CAPTASA 2019 Embassy Suites Lexington, Kentucky January 24 or 25, 2019 Quintin T. Chipley, M.A., M.D., Ph.D.

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1 Medication Assisted Treatment for Polysubstance Users who have Opioid Use Disorder CAPTASA 2019 Embassy Suites Lexington, Kentucky January 24 or 25, 2019 Quintin T. Chipley, M.A., M.D., Ph.D.

2 DISCLOSURES Quinn T. Chipley, M.A., M.D., Ph.D. has disclosed no relevant, real or apparent personal or professional financial relationships with proprietary entities that produce health care goods and services.

3 Limitations of Use This presentation is intended for the use of the 2019 annual conference of the Clinical Application of the Principles of Treatment for Substance Abuse and Addiction. All other uses are restricted unless the presenter s permission is given first in writing.

4 Mu Opioid Receptor Agonists Agonist means switches a receptor on 1) Methadone 2) Buprenorphine

5 Sources The material for the history of buprenorphine is taken from an excellent, well-balanced, and carefully researched article: Nancy D. Campbell and Anne M. Lovell. The History of the Development of Buprenorphine As an Addiction Therapeutic. Annals of the New York Academy of Sciences. Issue: Addiction Reviews It will be cited in the following slides as Campbell and Lovell, Common knowledge easily obtained by digital searches relates chemical compounds and pharmacology are not specifically cited. Other special references are given clearly and fully in slides.

6 METHADONE METHADONE EDDP EMDP (ACTIVE AGONIST) (INACTIVE) (INACTIVE)

7 METHADONE Cont. Trade Names are varied, but common are Dolophine and Methadose Taken Orally Only distributed through specified, licensed clinics. Some patients can qualify for take-home doses after well-established and determined to be a reasonable risk Metabolism varies extremely widely

8 Methadone in-clinic dose Methadone take-home dosing

9 Buprenorphine Buprenorphine, a semisynthetic opioid derived from thebaine (a molecule in the poppy), is isolated in 1966 by the British company Reckitt and Coleman, now named Reckitt Benckiser. They had hoped to find an analgesic for acute pain that would be as effective as morphine, but non-addictive and eligible for over-the-counter sales. Since 2002, it is an office- Based prescription MAT.

10 Metabolism of Buprenorphine Liver metabolism of buprenorphine creates the active agonist metabolite, norbuprenorphine. (This metabolite is also the precursor of buprenorphine in the manufacturing process.)

11 Fifth Period: 2002 Present (Continued) Temgesic, 0.2mg

12 Fifth Period: 2002 Present (Continued)

13 Fifth Period: 2002 Present (Continued) BOXED WARNINGS NAME (chemical/s), formulation, CSA Schedule Suboxone (buprenoprhine/nalox one), sublingual film, C-III Zubsolv (buprenoprhine/nalox one), sublingual tablet, C-III Bunavail (buprenorphine), C-III Butrans (buprenorphine), transdermal, C-III Belbuca (buprenorphine) buccal film, C-III INDICATION Opioid Dependence Opioid Dependence Opioid dependence RECOMMENDED DAILY DOSING OF OPIOID ADDICTION, ABUSE, AND MISUSE LIFE- THREATENING RESPIRATORY DEPRESSION ACCIDENTAL EXPOSURE NEONATAL OPIOID WITHDRAWAL SYNDROME RISKS FROM CONCOMITANT USE WITH CNS DEPRESSANTS 8mg - 16mg mg mg Pain 5-20 mcg/hour X X X X X Pain mcg X X X X X X = Black box warning in the prescribing information - = No boxed warning in the prescribing information

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16 Fifth Period: 2002 Present - Continued Probuphine Implant Illustrations

17 Sublocade: Buprenorphone extended release injection (Indivior)

18 Sublocade- Cont. INDICATIONS SUBLOCADE is indicated for the treatment of moderate to severe opioid use disorder in patients who have initiated treatment with a transmucosal buprenorphine containing product, followed by dose adjustment for a minimum of 7 days. SUBLOCADE should be used as part of a complete treatment plan that includes counseling and psychosocial support.

19 CAM2038 (no trade name yet) by Braeburn projected soon PLYMOUTH MEETING, Pa., July 16, 2018 /PRNewswire/ -- Braeburn announces that the U.S. Food and Drug Administration (FDA) has assigned a Prescription Drug User Fee Act (PDUFA) goal date of December 26, 2018 for its New Drug Application (NDA) for CAM2038, an investigational buprenorphine flexible-dose weekly and monthly subcutaneous depot injection for the treatment of adults with opioid use disorder (OUD). CAM2038 was previously granted Fast Track and Priority Review designations. CAM2038 is a potentially game-changing treatment for patients with OUD," said Mike Derkacz, President and CEO of Braeburn. "CAM2038 weekly and monthly provide a range of doses that align with the varying needs of patients and will be administered by a healthcare professional." If approved, CAM2038 would be the first and only injectable for OUD available in both weekly and monthly formulations that can be administered by healthcare professionals through all stages of a patient's recovery journey. CAM2038 is designed to permit "dose matching" to existing oral buprenorphine formulations and enables immediate treatment initiation with a depot injection without the need to complete an oral dose adjustment phase. Braeburn will continue to work closely with the FDA to advance the NDA for CAM2038 and help confront the worst public health crisis in the United States. (Taken from: )

20 Mu Opioid Receptor Antagonist Antagonist means that the molecule keeps the mu receptor from becoming activated The only significant medication is Naltrexone. There is an pill form for oral (swallowed) for daily dosing. There is a long-acting (28 day) injectable form for intramuscular administration to the gluteal muscle.

21 Naltrexone: metabolism Nalrexone 6-beta-nalrexol (Active antagonist) (Active antagonist)

22 Naltrexone versions

23 Relevant Research on Buprenorphine Robert Walker, MSW, LCSW, TK Logan, PhD, Quintin T. Chipley, MA, MD, PhD & Jaime Miller, BA. Characteristics and experiences of buprenorphine-naloxone use among polysubstance users. The American Journal of Drug and Alcohol Abuse. Received 08 May 2017, Accepted 03 Apr 2018, Published online: 25 Apr 2018 Download citation Free access for two years from publication. Cited in: Edward V. Nunes (2018) Buprenorphine in the real world: coming to terms with misuse and diversion. The American Journal of Drug and Alcohol Abuse. DOI: / Download citation

24 The origin and support for the idea The study was supported by a contract with the Kentucky Housing Corporation, an agency of the Commonwealth of Kentucky. The Bup-nx Working Group including Burns M. Brady, M.D., ASAM, Quinn T. Chipley, M.D., Patrick Fogarty, B.A., B.S., C.A.D.C., Greg Jones, M.D., ASAM, Cory Moneymaker, M.S.S.W., LCADC, Ridley Sandidge, B.A., CADA, Mike Townsend, M.S.S.W.

25 Special study of buprenorphine-naloxone use 1,674 Recovery Center clients responded to the bup-nx special study questions. 896 (60.7%) reported opiate/opioid use. The 896 opiate/opioid users were partitioned into 3 groups: No Bup-nx Use (n=223) Lifetime Bup-nx Use (n=241) Recent Bup Use (n=432 The data for this study were collected between September 1, 2015 and October 13, 2016 as part of an ongoing study of recovery center client outcomes in one state.

26 Substance use by Bup-nx groups Substance No Bup-nx Use (n=223) Lifetime Bupnx Use (N=241) Recent Bupnx Use (N=432) Smoking 83%a 90%b 91.9% b** E-cigs 20.2% a 29% b 31.3% b* Alcohol intoxication 52.9% 51.5% 52.1% Marijuana 55.2% a 53.1% a 64.4% b** Benzodiazepines 36.8% a 42.3% a 62.5% b*** Barbiturates 7.6% a 6.6% a 13.4% b** Stimulates, methamphetamine 48% a 47.3% a 68.8% b*** Cocaine 27.8% a 36.1% a 49.1% b*** Hallucinogens 8.1% a 8.3% a 14.4% b* Inhalants 3.6% 2.9% 6.5% Synthetic, designer drugs 12.1% a 7.5% a 18.3% b*** Average number of drug types used in past 6 months *p<.05; **p<.01; ***p<.001 Subscripts that differ indicate significant differences at p< ***

27 Bup-nx Among bup-nx users Method of obtaining bup-nx:** Lifetime Bup-nx Use (N=241) Recent Bup-nx Use (N=432) Prescription only 7.1% 4.2% Illegal only 68% 60% Both prescriptions and illegal means 24.9% 35.9% Bup-nx: ** Helped treat my drug problem 23.7% 25.2% Had no effect on my drug problem 42.7% 31.5% Made my drug problem worse 33.6% 43.3% *p<.05; **p<.01 Overdosed while taking bup-nx with other drugs or 5.4% 10%* alcohol

28 Among users with bup-nx prescriptions Lifetime Bup-nx Use (N=241) Recent Bup-nx Use (N=432) Did doctor: Advise attending recovery support meetings or substance misuse 70.1% 68.2% treatment/counseling Provide counseling about substance misuse 61% 61.8% Did you: Took other drugs or alcohol to get high while taking prescribed bup-nx 70.1% 83.8%* Sold, traded, or gave away any of the prescribed bup-nx *p< % 80.3%

29 Bup-nx users who got bup-nx illegally Lifetime Bup-nx Use (N=241) Recent Bup-nx Use (N=432) Obtained bup-nx without a prescription 92.9% 95.8% Bup-nx was used to: (n=224) (n=414) Get through rough days until preferred drug could be obtained Get a high, a buzz, or to feel euphoria Increase high by increasing bup-nx amount 84.8% 91.5%** 73.7% 81.2%* 54.5% 64%* Got information from other people and/or internet about how to boost bup-nx high 59.4% 66.4% *p<.05; **p<.01

30 Conclusions from this population Only one-quarter of users said bup-nx helped them with their substance use. 75% of bup-nx users reported that bup-nx either had no effect or a negative effect on their drug problems. Of the very few (4%-7%) obtaining bup-nx solely through a prescription, over 90% reported relief from withdrawal. However, over 80% of those who obtained bup-nx through illicit means reported using bup-nx until their preferred drug could be obtained and used it for its euphoriant effect. Diversion of this scheduled opioid agonist medication was rampant

31 CONTACT INFORMATION Quintin Chipley can be contacted by at