buprenorphine diversion: the elephant or the mouse in the ... · no salary (or = 1.6) ongoing...

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

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.


Buprenorphine is the 4th most diverted controlled substance in the U.S.

NFLIS Data available at: https://www.nflis.deadiversion.usdoj.gov.


CESAR FAX, April 9th, 2012: Vol. 21, Issue 14


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.


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


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


Bailey, et al. ASAM Poster Presentation, April 2015


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)

[email protected]

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