# Presentation: 536589

## The National Crisis of Prescription Opiate Abuse:  How can the FDA respond?

- Anesthetic & Life Support Drugs Advisory Committee
- March 29, 2007
- Art Van Zee,MD
- St. Charles Clinic
- St. Charles, VA.

## 		Since the advent of the
		    OxyContin tragedy—

FDA approval of:

			    Palladone
			    Avinza
			    Opana ER

- 		    OxyContin tragedy—
- FDA approval of:
- 			    Palladone
- 			    Avinza
- 			    Opana ER

## Sustained release opioids vs.immediate release opioids

- Efficacy, safety and risks

**Notes:**
  IT HAS BEEN CONVENTIONAL—ALMOST A STANDARD OF CARE IF YOU WILL—IN THE PAIN MANAGEMENT COMMUNITY TO USE 

SUSTAINED RELEASE OPIOIDS FOR CHRONIC NON-CANCER PAIN, WITH IR OPIOIDS FOR BREAKTHROUGH PAIN.  THE 
CONVENIENCE OF LESS FREQUENT DOSING AND THE –AT LEAST THEORETICAL CONSIDERATION THAT THERE MAY BE LESS ADDICTION POTENTIAL WITH A SR PREPARATION—HAS BEEN THE BASIS FOR THIS.   BUT,---In the context of nationally increasing prescription opioid abuse, I think it is important to look at the efficacy and safety of sustained release opioids versus immediate release opioids---since they do have some different risks.---The available studies published would suggest that immediate release opioids and sustained release opioids have comparable efficacy and safety.

IT HAS BEEN CONVENTIONAL—ALMOST A STANDARD OF CARE IF YOU WILL—IN THE PAIN MANAGEMENT COMMUNITY TO USE

SUSTAINED RELEASE OPIOIDS FOR CHRONIC NON-CANCER PAIN, WITH IR OPIOIDS FOR BREAKTHROUGH PAIN.  THE 
CONVENIENCE OF LESS FREQUENT DOSING AND THE—AT LEAST THEORETICAL CONSIDERATION THAT THERE MAY BE LESS 
ADDICTION POTENTIAL WITH A SR PREPARATION---HAS BEEN THE BASIS FOR THIS.   BUT---IN THE CONTEXT OF NATIONALLY

INCREASING PRESCRIPTION OPIOID ABUSE, I THINK IT IS USEFUL TO RE-EXAMINE THE EFFICACY AND SAFETY OF SUSTAINED RELEASE OPIOIDS VERSUS IMMEDIATE RELEASE OPIOIDS---SINCE THEY DO HAVE SOME DIFFERENT RISKS.----THE AVAILABLE PUBLISHED STUDIES WOULD SUGGEST THAT IMMEDIATE RELEASE OPIOIDS AND SUSTAINED RELEASE OPIOIDS HAVE COMPARABLE EFFICACY AND SAFETY.

##             Comparable

-             Comparable
-      Efficacy  &   Safety
-     Hale  Clin J Pain  ’99             BACK PAIN
-     Kaplan  J Clin Oncol ’98        CANCER
-     Stambaugh J Clin Pharm ’01  CANCER

**Notes:**
 FOR OXYCODONE IN BACK PAIN AND CANCER..........

## OxyContin--NDA--1995

- MEDICAL OFFICER REVIEW (MOR)
- Summary of Safety
- 	“  The best conclusion is that the efficacy
- of the CR (oxycodone) is equivalent to the IR,
- with an adverse event profile that is as good as
- the IR.  I would not allow a ‘better’ claim”
- 			--Curtis Wright, MRO

**Notes:**

--OxyContin has been labeled a wonder drug, a miracle
   drug, a drug that gives people’s life back to them.

--It is of interest to look at what some of the conclusions
   of the NDA for OxyContin submitted for FDA review
   in 1995.

## IR morphine vs. CR morphinein CancerComparable Efficacy and safetyDeschamps, J Pain Symptom1992 Walsh, Am J Clin Oncol, 1992 

**Notes:**
IN COMPARING IMMEDIATE RELEASE  WITH SUSTAINED RELEASE PREPARATIONS, FOR MORPHINE IN CANCER PAIN.....

##               Comparable

-           CR hydromorphone (Q12hr)
-               Comparable
-           Efficacy & Safety
-     Hays   Cancer   ’94                   CANCER
-     Bruera   J Clin Oncol  ’96         CANCER

**Notes:**
AND FOR HYDROMORPHONE IN CANCER PAIN, THE IMMEDIATE RELEASE AND THE SUSTAINED RELEASE FORMS HAVE COMPARABLE EFFICACY AND SAFETY.

##   Comparative efficacy and safety of long- 		acting opioids for chronic 
   non-cancer pain: a systematic review

         J Pain Symptom Manage, 2003
				Chou, et al

-    non-cancer pain: a systematic review
-          J Pain Symptom Manage, 2003
- 				Chou, et al

**Notes:**
AND CHOU AND COLLEAGUES FROM THE UNIVERSITY OF OREGON REVIEWING THE LITERATURE CONCLUDED THAT THERE WAS INSUFFICIENT EVIDENCE TO SAY THAT SUSTAINED RELEASE PREPARATIONS WERE MORE EFFECITVE OR SAFER THAN IMMEDIATE RELEASE PREPARATIONS, OR THAT THERE WAS ANY ONE PREPARATION SUPERIOR TO THE OTHERS IN ITS CLASS.

## 	Risks of sustained release opioids
		higher than IR opioids

---higher addiction risk when  abused

--higher risk of inadvertent 
	over-dose and death

- 		higher than IR opioids
- ---higher addiction risk when  abused
- --higher risk of inadvertent
- 	over-dose and death

## Patrick Stewart, 1980-2004

**Notes:**
PATRICK STEWART, BRIGHT, COLLEGE EDUCATED, LOTS OF PROMISE, THE SON OF A PLASTIC SURGEON AND AND EDUCATOR IN CALIFORNIA, NEVER AN ADDICT, DIED FROM DRINKING A COUPLE OF BEERS AND TAKING AN OFFERED AN OXYCONTIN AT A PARTY LAST JULY.  How many of us in the room today can say we have not made some unwise choices  in our youthful lives, and how many of us can be re-assured our children or our  grand-children will not  make some unwise choices.

## FDA

- Change the indications for sustained release opioids—
- ---available to all cancer patients
- ---in chronic non-cancer pain, available
- 	  on a “compassionate” use program

## FDA

- set the standard that only opioid
- products that are abuse resistant could be brought to the    			        marketplace

## FDA

- An empowered FDA with more capacity and capability to review
-     and regulate the marketing and
-     promotion of controlled drugs

## FDA

- require the use of a secure and
-     tamper proof means of     		  		dispensing controlled drugs

## Advanced Dispensing System

- GW Pharmaceuticals

## FDA

-      Have a meeting dedicated to     	review  the pertinent issues             	of the opiate abuse crisis
-         and craft a bold and
- 		 meaningful response