This document discusses abuse-deterrent opioid formulations and whether they are effective in reversing the opioid crisis. It summarizes that while OxyNEO is harder to abuse than previous formulations like OxyContin, overall opioid overdose and addiction rates have not declined. Patients often switch to other opioids like hydromorphone or heroin when unable to abuse newer formulations. Abuse-deterrent formulations alone will not solve the crisis without also addressing over-prescribing and reducing the overall supply of opioids. Local measures like education, naloxone distribution, and buprenorphine treatment can help reduce harms of the opioid epidemic.

1. Abuse-deterrent opioid
formulations: Quick fix or marketing
scam?
M Kahan MD
Inner City Addiction Rounds
September 2, 2014

2. The opioid crisis: Where are we now?
• Death rates from opioids are higher than ever
before
– 550 deaths in Ontario in 2010
• Opioid overdose has overtaken MVA as
leading cause of accidental death in US

3. Background
• Abuse deterrent formulation: an oral opioid
formulation that is difficult to use by a non-
oral route
• Purdue replaced OxyContin with OxyNEO
several years ago
• While OxyNEO is the first abuse-deterrent
formulation, OxyContin was the first
formulation to specifically promote abuse

4. Abuse promoting properties of
OxyContin
• Oxycodone has greater reinforcing properties
than equivalent doses of morphine
• OxyContin came in very high dose
formulations – up to 160 mg (240 mg MED)
per tablet
• Tablet easier to crush than MS Contin tabs
• Tablet’s outer shell enable immediate release
of opioid

5. Abuse promoting properties (2)
• Higher doses and non-oral routes of entry
cause a more rapid rise and higher peak in
serum opioid level
• This in turn produces more intense euphoria
(Marsch 2001)

6. Abuse-promoting properties (3): Dose
• Risks of overdose and addiction are strongly
associated with the opioid dose.
• In a study of 10,000 chronic pain patients on
opioids (Dunn 2010), those on 100 mg+ MED had
an 8.9-fold increase in overdose risk and a 1.8%
annual overdose rate, compared to patients
receiving 1-20 mg MED (annual overdose rate
0.2%).
• Matched case control study of patients on ODB
(Gomes 2011): 200 mg MED had 3x risk of fatal
OD, 100-199 mg/d had 2x risk

7. Why is dose a key determinant of
overdose?
• Euphoric effects dose related
• Addicted patients rapidly develop tolerance to
psychoactive effects so must escalate their dose
• Doctors increase the dose in response to patient’s
distress
• Younger patients with milder objective
biomedical illness & psychiatric comorbidity are
on higher doses than older, more ill patients

8. Purdue’s marketing caused abuse
Messages to doctors:
• Addiction is rare in chronic pain patients
• CR opioids are less addicting than IR opioids
• Opioids should be ‘dosed to effect’
• Opioids are remarkably effective for all types
of pain
• Reluctance to prescribe = “opioiphobia”

9. Root causes
• In other words, this is a Pharma Epidemic
• Focus should be on supply side reduction:
– Pharmaceutical industry
– Physicians
– Medical regulators
– Government funders
• To date, focus has been on finding the addicts

10. WILL ABUSE-DETERRENT
FORMULATIONS REVERSE THE OPIOID
PHARMA EPIDEMIC?

11. OxyNEO
• OxyNEO is the gold standard for abuse
formulations
• Outer shell has multiple heat-hardened layers
• Extremely hard to crush, even with a hammer
– Need industrial press
• Oxycodone covalently bound to a polymer
• Oxycodone-polymer forms a viscous gel when
exposed to water

12. OxyNEO (2)
• Therefore OxyNEO can’t be:
– Injected (veins clog up)
– Snorted (can cause death)
– Used sublingually, rubbed on gums etc.

13. OxyNEO (3): Is it working?
Evidence shows:
• Marked decline in number of patients attending
treatment for OxyNEO addiction versus
OxyContin (US data)
• In a study of 140,000 patients attending
addiction treatment programs in the US, rates of
oral abuse dropped by 17% from pre-OxyNEO
(2009) to post OxyNEO (2012)
• Rates of non-oral abuse (snorting, injecting)
dropped by 66% (Butler 2012)

14. BUT…
• Overall increase in rates of addiction and
overdose with Hydromorph Contin, Fentanyl,
heroin
• No overall decline in opioid and overdose rates
• “ Replacement of a widely prescribed opioid
formulation known for its abuse potential alone
may have had little impact on overall rates of
prescription opioids as a class” (Cassidy 2014)

15. Is it working (2)
• So patients who are already addicted are
switching to different opioids
• Many doctors are switching too
– OxyNEO only available on Exceptional Access
Program

16. Opioid Prescribing in Canada

17. Opioid Prescribing in Ontario

18. Oxycontin prescribing across provinces

19. Oxyneo prescribing across provinces

20. Hydromorph Contin prescribing across
provinces

21. Fentanyl prescribing across provinces

22. Newer abuse-deterrent formulations:
are they effective?
• Newer abuse deterrent formulations (eg
hydrocodone-naloxone) are not yet approved
for use in Canada
• Simply adding naloxone might deter injection
or intranasal use, but not oral or sublingual
use (naloxone has minimal oral bioavailability)
• Therefore not nearly as effective as OxyNEO

23. Abuse-deterrent formulations: Patent
protected
• Provincial formularies not willing to cover
abuse-deterrent formulations because they’re
too expensive
• So potent abuse-vulnerable opioids eg HM
contin are covered, while abuse-deterrent
formulations are not

24. Health Canada isn’t blocking tamper-
vulnerable opioids yet
• Health Canada has approved the use of
tamper-vulnerable generic Oxycontin
• Is considering Zohydro (CR hydrocodone), a
tamper vulnerable, potent opioid formulation
• Is also considering regulatory barriers on
abuse-vulnerable opioids

25. Does OxyNEO prevent addiction?
• Ie, will starting a high risk patient on OxyNEO
(rather than hydromorph contin) prevent
them from becoming addicted?
• Unlikely to completely prevent addiction:
– Most prescription opioid addicts were first
exposed to opioids through a physician’s
prescription for pain (Sproule 2009)
– Most took opioids orally at the beginning, only
switching to crushing etc as they were becoming
addicted

26. Preventing addiction (3)
• Many addicted patients continue to take
opioids primarily by the oral route
• Patients can (and do) become addicted to
OxyNEO
• A major determinant of euphoric effect is
dose
– OxyNEO comes in 40 mg tabs
– Average dose used by addicted patients admitted
to CAMH was 200 mg MED (120 mg OxyNEO)

27. Risks of abuse deterrent formulations
• Pharma companies will convince doctors that
abuse deterrent formulations prevent
addiction
– Doctors will continue to prescribe high doses to
high risk patients
• Governments, doctors might feel they’re
addressing the crisis when they’re not

28. How can we deal with this crisis at
local level?
• Medical Education
– Substance Use Network
– Supervision of residents and medical students
• Distribute naloxone through the ED to high
risk patients
– Easy to do!
• Buprenorphine to high risk patients in ED and
WMS

29. Local response
• Consultation to our physician colleagues to
encourage safe practices
• Advocacy
• Eg Naloxone
• Regulation of high doses