Transcript Slide 1

Buprenorphine and
Related Dynamics in a
Clinical Setting
November 12, 2012
Dean Babcock, MSW, LCSW, LCAC
Associate Vice President
Midtown Community Mental Health Center
Buprenorphine
• High affinity partial mu opioid agonist and kappa-opioid
antagonist prevents withdrawal, high, reduces craving;
advantage: very low risk from overdose
– Has effects of typical opioid agonists at lower doses
– Produces a ceiling effect at higher doses
– Binds to opioid receptors and is long-acting
• Dose: Typically 12-16 mg/day, initiated while patient is
in mild to moderate withdrawal, prescribed by
physicians who have completed a certification process
– Slow to dissociate from receptors so effects last even if one daily dose is
missed.
Buprenorphine
• Formulations: Buprenorphine only (Subutex), combined
with naloxone (4:1; Suboxone); film
• Each 8 mg tablet contains 2 mg of naloxone
• Each 2 mg tablet contains 0.5 mg of naloxone
• Sublingual tablet
• Dissolvable film
• Implantable
• Results: Very effective in reducing illicit opioid use
• FDA approved for use with opioid dependent persons
aged 16 and older
• Side effects: Constipation, drowsiness, headache
Probuphine
Buprenorphine Implants
Clinical trials have indicted that buprenorphine implants
are effective in the treatment of opioid dependence
over a 24 week period following implementation.
JAMA, Oct 13, 2012
Titan Pharmaceuticals Inc. has submitted a New Drug
application to the FDA . This is the first implantable
Formation of Buprenorphine that can provide six
Months of medication following a single treatment.
Suni Bhonole
Titan Pharmaceuticals, Oct 2012
Mu efficacy and opiate addiction
fentanyl
Full agonist morphine/heroin
hydromorphone
Positive
effect
=
addictive
Potentially lethal dose
Agonist + partial agonist
Partial agonist
- buprenorphine
potential
Antagonist - naltrexone
Buprenorphine is EFFECTIVE
• Buprenorphine is as effective as moderate doses
of methadone (Fischer et al., 1999; Johnson, Jaffee, &Fudula, 1992; Ling et al., 1996;
Schottenfield et al., 1997; Strain et al., 1994)
• Buprenorphine's partial agonist effects make it
mildly reinforcing, encouraging medication
compliance (Ling et al., 1998)
• After a year of buprenorphine plus counseling,
75% of patients retained in treatment compared
to 0% in a placebo-plus-counseling condition (Kakko
et al., 2003)
LOW RISK PROFILE OF
BUPRENORPHINE
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Less risk of respiratory depression
Lower level of physical dependence
Lower level of abuse
Discourages IV use
Diminished street value/diversion
Dosing flexibility 1-3 days
BARRIERS TO BUPRENORPHINE
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Just learning about it, training underway
STIGMA
Reluctance to use medications
Medication alone is just not enough
Cost ($8.00 a day)
Formulary
Reluctance of medical community
Misuse and diversion
Who can prescribe
buprenorphine?
Physicians who have received buprenorphine training and
obtained a federally approved waiver can prescribe
Subutex and Suboxone or approved generic equivalent
What are the adverse effects of
buprenorphine abuse?
According to the manufacturer’s safety information for
Suboxone, buprenorphine “can cause serious lifethreatening respiratory depression and death, particularly
when taken by the intravenous (IV) route in combination
with benzodiazepines or other central nervous system
(CNS) depressants (i.e., sedatives, tranquilizers, or
alcohol).” They also note that “intravenous misuse or taking
[Suboxone] . . . before the effects of full-agonist opioids
(e.g., heroin, hydrocodone, methadone, morphine,
oxycodone) have subsided is highly likely to cause opioid
withdrawal symptoms.” In addition, “chronic use of
buprenorphine can cause physical dependence.”
“Patients dependent on prescription opioids . . .
are most likely to reduce their opioid use during
the first several months of treatment while
receiving buprenorphine-naloxone; if tapered off
this medication, the likelihood of relapse to opioid
use or dropout from treatment is overwhelmingly
high” (p. E7).
Weiss, R.D., et. al., “Adjunctive Counseling During Brief and Extended BuprenorphineNaloxone Treatment for Prescription Opioid Dependence,” Archives of General
Psychiatry, Online First November 7, 2011
The amount of buprenorphine legally
available for distribution and sale has
increased
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 Subutex® or Suboxone® from
U.S. outpatient retail pharmacies increased from slightly
less than 20,000 in 2003 to more than 600,000 in 2009.
(Source: CESAR FAX,Vol. 20, Iss. 22 & 23)
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
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Buprenorphine has been smuggled into state prisons,
including those in Maine, Massachusetts, New Jersey, New
Mexico, Pennsylvania, and Vermont
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More than one-half of buprenorphine-related emergency
department (ED) visits are for the nonmedical use of the drug.
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The estimated number of ED visits related to the nonmedical
use of buprenorphine has more than tripled, from 4,440 in
2006 to 14,266 in 2009.
Estimate Number of Total Methadone and Buprenorphine
Drug Item Analyzed by State and Local Forensic Laboratories in
the U.S., 2003-2009
12000
10,459
10,774
10,361
10000
9,822
Methadone
8,172
8000
7,303
6,397
4,967
6000
5,627
4000
3,108
Buprenorphine
1,809
2000
0
21
2003
262
2004
540
2005
2006
2007
2008
2009
U.S. Drug Enforcement Agency (DEA), Office of Diversion Control, Special Report:
Methadone and Buprenorphine, 2003-2008, 2009
Nearly All Emergency Department Visits for the
Accidental Ingestion of Buprenorphine Occur in
Children Under the Age of Six
Estimated Number of Total Methadone and Buprenorphine Drug Items Analyzed by State and Local
Forensic Laboratories in the US, 2003-2009
12000
10000
8000
Methadone
6000
4000
2000
Buprenorphine
0
2003
2004
2005
2006
2007
2008
2009
Substance Abuse and Mental Health Services Administration (SAMHSA), Drug Abuse
Warning Network (DAWN), National Estimates of Drug-Related Emergency Department
Visits, 2004-2009
Estimated Number of Buprenorphine- and HydromorphoneRelated ED Visits More Than Doubles from 2006 to 2010
Drug name
(Common Brand Name)
# of ED Visits for
Nonmedical Use
Buprenorphine
(Suboxone, Subutex, Temgesic, Buprenex)
2006
4,440
2010
15,778
% Change
2006 to 2010
+255%
Adapted by CESAR from Substance Abuse and Mental Health
Services Administration (SAMHSA), National Estimates of DrugRelated Emergency Department Visits, 2004-2010
Majority of Buprenorphine-Certified Physicians Think
Buprenorphine Is Easier to Get Illegally Than Methadone
Perceptions of Buprenorphine Diversion/Misuse,
Physicians Federally Certified to Prescribe Buprenorphine
(n=8,194 from 2005 to 2009)
Adapted by CESAR from Johanson, C-E; Arfken, C. L.; di Menza, S.; and Schuster, C. R.,
“Diversion and Abuse of Buprenorphine: Findings from National Surveys of Treatment
Patients and Physicians,” Journal of Drug and Alcohol Dependence 120:190-195, 2012.
61% of Buprenorphine-Related Emergency Department
Visits for Nonmedical use
• Seeking substance abuse treatment
• Drug rehabilitation
• Medical clearance for admission to a drug treatment
or detoxification unit
• Taking more than the prescribed dose
• Taking buprenorphine prescribed for
another individual
• Deliberate poisoning with
buprenorphine by another person
• Documented misuse or abuse of
buprenorphine
• Adverse reactions
• Drug-drug interactions
• Drug-alcohol interactions resulting
from using buprenorphine for therapeutic
purposes
• Childhood poisoning
• Individuals who take a wrong medication by mistake
• Caregiver administering the wrong medicine by mistake
Substance Abuse and Mental Health Services Administration
(SAMHSA), Drug Abuse Warning Network, 2009: Selected Tables of
National Estimates of Drug-related Emergency Department
Reckitt Benckiser Pharmaceuticals Inc. to Voluntarily
Discontinue the Supply of Suboxone Tablets (buprenorphine
and naloxone sublingual tablets
The company received an analysis of data form U.S. Poison
Control Centers on September 15,2012 that found
consistently and significantly higher rates of accidental
unsupervised pediatric exposure with Suboxone Tablets
(buprenorphine and naloxone sublingual tablets [CIII] than
seen with Suboxone Film (buprenorphine and naloxone
sublingual form [CIII]. The rates for Suboxone Tablets were
7.8-8.5 times greater depending on the study period.
September 25, 2012
PATIENT PERCEPTIONS
1) Fight Withdrawal
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“[Some users] don’t want to get off [opioids] for good. They just want to not
be sick, so they have Suboxone stashed away for when they feel sick”
(TP, p. 115).
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“They [opiate addicts] use it … like Tylenol 3®, to use till they can get a fix.
[Suboxone is] a drug of convenience” (TP, p. 83).
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“Some start off using it …to assist with withdrawal, but find that they like
how it feels and become addicted” (TP, p. 34).
• “I quartered them [Suboxone] …to take the bare minimum, so I wouldn’t be
sick, but that way I could still use an opiate; I would buy them …to come off
other stuff, but it never worked that way. ‘Cuz you could get high off
Suboxone if you hadn’t had any opiates in a couple of days .
• If you are addicted to opiates, you take the smallest piece of Suboxone—it
makes you feel normal” (U, p. 133).
Department of Alcohol and Drug Addiction Services, Ohio Substance Abuse
Monitoring Network: Surveillance of Dug Abuse Trends in the State of Ohio,
January-June 2011
PATIENT PERCEPTIONS
2) Get High
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“If you are clean [opioid free], you will get very high from Suboxone”
(U, p. 17).
• “For a buzz … can snort Suboxone, as long as you don’t have other opiates in
the system” (U, p. 50).
• “If you are not addicted to opiates and you take a Suboxone, it’s very, very
strong. It can make you high for three days” (U, p. 133).
• “People … will use Xanax® a half-hour before Suboxone and will get high.
• Some clients say the effects are as good as, or better than, that of
OxyContin®” (TP, p. 17).
• “[A] lot of people are being introduced to opioids through Suboxone now
because, if they were not Suboxone users, the buprenorphine … the active
agent in Suboxone is giving them the opiate effect, and now they’re looking
for stronger opioids.
Department of Alcohol and Drug Addiction Services, Ohio Substance Abuse
Monitoring Network: Surveillance of Dug Abuse Trends in the State of Ohio,
January-June 2011
PATIENT PERCEPTIONS
3) Avoid Detection
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“Participants also reported that individuals who need to
avoid detection of drug use on urine drug screens
(probationers) use Suboxone because it is often not screened”
(Report, p. 4). “[Suboxone is] the institutional drug of choice”
(U, p. 17).
Department of Alcohol and Drug Addiction Services, Ohio Substance Abuse
Monitoring Network: Surveillance of Dug Abuse Trends in the State of Ohio,
January-June 2011
How is Suboxone Being Used?
“People typically put them …under their tongue, or they
chew them up. I’ve actually witnessed a couple people
shoot [inject] them up; I would eat the full 8 mg Suboxone”
(U, p. 132). “I snorted it … when I would take it. It made me
not sick” (U, p. 132). “Well, I shoot [Suboxone] in my neck,
so, um, it goes straight to you, you know” (U, p. 133). “I do
know a few people that when switched to the films
[Suboxone strips], they say that those are a lot easier to
shoot up [inject]. Yeah, ‘cause they dissolve in water; they
dissolve completely, and I’ve heard people say that those
actually work really well” (U, p. 133).
Department of Alcohol and Drug Addiction Services, Ohio Substance Abuse Monitoring Network: Surveillance of Drug Abuse
Trends in the State of Ohio, January-June 2011, 2011
Practical Objectives from the field
• Need closer monitoring
• Use of INSPECT REPORTS (pharmacy driven data on scheduled drug
prescriptions filled by pharmacies)
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High doses
Split doses
Securing of medications
Desire for drug – but not treatment
Interface with primary care medicine and large populations of
opiate prioritized patients, chronic pain, acute pain,
addiction.
Policy changes that may decrease
buprenorphine diversion and misuse
• The apparent increase in buprenorphine availability, diversion, and
nonmedical use suggest the need for buprenorphine policy changes.
• Current testing protocols, including those of medical examiners and drug
testing programs, should include routine testing for buprenorphine to
estimate the full magnitude of and to monitor buprenorphine diversion
and misuse.
• Physician education programs for prescribing buprenorphine, especially
strategies to detect and deter diversion and misuse, need to be
strengthened.