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Buprenorphine Diversion:
The Elephant or the
Mouse in the Room?
JAKE NICHOLS, PHARM.D., MBA
CAPE COD SYMPOSIUM ON ADDICTIVE DISORDERS
SEPTEMBER 15TH, 2017
Buprenorphine Diversion: The Elephant or
the Mouse in the Room?
Jake Nichols
9/15/2017
Glossary of Terms
Commercial Interest - The ACCME defines a “commercial interest” as any proprietary entity producing health care goods or services, with the exemption of non-profit or government organizations and non-health care related companies.
Financial relationships -Financial relationships are those relationships in which the individual benefits by receiving a salary, royalty, intellectual property rights, consulting fee, honoraria, ownership interest (e.g., stocks, stock options or other ownership interest, excluding diversified mutual funds), or other financial benefit. Financial benefits are usually associated with roles such as employment, management position, independent contractor (including contracted research), consulting, speaking and teaching, membership on advisory committees or review panels, board membership, and other activities from which remuneration is received, or expected. ACCME considers relationships of the person involved in the CME activity to include financial relationships of a spouse or partner.
Relevant financial relationships - ACCME focuses on financial relationships with commercial interests in the 12-month period preceding the time that the individual is being asked to assume a role controlling content of the CME activity. ACCME has not set a minimal dollar amount for relationships to be significant. Inherent in any amount is the incentive to maintain or increase the value of the relationship. The ACCME defines “’relevant’ financial relationships” as financial relationships in any amount occurring within the past 12 months that create a conflict of interest.
Conflict of Interest - Circumstances create a conflict of interest when an individual has an opportunity to affect CME content about products or services of a commercial interest with which he/she has a financial relationship.
Program Objectives
At the conclusion of the program, the participant will
be able to:
1. Describe the scope of buprenorphine diversion
in the U.S.
2. Compare rates of diversion of buprenorphine in
the U.S. to that of other large countries
3. Explain why patients may divert buprenorphine
4. Apply data obtained from clinical studies to help
identify those patients that may be more prone
to diverting buprenorphine
Buprenorphine Diversion
Buprenorphine Diversion
The Scope of the Problem
Distribution of Buprenorphine to retail and dispensing institutions (such as pharmacies, hospitals, practitioners, teaching institutions, researchers, analytical labs, and narcotic treatment programs) has increased from 13,475 in 2003 to 1,451,503 in 2010
The number of patients receiving a prescription for a buprenorphine product from U.S. outpatient retail pharmacies increased from slightly less than 20,000 in 2003 to more than 600,000 in 2009
The number of Buprenorphine drug items secured in law enforcement operations and analyzed by state and local forensic laboratories has increased from 21 in 2003 to 8,172 in 2009
CESAR Fax. April 9th, 2012. Vol. 21, Issue 14.
The Scope of the Problem
Buprenorphine is the 4th most diverted controlled substance in the U.S.
NFLIS Data available at: https://www.nflis.deadiversion.usdoj.gov.
The Scope of the Problem
CESAR FAX, April 9th, 2012: Vol. 21, Issue 14
The Scope of the Problem
According to the Drug Abuse Warning Network, an
estimated 21,483 emergency department visits were
associated with nonmedical use of buprenorphine in 2011,
nearly five times the 4,440 estimated number of
buprenorphine ED visits in 2006.
RADARS (Researched Abuse Diversion Addiction Related Surveillance), reported past-month prevalence in the
United States of IV BUP and BUP/NX misuse of 45.5% and
16.3%, respectively, by individuals presenting for opioid
abuse treatment
DEA Buprenorphine Briefing, July 2013
RADARS Data Dart, 2011
Sources of Diversion
Written
prescriptions
“Doctor Shopping”
Prescribing of low
doses
Theft
Physicians
Pharmacies
Illegal importation
Presence of
formulations not
available in the US
Large amounts
Internet
pharmacies
Diversion and Abuse of Buprenorphine: A Brief Assessment of Emerging
Indicators. Presented to SAMHSA by JBS International, Inc.
Buprenorphine
Mixed opioid agonist/antagonist with very high affinity
for the mu opioid receptor
Very low dissociation constant which generates a
long half-life
Naloxone is added to the formulation in a 4:1 ratio to
deter abuse
FDA created requirements for prescribing based on
experience with buprenorphine in Europe
Increases in diversion and non-medical use have
coincided with increases in waivered physicians and
prescribing of buprenorphine
Discussion Point #1
Why would a patient
divert buprenorphine?
Why Divert Buprenorphine?
A study of opioid-dependent treatment seekers found that illicit use of buprenorphine is associated with a desire for self-treatment of opioid dependence, pain, and depression, rather than a desire to achieve euphoria1
These findings are consistent with another study of buprenorphine injectors, which found that nearly 50% of participants had injected buprenorphine, but only a minority (12.67%) did so to experience euphoria2
1. Schuman-Olivier, et al. Journal of Substance Abuse Treatment, 39(1), 41–50, 2010.
2. Moratti, E., et al. Clinical Drug Investigation, 30, 3–11, 2010.
Why Divert Buprenorphine?
Estelle-Brown S, et al. Substance Use & Misuse, 49:1017–1024, 2014.
Discussion board users advocate for self-
management of buprenorphine use regardless of
whether in treatment or not
Many posts also remind people that self-
management is not treatment and the behavior is still
considered “addictive”
Suggests that most are getting it from a friend or
family member
Distrust of physicians and pharma companies is
widespread
Why Divert Buprenorphine?
Estelle-Brown S, et al. Substance Use & Misuse, 49:1017–1024, 2014.
Taste preference was a factor in diversion activity but
only around the time that Suboxone Film® was
brought to market
Desire to adopt a different delivery method other
than sublingually
Desire to be completely substance-free
Tablets tend to hinder while film tends to facilitate self-
management
Why Divert Buprenorphine?
Bailey, et al. ASAM Poster Presentation, April 2015
Why Divert Buprenorphine?
Bailey, et al. ASAM Poster Presentation, April 2015
Why Divert Buprenorphine?
Bailey, et al. ASAM Poster Presentation, April 2015
Why Divert Buprenorphine?
Cicero, T.J., et al., Factors contributing to the rise of buprenorphine misuse: 2008–
2013. Drug Alcohol Depend. (2014).
Buprenorphine Diversion - France
In 2004, of the 17 European countries in which buprenorphine treatment was available, 12 reported some misuse of buprenorphine, albeit often extremely rare
French surveys from medical insurance databases indicate that approximately 10% to 20% of patients collect prescriptions from more than one provider and/or filled prescriptions in several pharmacies
Diversion of buprenorphine via the intravenous route concerned 11% of outpatients
Proportion of buprenorphine misusers is higher among patients of low-threshold services (up to 41%)
Misuse of buprenorphine is reported to be quite common among homeless people living in urban regions
Fatseas M. et al., Curr Psychiatry Rep. 2007 Oct;9(5):358-64.
Buprenorphine Diversion - Finland
Most widely abused opioid
Most widely abused intravenous drug
Misuse increased around 2001 when the availability of heroin decreased
Among those entering treatment for opioid dependence, Aalto
et al. found that 29 of 30 patients (97%) reported buprenorphine
as their primary drug of abuse
Among a larger sample of syringe exchange program (SEP)
participants in Finland (n=176), buprenorphine was the most
frequently abused injection drug (73% of respondents), yet a
significant portion of these individuals reported using
buprenorphine in a therapeutic manner, to self-treat withdrawal or addiction
Yokell MA., et al. Curr Drug Abuse Rev. 2011 March 1; 4(1): 28–41.
Buprenorphine Diversion - Australia
Introduced in 2000 with very strict regulation; bup/nlx became
available in 2006 due to large issues with diversion
Allow supervised dosing at pharmacies
In two separate studies, about 1/3 of IDUs reported recent
buprenorphine injection; however, buprenorphine was the
primary drug of abuse in only about 10% of IDUs
A significant proportion had a prescription
In a cross-sectional study of clients receiving buprenorphine in
public clinics, about one-quarter (26.5%) had ever injected
buprenorphine and most patients reported wanting to take
their medication as prescribed
Yokell MA., et al. Curr Drug Abuse Rev. 2011 March 1; 4(1): 28–41.
Discussion Point #2
What harm, if any, is
generated through
buprenorphine
diversion?
Buprenorphine “Overdose”
CESAR Fax, Nov. 23, 2015; Vol.24, Issue 14
Physician Attitudes Towards Diversion
Beliefs About B/N Diversion & Recovery% Agree/
Strongly Agree
Used if person cannot find drug of choice 67.1
Used to prevent withdrawal 64.9
Is a concerning problem 62.5
Used for self-treatment of OUD 59.5
Is a dangerous problem 40.4
Used by people with OUD to get “high” 34.8
Discourages people getting formal help 30.5
Most addicts have used diverted B/N before
treatment29.2
Used because its cheaper than treatment 28.3
Schuman-Olivier et al. Am J Addict 2013;22:574–580
Physician Attitudes Towards Diversion
Causes of B/N Diversion% Agree/
Strongly Agree
Share it with peers who can’t find treatment 55.4
Lack of access to local affordable treatment 53.9
Poor insurance coverage for services 51.0
Clients often sell it for money 49.5
Many clients believe self-treatment is effective 48.6
Clients with Rx give it to others to get high 27.2
Doctors profiting from prescribing B/N irresponsibly 20.8
Schuman-Olivier et al. Am J Addict 2013;22:574–580
Discussion Point #3
What methods are
useful in detecting
possible issues of
diversion?
Evaluating Diversion Potential
Urine drug screens
▪ Bupe/norbupe
quantitative
▪ Utility of levels
▪ Adulterating/altering
urine sample
▪ Presence of illicit and/
or non-prescribed
meds
Pill/film/wrapper
counts
▪ Barcoded and
serialized packaging
▪ Photocopying
▪ “Renting” doses
Risk Factors for IV Misuse of
Buprenorphine
History of IVDU (OR =
13.2)
Current cannabis use
(OR = 3.4)
No salary (OR = 1.6)
Ongoing heroin use
during treatment was
found to be protective
(OR = 0.2)
Perception of bupe
dose as inadequate
(OR = 2.7)
History of suicidal
attempt or ideation
(OR = 2.6)
Number of years of
IVDU (1.05)
Lofwall MR, Walsh SL. J Addict Med 2014;00: 1–12.
Vidal-Trecan G, et al. Drug Alcohol Depend 2003;69:175–181.
Roux P, et al. DrugAlcohol Depend 2008;97:105–113.
Naloxone “Allergy”
Patients may claim naloxone allergy in order to
obtain buprenorphine (Subutex®), as street value
tends to be higher than combination product
Many clinicians believe that naloxone is the culprit for
regularly encountered side effects (ex. headache,
nausea)
Patients communicate and word spreads quickly as
to which clinics will prescribe buprenorphine; they
pass along what to claim/say in order to receive
Subutex®
Naloxone “Allergy”
True anaphylaxis/hypersensitivity to naloxone is RARE;
reported incidence is 0.01%
The following side effects have been reported as
common (1-10%) in clinical trials for all formulations
▪ Dizziness/headache
▪ Nausea/vomiting
The amount of naloxone absorbed is clinically
minute; any amount that happens to be absorbed is
likely destroyed by the liver rapidly
The elimination half life is 64 + 12 minutes in healthy
adults
Aberrant Behaviors
Behaviors Less Suggestive of an Addiction Disorder:
Aggressive complaining about the need for more drug
Drug hoarding during periods of reduced symptoms
Requesting specific drugs
Openly acquiring similar drugs from other medical sources
Unsanctioned dose escalation or other noncompliance
with therapy on one or two occasions
Unapproved use of the drug to treat another symptom
Reporting psychic effects not intended by the clinician
Resistance to a change in therapy associated with
“tolerable” adverse effects with expressions of anxiety
related to the return of severe symptoms
Portenoy RK, Payne R. Acute and chronic pain. In Lowinson JH, Ruiz P, Millman RB (eds): Comprehensive
Textbook of Substance Abuse, 3rd Edition. Baltimore: Williams and Wilkins; 1997: Table 57.1, Page 564.
Aberrant Behaviors Behaviors More Suggestive of an Addiction Disorder:
Selling prescription drugs
Prescription forgery
Stealing or “borrowing” drugs from others
Injecting oral formulations
Obtaining prescription drugs from nonmedical sources
Concurrent abuse of alcohol or illicit drugs
Multiple dose escalations or other noncompliance with therapy despite warnings
Multiple episodes of prescription “loss”
Repeatedly seeking prescriptions from other clinicians or from emergency rooms without informing prescriber or after warnings to desist
Evidence of deterioration in the ability to function at work, in the family, or socially that appear to be related to drug use
Repeated resistance to changes in therapy despite clear evidence of adverse physical or psychological effects from the drug
Portenoy RK, Payne R. Acute and chronic pain. In Lowinson JH, Ruiz P, Millman RB (eds): Comprehensive
Textbook of Substance Abuse, 3rd Edition. Baltimore: Williams and Wilkins; 1997: Table 57.1, Page 564.
Post-Test Assessment
1. True or False: The majority of individuals that
purchase buprenorphine from the street are using
it to avoid or self-medicate withdrawal
2. True or False: Less than 50% of physicians
surveyed stated that buprenorphine diversion is a
serious problem
3. True or false: Suboxone Film(R) cannot be
injected by IV drug users due to its viscosity when
dissolved in water
Jake Nichols, Pharm.D., MBA
Specialist in Medication Assisted Treatment Options
for Opioid Use Disorder
617-529-6312 (cell)