Abuse-Deterrent Formulation (ADF) Opioid Medications Mark Garofoli, PharmD, MBA, BCGP, CPE Director, Experiential Learning Program WVU School of Pharmacy Clinical Pain Management Pharmacist, WVU Medicine Center for Integrative Pain Management Opioid Risk Screenings Opioid Naïve Opioid Experienced Self Reported Self Reported • Drug Abuse Screening Test (DAST) • Current Opioid Misuse Measure (COMM) • Screener & Opioid Assessment for Patients with Pain (SOAPP) • Pain Medication Questionnaire (PMQ) • Prescription Drug Use Questionnaire, Patient (PDUQp) Provider Reported • Opioid Risk Tool (ORT) Provider Reported • Diagnosis, Intractability, Risk, & Efficacy Score (DIRE) • Prescription Drug Use Questionnaire (PDUQ) www.opioidrisk.com Opioid Risk Tool (ORT) Opioid Risk Tool (ORT) Female Male Family History of SUD Alcohol 1 3 Illegal Drugs 2 3 Prescription Drugs 4 4 Personal History of SUD Alcohol 3 3 Illegal Drugs 4 4 Low Risk 0 - 3 Prescriptions Drugs 5 5 Moderate Risk 4 - 7 Age 16-45 1 1 High Risk >/= 8 History of Preadolescence Yes 3 0 Sexual Abuse Psychological Disease ADHD, OCD, Bipolar, Schizophrenia 2 2 Depression 1 1 Total Score Where are these opioids coming from… Friend/Relative (Theft) Drug Dealer Rx from >1 MD Clinician/Office (Theft) Friend/Relative Rx from 1 MD (Buy) Friend/Relative (Free) 2017 DEA National Drug Threat Assessment. https://www.dea.gov/docs/DIR-040-17_2017-NDTA.pdf Opioid Abuse Transition Hydrocodone Oxycodone Oxycodone Combo Combo IR Sole ER/IR Heroin Tablets Products Products ($10/Bag) $5-10/Tab $10-15/Tab $1.50/mg Shah A, et al. Characteristics of Initial Prescription Episodes and Likelihood of Long-Term Opioid Use – United States, 2006-2015. Weekly / March 17, 2017 / 66(10); 265–269. Opioid Abuse Transition ADF Opioid Formulations Physical Aversion Barrier Hydrocodone Oxycodone Oxycodone Delivery Chemical Combo Combo IR Sole ER/IR Heroin System Barrier Tablets Products Products ($10/Bag) $5-10/Tab $10-15/Tab $1.50/mg Agonist/ antagonist Prodrug opioid Combination combinations of Any Shah A, et al. Characteristics of Initial Prescription Episodes and Likelihood of Long-Term Opioid Use – United States, 2006-2015. Weekly / March 17, 2017 / 66(10); 265–269. Types of Abuse-Deterrent Formulations (ADFs) ADF Type Description 1. Physical Barrier Prevent chewing, crushing, cutting, grating, or grinding 2. Chemical Barrier Resist extraction of the opioid through use of common solvents including water, alcohol or other organic solvents 3. Agonist/Antagonist Opioid Combinations Antagonist is added to the formulation to interfere with release if taken in any other way than it was intended 4. Aversion Substances are added to the dosage form to produce an unpleasant effect if the dosage form is manipulated prior to ingestion or if a higher dosage than directed is used 5. Delivery System Alternative delivery systems that are more difficult to manipulate (such as a depot injectable, an implant, or transdermal application) 6. Prodrug Medication contains a prodrug that lacks opioid activity until it has been transformed in the gastrointestinal tract 7. Combination of the above Mirror, Mirror, On the Wall… FDA ADF FDA ADF Studies Category 1 Category 2 Category 3 Category 4 In Vitro Pharmacokinetic Clinical Abuse Post Marketing Manipulation & Potential Extraction Abuse Deterrent Formulation (ADF) Opioids Active Ingredient Product FDA ADF Approval Formulation Xtampza ER® IN, IV, & PO Chew ER Capsule Xartemis ER® (+APAP) - IR/ER Tablet OxyContin® IN & IV ER Tablet oxycodone Troxyca® IN, IV, PO Crush ER Capsule Oxaydo® - IR Tablet RoxyBond® IN & IV IR Tablet ® tapentadol Nucynta ER - ER Tablet FDA Approved ADF Opioids hydromorphone Exalgo® - ER Tablet available on US Market Embeda® IN & PO Crush (July 2018) morphine Arymo® IV ER Tablet MorphaBond® IN & IV Hysingla® IN, IV, & PO Chew ER Tablet Zohydro ER® - ER Capsule hydrocodone Vantrela ER® IV ER Tablet Hydromet® - Liquid Tussigon® - Tablet benzhydrocodone Apadaz® - tablet pentazocine Talwin NX® - Tablet *Targiniq (oxycodone) & Opana (oxymorphone) are Off Market* http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3411218/ https://www.sciencedirect.com/science/article/pii/S0378517316304884 https://www.futuremedicine.com/doi/pdf/10.2217/pmt-2015-0005 https://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm337066.htm FDA Approved ADF Opioids on US Market (July 2018) Active Ingredient Product FDA ADF Approval Formulation Xtampza ER® IN, IV, & PO Chew ER Capsule oxycodone OxyContin® IN & IV ER Tablet Embeda® IN & PO Crush morphine Arymo® IV ER Tablet MorphaBond® IN & IV hydrocodone Hysingla® IN, IV, & PO Chew ER Tablet http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3411218/ https://www.sciencedirect.com/science/article/pii/S0378517316304884 https://www.futuremedicine.com/doi/pdf/10.2217/pmt-2015-0005 https://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm337066.htm ADFs, At What Cost? Physical Aversion Barrier Non-ADF Opioids ADF Opioids Delivery Chemical $11.60 Average Cost System Barrier $5.82 Average Cost $6.86 Break-Even Cost Agonist/ Prodrug antagonist opioid Combination combinations of Any https://icer-review.org/wp-content/uploads/2017/08/ADF_RAAG_080817.pdf Benz-hydrocodone/APAP Apadaz® • Prodrug of Hydrocodone (+APAP) covalently bonded with benzoic acid • Benzoic Acid: Typical food preservative • Ligand-Activated Technology (LAT®) • Also being studied with a methylphenidate prodrug • Controlled Substance Class 2 (just as hydrocodone/apap) • Indicated for the short-term (no more than 14 days) management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate NOT FDA approved as an abuse-deterrent formulation (ADF) opioid Benzhydrocodone/APAP 6.12/325mg = hydrocodone/APAP 7.5/325mg Clinical Pharmacology Online Database. 2018 Apadaz Package Insert. 2018 Abuse Deterrent Formulation (ADF) Opioids Novel Pipeline Multi-Pill Abuse-Resistance (MPAR™) • Take one to two MPAR™ pills at once Activated as intended Take many MPAR pills at once Pass through the system without being activated • Prevents accidental or intentional overdose from misuse http://www.ensysce.com/overdose-resistant-technology/ Sheading some (Blue)light on ADFs… “OxyCrisping” .