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The Role of Opioid Abuse Deterrents in Today’s HealthcareSandeepkumar BalabbigariErnest Mario School of Pharmacy, Pharm.D. Candidate 2016April 20th, 2016

Objectives

▪ Describe the defining characteristics of opioid abuse and abuse deterrent products

▪ Discuss the changes in opioid abuse prevalance and medical costs after the introduction of Abuse-Deterrent OxyContin

▪ Review the actions taken by the FDA and the pharmaceutical industry in response to the opioid abuse epidemic

“The most important thing we can do is reduce demand for drugs, and the only way that we reduce demand is by providing treatment and thinking about this as a public health problem and not just a criminal issue.

- Barack ObamaMarch 29, 2016

BackgroundWhat is Opioid Abuse?

How Prevalent is Opioid Abuse? How Much Does Opioid Abuse Cost Society?

Differentiating Abuse

Abuse2

Use of an illegal drug or excessive use or misuse of a legal drug beyond its intended purpose or prescription

Dependence1,2

Physiological condition in which the body has adapted to a drug’s effects upon repeated exposure

Addiction1

Psychological condition in which there is a craving or an inability to control impulses in engaging in a specific activity

1) The National Alliance of Advocates for Buprenorphine Treatment. http://www.naabt.org/addiction_physical-dependence.cfm. Published March 12, 2016. Accessed April 6, 2016. 2) Saint Xavier University. http://www.sxu.edu/student-life/counseling/aodp/self/subabuse.asp. Accessed April 6, 2016.

Mechanisms of AbuseMethods of Manipulation1

▪ Crushing or grinding into a fine powder or small particles

▪ Dissolving in solvents such as alcohol

▪ Extracting through exposure to hot or cold temperatures

Routes of Abuse2

▪Oral▪Parenteral▪ Inhalation▪Smoking

1) Teva Pharmaceuticals USA, Inc. http://painmatters.com/healthcare-professionals/understanding-abuse-misuse.aspx. Published December 2015. Accessed April 6, 2016. 2) Teva Pharmaceuticals USA, Inc. http://painmatters.com/docs/BB157_WM.pdf Published April 2015. Accessed April 6, 2016.

Signs & SymptomsofOpioidAbuse

Constipation

Emotional Changes

Constricted Pupils

IV Track Marks

DeterioratingAppearance &

Hygiene

Acetaminophen Toxicity

Stolbach, A, et al. Acute opioid intoxication in adults. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2016. Accessed April 6, 2016.

Prevalence

Free from Relatives

and Friends51%

Doctor's Precription

22%

Other27%

Source of Opioids1

4.3 million Americans engaged in non-medical use of prescription painkillers within the past month. 1.9 million meet criteria for prescription painkillers use disorder.1

1.4 million people used prescription painkillers non-medically for the first time in the past year. The average age of first-time abusers was 21.2 years.1

05000

1000015000200002500030000

Opioid Overdose Deaths2

0

5000

10000

15000

200002500030000

2008 20122014

1) Substance Abuse and Mental Health Services Administration. http://www.samhsa.gov/atod/opioids. Published February 23, 2016. Accessed April 8, 2016. 2) Centers for Disease Control and Prevention. http://www.cdc.gov/drugoverdose/epidemic/index.html. Published March 14, 2016. Accessed April 8, 2016.

Cost

$58.4 Billion

$26.2 Billion

$24.2 Billion

Estimated total societal costs of prescription opioid abuse in 2011

45% of total societal costs were associated with healthcare costs

92.4% of healthcare costs were due to excess medical and prescription costs

Kirson N, et al. American Academy of Pain Medicine. 2014

DeterrentsHow Do Prescription Painkillers Combat Opioid Abuse?

No opioid formulation can prevent the most common method of abuse: ingestion of a large number of intact dosage forms

Opioid products can be formulated with abuse-

deterrents to make their intentional nontherapeutic

use more difficult, less attractive, or less rewarding

The Medical Letter. http://secure.medicalletter.org/w1476a. Published August 31, 2015. Accessed April 6, 2016.

Currently ApprovedAbuse Deterrent Formulations (ADF)

OxyContin®1

(Oxycodone HCl)▪ More resistant to

breaking or crushing▪ Forms viscous gel when

dissolved ▪ 17% and 66% reductions

in oral and non-oral abuse, respectively

Embeda® 1

(Morphine sulfate and Naltrexone HCl)▪ Formulated as capsules

of ER morphine pellets that contain a sequestered core of naltrexone

▪ Naltrexone is only released if formulation is manipulated

Hysingla® ER1,2

(Hydrocodone bitartrate)▪ Utilizes RESISTEC

technology▪ Increased tablet

hardness ▪ Forms viscous gel when

dissolved

Significantly lower “Drug Liking”, “Drug High”, and “Take Drug Again” compared to previous formulations

1) The Medical Letter. http://secure.medicalletter.org/w1476a. Published August 31, 2015. Accessed April 6, 2016. 2) Weinstein SM. Therapeutics and Clinical Risk Management. 2009

New OxyContinFormulation

Potential Abuse-Deterrent TechnologiesDETERx▪ Drug molecules are

formulated into a fatty-acid-ionic complex

▪ Bioequivalence and time-release properties remain unchanged even after manipulation

Bio-Activated Molecular Delivery (Bio-MD)▪ Drug molecules are bound to

an amino-acid mask▪ Drug remains inactive until

amino-acid mask is cleaved▪ Systemic exposure is not

increased by chewing, crushing, or dissolvingthe formulations

Moorman-Li R., et al. Pharmacy and Therapeutics, 2012

ImpactWhat Effect Have Abuse-Deterrent Formulations

Had On Opioid Abuse Prevalance?

Changes in Opioid Abuse Prevalence Associated with ADF OxyContin

232,875 adults assessed for substance abuse problems using the computerized Addiction Severity Index-Multimedia Version (ASI-MV)

Designed to assess trends of past 30-day abuse and changes in abuse patterns after ADF OxyContin was introduced

ADF = Abuse-Deterrent Formulation

Prevalence of abuse was measured by the proportion of subjects with past 30-day abuse

Cassidy T, et al. American Academy of Pain Medicine. 2014


Abuse BeforeADF OxyContin

Abuse AfterADF OxyContin

Relative Percent Change

Statistically Significant?

All Prescription

Opioids 16.94% 18.36% +8.3% YesImmediate

Release (IR) Opioids 9.70% 10.72% +2.5% No

Extended Release (ER)

Opioids 12.57% 12.88% +10.5% YesData presented as percent of all subjects assessedADF = Abuse-Deterrent Formulation



Abuse BeforeADF OxyContin

Abuse AfterADF OxyContin

Relative Percent Change

Statistically Significant?

Oxycodone ER 6.49 5.08 −21.7% YesOxymorphone ER 0.32 0.94 +190.9% Yes

Morphine ER 1.13 1.10 -2.65% NoBuprenorphine 2.42 4.47 +84.7% Yes

Heroin 5.55 4.94 -10.99% Yes


Data presented as percent of all subjects assessedADF = Abuse-Deterrent Formulation

The introduction of ADF OxyContin hadlittle impact on the

overall prevalence of prescription opioid abuse.

ADF = Abuse-Deterrent Formulation



ImpactWhat Effect Have Abuse-Deterrent Formulations

Had On Healthcare Costs?

Medical Cost Savings Associated with ADF OxyContin

Measure changes in number of

opioid abuse diagnoses

Estimate the excess medical

costs associated with

diagnosed opioid abuse

Determine the cost savings of ADF OxyContin

ADF = Abuse-Deterrent FormulationRossiter L, et al. Journal of Medical Economics. 2014

Reduction of 48,737 opioid

abusers

$8,814 is the average annual excess medical

costs for an opioid abuser

$430 million annual medical

cost savings

Medical Cost Savings Associated with ADF OxyContin


$430,000,000Annual medical cost savings associated with the

introduction of ADF OxyContin


$286 $573Potential range of annual medical cost savings (millions)

ResponseHow Has the Opioid Abuse Epidemic

Affected Stakeholders?

FDAResponse

Risk Evaluation and Mitigation Strategy (REMS) Program1

Requires companies that produce ER/LA opioid analgesics to provide training and education for both prescribers and patients

ER/LA = Extended-release/Long-acting

Abuse-Deterrent Opioids - Evaluation and Labeling Guidance for Industry2

Explains the pre-market studies needed for the approval of abuse-deterrent claims inproduct labeling

Opioids Action Plan3

Comprehensive list of initiatives to be taken by the FDA with the intent of reducing opioid abuse and overdose deaths in the United States

1) U.S. Food and Drug Administration. http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm163647.htm. Published January 27, 2016. Accessed April 11, 2016. 2) U.S. Food and Drug Administration. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM334743.pdf. Published April 2015. Accessed April 11, 2016. 3) U.S. Food and Drug Administration. http://www.fda.gov/NewsEvents/Newsroom/FactSheets/ucm484714.html. Published February 5, 2016. Accessed April 11, 2016.

Industry Response

Teva Pharmaceuticals USA, Inc. http://painmatters.com/people-affected-by-pain/community-resources-people-affected-chronic-pain.aspx. Published December 2015. Accessed April 13, 2016.

Conclusion

Abuse deterrent formulations may

reduce the abuse of a specific drug but are

not the “magic bullet” to solving the opioid

abuse epidemic.

The government, pharmaceutical industry,

healthcare providers, and patients all have a role to play in reducing

opioid abuse.

Thank you!BackgroundQuestions?

Download - Opioid Abuse

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