There is progressive increase in use of opioids for pharmaceutical purpose in AUSTRALIA. There are serious unintended consequences of pharmaceutical opioid use.

1. The use and unintended
consequences of pharmaceutical
opioids in Australia?
Michael Farrell

2. The Difference is Research
The Difference is Research
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Disclosures
Mundipharma Australia (who market Reformulated OxyContin® and
Targin®) provided travel support for this meeting.
The NOMAD study was funded via an investigator-driven, untied
educational grant from Mundipharma Australia. The funder has no
role in the design, conduct, analysis, interpretation or decision of
what/where to publish.
I have also received untied educational grants for post-marketing
surveillance of new opioid substitution therapy medications by
Reckitt Benckiser, also conducted without any involvement of RB in
the design, conduct, analysis or publication of findings.

3. The Difference is Research
The Difference is Research
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Overview
1. Utilisation of pharmaceutical opioids
2. What unintended consequences are causing concern?
3. People with chronic non-cancer pain using opioids
4. Use of Fentanyl by PWID in Australia

4. 1. Utilisation of pharmaceutical opioids

5. Availability of opioids for pain management (2011-13)
Berterame et al (2016) Use of and barriers to access to opioid analgesics: a worldwide, regional, and national study.
The Lancet.

6. 6
Australia: PBS opioid dispensings
Blanch et al (2014). An overview of the patterns of prescription opioid use, costs and related harms in Australia.
BJ Clinical Pharmacology.
15-fold increase in dispensings
processed, 1992-2012
Issues:
• Opioids costing less than co-
payment threshold
• Authorities
• Private scripts
• Non-PBS listed opioids
• Non-prescribed (OTC) opioids
• Dispensing ≠ consumption

7. 7
The picture in 2013: PBS opioid dispensings
vs. prescription opioid unit sales
0
2,000,000
4,000,000
6,000,000
8,000,000
10,000,000
12,000,000
14,000,000
16,000,000
18,000,000
Strong opioids Other
prescribed
opioids
OTC codeine
Number of PBS prescriptions
dispensed
Number of packs sold
Strong opioids : morphine, oxycodone, buprenorphine patch, methadone tablet, fentanyl, hydromorphone
Other prescribed opioids : prescription codeine, dextropropoxyphene, tramadol, tapentadol
Over-the-counter opioids : codeine products available at pharmacies without a doctor’s prescription

8. 8
What does opioid consumption look like?
• It’s clearly increasing
• Reliance on aggregate PBS statistics will lead to a likely
underestimation of consumption: OTC consumption is
considerable
• Consumption higher in rural and regional areas and areas
with more disadvantage
• Need analyses of person-level data to examine (i)
whether this is a problem, and (ii) how much of this is a
problem
• AND we need direct data on patterns of consumption
(e.g. POINT and NOMAD study)

9. 2. Unintended consequences of opioid use

10. 10
Concerns accompanying opioid use
• Non-adherent use
o Stockpiling
o Doctor shopping
o Tampering
• Diversion
o Diversion to others
o Use of someone else’s medication
• Dependence
• Overdose
Larance et al (2011) Definitions related to the use of pharmaceutical opioids: Extra-medical use,
diversion, non-adherence and aberrant drug behaviours. Drug and Alcohol Review, 30, 236–245.

11. 11
Changing nature of opioid-related deaths
380
182 175
234
278
217
107
195
274 288
0
100
200
300
400
500
600
700
800
900
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009
heroin only morphine only methadone & bup
codeine only oxycodone only fentanyl only
several opioids
Source: National Coronial Information System (NCIS); Roxburgh et al (MJA, 2011); Roxburgh et al (2013)
27%
54%
19%
recorded idu history no idu history not known
52%
18%
30%
chronic pain no chronic pain not known

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Potential risk factors for poorer clinical outcomes:
• Mental health problems
• History of drug and alcohol use problems
• Experience of trauma
• More complex pain problems
• Other illnesses and disabilities
• Other medications
Not everyone is at similar risk for
adverse outcomes

13. 3. People living with chronic non-cancer
pain and using opioids

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• Chronic non-cancer pain (CNCP) is a common complaint
• CNCP has a major impact on quality of life, mental health, health status,
relationships and employment
• There have been considerable increases in prescribing of opioids for CNCP
• Concern about harms related to pharmaceutical opioids
– Will there be greater problems with opioid dependence?
– Will there be considerable diversion of these medications?
– Is long-term use of opioids for chronic pain effective?
Background

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Sample: people living with chronic non-cancer pain, prescribed opioids >=6 weeks
Recruitment across community pharmacies in Australia, with Pharmacy Guild
support:
• Contacted 93% (n=5,332) of all community pharmacies in Australia via fax
and phone
• 33% of pharmacies agreed to be involved in recruitment
Four assessment waves:
• Baseline n = 1,514
• T2 follow up (3 months) 82% follow-up
• T3 follow up (12 months) 83% follow-up
• T4 follow up (24 months) 83% follow-up
Permission to obtain medical records from Medicare for access to Medicare claim
history and prescription history as well as other health records
POINT cohort study design
Campbell et al (2014). Cohort protocol: The Pain and Opioids IN Treatment (POINT) study. BMC Pharmacol & Toxicol.
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Pain and treatment experience
Median time experiencing pain 10 years
Median time to opioid prescription after pain
onset
12 months
On some type of opioid continuously (Median) 4 years
More than one pain condition 85%
Median pain conditions in the previous year 3
Back or neck problems (most common
condition)
76%
Median other chronic physical health problems 1
Campbell et al (2015). The Pain and Opioids IN Treatment (POINT) study: Characteristics of a cohort using opioids to
manage chronic non-cancer pain. Pain.

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The Difference is Research
Current mental disorders
0 10 20 30 40 50
Moderate/severe depression
Moderate/severe Anxiety
Agoraphobia
Panic attacks
Post Traumatic Stress Disorder
Social phobia
Borderline Personality Disorder
Proportion (%)
Campbell et al (2015). The Pain and Opioids IN Treatment (POINT) study: Characteristics of a cohort using opioids to
manage chronic non-cancer pain. Pain.

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Prescription opioid use in the POINT cohort
0
10
20
30
40
50
60
70
Oxycodone Morphine Buprenorphine
Proportion
(%)
• Prescribed opioids for a
median of 4 years
• 20% currently
prescribed ≥2 Schedule
8 opioids
• 63% also taking over-
the-counter opioids
• Median oral morphine
equivalent (OME) mg
per day – 75mg
• 15% taking over 200
OME per day
Campbell et al (2015). Correlates of pharmaceutical opioid use and dependence among people living with chronic pain:
Findings from the Pain and Opioids IN Treatment (POINT) study. Pain Medicine
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Problematic use of pharmaceutical opioids
19

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• One in twelve (8.5%) met lifetime ICD-10 criteria for
pharmaceutical opioid dependence
• One in ten (10.1%) met criteria ICD-10 criteria for harmful
use
• One in five (18.6%) met lifetime criteria for ICD-10
pharmaceutical opioid use disorder
• One in twenty (5%) were dependent in the past year
• Younger, more likely to engage in non-adherent behaviours, history of
benzodiazepine dependence
• All scored intermediate-to-high on Prescribed Opioids Difficulties Scale
Dependence in POINT cohort (ICD-10)
20
Campbell et al (2015). Correlates of pharmaceutical opioid use and dependence among people living with chronic pain:
Findings from the Pain and Opioids IN Treatment (POINT) study. Pain Medicine

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Indicators of problematic use, by dose
0
10
20
30
40
50
60
70
80
< 20mg
OME
21-90mg
OME (ref)
91-199mg
OME
>200mg
OME
Proportion
(%)
% lifetime ICD-10
pharmaceutical opioid
dependence
%lifetime ICD-10 harmful
pharmaceutical opioid use
% at least some non-
adherence, past 3 months
% intermediate-high (>8)
score on the prescribed op
*
**
*
% intermediate-high on
PODS (>8)
Campbell et al (2015). Correlates of pharmaceutical opioid use and dependence among people living with chronic pain:
Findings from the Pain and Opioids IN Treatment (POINT) study. Pain Medicine
21
**
**
***
***
**
**

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Trends in Fentanyl injecting and deaths
in Australia

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Opioid Use in Australia
Heroin and Pharmaceutical opioid
injecting
79
66 66 65
69
65
56
58
60
64 63
61
59 60 60
58
56 57
40
50
45
46
41
49 50
47
42 43
39 39
35
35
28
27
27
16
22
26 26
29 28
31 33
31
27
19
16 13
6
8 9
8 7
0
10
20
30
40
50
60
70
80
90
100
%
People
who
inject
drugs
Heroin injected Morphine Injected
Oxycodone Injected Fentanyl Injected
Source: Illicit Drug Reporting
System

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Results: Fentanyl injected on site
2012 to 2017
0
50
100
150
200
250
300
350
400
450
500
Sep-12 Jun-13 Mar-14 Dec-14 Sep-15 Jun-16 Mar-17
Number
of
injections
Fentanyl

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Pharmaceutical opioid deaths (by opioid)
per million population
0
1
2
3
4
5
6
7
8
9
10
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
Deaths
per
million
population morphine oxycodone tramadol fentanyl
Source: NCIS; Roxburgh et al, Drug and Alcohol
Dependence 2017

26. The Difference is Research
The Difference is Research
•Thanks to our participants in all the studies mentioned here
•Collaborators : Louisa Degenhardt, Gabrielle Campbell, Amanda Roxburgh, Natasa Gisev, Suzi Nielsen,
Sarah Larney, Elena Cama, Wayne Hall, Nicholas Lintzeris, Richard Mattick, Raimondo Bruno, Amy
Peacock, Milton Cohen, Robert Ali, Nancy White, Timothy Dobbins, Lucy Burns, Adrian Dunlop, Michael
Farrell, Fiona Shand
•Advisory Committee (POINT): Fiona Blyth, Lesley Brydon, Elizabeth Carrigan, Malcolm Dobbin, Julia
Fleming, Roger Goucke, Simon Holliday, Denis Leahy, Andrea Mant, Jake Najman, Milana Votrubec, Jason
White
•Associate Investigators and Advisory Committee (NOMAD): Lesley Brydon, Gabrielle Campbell, Apo
Demirkol, Malcolm Dobbin, Adrian Dunlop, Angella Duvnjak, Paul Haber, Marianne Jauncey, Robert Kemp,
Richard Mattick, Suzanne Nielsen, Amy Peacock, Nghi Phung, Ann Roche, Nancy White and Hester Wilson
•POINT study team: Gabrielle Campbell (coordinator), Bianca Hoban, Kimberley Smith, Ranira Moodley,
Sarah Freckleton, Rachel Urquhart-Secord, Teleri Moore, Courtney O’Donnell
•NOMAD study team : Ivana Kihas, Toni Hordern, Amy Peacock, Nancy White, Elena Cama, Dominic Oen,
Oluwadamisola and our team of interviewers
•NHMRC project grant: #1022522 (POINT study)
•NHMRC fellowships: Briony Larance, Louisa Degenhardt, Suzanne Nielsen, Richard Mattick
•Mundipharma: Untied educational grant; Billy Henderson
•Pharmacy Guild of Australia
Acknowledgements

27. 28
Thank you!
Louisa Degenhardt
Gabrielle Campbell
Briony Larance
Amanda Roxborough
Research Fellow (NHMRC ECF)
NDARC, UNSW Australia
: (02) 9385 0241
 : (02) 9385 0222
 : Michael.Farrell@unsw.edu.au