To view an archived recording of this presentation please click the following link: http://pho.adobeconnect.com/p2j5qb5jvf4/ Please scroll down this file to view a copy of the slides from the session.
PublicHealthOntario.ca
Helpful tips when viewing the recording:
• The default presentation format includes showing the “event index”. To close the events index, please click on the following icon and hit “close”
• If you prefer to view the presentation in full screen mode, please click on the following icon in the top right hand corner of the share screen
Opioid Use and Overdose in Ontario:
Measuring Policy Impact and Public Health Implications
PHO Grand Rounds
November 8, 2016
Tara Gomes
Outline
• Patterns in prescription opioid use, overdose
and public health implications in Ontario
• Potential and realized impact of various policies
and strategies designed to address
inappropriate opioid prescribing
• Future directions
2
History of Opioids
• Opium has been used for several thousand years
• Superb analgesic – also produces euphoria
• Adverse effects have been recognized over time including addiction, respiratory/CNS depression and death
Now produced
• Illegally heroin
• Legally prescription drugs
Opioids in the 20th Century
• Limited use of opioids, Increasing recognition that opioids were effective and safe for acute pain and treatment of pain due to advanced cancer
• 1986: Publication by Portenoy & Foley: – Chronic use of opioid analgesics in non-malignant pain: report
of 38 cases. Only 4 patients were prescribed >40 MEQ daily – Concluded that: “…opioid maintenance therapy can be a safe,
salutary and more humane alternative to the options of surgery or no treatment in those patients with intractable non-malignant pain and no history of drug abuse.”
• 1996: OxyContin approved by Health Canada
– 2000, drug was added to Ontario’s public drug formulary
Portenoy et al. 1986. Pain. 25(2): 171-186
Opioid Prescribing Trends in
Ontario, Canada
23 per 1000 229 per 1000 OxyContin added to
Formulary
Dhalla et al. CMAJ 2009 Dhalla et al. CMAJ 2009. Updated
Increasing Rates of Opioid
Related Deaths
Gomes et al. Addiction. 2014
N=144
N=571
OxyContin added to Formulary
Characteristics of Opioid Overdose
Deaths
http://odprn.ca/wp-content/uploads/2015/04/Opioid-deaths-formal-report_19Nov2014.pdf
Public Health Impact
2010: • 1 in 8 deaths among young
adults related to opioid overdose
Gomes et al. Addiction. 2014 Not for further distribution
Drug Overdose Deaths in North
America
http://www.cdc.gov/homeandrecreationalsafety/rxbrief/ http://www.cdc.gov/drugoverdose/pdf/policyimpact-prescriptionpainkillerod-a.pdf
By 2014…
• Canada and USA have the highest opioid consumption per capita in the world
– Canada: 967 mg MEQ dispensed per capita, annually
– USA: 701 mg MEQ dispensed per capita • Note: consumption does not include hydrocodone. Inclusion of hydrocodone leads
to USA having higher consumption than Canada
http://ppsg-production.heroku.com/chart https://ppsg.medicine.wisc.edu/
Widespread Concern, But Local
Variation
Opioid Prescribing
ED Visits for Overdose
Hospitalizations for Overdose
Opioid-Related Deaths
HOW DID WE GET HERE?
Opioid Dose
12
Opioid Dose Thresholds
http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020553s060lbl.pdf
Clinical Guidelines
• Canadian Guidelines published in 2010
• Suggested that the risks of long-term, high-dose opioid use for chronic non-cancer pain (abuse, addiction, diversion and opioid-related side effects including death) often exceed their benefits.
• Several recommendations, including:
• Similarly, US Guidelines in 2007 and 2009 listed thresholds of 120-200mg MEQ
Chronic non-cancer pain can be managed effectively in most patients with dosages at or below 200 mg/day of morphine or equivalent. Consideration of a higher dosage requires careful reassessment of the pain and of risk for misuse, and frequent monitoring with evidence of improved patient outcomes.
http://nationalpaincentre.mcmaster.ca/opioid/
Upper Dose Thresholds
• Thresholds based on clinical opinion – no evidence to suggest: – How frequently people are prescribed doses at this level
– What is an appropriate dose threshold to avoid adverse events
Trends in High Dose Prescribing:
>200 mg MEQ
33%
Median daily dose: 270 mg MEQ
22%
Gomes et al. Open Med. 2011 Gomes et al. Open Medicine. 2011. 5(1): E13-E22
Trends in High Dose Prescribing:
>400 mg MEQ
14%
Median daily dose: 613 mg MEQ
9%
Gomes et al. Open Med. 2011 Gomes et al. Open Medicine. 2011. 5(1): E13-E22
Upper Dose Thresholds
• Thresholds based on clinical opinion – no evidence to suggest: – How frequently people are prescribed doses at this level
– What is an appropriate dose threshold to avoid adverse events
Opioid Dose and Risks
Opioid Dose Adjusted OR, 95% CI
20-49mg MEQ 1.32 (0.94-1.84)
50-99mg MEQ 1.92 (1.30-2.85)
100-199mg MEQ 2.04 (1.28-3.24)
≥200mg MEQ 2.88 (1.79-4.63)
Opioid Dose Adjusted OR, 95% CI
20-49mg MEQ 1.21 (1.02 to 1.42)
50-99mg MEQ 1.29 (1.06 to 1.57)
100-199mg MEQ 1.42 (1.15 to 1.76)
≥200mg MEQ 1.23 (1.02 to 1.49)
Risk of Opioid-Related Death
Risk of Injury in Motor Vehicle Accident (as
Driver)
Gomes et al. Arch Int Med. 2011. 171(7): 686-691.
Gomes et al. JAMA IM. 2013. 173(3): 196-201.
Absolute Risk is High
32,449 individuals initiating opioid therapy in Ontario and continuing for
3 months or more.*
1 of 55 escalate to high dose (>200MME) opioid therapy
1 of 550 die of an opioid overdose
Median follow-up of ~6 months
Important differences between men and women: Men 44% more likely to escalate dose, and twice as likely to die of opioid overdose
*Ontario public drug program only
Kaplovich et al. PLOS One. 2015.
Clinical Guidelines
Canadian Guidelines US Guidelines
200mg MEQ
120-200mg MEQ
50-90mg MEQ ??
2009 2009
2017 2016
Impact on Clinical Practice?
POLICIES, IMPACT, AND
UNINTENDED CONSEQUENCES
22
Ongoing Evolution of Policies,
Programs and Drug Availability
23
1996: OxyContin approved by Health Canada
2000: OxyContin added to Ontario Formulary
2007: Purdue settles marketing lawsuit
April 2010: Canadian Guidelines Released
August 2010: TD LA Oxycodone introduced in US
February 2012: TD LA Oxycodone introduced in Canada
December 2012: Generic OxyContin introduced in Canada
March 2016: US CDC Revised Guidelines Released
April 2016: B.C. declares public health emergency
November 2011: Ontario’s NSAA comes into force
Ongoing Evolution of Policies,
Programs and Drug Availability
24
1996: OxyContin approved by Health Canada
2000: OxyContin added to Ontario Formulary
2007: Purdue settles marketing lawsuit
April 2010: Canadian Guidelines Released
August 2010: TD LA Oxycodone introduced in US
February 2012: TD LA Oxycodone introduced in Canada
December 2012: Generic OxyContin introduced in Canada
March 2016: US CDC Revised Guidelines Released
April 2016: B.C. declares public health emergency
November 2011: Ontario’s NSAA comes into force
Ontario Narcotics Safety and
Awareness Act: November 2011
• Objectives:
– Promote appropriate prescribing and dispensing practices for narcotics and other controlled substances
– Identify and reduce the abuse, misuse and diversion of these drugs – Reduce the risk of addiction and death from the abuse or misuse of
these drugs.
• Key Initiatives: – Ministry of Health can collect, use, and disclose information that
relates to the prescribing and dispensing of monitored drugs – Narcotics Monitoring System (March 2012)
– Prescriber must be identified on prescriptions
– Warnings in effect for double doctoring and polypharmacy
Evaluating Impact
• Objective: Did Ontario’s policies lead to any shifts in
inappropriate prescribing of monitored drugs?
– Opioids
– Benzodiazepines
– Stimulants
• “Potentially inappropriate use”
– Early refill (ie prescription dispensed within 7 days of a
previously filled Rx of 30 day duration or higher)
– Different pharmacy dispensed the drug
– Different prescriber wrote prescription for drug
26
Prevalence of Inappropriate
Prescribing of Monitored Drugs in
Ontario
Reduced to 1%
However, ~10,000 prescriptions for monitored drugs still met this definition in May 2013, which is very likely representative of misuse
Gomes et al. CMAJ Open. 2014
What can this tell us?
• Improved data access and enhanced warnings for
pharmacists has led to measurable reductions in
potentially inappropriate dispensing behaviour
• But…still high degree of potentially inappropriate
prescribing. Due to?
– Prescribers not having access to database
– Too many different forms of ID allowed
– Poor use of data for monitoring/surveillance
28
Ongoing Evolution of Policies,
Programs and Drug Availability
29
1996: OxyContin approved by Health Canada
2000: OxyContin added to Ontario Formulary
2007: Purdue settles marketing lawsuit
April 2010: Canadian Guidelines Released
August 2010: TD LA Oxycodone introduced in US
February 2012: TD LA Oxycodone introduced in Canada
December 2012: Generic OxyContin introduced in Canada
March 2016: US CDC Revised Guidelines Released
April 2016: B.C. declares public health emergency
November 2011: Ontario’s NSAA comes into force
Tamper-Deterrent Formulation
• April 2010: US FDA approved a new tamper-deterrent formulation of OxyContin (called “OxyContin-OP”)
• August 2010: US production of the original OxyContin stopped
• February 2012: Canadian production of original OxyContin stopped
?
Reformulation and Opioid
Prescribing in the US and Canada
• In Canada, the original OxyContin formulation remained available until February 2012.
2010 2013 2011 2012
August 2010: Tamper-deterrent LA Oxycodone replaces OxyContin in the USA
February 2012: Tamper-deterrent LA Oxycodone introduced in Canada
Present
OxyContin Reformulation:
Unintended Consequences
• Did dispensing of OxyContin in areas of Canada close to US border crossings increase following the introduction of OxyContin-OP in the US?
OxyContin Reformulation:
Unintended Consequences
• Opioids dispensed by pharmacies close to the US-Canada border (Ontario only) between April 1, 2010 and February 29, 2012
• 6 Border Crossings of Interest: – Ambassador Bridge (Detroit – Windsor)
– Detroit-Windsor Tunnel (Detroit – Windsor)
– Blue Water Bridge (Port Huron – Sarnia)
– Queenston-Lewiston Bridge (Lewiston – Niagara Falls
– Rainbow Bridge & Whirlpool Rapids Bridge (Niagara Falls – Niagara Falls)
Number of OxyContin Tablets
Dispensed
Gomes et al. Open Medicine. 2012. 6(4) Gomes et al. Open Medicine. 2012
Number of OxyContin Tablets
Dispensed
Gomes et al. Open Medicine. 2012. 6(4) Gomes et al. Open Medicine. 2012
Warnings
• Ontario College of Pharmacists
• College of Physicians and Surgeons of Ontario
Number of OxyContin Tablets
Dispensed
Gomes et al. Open Medicine. 2012. 6(4) Gomes et al. Open Medicine. 2012
Almost 250,000 excess OxyContin tablets dispensed near the Tunnel between August 2010 and October 2011.
Ongoing Evolution of Policies,
Programs and Drug Availability
38
1996: OxyContin approved by Health Canada
2000: OxyContin added to Ontario Formulary
2007: Purdue settles marketing lawsuit
April 2010: Canadian Guidelines Released
August 2010: TD LA Oxycodone introduced in US
February 2012: TD LA Oxycodone introduced in Canada
December 2012: Generic OxyContin introduced in Canada
March 2016: US CDC Revised Guidelines Released
April 2016: B.C. declares public health emergency
November 2011: Ontario’s NSAA comes into force
Uptake of Generic LA Oxycodone:
Inconsistency across Canada
39
Ontario Quebec
47% 13%
Gomes et al. 2015. CNODES Analysis. Available: http://www.researchgate.net/publication/279770891
Ongoing Evolution of Policies,
Programs and Drug Availability
40
1996: OxyContin approved by Health Canada
2000: OxyContin added to Ontario Formulary
2007: Purdue settles marketing lawsuit
April 2010: Canadian Guidelines Released
August 2010: TD LA Oxycodone introduced in US
February 2012: TD LA Oxycodone introduced in Canada
December 2012: Generic OxyContin introduced in Canada
March 2016: US CDC Revised Guidelines Released
April 2016: B.C. declares public health emergency
November 2011: Ontario’s NSAA comes into force
The emergence of fentanyl
• BC: – 302 fentanyl deaths from January to August
2016
– In 2015, 97 fentanyl deaths over same period
• Alberta: – Rise in fentanyl deaths from 6 in 2011 to 274
in 2015
• Ontario: – 198 fentanyl deaths in 2015
– Up from 176 fentanyl deaths in 2014
41
Public Health Emergency declared: April 2016
Opioid Strategy
Announced October 2016
Improved Surveillance announced:
October 2016
Current Shifts and Future Directions:
Ontario’s Opioid Strategy
Improved Surveillance
Delisting High Strength Formulations
Broad access to Naloxone
Development of Opioid Prescribing Standards
Improved access to pain clinics and addiction services
Patch for Patch program for fentanyl
What impact will this have?
Unanticipated Consequences?
http://odprn.ca/research/research-reports/high-strength-opioid-formulations-in-ontario-by-the-numbers/
Unanticipated Consequences?
“Medical Abandonment”
• In the US, after release of CDC guidelines, concerns
raised about potential for ‘opioid abandonment’ and
transition to heroin
https://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates
Moving Towards the Future
• Ongoing Monitoring of anticipated and unanticipated impacts of policies/programs
• Considering two distinct target populations: – Those currently using opioids (particularly at high doses)
– Those who might be started on opioids
• Evaluating impact of revised clinical guidelines and prescribing standards: – Will this change behaviour?
• Anticipating the next drug of abuse: – Carfentanil?
– Hydromorph Contin?
