In 2011, the White House published “Epidemic: Responding to America's Prescription Drug Abuse Crisis,” which outlined a comprehensive strategy for responding to America’s prescription drug abuse crisis. This action was triggered by an alarming increase in drug overdose deaths in the United States from 1999 to 2010. During this time, overdose deaths from opioid pain relievers quadrupled, and have continued to increase.
The FDA’s role in the overall initiative has been to enact labeling and educational material requirements for opioid drug products to increase awareness and knowledge among medical practitioners and patients. In addition, the FDA placed a high priority on working with the pharmaceutical industry to encourage the development of abuse-deterrent formulations.
“The science of abuse-deterrent medication is rapidly evolving, and the FDA is eager to engage with manufacturers to help make these medications available to patients who need them,” said FDA Commissioner Margaret A. Hamburg, M.D. “We feel this is a key part of combating opioid abuse. We have to work hard with industry to support the development of new formulations that are difficult to abuse but are effective and available when needed.”
To provide a framework for the industry, two guidance documents have been released by the FDA: Abuse-Deterrent Opioids—Evaluation and Labeling Guidance for Industry, which was issued as a final guidance in April 2015, and General Principles for Evaluating the Abuse Deterrence of Generic Solid Oral Opioid Drug Products, which was issued as a draft guidance in March 2016.
The industry has moved quickly to formulate and release abuse-deterrent opioid products even though questions were initially raised regarding the effectiveness of this strategy. However, sufficient time has passed that some insight into the effectiveness of these products has become available.
For example, the Contin® Extended-Release formulation of oxycodone developed by Purdue Pharma in 1972 was widely misused and abused through non-oral administration, such as snorting or injecting after crushing or dissolving the tablets. Survey data gathered at drug treatment centers prior to the Oxycontin® reformulation reported that 53% of abusers snorted it, 55% ingested it orally and 36% injected it
To address this, Purdue Pharma released a reformulated Oxycontin® in 2010. This patented formulation was extremely difficult to crush, effectively eliminating inhalation as a route of abuse for Oxycontin®, and included a gelling agent intended to make it very difficult to extract and inject Oxycodone. While difficult to measure directly, there is some evidence that this approach was successful in deterring abuse.
The Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS®) System, a nonprofit operation of the Rocky Mountain Poison and Drug Center that tracks reports of abuse, misuse and diversion of prescription drugs, reported that in the 12-month period following the approval of reformulated Oxycontin® in 2010, there was a 43% decline in intentional overdoses reported to poison control centers and a 31% decline in Oxycontin® prescriptions issued by physicians.
In addition, three and a half years after the release of reformulated Oxycontin®, a post marketing study was conducted to evaluate changes “in the community” relating to abuse, misuse, overdose, and death.
The study sought to understand whether the abuse-deterrent formulation resulted in fewer cases of abuse, or a net decrease in abuse and increased use of heroin. Some of the conclusions of the study were:
- The magnitude of the reduction in rates of abuse of Oxycontin® ranged from 30% to 85%, depending on the cohort.
- Rates of patient misuse of Oxycontin® decreased by 29–43%.
- Diversion events reported by law enforcement officials decreased by 66%.
- By the third year after the reformulation, the number of deaths and overdose deaths reported to the manufacturer decreased by as much as 85%.
Details of the post marketing study published in the American Society for Clinical Pharmacology and Therapeutics’ journal and can be accessed by clicking here.
This study and others of a similar nature are examples of the positive impact that abuse-deterrent prescription drug formulations are having on the overall crisis. To read more about the approach behind abuse-deterrent formulations and the studies required for successful reformulation, see Alcami’s white paper on this topic, “Abuse-Deterrent Studies for Controlled Drugs – A Changing Landscape.”