National DST Guidelines

(Buprenorphine & Buprenorphine / Naloxone)

Dr Philip George
Senior Lecturer, Psychiatry
International Medical University of Malaysia

Dr Raminder Kaur
Consultant Psychiatrist
Hospital Kuala Lumpur

Federation of Private Medical Ministry of Health

Practitioners Associations, Malaysia Malaysia
 Background
400-800K drug users in Malaysia

29 Pusat Serentis nationwide

detains 8,000 to 9,000 drug users at any one time
drug users are detained up to 2 yrs

High prevalence of relapse among rehabilitated drug users

(70-90%)

Illicit drug use results in HIV and Hep C as a consequence of

needle sharing practices

Malaysia 2nd highest adult prevalence and highest

proportion of HIV due to injecting drug use in Western Pacific
region.
 Harm Reduction Programme Drug
Substitution Treatment

2001:
Buprenorphine introduced in 2001
Effective in preventing withdrawal symptoms, easy to use and
having a good safety profile have encourage the medical
community to start treating opioid dependent individuals

Currently:
300 medical practitioners currently providing drug substitution
treatment
 National Drug Substitution Therapy

Rationale for Development of Suboxone

(Buprenorphine / Naloxone Combination)

Transfer from and to Methadone Treatment

Supervised / Unsupervised / Take Away / Missed Doses

Overdosing & Minimising Risk of Diversion

Prescribing & Dispensing Issues

 National Drug Substitution Therapy

Rationale for Development of Suboxone

(Buprenorphine / Naloxone Combination)

Transfer from and to Methadone Treatment

Supervised / Unsupervised / Take Away / Missed Doses

Overdosing & Minimising Risk of Diversion

Section 6
Prescribing & Dispensing Issues
WHAT is Drug Substitution Therapy?
Drug The administration under medical
Substitution supervision of a prescribed medicine with
Treatment similar action to the drug of dependence

One of the components of Harm Reduction

For drug addicts

Replaces dangerous drugs (e.g. heroin

and morphine) with prescribed medication
of similar action but of much lower
addictive / sedative effects

AIM: Prevent / reduce negative health

AIM consequences associated with risky
behaviours of injecting drugs
WHY Drug Substitution Therapy?
Reduce relapse among opiate dependents

Improve the physical and mental condition of opioid dependents

Reduce spread of injection among IVDU and those sharing needles

(eg HIV, hepatitis B and C)

Improve psychosocial functioning, including ability to obtain

or remain in gainful employment and to improve their social
adaptation and integration into the society

Reduce criminal activities amongst opiate dependents

NDST Requirements
Prescriber must be a registered medical doctor
in Malaysia with valid practicing certificate

Practicing in: private clinic / hospital

that have fulfilled the requirements of the Private Healthcare Facilities
And Services Act 1998, Regulations 2006
General Hospitals

Undergone all necessary training and all CME / CPD requirements

Comply with all law / regulations in Malaysia

Comply with all relevant Guidelines issued by the MOH

Registered and accepted the terms of the NDST Registry

NDST Prescribing Requirements

Combination of buprenorphine / naloxone will be made available to

to all trained practitioners registered with the NDST Registry.

Buprenorphine will only be available in Hospital and Specialised

Addiction Centres for the following:

- Hypersensitivity to naloxone component

- Initial transfers from methadone treatment
- Pregnancy (no clinical data has been established in this group of
patients)

Buprenorphine and Buprenorphine / Naloxone treatment assumes

DOT (daily observed treatment).

Takeaway doses are only allowed to patients stabilized on

treatment, not less than 4-6 weeks after initiating therapy.
Treatment Challenges
Difficulties managing complicated patients, resulting in
poor retention and remission in treatment.

Lack of supervision when prescribing buprenorphine

leads to poor adherence, diversion and abuse of
medication.

Shift in injecting practices i.e. from heroin to

buprenorphine + benzodiazepam
DST Registry
Objective: To encourage appropriate prescribing and
reduce diversion of buprenorphine and methadone.

Allows drug abusers who manipulate the system (doctor

hopping) to be identified.

Required: All doctors and patients to register with DST

Registry.
DST Category
 National Drug Substitution Therapy

Rationale for Development of Suboxone

(Buprenorphine / Naloxone Combination)

Transfer from and to Methadone Treatment

Supervised / Unsupervised / Take Away / Missed Doses

Overdosing & Minimising Risk of Diversion

Prescribing & Dispensing Issues

Rationale for Suboxone
(Buprenorphine / Naloxone Combination)
Provide a product less abusable by injection by opioid
dependent subjects
Injecting Suboxone causes severe withdrawal
Encourage sublingual use of buprenorphine
Safer as take-away medication
What sort of effects do you think
Subutex / Suboxone will have on the
following customers?

1. Dependent heroine user

2. Non-dependent heroine user
3. Opiate nave
4. Monobuprenorphine maintenance
5. Methadone maintenance dose
Effects Of Mono and Combination Preparations of
Buprenorphine in Various Situations
Suitability for Buprenorphine &
Buprenorphine/Naloxone Treatment

Indications
Opioid-dependent
15 years or older
Good family support
Agree to adhere to treatment regulations

Contraindications
Hypersensitivity and/or severe side-effects
from previous BPN treatment
Pregnancy / breast feeding
Severe respiratory / hepatic insufficiency
Suitability for Buprenorphine &
Buprenorphine/Naloxone Treatment

CAUTION:

Polydrug use
Concomitant medical conditions
Concomitant psychiatric conditions
Suffering chronic pain
Transfer from methadone maintenance
Uncertain tolerance
Care Contact
The participation of an informed patient in the clinical
decision-making process is essential in the treatment of
all opioid dependence.

All patients commencing treatment with BPN must agree

to treatment regulations

Details in the Registry

Permits & Registration of Patients

Buprenorphine is registered as a psychotropic and

poison medication.

Only trained and certified medical practitioners are allowed to

prescribe buprenorphine for the management of
opioid dependence.
 National Drug Substitution Therapy

Rationale for Development of Suboxone

(Buprenorphine / Naloxone Combination)

Transfer from and to Methadone Treatment

Supervised / Unsupervised / Take Away / Missed Doses

Overdosing & Minimising Risk of Diversion

Prescribing & Dispensing Issues

Transfer from methadone maintenance
treatment

Typical maintenance dose: 8 16mg/day

Optimal dose: Sufficient to diminish the discomfort of

withdrawal for the full interdosing interval

Administer buprenorphine at least 24 hours after the

last dose of methadone

The maximum recommended daily dose of

buprenorphine is 24mg.
A dose of 32mg is suitable for patients on alternate-
day / 4x-a-week dosing regimes
Cessation of buprenorphine maintenance
treatment

Rates of Dose Reduction

Dose of Buprenorphine Reduction Rate

>16 mg 4mg per week or fortnight

8-16 mg 2-4mg per week or fortnight

<8 mg 2mg per week or fortnight

 Transferring to methadone

Intolerable side effects to buprenorphine

Inadequate response with buprenorphine treatment.
Buprenorphine is not available.
Complications with antagonists and analgesics.

Methadone can be commenced 24 hrs after the last

dose of buprenorphine, at an initial daily dose not
exceeding 40mg.
 National Drug Substitution Therapy

Rationale for Development of Suboxone

(Buprenorphine / Naloxone Combination)

Transfer from and to Methadone Treatment

Supervised / Unsupervised / Take Away / Missed Doses

Overdosing & Minimising Risk of Diversion

Prescribing & Dispensing Issues

 Supervised Daily Administration

Objectives

To allow close supervision and monitoring of patients
To minimize the risk of diversion to the black market
To minimize the risk of injection of crushed
buprenorphine tablets
To minimize risk of consumption other than as
prescribed
 Unsupervised Doses Take away doses

Improving access to treatment by reducing travel

difficulties
Reducing congregation at dispensing points
Promoting self-respect and autonomy of patients
Take-Away Doses

Risks

Benefits

Requirements

Contraindications

Levels of Supervised Dosing

 Take-Away Doses
Risks

Hoarding and deliberate overdose of self or others

Use in dangerous combination with other sedative drugs
Self-administration by injection, with the potential for
bacterial infection and blood-borne viral transmission
Diversion for illicit use or trafficking
Accidental overdose (by children or other non-tolerant
substance misusers)
Poor compliance with treatment plan
Sharing of dose with partner or associates.
 Take-Away Doses
Benefits

Lessen constraints on stable patients

Minimal disruption from the demands of daily supervised
dosing.
Recognizing and rewarding stable patients (Incentive)
improves outcomes in opioid substitution treatment
Unusual situations (court appearances, holidays,
conferences, etc)
Contribute to the acceptability of prolonged
pharmacotherapy maintenance and patient retention in
treatment
 Take-Away Doses
Requirements

Only prescriber may authorize take-away doses

To authorize take-away doses the patient should be stable
on treatment
Patient should be clinically assessed prior to authorizing
take-away doses and the patients stability documented
Person administering doses should be contacted to confirm
that recent behaviour and dose collection has been stable
TAD should not be available to patients in their 1st month of
treatment
TAD should be the same dose as that normally consumed
TAD should not be available if there is concern over misuse
 Take-Away Doses
Contraindications

Unstable patterns of substance use

Significant unstable psychiatric conditions
Unstable medical conditions
Possibility of diversion or inappropriate use of methadone
or buprenorphine
Requires assessment of stability of patients home environment

Reasonable concerns about diversion of doses for illicit or

unsanctioned use
Take-Away Doses
Levels of supervised dosing
Stable drug use, and suitability for
unsupervised dosing, is indicated by:
Regular attendance at appointments
Urine drug screens provided when requested
No or infrequent additional opioid use
Benzodiazepine use if absent or at low levels and strict
medical supervision
No alcohol abuse
No use of stimulants
No intoxicated presentations / overdoses in prior 3 months
No missed doses in past 4 weeks
No signs of injection / puncture marks
Continued high-risk drug use
Cease take-away dose
Ensuring supervised consumption
Daily dosing regimes
Drug Testing (eg on-site urine screens)

Transfer to another pharmacotherapy (eg methadone)

may be indicated if:
There is little or no response to an increase in medication
The patient is already on a high dose of medication
An increase in dose is considered unsafe by the prescriber
Patient is persistently diverting their dose
Patient attends irregularly, frequently missing scheduled
doses
Continued high-risk drug use
Cease take-away dose
Ensuring supervised consumption
Daily dosing regimes
Drug Testing (eg on-site urine screens)

Transfer to another pharmacotherapy (eg methadone)

may be indicatedTransfer
if: to a
Specialized Drug
There is little or no response Treatment
to an Unit
increase in medication
The patient is already on a high dose of medication
An increase in dose is considered unsafe by the prescriber
Patient is persistently diverting their dose
Patient attends irregularly, frequently missing scheduled doses
Missed Doses
1. Contact prescriber. Buprenorphine dose
prescribed should be sufficient to last until the
next scheduled dose.
2. If unable to reach prescribing doctor, no
buprenorphine can be dispensed. However, this
increases the risk that the patient will drop out of
treatment.

>1 wk dose: Reinducted into BPN treatment

<1 wk dose: Continue on their maintenance dose
(provided there is no evidence of acute intoxication with opioid, alcohol, or
benzodiazepines)
 National Drug Substitution Therapy

Rationale for Development of Suboxone

(Buprenorphine / Naloxone Treatment)

Transfer from and to Methadone Treatment

Supervised / Unsupervised / Take Away / Missed Doses

Overdosing & Minimising Risk of Diversion

Prescribing & Dispensing Issues

 Overdose

Less risk of lethal overdose

Risk present with the opioid nave
Safer around children
Risk increases when mixed with other sedatives
High doses of antagonist needed for overdose
reversal
 Minimizing risk of diversion

1. Patients should have their mouth cavity inspected prior to

receiving their dose.

2. Dose may be given in large broken pieces and dispensed into

a clear plastic cup. Powdering of drug should be avoided
since it promotes both 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. Contents of cup should be tipped under the tongue and then

the oral cavity inspected to confirm placement under the
tongue.
 Minimizing risk of diversion

4. Patients should be told that 3 5 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.

Where there is ongoing misuse of the medication,

patients should be warned that they may have to be
transferred from buprenorphine treatment to
methadone, which is easier to supervise, or
terminated from treatment.
 Pregnancy & Lactation

Methadone maintenance is the first line treatment of

opiate dependence in pregnancy.

Buprenorphine is a Category C drug,

which has implications for 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 established.
 National Drug Substitution Therapy

Rationale for Development of Suboxone

(Buprenorphine / Naloxone Combinations)

Transfer from and to Methadone Treatment

Supervised / Unsupervised / Take Away / Missed Doses

Overdosing & Minimising Risk of Diversion

Prescribing & Dispensing Issues

Prescribing Requirements

Name + Address of prescribing doctor who has been authorised to

prescribe.

Patients name + address

Date of prescription

Preparation to be dispensed

Dose of drug to be dispensed in mg (words + numbers)

Different dose schedules must be written separately

(e.g. 24 hr doses, 2-day or 3-day doses)

Beginning and end dates of the prescription

Written Agreement

Physician should employ the use of a written agreement

between physician and patient addressing the following:

Alternative treatment options

Regular toxicologic (urine) testing for drugs of abuse and

therapeutic drug levels

Duration of direct observed treatment, including when take

away doses are allowed.

Reasons for which drug therapy may be discontinued

(i.e. violation of agreement)
Dispensing

1st month of treatment Only DOT (Direct Observed

Treatment) allowed

Weekend doses / Take away doses can be considered

thereafter if patient shows improvement in lifestyle
changes and urine toxicology remains negative

OTC dispensing STRICTLY PROHIBITED.

Under normal circumstances, a friend or family member

will not be allowed to collect the patients medication on
his/her behalf.
Protocols for administering buprenorphine

Prior to administering the medication, staff must:

Establish the identity of the patient

Confirm that the patient is not intoxicated

Check dose and currency of the prescription

a patient cannot be dosed if a prescription is not current

Check that the current day is a dose day on the patients regime

Confirm the dose for the current day if it is an alternate-day or

3x-a-wk regime
Arrangements to cover absence from practice

Document and maintain up-to-date individual patient management

plans in the patients records, so as to enhance communication with
colleagues

Make arrangements for a colleague (preferably an approved

pharmacotherapy prescriber) to continue the documented
management plan for each patient

Request that any deputizing colleague record treatment changes in

the patient notes
What if deputizing practitioner is not accredited to prescribe
pharmacotherapies ?

Document and maintain up-to-date individual patient management

plans in the patients records, so as to enhance communication with
colleagues

Make arrangements for a colleague (preferably an approved

pharmacotherapy prescriber) to continue the documented
management plan for each patient
Management by deputizing prescribers

Continue the usual management plan and dosage regimen as

documented in the clinical record.

It is acceptable to reduce dose if patient is experiencing toxicity.

Limit the duration of the prescription to the expected period of

absence of the usual prescriber, indicating precise starting and
finishing dates

Arrange for the usual prescriber to review the patient asap thereafter

Document details of consultations and pharmacotherapy

prescriptions in the patients notes.
Appendix 1: Medications metabolised by
cytochrome P450 3A4
Appendix 2: Scales for assessing opioid
withdrawal
Appendix 2: Scales for assessing opioid
withdrawal
Appendix 2: Scales for assessing opioid
withdrawal
Appendix 2: Scales for assessing opioid
withdrawal