Download Title, Arial bolded 32pt - Pfizer Medical Information

Prescription Opioid Abuse: Abuse-Deterrent
Opioids as Part of a Multipronged Approach
For Pfizer Use Only
Table of Contents
•Chronic Pain and Prescription Opioids
•Source of Prescription Opioids and Patient Risk Assessment
•Routes of Prescription Opioid Abuse & Adverse Health Outcomes
•FDA Evaluation and Labeling of Abuse-Deterrent Opioids (ADOs)
•The Potential Role of Abuse-Deterrent Opioids (ADOs) in Helping
to Deter Opioid Abuse
2
For Pfizer Use Only
Chronic Pain: A Serious Public Health Issue
• Chronic pain is a major concern for individuals, families, and
society, with an increasing prevalence, cost, and impact on quality
of life
• Millions of Americans are affected by
chronic pain1
• Estimated annual cost of $560-635 billion2
• While the use of prescription opioids has been linked to abuse,
misuse, diversion , these medications still serve as an efficacious
treatment option for patients in the management of chronic pain 3-5
• However, clinical guidelines for chronic pain recommend that
opioids be considered only after an adequate trial of non-opioid
options5-9
1.
2.
3.
4.
5.
IOM. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research.
Washington, DC: The National Academies Press; 2011.
Gaskin DJ, Richard P. J Pain. 2012;13(8):715-724
Moore RA, McQuay HJ, Moore RA, McQuay HJ. Prevalence of opioid adverse events in chronic nonmalignant pain: systematic review of randomized trials of oral opioids. Arthr ResTher. 2005;7(5):R10461051.
Noble M, Tregear SJ, Treadwell JR, Schoelles K. Long-term opioid therapy for chronic noncancer pain:
A systematic review and meta-analysis of efficacy and safety. J Pain Symptom Manage. 2008;35:214228
Fine, PG. Opioid therapy as a component of chronic pain management: Pain experts weigh in on key
principles to optimize treatment. Topics in Pain Management. 2008;23(10):1-8.)
5.
6.
7.
8.
9.
Utah Department of Health. Utah Clinical Guidelines on Prescribing Opioids for
Treatment of Pain. Salt Lake City, UT: Utah Dept of Health; 2009.
Manchikanti L et al. Pain Physician. 2012;15(3 suppl):S67-S116.
Chou R et al. J Pain. 2009;10(2):113-130.
US Department of Veterans Affairs, US Department of Defense. VA/DoD Clinical
Practice Guideline for Management of Opioid Therapy for Chronic Pain. Version 2.0.
Washington, DC: US Dept of Veterans Affairs, US Dept of Defense; 2010.
Washington State Agency Medical Directors’ Group (AMDG). Interagency Guideline
on Opioid Dosing for Chronic Non-cancer Pain: An Educational Aid to Improve Care
and Safety With Opioid Therapy. 2010 Update. Olympia, WA: Washington State
3
Agency Medical Directors Group; 2010
For Pfizer Use Only
Opioids Are Frequently Used to Treat Pain, Even Though
Guidelines Recommend Use Only After Other Therapies
Opioid Prescriptions Dispensed by Retail Pharmacies (US, 1991-2015)1
250
196
No. Prescriptions (in millions)
200
202
210
216 214
204
184
181
174
138 142
150
149
155
196
163
126
116
100
76
79
82
85
87
94
97
105
50
0
1991
1.
1993
1995
1997
1999
2001
2003
2005
2007
2009
Adapted f rom Volkow ND. America’s Addiction to Opioids: Heroin and Prescription Drug Abuse. NIDA Web site. http://www.drugabuse.gov/about-nida/legislativeactiv ities/testimony-to-congress/2015/americas-addiction-to-opioids-heroin-prescription-drug-abuse. Published May 14, 2014. Accessed February 9, 2016.
2011
2013
2015
4
For Pfizer Use Only
The Increase in Opioid Prescriptions Is Associated
With Serious Health Consequences
Prescription opioid overdose deaths quadrupled from 1999-20101;
emergency department (ED) visits increased by 183% from 2004-20112
488,004
16,651
15,000
12,000
Overdose
Deaths
500,000
400,000
300,000
ED Visits
9,000
200,000
6,000
172,738
100,000
4,030
3,000
0
No. Opioid-related ED Visits
No. Prescription Opioid-related Deaths
18,000
53% to 80% of people
who die from prescription
opioid overdoses have a
history of chronic pain3-5
0
1999
2001
2003
2005
2007
2009
2011
1. CDC. MMWR Morb Mortal Wkly Rep. 2013;62(12):234.
2. SAMHSA. Drug Abuse Warning Network, 2011: National Estimates of Drug-Related Emergency Department Visits. Rockville, MD: SAMHSA; 2013.
HHS Publication No. (SMA) 13-4760, DAWN Series D-39.
3. Lanier WA et al. Presented at: Annual Epidemic Intelligence Service Conference; April 19-23, 2010; Atlanta, GA.
4. Paulozzi LJ et al. Addiction. 2009;104(9):1541-1548.
5. HHS. Addressing Prescription Drug Abuse in the United States. Washington, DC: HHS; September 2013.
http://www.cdc.gov/HomeandRecreationalSafety/pdf/HHS_Prescription_Drug_Abuse_Report_09.2013.pdf. Accessed July 10, 2014
5
For Pfizer Use Only
Opioid Deaths Are Only Part of the Story
The CDC estimates that for every opioid
overdose death in 2010, there were:
10
Abuse treatment admissions*
26
ED visits for misuse/abuse†
108
who abused/were dependent ‡
733
past-year
nonmedical users‡
Note: Compiled by CDC from separate 2010 databases
*Treatment admissions are for primary use of opioids: Treatment Exposure Data Set.
†ED visits: Drug Abuse Warning Network (DAWN) https://dawninfo.samhsa.gov/default.asp.
‡Abuse/dependence and nonmedical use: National Survey on Drug Use and Health.
CDC. Primary Care and Public Health Initiative. Prescription Drug Abuse and Overdose: Public Health Perspective. October 24, 2012.
http://w ww.cdc.gov/primarycare/materials/opoidabuse/docs/pda-phperspective-508.ppt. Accessed February 9, 2016.
6
For Pfizer Use Only
Prescription Opioid Abuse: CDC Statistics
Today, at least half of all U.S. opioid overdose deaths involve a prescription
opioid.1
• Overdose deaths involving prescription opioids have quadrupled since 1999 1
• From 1999 to 2014, more than 165,000 people have died in the U.S. from
overdoses related to prescription opioids.1
• In 2014, more than 14,000 people died from overdoses involving prescription
opioids.1
• In 2014, almost 2 million Americans abused or were dependent on prescription
opioids.2
1CDC.
Wide-ranging online data for epidemiologic research (WONDER). Atlanta, GA: CDC, National Center for Health Statistics; 2016. Available at
http://w onder.cdc.gov.
2Substance Abuse and Mental Health Services Administration, National Survey on Drug Use and Health, 2014.
7
For Pfizer Use Only
The Increase in Opioid Prescriptions Has Been Associated With
a Dramatic Rise in Overdose Deaths
Deaths per 100,000 Population
Age-Adjusted Opioid Overdose Death Rates1*
10
Drug overdose deaths involving opioids (total, including heroin)
Natural and semisynthetic opioids (eg, morphine, oxycodone, hydrocodone)
Synthetic opioids excluding methadone (eg, fentanyl, tramadol)
Methadone
Heroin
8
6
4
2
0
2000
2002
2004
2006
2008
2010
2012
2014
*Age-adjusted death rates calculated by applying age-specific death rates to the 2000 US standard population age distribution. Overdose
deaths involving opioids identified using ICD-10 codes. Deaths might involve >1 drug.
1.
2.
3.
Rudd RA et al. MMWR Morb Mortal Wkly Rep. 2016;64(50-51):1378-1382.
Lanier WA et al. Presented at: Annual Epidemic Intelligence Service Conference; April 19-23, 2010; Atlanta, GA.
Paulozzi LJ et al. Addiction. 2009;104(9):1541-1548.
8
For Pfizer Use Only
Source of Prescription Opioids and
Patient Risk Assessment
For Pfizer Use Only
Understanding the Terminology
Term
Definition
Misuse1
• Intentional therapeutic use of a drug product in an inappropriate
way
• Specifically excludes the definition of abuse
Abuse1
• Intentional, nontherapeutic use of a drug product or substance,
even once, to achieve a desirable psychological or physiological
effect
Diversion2
• Intentional removal of a medication from legitimate distribution
and dispensing channels
• Also involves the sharing or purchasing of drugs between family
and friends, or individual theft from family and friends
1. FDA. Guidance for Industry: Abuse-Deterrent Opioids—Evaluation and Labeling. Rockville, MD: FDA; 2015.
2. Webster L et al. J Opioid Manag. 2011;7(3):235-245. 2015.
3.
Webster L et al. J Opioid Manag. 2011;7(3):235-245.
10
For Pfizer Use Only
According to a 2013 Survey, About 70% of Nonmedical Users of
Prescription Pain Relievers Get Them From Friends or Relatives
Sources Where Users
Obtained Pain Relievers
Original Sources of Pain
Relievers Obtained “Free From
Friend or Relative”
>1 Doctor,
2.6%
1 Doctor,
21.2%
Other,*
4.3%
Free From
Friend or
Relative, 53.0%
Internet,
0.1%
Drug Dealer
or Stranger,
4.3%
>1 Doctor, 3.3%
1 Doctor,
83.8%
Free From Other Friend
or Relative, 5.1%
Bought/Took From
Other Friend or
Relative, 4.9%
Drug Dealer or
Stranger, 1.4%
Bought/Took
From Friend
or Relative,
14.6%
Other, 1.2%*
Internet, 0.3%
Note: Due to rounding, percentages do not add up to 100%.
*Other includes: “Wrote Fake Prescription,” “Stole from Doctor’s Office/Clinic/Hospital/Pharmacy,” and “Some Other Way.”
SAMHSA. Results from the 2013 National Survey on Drug Use and Health: Summary of National Findings. NSDUH Series H-48, HHS Publication No. (SMA) 14-4863.
Rockville, MD: SAMHSA; September 2014.
11
For Pfizer Use Only
Identifying Patients at High Risk for Opioid Misuse and
Abuse Is Extremely Challenging
Based on a Study of
Primary Care Physicians
100%
N=367 patients confirmed
as at
high risk for opioid
misuse and abuse*
Only 5% correctly
identified as at high risk
(n=18)
20%
PCP assignment
of risk among
these confirmed
high-risk patients†
5%
Incorrectly
identified
as at low risk
(n=73)
74%
Incorrectly identified
as at moderate risk
(n=275)
Open-label, nonrandomized, noncomparative study in which PCPs were asked to identify patients at high risk for opioid misuse and abuse.
*Confirmed using SOAPP®-R (Screener and Opioid Assessment for Patients With Pain-Revised, a patient-completed 24-item questionnaire to identify
risk for future misuse and/or abuse of opioids). For this study, SOAPP®-R score 0-9 = low risk; 10-21 = moderate risk; and 22 = high risk.
†Patients at high risk for opioid abuse (SOAPP® -R score ≥22 at baseline). Due to rounding, percentages do not add up to 100%, and n’s do not = 367.
Brow n J et al. J Opioid Manag. 2011;7(6):467-483.
12
For Pfizer Use Only
Routes of Prescription Opioid Abuse &
Adverse Health Outcomes
For Pfizer Use Only
Prescription Opioids Can Be Misused and Abused
by Different Routes
Examples of Abuse Methods1,3
Swallowed whole
or chewed
 The most common form
of abuse is swallowing a
number of intact capsules
or tablets to achieve a
feeling of euphoria1
1.
2.
3.
Crushed then swallowed,
snorted or smoked
Crushed, dissolved,
then injected
 Product manipulated in pursuit of more intense high resulting
from rapid increase in opioid in the blood2
 Methods vary among products, based on pharmacokinetic
properties, bioavailability via different routes, ease of
tampering, nature of euphoria, and presence of dangerous
excipients2
FDA. Guidance for Industry: Abuse-Deterrent Opioids—Evaluation and Labeling. Rockville, MD: FDA; 2015.
Katz N et al. Am J Drug Alcohol Abuse. 2011;37(4):205-217.
Vietri J et al. Pain Med. 2014;15(12):2064-2074.
14
For Pfizer Use Only
In a 2012 Survey, Half of People Abusing Prescription
Opioids Reported Product Manipulation1
Abuse Methods Involving Manipulation of the Product 2
Swallowed whole
or chewed
Crushed then swallowed,
snorted or smoked
Crushed, dissolved,
then injected
 The most common form of abuse is swallowing a number of intact capsules or
tablets to achieve a feeling of euphoria1
 Product manipulation is more common with extended-release opioids, due to a
higher drug content, than with immediate-release opioids3
1.
2.
3.
Vietri J et al. Pain Med. 2014;15(12):2064-2074.
FDA. Guidance for Industry: Abuse-Deterrent Opioids—Evaluation and Labeling. Rockville, MD: FDA; 2015.
Katz N et al. Am J Drug Alcohol Abuse. 2011;37(4):205-217.
15
For Pfizer Use Only
ER Opioids Are Tampered With for Purposes of
Misuse and Abuse
Abuse of ER Formulations of Prescription Opioid Medications by
Route of Administration (June 1, 2009 to August 8, 2010*)
80
Percentage of
Persons Abusing
61.8
60
54.5 52.7
46.7
35.7
40
45.7
38.2
25.3
20
8.6
6.4
0
ER Oxycodone
Oral
0.9
0.2
ER Oxymorphone
Snorting
Smoking
ER Morphine
Injecting
*Prior to introduction of reformulated ER oxycodone and ER oxymorphone.
Note: Percentages for each drug do not add up to 100% because respondents could report multiple routes of administration.
Adapted from Butler S et al. J Pain. 2013;14(4):351-358. Used with permission.
16
For Pfizer Use Only
In One Study, Patients Admitted to an Abuse Treatment Center
Reported Progression From Oral Ingestion to Snorting/Injection
Route of Administration at
Treatment Admission
(n = 133/187)
Initial Route of Administration
(n = 112/187)
Injecting, <1%
Oral,
14%
Snorting,
16%
Mean duration of
prescription opioid
use: 19.2 months*
Oral, 83%
Injecting,
26%
Snorting, 62%
Study looked at route of administration of controlled-release oxycodone at initiation of use/misuse and admission to an addictiontreatment center (October 2000 to March 2002; N = 187).
*Average time between first use/misuse and addiction-treatment admission.
Hays LR. J Addict Dis. 2004;23(4):1-9.
17
For Pfizer Use Only
Non-oral (vs Oral) Misuse and Abuse Is Associated With
Up to a Twofold Higher Risk for Severe Health Consequences
Proportion of Cases of
Misuse/Abuse
Inhaling,
5% Injecting,
3%
Percentage of Cases Leading to
Major Effect* or Death
16.5%
Oral,
92%
8.6%
Oral
*Symptoms that were life-threatening or resulted in significant residual disability or disfigurement.
Katz N et al. Am J Drug Alcohol Abuse. 2011;37(4):205-217.
10.2%
Inhaling
Injecting
18
For Pfizer Use Only
FDA Evaluation and Labeling of
Abuse-Deterrent Opioids (ADOs)
For Pfizer Use Only
.
.
FDA Considers Development of Abuse-Deterrent
Opioids To Be a “High Public Health Priority”
FDA Guidance
• Abuse-deterrent properties are defined as those
shown to meaningfully deter abuse, even if
they do not fully prevent it
• Abuse-deterrent technologies to date are
intended to make:
Issued April 20151
‐ manipulation (crushing, chewing, dissolving,
extracting) of the opioid more difficult, or
‐ the effect of the manipulated opioid
less attractive or rewarding
• FDA guidance describes the studies to be
conducted to demonstrate a given formulation
has abuse-deterrent properties, how studies will
be evaluated, and what labeling claims may be
approved based on results. FDA remains
supportive of ADO development. 2
“One potentially important step
towards the goal of creating safer
opioid analgesics has been the
development of opioids that are
formulated to deter abuse. FDA
considers the development of
these products a high public health
priority.”
 FDA Guidance for Industry: Abuse-Deterrent
Opioids — Evaluation and Labeling (April
2015)
FDA. Guidance for Industry: Abuse-Deterrent Opioids—Evaluation and Labeling. Rockville, MD: FDA; 2015.
Califf, Robert M., Janet Woodcock, and Stephen Ostroff. "A Proactive Response to Prescription Opioid
Abuse." New England Journal of Medicine (2016).
20
For Pfizer Use Only
Potential Abuse-Deterrent Opioid Product Categories
(FDA Defined)
Technology
Description
• Physical barriers can prevent/deter manipulation
Physical/chemical
barrier
• Chemical barriers can resist extraction of the opioid
Agonist/antagonist
combination
• Antagonist added to interfere with, reduce, or defeat euphoria associated
with abuse
Aversion
• Substances can be added to the product to produce an unpleasant effect if the
dosage form is manipulated or is used at a higher dosage than directed
Delivery system
• Drug-release design or method of drug delivery (eg, depot injectable) offers
resistance to abuse
New molecular
entities and prodrugs
• Physical and chemical barriers can change the physical form of an oral drug,
rendering it less amenable to abuse
• Properties could include the need for enzymatic activation, different receptorbinding profiles, slower penetration into the CNS, or other novel effects
• Prodrugs with abuse-deterrent properties could provide a chemical barrier to the in
vitro conversion to the parent opioid, which may deter abuse of the parent opioid
Combination
• Two or more of the above methods
Novel approaches
• Novel approaches or technologies not captured in the previous categories
FDA. Guidance for Industry: Abuse-Deterrent Opioids—Evaluation and Labeling. Rockville, MD: FDA; 2015.
21
For Pfizer Use Only
Premarketing
studies
2015 FDA Guidance: Premarketing and
Postmarketing Studies of Abuse Deterrence
Category 1: Laboratory-based in vitro
manipulation and extraction
Purpose: evaluate in vitro the ease with which
the abuse-deterrent properties can be
defeated or compromised
Category 2: Pharmacokinetic
Purpose: understand the in vivo properties of
the formulation by comparing PK profiles
Category 3: Clinical abuse potential*
Purpose: measure and collect subjective
response data predictive of the likelihood of
product abuse
Category 4: Postmarketing studies
Purpose: determine whether the marketing of
a product with abuse-deterrent properties
results in meaningful reductions in abuse
*Also known as human abuse liability (HAL) studies.
FDA. Guidance for Industry: Abuse-Deterrent Opioids—Evaluation and Labeling. Rockville, MD: FDA; 2015.
22
For Pfizer Use Only
Category 1: Laboratory-Based in vitro
Manipulation and Extraction Studies
Purpose: evaluate in vitro the ease with which the
abuse-deterrent properties can be defeated or compromised
• Designed with knowledge of properties of formulation and abuse methods
• Should fully characterize abuse-deterrent properties and effort to defeat
them
• Assess simple and sophisticated mechanical and chemical ways
to manipulate:
‒ Defeating or compromising the controlled release of an opioid from an
ER formulation
‒ Preparing an IR formulation for alternative routes of administration
‒ Separating opioid antagonist, if present, from opioid agonist
• Compare to appropriate non-ADO formulations
FDA. Guidance for Industry: Abuse-Deterrent Opioids—Evaluation and Labeling. Rockville, MD: FDA; 2015.
23
For Pfizer Use Only
Hypothetical Example of a Category 1
Extractability and Syringeability Study
Extractability
Syringeability
Amount of drug from new formulation
and comparator that can be extracted
after soaking for increasing lengths
of time in various liquids
Whether the dissolved product
can be drawn up into a syringe, based
on the temperature, plunger speed,
and needle size
ADO
Non-ADO
Cola
1%
91%
Hot tea
6%
60%
Vinegar
Baking soda
solution
0%
1%
Drug composition may vary based on technology.
ADO
Non-ADO
18 gauge
YES
YES
21 gauge
NO
YES
25 gauge
NO
YES
90%
74%
24
For Pfizer Use Only
Data for illustrative purposes only.
Category 2: Pharmacokinetic Studies
Purpose: understand the in vivo properties of the
formulation by comparing PK profiles
Plasma Drug Concentration (ng/ml)
Crushed ER Opioid
(non-abuse-deterrent)
Crushed ER Opioid
(abuse deterrent)
Chewed ER Opioid
(abuse deterrent)
Intact ER Opioid
(abuse deterrent)
0
2
4
6
8
Time (hours)
10
12
Graph for illustrative purposes only.
“The rate of rise of drug concentration should be assessed when possible, because it is thought to contribute to
differential abuse potential among drugs, formulations, and routes of administration.”
 FDA Guidance for Industry: Abuse-Deterrent Opioids— Evaluation and Labeling (April 2015)
FDA. Guidance for Industry: Abuse-Deterrent Opioids—Evaluation and Labeling. Rockville, MD: FDA; 2015.
25
For Pfizer Use Only
Category 3: Clinical Abuse Potential* Studies
Purpose: measure and collect subjective response data predictive
of the likelihood of product abuse 1
• Pharmacology assessments that provide unique information relevant to CNS-active
drugs1
• Compare subjective responses to “drug liking,” “drug high,” and
“willingness to take drug again” for each active agent and placebo2
Study design principles2:
• Randomized, double-blind, placebo-controlled,
positive comparator–controlled, crossover
• Enrollment of an appropriate abusing population
• Prequalification phase
• Relevant routes of administration
• Preparation of samples with consideration
of blinding
Visual Analog Scale
Do you like the drug effect
that you are feeling now?
Strong
disliking
0
− Potential use of a proxy solution for IV injection
Strong
liking
50
100
Neither like
nor dislike
*Also known as human abuse liability (HAL) studies.
1.
2.
FDA. Guidance for Industry: Assessment of Abuse Potential of Drugs [draft guidance]. Rockville, MD: FDA; January 2010.
FDA. Guidance for Industry: Abuse-Deterrent Opioids—Evaluation and Labeling. Rockville, MD: FDA; 2015.
26
For Pfizer Use Only
Understanding Clinical Abuse Potential Study Data
Strong
drug liking
Emax (maximal response)
Neutral
Placebo
Crushed non-ADO
Intact ADO
Crushed ADO
Strong
drug disliking
Time
Graph for illustrative purposes only.
FDA. Guidance for Industry: Abuse-Deterrent Opioids—Evaluation and Labeling. Rockville, MD: FDA; 2015.
27
For Pfizer Use Only
Category 4: Postmarketing Studies
Purpose: determine whether the marketing of a product with
abuse-deterrent properties results in meaningful reductions in
abuse, misuse, and related adverse clinical outcomes
Examples of abuse-related clinical outcomes
Addiction data
Overdoses/poisonings
Deaths
“Given the changing landscape, a numerical threshold cannot define
what would be considered a meaningful reduction.”
 FDA Guidance for Industry: Abuse-Deterrent Opioids — Evaluation and Labeling (April 2015)
FDA. Guidance for Industry: Abuse-Deterrent Opioids—Evaluation and Labeling. Rockville, MD: FDA; 2015.
28
For Pfizer Use Only
Where to Find Abuse-Deterrent Data and Labeling
• Refer to prescribing information section 9: DRUG ABUSE AND
DEPENDENCE
‐ Includes descriptions and data regarding the specific product’s abusedeterrent studies (will vary by product)
• If such information does not appear in a product’s labeling under
section 9, that product is not an ADO, by FDA standards
The pharmacokinetic data demonstrate that crushing [Tradename] results in the
simultaneous release and rapid absorption of opioid and antagonist. These data
along with the results from oral and intranasal clinical abuse potential studies and a
clinical abuse potential study of intravenous opioid and antagonist to simulate
crushed [Tradename] indicate that [Tradename] has properties that are expected to
deter abuse via the oral, intranasal, and intravenous routes. However, abuse of
[Tradename] by these routes is still possible.
 Example of potential labeling for an ADO with category 2 and 3 data
FDA. Guidance for Industry: Abuse-Deterrent Opioids—Evaluation and Labeling. Rockville, MD: FDA; 2015.
29
For Pfizer Use Only
The Potential Role of Abuse-Deterrent
Opioids in Helping to Deter Opioid Abuse
For Pfizer Use Only
Progression of Opioid Abuse: A Multipronged
Approach in Addressing Abuse
Potential Strategies
Initial Opioid
Treatment
• Patient
Agreements
• Patient
Education
• Safe storage
& Disposal
• PDMP1
• ADOs
Suspected
Abuse or
Misuse
• Urine Tests
• Pill limits
Addiction
• MedicationAssisted
Treatment
Programs
Overdose
• Naloxone
• Addiction Counseling
1Dow ell,
Deborah, Tamara M. Haegerich, and Roger Chou. "CDC guideline for prescribing opioids for chronic pain—United States, 2016." JAMA (2016).
Richard C., et al. Trends in opioid analgesic abuse and mortality in the United States. New England Journal of Medicine 372.3 (2015): 241-248.
3Coplan, Paul M., et al. Changes in oxycodone and heroin exposures in the National Poison Data System after introduction of extended‐release oxycodone
31
w ith abuse‐deterrent characteristics. Pharmacoepidemiology and drug safety 22.12 (2013): 1274-1282.
2Dart,
For Pfizer Use Only
Epidemiological Data From Actual Use Indicate That
Abuse-Deterrent ER Oxycodone Reduced Its Abuse
Among Patients Reporting Abuse of Prescription Opioids,
Abuse* of ER Oxycodone Decreased 50% After Introduction of its Reformulation
Past-30-Day Abuse, %
25
20
15
10
23.7%
June 1, 2009 ̶
August 8, 2010
49% reduction in
abuse of opioid
(P<.0001)
12.1%
August 9, 2010 ̶
March 31, 2012
5
0
Before Reformulation
(n=2894/12,211)
After Reformulation
(n=1705/14,091)
* In past 30 days.
Using the Addiction Severity Index-Multimedia Version (ASI-MV), 140,496 subjects were assessed for substance use problems at 357 US centers, which
were part of the NAVIPPRO surveillance system. Data collected during a 34-month period (11 quarters) from June 1, 2009 to March 31, 2012. Among
total sample, 18.8% reported abuse of any prescription opioid.
Butler S et al. J Pain. 2013;14(4):351-358.
32
For Pfizer Use Only
Impact of a Tamper Resistant Opioid Formulation:
NAVIPPRO Data Shows a Change in Frequency of Abuse
The average number of days in the past 30 days abusing ER
oxycodone and comparators before and after the introduction of ADO
oxycodone ER
Original
Oxycodone ER
(Days)
Before period
(6/09-8/8/10)
After Reformulated
ADO Oxycodone ER
(Days)
(8/9/12-3/31/12)
Pre-Post
Percentage
Change
ER oxycodone
10.8
7.5
-30.4%*
ER oxymorphone
5.1
7.8
+52.2%*
ER morphine
9.1
10.0
+10.6%†
N=140,496 individuals assessed for substance abuse treatment at 357 U.S. centers
Butler, et al. 2013. J. Pain, Vol.14, No.4 (April), 2013
*p<.0001, † p=0.0909
33
For Pfizer Use Only
Summary of Observed Changes in ER Oxycodone
Upon Introduction of ADO ER Oxycodone
Observation
Data Source
Timeframe
Change
Self reported abuse
NAVIPPRO Drug
Treatment1
1 year prior, 18 months
post
Self reported abuse
RADARS Opioid
Treatment Program2
5.5 years prior, 3 years post
Decreased
(% not reported)
Self reported abuse
RADARS Survey of
Key Informants2
2.5 years prior, 3 years post
Decreased
(% not reported)
Drug abuse related poison
center exposures
RADARS Poison
Center Exposures3
1 year prior, 2 years post
-36%
(P<0.001)
Drug diversion rates
RADARS Drug
Diversion 4
2 years prior, 18 months
post
-53%
(P<0.001)
Drug price – law
enforcement
RADARS Drug
Diversion 4
Time of switch to 1 year
post
-22%
(P=0.002)
Self reported street price
RADARS StreetRX5
Single time period
comparison post switch
-37%
-41%
(P<0.0001)
1. Butler, et al. 2013. J. Pain, Vol.14, No.4 (April), 2013, 2. Dart et al. NEJM, 372; 3, January 2015; Coplan et al Pharmacoepidemiology and Drug
Safety 2013; 22: 1274–1282; 4. Severtson et al. , J Pain, Vol 14, No 10 (October), 2013: pp 1122-1130, 5. RADARS System Technical Report, 2014Q1, Data from StreetRx
34
For Pfizer Use Only
Prescription Opioid Abuse: Consider ADOs as part
of a Multipronged Approach
Those who abuse often obtain
opioids from legitimate
prescriptions 4
Opioid abuse is a
growing epidemic,
as shown in overdose
deaths, and all patients
are at risk1,2
Oral overconsumption is
most common; non-oral
misuse and abuse has a higher
rate of severe consequences 5
ADO technologies
are intended to make
product manipulation
more difficult or
the effect of the
manipulated product
less rewarding3
1.
2.
3.
SAMHSA, CBHSQ. The DAWN Report: Highlights of the 2011 Drug Abuse Warning
Network (DAWN) Findings on Drug-Related Emergency Department Visits. Rockville,
MD: SAMHSA; February 22, 2013.
Rudd RA et al. MMWR Morb Mortal Wkly Rep. 2016;64(50-51):1378-1382.
FDA. Guidance for Industry: Abuse-Deterrent Opioids—Evaluation and Labeling.
Rockville, MD: FDA; 2015.
Consider ADOs as part
of a multipronged approach
to responsible opioid
prescribing6
4.
5.
6.
SAMHSA. Results from the 2013 National Survey on Drug Use and Health: Summary
of National Findings. NSDUH Series H-48, HHS Publication o. (SMA) 14-4863.
Rockville, MD: SAMHSA; September 2014.
Katz N et al. Am J Drug Alcohol Abuse. 2011;37(4):205-217.
Webster LR, Fine PG. J Pain. 2010;11(7):602-611.
35
35
For Pfizer Use Only