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

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.

Overview Utilisation of pharmaceutical opioids What unintended consequences are causing concern? People with chronic non-cancer pain using opioids Use of Fentanyl by PWID in Australia

1. Utilisation of pharmaceutical opioids

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.

Australia: PBS opioid dispensings 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 There have been considerable increases in prescribing of opioids: a 15-fold overall increase in PBS-subsidised opioid dispensings between 1992-2012 Blanch et al (2014). An overview of the patterns of prescription opioid use, costs and related harms in Australia. BJ Clinical Pharmacology.

The picture in 2013: PBS opioid dispensings vs The picture in 2013: PBS opioid dispensings vs. prescription opioid unit sales 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

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)

2. Unintended consequences of opioid use

Concerns accompanying opioid use Non-adherent use Stockpiling Doctor shopping Tampering Diversion Diversion to others 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.

Changing nature of opioid-related deaths Over the period of monitoring… Source: National Coronial Information System (NCIS); Roxburgh et al (MJA, 2011); Roxburgh et al (2013)

Not everyone is at similar risk for adverse outcomes 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

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

Background 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?

POINT cohort study design 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 Campbell et al (2014). Cohort protocol: The Pain and Opioids IN Treatment (POINT) study. BMC Pharmacol & Toxicol. 15

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.

Current mental disorders 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.

Prescription opioid use in the POINT cohort 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 18

Problematic use of pharmaceutical opioids 19

Dependence in POINT cohort (ICD-10) 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 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 20

Indicators of problematic use, by dose *** ** ** *** ** ** Efficacy 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

Trends in Fentanyl injecting and deaths in Australia

Opioid Use in Australia Heroin and Pharmaceutical opioid injecting Source: Illicit Drug Reporting System

Results: Fentanyl injected on site 2012 to 2017

Pharmaceutical opioid deaths (by opioid) per million population Source: NCIS; Roxburgh et al, Drug and Alcohol Dependence 2017

Acknowledgements 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

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