# Presentation: 307246

## Prescription Drug Abuse

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

**Notes:**
Recent media reports of abuse of a currently popular opioid analgesic have directed public attention to the long known potential for abuse, misuse and diversion of prescription opioid analgesics.  

The Agency has always taken abuse potential into consideration during the review process.  

## Approaches to Managing Abuse Potential

-  Scheduling under the Controlled Substances Act
-  Labeling
-  Risk Management Plan
-  Formulation changes
-  Restricted distribution

**Notes:**
There are several approaches to addressing abuse potential that the Agency considers.  

I am going to focus on the RMP which can incorporate many aspects of addressing abuse potential.

## Risk Management Plans

-  Identification of key events to monitor
-  Prevention of abuse and diversion
-  Importance of proper patient selection

**Notes:**
RMPs are under consideration with increasing frequency as a tool to be utilized with opioid analgesics.  I will present possible features that may be particularly relevant to this group of drugs.   

## Risk Management Plans

-  Issues related to drug substance
-  Formulation issues
-  Prior experience

## Risk Management Plans

-  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

**Notes:**
Tracking and quantifying abuse, misuse and diversion can be particularly challenging.  

Company sponsored hotlines and MedWatch collect spontaneous reports.  

The databases discussed yesterday by Dr. Dal Pan provided a considerable amount of this information in addition to State authorities.  

Creative approaches are welcome as long as they can be validated in some manner.  

## Risk Management Plans

-  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

**Notes:**
Programs to prevent abuse, misuse and diversion overlap interventions  intended to decrease such activity that is already ongoing

Education can take the form of continuing education programs, Dear Healthcare Provider letters, patient package inserts.

Expert Advisory Panels have been used for  the development of educational materials or surveillance systems.  

Efforts with law enforcement have included educational materials, using country specific indicia (markings).  

## Risk Management Plans

-  Specific event reporting
-  Assessment of effects of educational efforts

**Notes:**
Monitoring efforts can take many forms.  
Reviews of specific events in the databases
Assuring proper promotional practices and educational campaigns through audits

Reporting of these audits and surveillance activities.  

## Prescription Abuse - Vignettes

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

**Notes:**
I will now present 3 vignettes to highlight some past efforts that have demonstrated a measure of success.  

While based on actual products, I have changed some of the specific features in the vignettes to keep the discussion focused on concepts that can be applied broadly.  

## 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

## 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

## 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

## 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

## 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

## 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

## 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

## 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

## 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

## Prescription Abuse - Vignettes

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

## 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.

## 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?

## 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.