Opioids and abuse, misuse and dependence CONFIDENTIAL Medicines Adverse Reactions Committee Meeting date 3/12/2020 Agenda item 3.2.2 Title Opioids and abuse, misuse and dependence Submitted by Medsafe Pharmacovigilance Paper type For advice Team Active ingredient Product name Sponsor Buprenorphine Codeine Dihydrocodeine Fentanyl See Annex 1 for the full list of opioids approved in New Zealand Methadone Morphine Oxycodone Pethidine Tramadol PHARMAC funding All opioids in Annex 1 have at least one product funded on the Hospital and Community Schedules. Previous MARC 169th meeting – held 9 March 2017: Concomitant use of opioids, benzodiazepines meetings and other CNS depressants and the risk of serious side effects International action • FDA - Risk Evaluation and Mitigation Strategy (REMS) required for all opioids; prescribing information updates • MHRA – warnings on package labelling, updates to prescribing information, safety leaflets for patients • TGA – smaller pack sizes, boxed warnings and class statements in prescribing information and consumer medicine information, indication review • Health Canada – Mandatory risk management plans for prescription opioids, Warning sticker and patient information handout Prescriber Update The following is a list of recent articles only. • Spotlight on tramadol including updated advice for use in children June 2020 • Spotlight on Codeine June 2018 • Medicines Interacting with Methadone June 2018 • Transdermal Opioid Patches - Stick to the Correct Application March 2020 Classification See Annex 1. Medicines Regulations 1984 and the Misuse of Drugs Act 1975. Usage data See section 2.5 Advice sought The Committee is asked to advise: • Whether there is evidence of an abuse, misuse and dependence problem with opioids in New Zealand? Medicines Adverse Reactions Committee: 3 December 2020 Page 1 of 64 Opioids and abuse, misuse and dependence CONFIDENTIAL TABLE OF CONTENTS 1 PURPOSE ................................................................................................................................................................................................. 4 2 BACKGROUND ...................................................................................................................................................................................... 4 2.1 Pain ................................................................................................................................................................................................ 4 2.2 Opioids ......................................................................................................................................................................................... 4 2.2.1 Approval, classification and funding ........................................................................................................................... 5 2.2.2 Indications .............................................................................................................................................................................. 7 2.2.3 Mode of action ..................................................................................................................................................................... 7 2.2.4 Pharmacogenomics ............................................................................................................................................................ 8 2.3 Misuse, abuse, dependence ................................................................................................................................................. 9 2.4 Opioid prescribing guidelines ........................................................................................................................................... 10 2.4.1 Acute pain ............................................................................................................................................................................ 10 2.4.2 Chronic non-cancer pain ................................................................................................................................................ 11 2.4.3 Misuse, addiction, opioid substitution therapy ..................................................................................................... 12 2.5 Usage data ................................................................................................................................................................................ 13 2.5.1 Pharmaceutical collections ............................................................................................................................................ 13 2.5.2 Health Quality and Safety Commission of New Zealand (HQSC) .................................................................. 14 3 INTERNATIONAL REGULATORY ACTION ................................................................................................................................. 17 3.1 United States of America (USA) ........................................................................................................................................ 17 3.1.1 Classification ........................................................................................................................................................................ 17 3.1.2 Background .......................................................................................................................................................................... 18 3.1.3 Regulatory actions ............................................................................................................................................................ 19 3.2 United Kingdom (UK) ............................................................................................................................................................ 21 3.2.1 Classification ........................................................................................................................................................................ 21 3.2.2 Background .......................................................................................................................................................................... 21 3.2.3 Regulatory actions [49, 50] ............................................................................................................................................ 22 3.3 Australia ..................................................................................................................................................................................... 23 3.3.1 Classification ........................................................................................................................................................................ 23 3.3.2 Background .......................................................................................................................................................................... 24 3.3.3 Regulatory actions [52-54] ............................................................................................................................................ 24 3.4 Canada ........................................................................................................................................................................................ 26 3.4.1 Classification ........................................................................................................................................................................ 26 3.4.2 Background .......................................................................................................................................................................... 26 3.4.3 Regulatory actions ............................................................................................................................................................ 27 4 OTHER INFORMATION .................................................................................................................................................................... 30 4.1 New Zealand information ................................................................................................................................................... 30 4.1.1 Data sheets .......................................................................................................................................................................... 30 Medicines Adverse Reactions Committee: 3 December 2020 Page 2 of 64 Opioids and abuse, misuse and dependence CONFIDENTIAL 4.1.2 Opioid dependence [12] ................................................................................................................................................. 35 4.1.3 Published literature .......................................................................................................................................................... 35 4.1.4 National collections .......................................................................................................................................................... 40 4.1.5 CARM data ........................................................................................................................................................................... 47 4.1.6 National Poisons Centre ................................................................................................................................................