increased plasma
methadone levels

Reduced urinary
excretion of methadone

Zidovudine

Clinically important

Raised plasma levels of


zidovudine. No effects
on methadone levels

Unknown

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Drug

Status of Interaction

Effect

Mechanism

Zopiclone

Clinically important

Enhanced sedative and


respiratory depressant
effect

Additive CNS depression

Other opioid
agonists

Clinically important

Enhanced sedative effect


Enhanced respiratory
depression.

Additive CNS depression

Other CNS
depressant
drugs (eg
neuroleptics,
hyoscine)

Clinically important

Enhanced sedative effect


which is dose dependent

Additive CNS depression

This table is based on a similar table published in:


Department of Health, The Scottish Office Department of Health, Welsh Office, Department of
Health and Social Services Northern Ireland (1999) Drug Misuse and Dependence Guidelines on
Clinical Management. Her Majestys Stationary Office. Norwich.

99
95

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Appendix 2 Medications Metabolised by Cytochrome P450 3A4


This information is based on the listing at http://medicine.iupui.edu/flockhart/table.htm
Inhibitors (potentially
increasing
blood levels of
buprenorphine)
HIV Antivirals:
Delaviridine
Indinavir
Nelfinavir
Ritonavir
Other:
Amiodarone
Cimetidine
Clarithromycin
Erythromycin
Fluconazole
Fluvoxamine
Grapefruit juice
Itraconazole
Ketoconazole
Nefazodone
Norfloxacin
Verapamil

Substrates

Macrolide antibiotics:
Clarithromycin
Erythromycin
Anti-arrhythmics:
Quinidine
Benzodiazepines:
Alprazolam
Diazepam
Midazolam
Immune modulators:
Cyclosporine
Tacrolimus
HIV Antivirals:
Indinavir
Nelfinavir
Ritonavir
Saquinavir
Prokinetic
Cisapride
Antihistamines:
Astemizole
Calcium Channel
Blockers:
Amlodipine
Diltiazem
Felodipine
Nifedipine
Verapamil

100
96

HMG CoA Reductase


Inhibitors:
Atorvastatin
Cerivastatin
Lovastatin
NOT pravastatin
Simvastatin
Steroids:
Estradiol
Hydrocortisone
Progesterone
Testosterone
Miscellaneous:
Buspirone
Dapsone
Fentanyl
LAAM
Methadone
Ondansetron
Propranolol
Quinine
Tamoxifen
Trazodone
Zolpidem

Inducers (potentially
decreasing
blood levels of
buprenorphine)
HIV Antivirals:
Efavirenz
Nevirapine
Other
Barbiturates
Carbamazepine
Glucocorticoids
Modafinil
Phenobarbital
Phenytoin
Rifampin
St Johns wort

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Appendix 3 Patient Identification

Item
No

Check

Points
with
Photo

Points
without
Photo

1
12
3

Photo Identity Card


Current Australian passport
Minor [18yrs or less] with a parent or guardian

100
100
100

24
5

Current International passport


Patient known to the Medical practice for more than 5 years

100
75

36

Current Western Australian motor drivers licence or firearm


licence

100

25

47

Acknowledgment of current name/date of birth/address from


records held by a Government Authority
Licence or permit issued under Australian law other than item 2
Identity card or licence issued by a Government Authority
outside of Australia
Current identification card with name/date of birth/address
issued by a Government Authority
Current identification card with name/date of birth/address
issued by a tertiary institution

40

25

40
40

25
25

40

25

40

25

Acknowledgment of current name/date of birth/address from a


recognised professional body or trade association
Medicare card
Healthcare card
Under 18 card
Credit card

40

25

58
69
710
811
912
13
14
15
10
11
12
13
14
15
16

25
25
25
25

Acknowledgment of current name/date of birth/address from


records held by a public utility
Acknowledgment of current name/date of birth/address from
records held by a telephone utility

25

Name and address on the Australian electoral roll


Acknowledgment of current name/date of birth/address from
records held by a financial body
Acknowledgment of current name/date of birth/address from
owner or managing agent of rented domestic/business premises
Acknowledgment of current name/date of birth/address from an
insurance company

25
25

Certified copy or extract of a birth certificate; a citizenship


certificate or a marriage certificate
Authorised Identification Form ie tattoos, scars, height, and hair
colour.

25

25

25
25

101
97

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Appendix 4 Urinalysis
Drug

Approximate detection time

Alcohol

2 14 hours

Amphetamines

2 days

Barbiturates

Short acting 1 day


Long acting 2 3 weeks

Bezodiazepines

Therapeutic dose 3 days


Chronic dosing 4 6 weeks

Cannabinoids

Moderate smoker (4 X per week) 5 days


Heavy smoker (daily) 10 days
Heavy smoker (daily for months) 20 days or
more

Cocaine

2 4 days

Methadone

3 days

Opiates

2 days

PathCentre (2002) Drug Testing in the Workplace. Nedlands, W.A.

102
98

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Appendix 5 Resources for Health Professionals


Clinical Advisory Service (CAS)
Telephone: 9442 5042
Toll Free: 1800 688 847
Fax: 9471 0444
Provides 24-hour support and advice on the management of community based methadone and
buprenorphine patients. Services are provided by a Next Step Specialist Drug and Alcohol Service
on-call Medical Officer.

Community Clinical Programs, Next Step


Telephone: 9219 1907 / 9219 1913
Fax: 08 9471 0444
8.30 4.30 Monday to Friday
Provides information and support to clients currently on methadone and buprenorphine treatment
in WA. Assists with the transfer of clients to other service providers in WA, interstate and
overseas

Alcohol and Drug Information Service (ADIS)


Telephone: 9442 5000 / Toll free Country 1800 198 024
The Alcohol and Drug Information Services (ADIS) is a 24-hour state-wide telephone service that
provides counselling, information and referral for those concerned with their own or another
person's abuse of alcohol and other drugs. ADIS also provides information and referral support to
health professionals.

Women and Newborn Drug and Alcohol Service


KEMH
Telephone: 08 9340 2222

103
99

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Appendix 6 Resources for Patients


Next Step Specialist Drug and Alcohol Services
Next Step provides services for individuals requiring short-term intensive treatment detoxification
from alcohol, heroin and other illicit drugs from the Drug & Alcohol Centre in East Perth. Two
additional outpatient clinics are also available for the southern and northern corridors. The
Next Step detoxification program operates closely with the drug and alcohol non-government
organisations to facilitate the transfer of detoxified patients into these agencies' long-term drugfree programs.
East Metropolitan Drug and Alcohol Centre
32 Moore Street
East Perth 6004
Telephone: 9219 1919
Fax: 9221 3089

North Drug & Alcohol Centre


U3/26 Dugdale Street
Warwick 6024
Telephone: 9246 6767

South Metropolitan Drug & Alcohol Service


Level 3/22 Queen Street
Fremantle 6160
Telephone: 9430 5966

Next Step Drug and Alcohol Services -Youth


Service
32 Moore Street, East Perth 6004
Telephone: 9219 1919

Alcohol and Drug Information Service (ADIS)


Telephone: 9442 5000 / Toll free Country 1800 198 024
The Alcohol and Drug Information Services (ADIS) is a 24-hour state-wide telephone service that
provides counselling, information and referral for those concerned with their own or another
person's abuse of alcohol and other drugs. ADIS also provides information and initial assessment
for patients wishing to start or already in treatment.

Parent Drug Information Service (PDIS)


Telephone: 9442 5050 / Toll free Country 1800 653 203
PDIS is a 24-hour state-wide telephone service that provides counselling, information and referral
for parents concerned with their own or another person's abuse of alcohol and other drugs.
Support is offered to parents by specially trained parent volunteers who have experienced drug
use in their own families.

Community Clinical Programs Next Step


Telephone: 9219 1907 or 9219 1913
Provides a telephone advice and support service for current CPOP patients. The service is able
to assist with locating prescribers and dispensing pharmacies, arranging transfers and assistance
with other problems with treatment provision

104
100

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Additional Service Providers


There are a range of additional services providers. ADIS can assist health professionals with
information on the services available. Two additional key services for clients dependent on
opioids are

Hepatitis Council
Suite 3, 85 Stirling Street, Northbridge
Telephone: 1800 800 070

Western Australian Substance Users Association (Inc) (WASUA)


444 William St Northbridge WA 6003
email: wasua@wantree.com.au
Telephone: 9321 2877
Fax: 9321 4877

105
101

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Appendix 7 Assessment of acute intoxication


Class of Drug

102

Intoxication

Overdose

Opioids
(eg methadone, heroin,
morphine)

Constriction of pupils
Itching/scratching
Sedation/somnolence
Lowered blood pressure
Slowed pulse
Hypoventilation

Loss of consciousness
Respiratory depression
Pinpoint pupils
Hypotension
Bradycardia
Pulmonary oedema

Alcohol

Relaxation
Disinhibition
Impaired coordination
Impaired judgement
Decreased concentration
Slurred speech
Ataxia
Vomiting

Disorientation/confusion
Respiratory depression
Loss of consciousness
Loss of bladder control

Benzodiazepines
(eg diazepam, oxazepam,
flunitrazepam)

Disinhibition
Sedation
Drooling
Incoordination
Slurred Speech
Lowered blood pressure
Dizziness

Stupor/coma
Ataxia
Confusion
Respiratory depression

Stimulants
(eg amphetamines, cocaine)

Hyperactivity
Restlessness
Agitation
Anxiety/nervousness
Great dilation of pupils
Elevated blood pressure
Increased pulse
Raised temperature
Sweating
Tremor

Panic attacks
Acute paranoid psychosis
Seizures
Cardiac arrhythmias
Myocardial ischaemia
Hypertensive crisis
Cerebrovascular accidents
Hyperpyrexia
Dehydration

Cannabis

Relaxation
Decreased concentration
Decreased psychomotor
performance
Impaired balance
Conjunctival infection

Paranoid psychosis
Confusion
Agitation
Anxiety/panic
Hallucinations

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Signs and symptoms to look for/enquire about.


Intoxication

Toxicity

Slurred speech
Unsteady gait
Drowsiness
Pupil constriction
Conjunctival infection
Alcoholic foetor
Disinhibition
Drooling
Dizziness
Itching/scratching

Drowsiness
Shallow breathing
Poor circulation
Lowered temperature
Slow pulse
Nausea and vomiting
Headache
Confusion

From NSW Methadone Maintenance Treatment Clinical Practice Guidelines. Used with permission.

103

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Appendix 8 Diversion
Minimising the Risk of Diversion
To minimise the risks of diversion, patients should be provided with clear guidance on how and
why medication is given, and how they should present during observed consumption to avoid
unnecessary suspicion of diversion.
Buprenorphine
1. Patients should have their mouth cavity inspected prior to receiving their dose (gum, lollies
should be removed).
2. The dose should be crumbled to large coffee granule size (to reduce potential for diversion)
and dispensed into a clear plastic cup. Powdering of the drug should be avoided since it
promotes both the rapid development of an easily swallowed particulate solution and the
pasting of the drug into the top of the gums where it might be removed from the clinic.
3. The contents of the cup should be tipped under the tongue and then the oral cavity inspected
to confirm placement under the tongue.
4. Patients should be told that three to five minutes is the time required to get the most from
the drug and advised not to swallow their saliva during this period as buprenorphine is not
effectively absorbed if swallowed.
5. Patients should have their mouth cavity inspected after they report having absorbed the
entire drug sublingually prior to leaving the dosing site.
Methadone
1. Patients should have their mouth cavity inspected prior to receiving their dose (gum, lollies
should be removed). Check sleeves (ask clients to remove coats and roll up sleeves) to ensure
receptacles are not hidden for spitting dose into.
2. Use an individual disposable cup for each patient, do not pour methadone into another drink
container.
3. Add water (or other drink) as per clients request to the dose. Monitor throat for swallowing
action.
4. Inspect mouth cavity to ensure dose swallowed and talk with client after dosing, ensuring
client opens mouth and talks normally.
Possible indicators of diversion or attempted diversion
It is difficult to provide absolute indicators therefore the following must be assessed in the
context in which they occur and with regard to knowledge of the client. Video surveillance is
recommended.
Receptacles in the mouth such as plastic caps, glad wrap
Not wanting to stay for supervision
Causing distractions
Reading books, magazines etc close to face
Touching mouth with hand or sleeve
Browsing shop
Spitting, coughing, sneezing
Out of character behaviour, nervousness, being over-nice, watching pharmacist closely

104

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Appendix 9 Neonatal Withdrawal Scoring Instrument


ROYAL PRINCE
ALFRED HOSPITAL

WARD
MRN
SURNAME

KING GEORGE V HOSPITAL

OTHER

JOHN SPENCE NURSERY

NAMES
DOB/SEX

NEONATAL WITHDRAWAL SCORING CHART (TERM INFANTS)

MR 520
DATE AND TIME IN HOURS

GASTROINTESTINAL
DISTURBANCES

METABOLIC/VASOMOTOR/
RESPIRATORY
DISTURBANCES

CENTRAL NERVOUS SYSTEM DISTURBANCES

SYSTEM

SIGNS & SYMPTOMS

S
C
O
R
E

High-Pitched Cry
Continuous High-Pitched Cry
Sleeps <1 hour after feeding
Sleeps <2 hours after feeding
Sleeps<3 hours after feeding
Mild Tremors Disturbed
Mod-Severe Tremors Disturbed
Mild Tremors Undisturbed
Mod-severe Tremors Undisturbed
Increased Muscle Tone
Excoriation (Specify area)

2
3
3
2
1
1
2
3
4
2
1

Myoclonic jerks
Generalised Convulsions
Fever (37.3o-38.3oC)
Fever (38.4oC and higher)
Frequent Yawning (>3-4 times)
Nasal Stuffiness
Sneezing (>3-4 times)
Nasal Flaring
Respiratory Rate >60/min
Respiratory Rate >60/min
with Retractions
Excessive Sucking
Poor Feeding
Regurgitation
Projectile Vomiting
Loose Stools
Watery Stools
TOTAL SCORE
SCORERS INITIALS

3
5
1
2
1
1
1
2
1
2
1
2
2
3
2
3

From NSW Methadone Maintenance Treatment Clinical Practice Guidelines. Used with permission.

105

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Appendix 10 Opiate Withdrawal Scales


The Subjective Opiate Withdrawal Scale (SOWS)
Date

Time

PLEASE SCORE EACH OF THE 16 ITEMS BELOW ACCORDING TO HOW YOU FEEL

NOW
(CIRCLE ONE NUMBER)

SYMPTOM

A LITTLE

NOT AT ALL

MODERATELY

QUITE A BIT

EXTREMELY

I feel anxious

I feel like yawning

I am perspiring

My eyes are teary

My nose is running

I have goosebumps

I am shaking

I have hot flushes

I have cold flushes

10 My bones and muscles ache

11 I feel restless

12 I feel nauseous

13 I feel like vomiting

14 My muscles twitch

15 I have stomach cramps

16 I feel like using now

Range 0-64. Handelsman, L., Cochrane, K. J., Aronson, M. J. et al. (1987)


Two New Rating Scales for Opiate Withdrawal, American Journal of Alcohol Abuse, 13, 293-308.

106

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Objective Opioid Withdrawal Scale (OOWS)


Date

Time

OBSERVE THE PATIENT DURING A

5 MINUTE OBSERVATION PERIOD


THEN INDICATE A SCORE FOR EACH OF THE OPIOID WITHDRAWAL SIGNS LISTED BELOW
(ITEMS 1-13). ADD THE SCORES FOR EACH ITEM TO OBTAIN THE TOTAL SCORE

SIGN

MEASURES

Yawning

0 = no yawns

1 = 1 yawn

Rhinorrhoea

0 = < 3 sniffs

1 = 3 sniffs

Piloerection (observe arm)

0 = absent

1 = present

Perspiration

0 = absent

1 = present

Lacrimation

0 = absent

1 = present

Tremor (hands)

0 = absent

1 = present

Mydriasis

0 = absent

1 = 3 mm

Hot and Cold flushes

0 = absent

1 = shivering/huddling for warmth

Restlessness

0 = absent

1 = frequent shifts of position

10

Vomiting

0 = absent

1 = present

11

Muscle twitches

0 = absent

1 = present

12

Abdominal cramps

0 = absent

1 = Holding stomach

13

Anxiety

0 = absent

1 = mild severe

TOTAL SCORE

SCORE

Range 0-13
Handelsman, L., Cochrane, K. J., Aronson, M. J. et al. (1987) Two New Rating Scales for Opiate
Withdrawal, American Journal of Alcohol Abuse, 13, 293-308

107

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Appendix 11 Withdrawal States from Commonly Used Drugs


Drug class

Onset

Duration

Symptoms

Opioids

8-12 hours (short


acting). Delayed
for longer acting
opioids.

Peaks 2-4
Ceases 7-10 days
(short acting).
Longer for long
acting opioids.

anxiety, muscle tension, muscle


and bone ache, muscle cramps,
sleep disturbance, sweating, hot
and cold flushes, piloerection
(goosebumps), yawning,
lacrimation, rhinorrhea, abdominal
cramps, nausea, vomiting,
diarrhoea, palpitations, elevated
blood pressure, elevated pulse,
dilated pupils

Alcohol

As blood alcohol
falls, depends on
rate of fall and
hours after last
drink.

5-7 days

anxiety, agitation, sweating,


tremor, nausea, vomiting,
abdominal cramps, diarrhoea,
anorexia, craving, insomnia,
elevated blood pressure, elevated
pulse, temperature, headache,
seizures, confusion, perceptual
distortions, disorientation,
hallucinations, hyperpyrexia.

Benzodiazepines

1-10 days
depending on halflife

3-6 days

anxiety, insomnia, muscle


aching and twitching, perceptual
changes, feelings of unreality,
depersonalisation, seizures.

Stimulants

8-36 hours

Several days,
occasionally 2-3
weeks

lethargy, depression, irritability,


hyperphagia, anhedonia,
dysphoria, desire for sleep
increased.

Cannabis

Usually days

Weeks

irritability, anxiety, insomnia,


anorexia, sweating, muscle
spasms, headaches.

From NSW Methadone Maintenance Treatment Clinical Practice Guidelines.

108

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Appendix 12 Further reading and references


Avants SK, Margolin A, Sindelar JL, Rounsaville BJ, Schottenfeld R et al. Day treatment versus
enhanced standard methadone services for opioid dependent patients: a comparison of clinical
efficacy and cost. American Journal of Psychiatry 1999; 156 (1): 27-33
Department of Health, Government of Western Australia, Guidelines for Responding to Child
Abuse and Neglet and the Impact of family and Domestic Violence. WA Doh 2004.
Department of Health, The Scottish Office Department of Health, Welsh Office, Department of
Health and Social Services Northern Ireland. Drug Misuse and Dependence Guidelines on Clinical
Management. Her Majestys Stationery Office: 1999.
Dilppoliti D, Davoli M, Perrucci CA, Pasqualini F, Bargagli AM. Retention in treatment of heroin
users in Italy: the role of treatment type and methadone maintenance dosage. Drug and Alcohol
Dependence 1998; 52:167-171.
Drug and Alcohol Services Council (1994) Private Methadone Program. Policies and Procedures.
Adelaide: Author.
Gowing, L.R.; Ali, R.L.; & White, J. (2000). The management of opioid withdrawal: an overview
of research literature. DASC Monograph No 9, Research Series. Drug & Alcohol Services Council.
Griffith JD, Rowan-Szal GA, Roark RR, Simpson DD. Contingency management in outpatient
methadone treatment: a meta-analysis. Drug and Alcohol Dependence 2000;58(1): 55-66.
Humeniuk R, Ali R, White J, Hall W, Farrell M (Eds) Proceedings of expert workshop on the
induction and stabilisation of patients onto methadone. National Drug Strategy Monograph 39.
Commonwealth Department of Health and Aged Care, Canberra: 2000
Jarvis T, Tebbutt J & Mattick R (1995) Treatment Approaches for Alcohol and Drug Dependence.
John Wiley and Sons Sussex, England
Latowsky M. Improving detoxification outcomes from methadone maintenance treatment: the
interrelationship of affective states and protracted withdrawal. J Psychoactive Drugs 1996; 28(3):
251-7
NSW Health Department (1999) New South Wales Methadone Maintenance Treatment Clinical
Practice Guidelines. Sydney: Author.
NSW Department of Health. National clinical guidelines for the management of drug use during
pregnancy, birth and the early development years of the new born. March 2006, Commonwealth
of Australia
Nunes EV, Quitkin FM, Donovan SJ, Deliyannides D, Ocepek-Welikson K et al. Imipramine
Treatment of opiate dependent patients with depressive disorders. Archives of General
Psychiatry 1998; 55:153-60.
Petry NM A comprehensive guide to the application of contingency management procedures in
clinical settings. Drug and Alcohol Dependence 2000; 58 (1):9-25.
Preston A The New Zealand Methadone Briefing 1999. Drugs and Health Development Project.

109

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Wellington New Zealand: 1999


Prochaska JO, DiClemente CC & Norcross JC (1997) In search of how people change: applications
to addictive behaviours. In Addictive Behaviours: Readings on etiology, prevention and
treatment. Edited by G A Marlatt and G R VandenBos. Washington DC: American Psychological
Association, pp 671-696.
Royal Australian College of General Practitioners. Hepatitis C. A management guide for general
practitioners. Australian Family Physician December 1999 Volume 28 Special Issue.
Strain EC, Bigelow GE, Liebson IA, Stitzer ML Moderate versus high dose methadone in the
treatment of opioid dependence: a randomised controlled trial. JAMA 1999: 281(11):1000-5.
Ward J, Mattick R, & Hall W (Eds) Methadone maintenance treatment and other opioid
replacement therapies. Harwood Academic Publishers, Amsterdam: 1998

110

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

APPENDIX 13: FORM TEMPLATES


1. Takeaway Dose of Opioid Pharmacotherapy
2. Methadone treatment patient consent
3. Subutex treatment patient consent
4. Suboxone treatment patient consent
5. Subutex in pregnancy patient consent
6. High dose methadone transfer consent
7. Benzodiazepine client contract
8. Pain medication client contract
9. Pharmacy dosing client contract

111

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Takeaway dose application:

for pharmacotherapy prescribed to


an opioid dependent person
Methadone
Suboxone
Subutex
NB Takeaway doses of Subutex are not permitted other than in very exceptional circumstances, see over.
1. Patients personal details
(please use block letters)

HDWA Authorisation No.

Surname

Given name(s)

Date of Birth

Telephone No.

2. Current Dose

mg.

3. Number of takeaway doses requested


4. Ongoing

Temporary

pw

(if temporary from ____/____/_____ to ____/____/_____ )



6. Current Pharmacy (block letters)


7. Patient Review (see stability criteria over page)

The patient is stable and there are no contraindications to prescribing takeaway doses.
Yes

No (If No, takeaway doses cannot be provided)

8. Number of takeaway doses is within the schedule allowed (see over for schedules)

Yes
No

(no further approval required, complete declarations and file on patient file)
(complete information overleaf and fax both pages and any supporting evidence to CAS
on 9471 0444)

NB: All takeaway doses of Subutex are considered to be outside of the schedule and approval from
CAS must be obtained before scripts are provided
DECLARATION BY PATIENT
I understand that there are safety requirements for takeaway doses and undertake responsibility for the
safe use of the takeaway doses that I will receive.
1. Takeaway doses must be stored in a place that is out of each of children. A locked cabinet is ideal.
2. In order to reduce the risk of theft, the whereabouts of the dose should not be made known to
others.
3. The dose must be consumed according to the directions given by the prescriber. When more than
one takeaway dose is provided, each dose must be taken on the day for which it is prescribed. Doses
should not be stockpiled and no more than the prescribed daily dose should be taken.
4. Doses are not to be sold or given away.
There will be no replacement of doses that are spilled, vomited, lost or stolen. If any of these occur,
my prescriber must be notified as soon as possible.
Signed (Patient)

Date

DECLARATION BY PRESCRIBER
I certify


(a) that I have clinically assessed the patient as suitable for takeaway doses
(b) provided advice regarding storage and access to the takeaway dose(s), especially
with regard to children, and
(c) I have witnessed the above signature

Signed (Prescriber)

Date

Prescribers Name (Printed)




112

C-POP Authority to prescribe takeaways

5. Reason(s) for Request

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

To prescribe takeaway doses outside of the schedule of frequency to stable clients or to provide takeaway
doses of Subutex, approval must be obtained from CAS. Complete the additional information below and the
declarations on the front page. Then fax both sides of this form to CAS on 9471 0444.
Please describe the special circumstances warranting takeaways outside of the schedule or takeaway doses
of Subutex (attach any supportive documentation e.g: evidence of employment)

Office use only


Approved / Not approved
Date _____/______/______

CAS Consultant

Indications of stability
No recent injection sites
In a maintenance program for treatment more than 6
months
Regular and reliable contact with the prescriber and
pharmacy

Suitable, stable accommodation


Functional social behaviour
Not had problems with previous takeaways (where
applicable

Contraindications to takeaway doses


Diversion or attempted diversion in the last 6 months
Episodes of intoxication or hazardous use of other
drugs in the last 3 months.
Frequently missed dosing and/or appointments

Unstable or acute psychiatric condition


Child protection concerns
Attendance in crisis

SCHEDULES OF FREQUENCY (for more information see Section 4 of the Policy and Procedure manual)

Methadone
Time in treatment*

Number of takeaway doses permitted

Less than 6 months

Limited to exceptional circumstances.

6 - 12 months

After six months of continuous treatment and where the patient is assessed as stable and is working towards achieving treatment goals, they may be eligible for one
takeaway dose of methadone per week.

12 - 24 months

After 12 months of continuous treatment and where the patient has demonstrated
stability with one takeaway dose per week they may be eligible for two non-consecutive takeaway doses per week.

More than 24 months

After 2 years of continuous treatment and where the patient has demonstrated stability with two takeaway doses per week they may be eligible for 3 takeaway doses
of methadone per week. Only two of these may be consecutive.

Suboxone
Time in treatment*

Daily Dosing

Dosing every second day

Less than 6 months

Limited to exceptional circumstances.

6 - 24 months

1 per week

More than 24 months

2 per week

Dosing every third day

1 per week

*NB: Duration refers to continuous period of dosing with either methadone or buprenorphine. It does not refer to
continuity with the same service provider. This allows for transfers between service providers for stable clients.

113

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Surgery stamp

I
(patient name) voluntarily consent to starting
treatment with methadone. I understand that methadone is a long acting, addictive opioid drug that
is prescribed as treatment for opioid dependency. I understand that the duration of treatment will
be tailored to meet my particular needs in consultation with my doctor.
I have been given written information about the potential side effects of methadone and the
conditions associated with methadone treatment. I have read and understood the treatment
requirements. I am aware that other treatment options are available. These include detoxification,
counselling, residential rehabilitation and other medications such as buprenorphine and naltrexone. I
also understand it is my responsibility to be aware of the drug and alcohol policy of my employer.
I understand that the objectives of methadone treatment are to:
Reduce my opioid drug use and to help me become drug free
Reduce my risk of overdose and of contracting or transmitting blood borne diseases
Improve my physical, psychological and social well-being.
I understand that before I can receive methadone, authorisation must be obtained from the W.A.
Department of Health and my name will be included on the register of notified drug addicts. I
understand that methadone is taken orally in the form of a liquid that is swallowed and that I will
need to attend a community pharmacy for daily supervised methadone dispensing.
I understand that the disadvantages of methadone treatment include the following:
Methadone is a drug of dependency and can result in withdrawal symptoms if I stop or reduce
my dose.
The requirement for supervised dosing imposes restrictions on employment and travel.
There is a daily dispensing fee, set by the pharmacy that I must pay before each dose.
Methadone effects capacity to drive, operate machinery or work at heights during the early
stages of treatment or following dose increases. I understand that I have to refrain from
these activities during this time.
I have been informed that there are risks associated with methadone treatment during pregnancy
and understand that if I become pregnant I must advise my prescribing doctor as soon as possible to
discuss treatment options.
I am aware that methadone is dangerous to combine with other sedating drugs or medications such
as other opioids (e.g. heroin, morphine, codeine), benzodiazepines or alcohol. I understand that
there is a risk of overdose and death from this effect.
I understand that I have given permission for the sharing of information relevant to my treatment
to the Department of Health, Next Step and my pharmacy as stated on the application for authority
form.

Patient:

Date:

114

GP:
(signature)


(signature)

Next Step Community Clinical Programs template Methadone Treatment Consent July 2007

METHADONE TREATMENT
CONSENT FORM

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Surgery stamp

I
(patient name) voluntarily consent to starting
treatment with Subutex. I understand that Subutex is a long acting, addictive opioid drug that is
prescribed as treatment for opioid dependency. Subutex must be administered sublingually (under
the tongue).
I have been given written information about the potential side effects of Subutex and the conditions
associated with Subutex treatment. I have read and understood the treatment requirements. I
am aware that other treatment options are available. These include detoxification, counselling,
residential rehabilitation and other medications such as buprenorphine and naltrexone. I also
understand it is my responsibility to be aware of the drug and alcohol policy of my employer.
I understand that the objectives of Subutex treatment are to:
Reduce my opioid drug use and to help me become drug free
Reduce my risk of overdose and of contracting or transmitting blood borne diseases
Improve my physical, psychological and social well-being.
I understand that before I can receive Subutex, authorisation must be obtained from the W.A.
Department of Health and my name will be included on the register of notified drug addicts. I
understand that Subutex is taken orally in the form of a liquid that is swallowed and that I will need
to attend a community pharmacy for daily supervised Subutex dispensing. Takeaway doses are not
usually allowed other than in very exceptional circumstances.
I understand that the disadvantages of Subutex treatment include the following:
Subutex is a drug of dependency and can result in withdrawal symptoms if I stop or reduce
my dose.
The requirement for supervised dosing imposes restrictions on employment and travel.
There is a daily dispensing fee, set by the pharmacy that I must pay before each dose.
Subutex effects capacity to drive, operate machinery or work at heights during the early
stages of treatment or following dose increases. I understand that I have to refrain from
these activities during this time.
I have been informed that there are risks associated with Subutex treatment during pregnancy and
understand that if I become pregnant I must advise my prescribing doctor as soon as possible to
discuss treatment options.
I am aware that Subutex is dangerous to combine with other sedating drugs or medications such as
other opioids (e.g. heroin, morphine, codeine), benzodiazepines or alcohol. I understand that there
is a risk of overdose and death from this effect.
I understand that I have given permission for the sharing of information relevant to my treatment
to the Department of Health, Next Step and my pharmacy as stated on the application for authority
form.

Patient:

Date:

GP:
(signature)

Next Step Community Clinical Programs template Subutex Treatment Consent July 2007

BUPRENORPHINE
(SUBUTEX) TREATMENT
CONSENT FORM

(signature)

115

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Surgery stamp

I
(patient name) voluntarily consent to starting
treatment with Suboxone. I understand that Suboxone is a long acting, addictive opioid drug that is
prescribed as treatment for opioid dependency. I understand that the duration of treatment will be
tailored to meet my particular needs in consultation with my doctor.
I have been given written information about the potential side effects of Suboxone and the
conditions associated with Suboxone treatment. I have read and understood the treatment
requirements. I am aware that other treatment options are available. These include detoxification,
counselling, residential rehabilitation and other medications such as buprenorphine and naltrexone.
I also understand it is my responsibility to be aware of the drug and alcohol policy of my employer.
I understand that the objectives of Suboxone treatment are to:
Reduce my opioid drug use and to help me become drug free
Reduce my risk of overdose and of contracting or transmitting blood borne diseases
Improve my physical, psychological and social well-being.
I understand that before I can receive Suboxone, authorisation must be obtained from the W.A.
Department of Health and my name will be included on the register of notified drug addicts. I
understand that Suboxone is taken orally in the form of a liquid that is swallowed and that I will
need to attend a community pharmacy for daily supervised Suboxone dispensing.
I understand that the disadvantages of Suboxone treatment include the following:
Suboxone is a drug of dependency and can result in withdrawal symptoms if I stop or reduce
my dose.
The requirement for supervised dosing imposes restrictions on employment and travel.
There is a daily dispensing fee, set by the pharmacy that I must pay before each dose.
Suboxone effects capacity to drive, operate machinery or work at heights during the early
stages of treatment or following dose increases. I understand that I have to refrain from
these activities during this time.
I understand that Suboxone has not been cleared for use during pregnancy and if I become pregnant
I must advise my prescribing doctor as soon as possible to discuss treatment options.
I am aware that Suboxone is dangerous to combine with other sedating drugs or medications such as
other opioids (e.g. heroin, morphine, codeine), benzodiazepines or alcohol. I understand that there
is a risk of overdose and death from this effect.
I understand that I have given permission for the sharing of information relevant to my treatment
to the Department of Health, Next Step and my pharmacy as stated on the application for authority
form.

Patient:

Date:

116

GP:
(signature)


(signature)

Next Step Community Clinical Programs template Subutex Treatment Consent July 2007

BUPRENORPHINENALOXONE (SUBOXONE)
TREATMENT
CONSENT FORM

Consent form for buprenorphine (subutex) treatment


During Pregnancy/Breastfeeding

I,
am currently regularly taking buprenorphine for the management of my opiate dependence, and
wish to continue treatment with buprenorphine during my pregnancy / period of breastfeeding,
rather than:
transfer to methadone, or
withdraw from buprenorphine
In making this decision, I understand that:
the safety of buprenorphine during pregnancy or breastfeeding remains uncertain at this
stage,
pregnancy and breastfeeding are currently listed as contraindications for the use of
buprenorphine in Australia by the Therapeutic Goods Administration,
I will need to attend regularly (and as directed) for antenatal care at
Hospital,
I will need to attend regularly for appointments with my treatment team at


I give permission for my prescribing doctor to consult with my obstetric health care service
providers on my progress.

Yes

No

I have been provided with written information about buprenorphine and all my questions have
been answered

Client signature:

Date:

Date:

Witness name:

(PLEASE USE BLOCK LETTERS)

Date:

Witness signature:

Next Step Community Clinical Programs template Subutex in PREGNANCY CLIENT Consent July 2007

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

117

Client consent form for transfer to buprenorphine


from a methadone dose greater than 40mg

I,

(full name)

(date of birth) have been taking

mg methadone since

(date of commencement of current dose). I wish to undertake a transfer to


buprenorphine treatment.
In making this decision, I understand that:
the procedure for transferring to buprenorphine from doses of methadone higher than 40mg is
experimental
there are risks associated with undertaking this transfer including the likelihood of
experiencing withdrawal symptoms.
I have chosen to undertake this transfer with _____________________________________ (name of
prescribing doctor).
The procedure for making the transfer and the risks associated with this procedure has been
fully explained to me.
I have been provided with written information on buprenorphine.

My last dose of methadone was

mg on

(date) at

am/pm

at

My first dose of buprenorphine will be

(pharmacy).

mg on

(date) at

am/pm at

(pharmacy).

Client signature:

Date:

Date:

Witness name:

(PLEASE USE BLOCK LETTERS)

Date:

Witness signature:

118

Next Step Community Clinical Programs template HIGH DOSE METHADONE TRANSFER CLIENT Consent July 2007

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Pain medication agreement


understand that I am about to be prescribed

Next Step Community Clinical Programs template PAIN MEDICATION CLIENT Consent July 2007

I,

, a regulated medication for the purpose of helping me with my pain.


For this reason I agree to the following special conditions.
I understand that my pain will probably not be completely controlled. However these
medications will be used in order to achieve the following aims.

This is a trial of medications. If these aims are not achieved by


will be slowly ceased.

the medication

I will obtain these medications only from my doctor Dr


It is my responsibility to ensure that my medication supply is sufficient and to plan review
appointments with my doctor so that my medication does not run out after hours.

In extreme emergencies, should I need to seek an alternative supply, I will inform my doctor
as soon as possible and arrange an appointment to discuss the management plan and future
prescribing options.

I understand that there is a risk of becoming dependent on these medications.


I understand that initially, I may feel sleepy and less alert and that this may mean it is
dangerous to drive or operate machinery. At all times this medication can interact with other
sedative medications, making this effect worse.
I understand that this medication can be dangerous if taken by others and that it cannot be
replaced if lost or stolen. I understand that it is my responsibility to ensure the safety of this
medication.
I understand that if I do any of the following, my medication may be terminated immediately.
Become aggressive or abusive at the surgery or pharmacy
Forge scripts or sell the medications
Obtain other supply of regulated medication without informing my doctor
Use the medication in a way that it was not prescribed
Repeatedly lose medication and request further supplies
I agree that my prescriber may obtain information about previous prescriptions for
benzodiazepines and other medications from the Health Insurance Commission, the
Department of Health and

Patient signature:

GP signature:

Date:

Date:

119

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Benzodiazepines are sedative drugs which have been used to treat anxiety and insomnia. However
there are a number of problems that can occur with the use of these drugs.
Benzodiazepines can cause sleepiness, confusion, short-term memory loss and unsteadiness
(therefore increasing the risk of accidents, injury and falls). Benzodiazepines can be dangerous
when combined with alcohol, illegal drugs or many prescription medicines. Use of benzodiazepines
can also make driving dangerous.
Benzodiazepines are addictive drugs and will only be prescribed in a controlled manner. In order to
make sure that these are prescribed safely, I agree that:

1. Dr
may obtain information about previous prescriptions for benzodiazepines and other medications
from the Health Insurance Commission, the Department of Health and

2. I will attend appointments on time as agreed and I will not seek benzodiazepine supplies earlier
than the agreed date.
3. I will not seek supplies from other practices except in extreme emergencies. Should such an
emergency occur, I will attend this practice at the first available chance to discuss the plan for
further prescribing.
4. Once a prescription has been written or a drug has been dispensed it is my responsibility to
make sure that the script or the drug is safe. No repeat scripts will be written for lost or stolen
medication or scripts.
5. I will not give away or sell any of these supplies and will only take this medication as directed by
my doctor.
6. If I am not able to stay within this agreement, I understand that my prescriptions may be ceased.

I,
(print patient name) have read the information on this page and agree to the above conditions.

Patient signature:

GP signature:

120

Date:

Date:

Next Step Community Clinical Programs template BENZODIAZEPINE MEDICATION


CLIENT Consent July 2007

Benzodiazepine information and agreement

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

PHARMACY - CLIENT CONTRACT


The following contract is to be signed by clients participating in the Community Program for
Opioid Pharmacotherapy Program (CPOP) to ensure doses are dispensed as discreetly as possible
and without disrupting the normal daily operations of the pharmacy.
It is important to understand these guidelines fully before enrolling with this dispensing site.
1. METHADONE - I must drink my methadone as per prescription instructions and program
guidelines. It is my responsibility to satisfy the duty pharmacist that I have swallowed my
dose by:
drinking my dose in front of the duty pharmacist [unless otherwise authorised by my
methadone prescriber]
speaking to the duty pharmacist immediately after swallowing my dose.
2. BUPRENORPHINE - I must take my medication as per prescription instructions and program
guidelines. It is my responsibility to satisfy the duty pharmacist that my dose has dissolved
by:
Placing my dose under my tongue and waiting until the pharmacist says I may leave the

pharmacy [unless otherwise authorised by my buprenorphine prescriber]. This may take


up to eight minutes.
3. My medication will not be dispensed to me if, in the opinion of the duty pharmacist, I present
as apparently intoxicated or behaving as if under the influence of alcohol and/or drugs.
4. I understand that if I am troubled by nausea and vomiting, no dose of methadone will be
replaced unless the duty pharmacist has seen me vomit and my prescriber has authorised a
replacement dose.
5. I understand that no dose of buprenorphine will be replaced if the dose is accidentally
handled by me, dropped, chewed or swallowed, unless specifically authorised by my
prescriber.
6. Rudeness, verbal abuse, disruptive or threatening behaviour and acts of violence are
unacceptable and will result in restriction or cancellation of community dispensing & possible
termination of my treatment and/or police involvement.
7. Any suspicion of drug dealing or other criminal activity on or within the vicinity of these
premises will result in the police being called.
8. I must attend for my dose at the times nominated by this dispensing site. If for any reason I
am unable to attend during these times I understand I will have to miss that days dose.
9. I must dose at this site on the days/dates arranged by my prescriber. Exceptions to this are
only given in cases of medical emergency and must be authorised by my prescriber.
10. Missing two or more consecutive scheduled doses means I cannot be dosed by this pharmacy
until I have been reviewed by my prescriber. A pattern of missed consecutive scheduled doses
may result in the cessation of my treatment.
11. I will keep appointments as scheduled by my prescriber. Failure to do so may result in my
dispensing site being instructed to cease dosing me.

121

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

12. Overdue payments will lead to termination of my community dispensing arrangements.


13. If difficulties or problems arise in any area, I agree to discuss these with my prescriber.
14. If for any reason the community pharmacy refuses to continue my daily dosing, it is my
responsibility to discuss this with my prescriber.
15. If I am unable to find another community dispensing site willing to dispense to me, I
understand I may be required to commence a detoxification [reduction] regimen.
16. I also give permission for my prescriptions to be faxed to my dispensing outlet and for the
duty pharmacist and my prescriber to exchange information concerning my medical history,
social well-being and/or any other relevant information related to my participation in this
treatment program.
17. I understand community pharmacists have an obligation to report breaches of this contract
to my prescriber.
SPECIAL TIMES/CONDITIONS AND/OR CHARGES RELATING TO THIS PHARMACY/DISPENSING SITE:


I have read, understood and accept the conditions printed above.


CLIENT NAME

SIGNATURE

DATE

DUTY PHARMACISTS
NAME

SIGNATURE


DATE

Pharmacy Stamp or name

* A copy should be retained by both the pharmacy and the client.

122

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Appendix 14 Drugs of Dependence recording requirements


Drug Register Recording
Methadone and buprenorphine are drugs of addiction and usage must be recorded in a Drugs of
Addiction Register. Separate registers are used for methadone (HA 212) and buprenorphine (HA
176) and are available form your wholesaler. Methadone for use outside of the CPOP is to be
purchased and recorded separately from the CPOP with a separate running balance.
All quantities of methadone and buprenorphine received from the wholesalers and supplied to the
patient must be recorded in the appropriate register.
When a dose is administered to the patient the recordable details must be entered in the register
on the day of the transaction.
If a takeaway dose is dispensed it is recommended that this entry be clearly marked as a takeaway
dose.
All records must be kept for a period of no less than seven years from the date of the last entry.

Patient Dosing Sheets


Each patient is required to have a Patient Dosing Sheet that documents individual patients
daily dosing history. This record sheet can be used as an aid to review patient compliance (e.g.
monitoring missed doses, intoxicated presentations etc). The dosing sheet also enables easier
completion of the monthly transaction reports. A template Patient Dosing Sheet (Appendix 15) is
available for photocopying for multiple use. Alternatively dosing sheets tailored to each quarter of
the year can be ordered free of charge from Community Clinical Programs at Next Step (08) 9219
1913.

Drugs of Addiction Transaction Report


A monthly Pharmacy Report Form must be completed and faxed or included with the Drugs of
Addiction Transaction Report, to the Department of Health by the seventh day of the following
month.
The Pharmacy Report Form requires the following details for each patient administered or
supplied with methadone or buprenrophine:
Indicate with M, B or X whether the drug is Methadone (M), Subutex (B) or Suboxone (X)
The patients name in full
The HDWA authorisation number as endorsed by the prescriber on the prescription.
The last dose (in milligrams) administered or supplied that month.
The number of takeaway doses supplied
The number of missed doses
Indication of patients who commenced or ceased dosing at the pharmacy that month.

123

Keep a copy of this report for


your own records.
Fax completed form to
9388 4988

Methadone Subutex - Suboxone


Pharmacy Report Form
PBS Approval No.

For the Month of


Drug
M, B
or X

Year
Patient Name
(First name and Surname)

Certified as complete and correct:


HDWA
No.

1*

2*

Dose
#
in (mg)

Number Of Doses
Missed

Takeaways


Print Pharmacists Name



M ,B or X
HDWA No.
1*
2*
#

Pharmacists Signature

Date

Please indicate whether Methadone (M), Subutex (B) or Suboxone (X)


The HDWA number endorsed by the prescriber on the prescription.
Tick column if patient is new to pharmacy.
Tick column if patient ceases receiving Methadone, Subutex or Suboxone from pharmacy.
The last dose the patient received for the month.

This report is to reach the Department of Health no later than seven (7) days after the end of the month
during which the transactions occurred and may be sent with the Drugs of Dependence
monthly transaction report.
All correspondence to the Manager, Drugs of Dependence, Department of Health, PO Box 8172, Perth Business Centre, Perth WA 6849
For further information telephone 08 9388 4945 or fax 08 9388 4988

124

Community Program for opioid Pharmacotherapy

Pharmacy Name

Pharmacy Report Form

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

June

May

April

March

February

January

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Suboxone

PHARMACOTHERAPY DOSE RECORD SHEET commencing JANUARY

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

125

126

December

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22

22

22

23

23

23

23

23

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24

24

24

24

24

24

25

25

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25

DRUG: Methadone

26

26

26

26

26

26

27

27

27

27

27

27

28

28

28

28

28

28

Subutex

29

29

29

29

29

29

30

30

30

30

30

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31

31

31

31

Suboxone

PHARMACOTHERAPY DOSE RECORD SHEET commencing JULY

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

127

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

128

Clinical policies and procedures for the use of methadone


and buprenorphine in the treatment of opioid dependence

HP3344 OCT2007 22415

Drug and Alcohol Office, 2006

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