1. Prescription Drug Abuse Sharon Hertz, M.D. Medical Officer Division of Anesthetic, Critical Care and Addiction Drug Products Food and Drug Administration

2. Scheduling under the Controlled Substances Act Labeling Risk Management Plan Formulation changes Restricted distribution Approaches to Managing Abuse Potential

3. 1. Key Messages Identification of key events to monitor Prevention of abuse and diversion Importance of proper patient selection Risk Management Plans

4. 2. Identification of Risk Potential Issues related to drug substance Formulation issues Prior experience Risk Management Plans

5. 3. Programs to identify abuse, misuse, diversion Spontaneous reporting - hotline, MedWatch DAWN, TESS, IMS, SAMHSA (TX centers) State Drug Control Authorities/Boards of Pharmacy Special registries, pediatric databases Pharmacy surveys Literature/Media reports Risk Management Plans

6. 4. Prevention/Intervention Programs Education - Physician, Pharmacist, Patient Tamper resistant prescription pads Special storage needs - Physician/Patient Child resistant packaging Black box warnings Restricted access to targeted populations Expert Advisory Boards Cooperative efforts with law enforcement Risk Management Plans

7. 5. Monitoring Efforts Specific event reporting Assessment of effects of educational efforts Risk Management Plans

8. Prescription Abuse - Vignettes 1. Post-marketing surveillance followed by scheduling 2. Scheduling followed by reformulation 3. Proactive Risk Management Plan

9. Prescription Abuse - Vignettes Drug A Parenteral opioid agonist/antagonist analgesic approved for hospital use Abuse liability considered to be low risk Not scheduled Little abuse reported

10. Prescription Abuse - Vignettes Drug A cont’d Nasal spray formulation developed for outpatient use Abuse potential revisited with FDA Advisory Committee Abuse potential considered low, postmarketing surveillance program recommended

11. Prescription Abuse - Vignettes Drug A cont’d After release, concerns over abuse result in petition for scheduling by DEA DAWN and FDA postmarketing safety databases were reviewed

12. Prescription Abuse - Vignettes Drug A cont’d FDA-DEA surveyed of State Authorities: - 80% of responding state authorities confirmed cases of nonmedical use and diversion - Typical drug seeking behavior linked to the nasal spray: falsification of prescriptions, doctor shopping, requests for early refills - Reports of abuse increased

13. Prescription Abuse - Vignettes Drug A cont’d A request to DEA to place Drug A nasal spray in Schedule IV of the CSA was granted. Following scheduling (and dissemination of relevant educational information) abuse-related reports began to decrease in the setting of stable numbers of Rx’s

14. Prescription Abuse - Vignettes Drug B Oral opioid agonist/antagonist Over first decade of distribution, reports of abuse, diversion, overdose, and death increase Intravenous abuse of crushed tablets noted

15. Prescription Abuse - Vignettes Drug B cont’d Addition to Schedule IV of the CSA - no impact on reports of abuse and diversion Reformulation with naloxone, original withdrawn Dramatic decline in reports of abuse

16. Prescription Abuse - Vignettes Drug C Novel formulation of Schedule II narcotic Intended for narrow target pain population Concerns of accidental exposure to non-opioid tolerant individuals, and risk of abuse and diversion result in RMP prior to approval

17. Prescription Abuse - Vignettes Drug C cont’d Features of RMP: - Limit to patients with labeled indication - Corrective letters to off-label prescribing physicians - Limited detailing by sponsor - Patient education materials, cabinet locks - Surveys of participating pharmacies

18. Prescription Abuse - Vignettes Drug C cont’d Result of risk management efforts: Limited reports of misuse.

19. Approaches to Managing Abuse Potential The Agency is aware of problems of abuse, misuse, and diversion of prescription narcotic analgesics and the need for adequate pain management for legitimate patients.

20. Approaches to Managing Abuse Potential 1. Discuss the adequacy of the available data to determine the prevalence of addiction among patients treated with opioids for chronic pain. 2. Discuss the methods for assessing and monitoring addiction in the clinical setting. Are there methods that may be extended to the Clinical Trials setting?

21. Approaches to Managing Abuse Potential 3. In the context of increasing awareness of the problems of diversion and addiction to prescription opioids among patients and non-patients, comment on what measures might be appropriate to consider in the development of an overall risk management strategy that could reduce abuse and diversion without restricting access to drugs by patients in need of treatment.