Abuse Deterrent Drug Formulations

Description

Abuse-deterrent prescription drug formulations are designed to inhibit prescription drugs’ abusive properties. These alterations can take many forms, including physical alterations (alterations to a drug’s manufactured form that are designed to deter individuals from extracting its active ingredient) and pharmacological alterations (adding an active ingredient that reduces or prevents the “high” associated with abuse).

Objective(s)

To deter prescription drug diversion and abuse

Typical Elements

  • As of February 2015, the U.S. Food and Drug Administration (FDA) does not require any specific abuse-deterrent formulations. However, the FDA does require that prescription drug manufacturers warn of the risks of abuse in drug labels and marketing, and it regulates the use of abuse-deterrent marketing claims (FDA, 2013; Woodcock, 2014).
  • The FDA also has the authority to withdraw or block approval for a prescription drug if there is an otherwise identical prescription drug that contains abuse deterrents (FDA, 2013; Woodcock, 2014).
  • As of February 2015, the FDA has approved at least 11 abuse-deterrent formulations (Webster et al., 2011); however, only 3 meet FDA standards for abuse-deterrent marketing claims (Woodcock, 2014).
    • Note: The FDA has also begun approving non-opioid prescription drugs for pain management, approving five such drugs over the past 10 years.
  • Categories of abuse-deterrent formulations include the following (FDA, 2013):
    • Physical barriers: Changing the drug composition to prevent chewing, crushing, cutting, grating, or grinding
    • Chemical barriers: Changing the drug composition to prevent opioid extraction, using solvents
    • Agonist/antagonist combinations: Adding an active ingredient that reduces or prevents the “high” associated with abuse
    • Aversion formulations: Adding an active ingredient that causes an unpleasant sensation if the drug is altered or taken at a high dosage
    • Delivery system alterations: Changing the method of drug delivery to one more resistant to abuse (e.g., from oral tablets to patches or implants)
    • Prodrug alterations: Changing the drug composition so the drug is inert until reaching the gastrointestinal tract
  • The FDA recommends that the development of a new abuse-deterrent formula should include data from three types of studies (although there can be exceptions) in order to obtain a “full and scientifically rigorous understanding” of the formula’s effect on the drug’s potential for abuse (FDA, 2013, p. 5):
    • Laboratory manipulation and extraction studies, which evaluate individuals’ ability to overcome or compromise the proposed formulation
    • Pharmacokinetic studies, which examine the biological properties of the proposed formulation, including the effects of continued abuse attempts
    • Clinical abuse potential studies, which assess the impact of the proposed formulation on its effectiveness at making abuse of the drug “less attractive or less rewarding” (FDA, 2013, p. 2)
  • The FDA has created four tiers of marketing claims (FDA, 2013):
    • The drug is formulated with physicochemical barriers to abuse
    • When the drug is manipulated, it is expected to reduce or block the effect of the opioid
    • The drug is expected to result in a meaningful reduction in abuse
    • The drug has demonstrated reduced abuse in a community
  • Drug manufacturers are now required to submit evaluation data supporting their claims.

Populations

Drug manufacturers

Outcomes

Among anonymous survey respondents with an opioid dependence, the abuse-deterrent formulation of OxyContin has been linked to the following (Cicero, Ellis, & Surrat, 2012):

  • A decrease in the selection of OxyContin as the primary drug of abuse from 35.6% to 12.8% of respondents over 21 months
  • A decrease in past-30-day abuse of OxyContin from 47.4% to 30.0%
  • No evidence that individuals ceased their drug abuse:
    • 24% of respondents overcame the abuse-deterrent formulation
    • 66% of respondents switched to another opioid (heroin, most often)

Guidelines

Abuse-Deterrent Opioids—Evaluation and Labeling: Guidance for Industry. 

Acknowledged by

U.S. Department of Health and Human Services. Addressing Prescription Drug Abuse in the United States: Current Activities and Future Opportunities.

References

Cicero, T., Ellis, M., & Surrat, H. (2012). Effect of abuse-deterrent formulation of OxyContin. New England Journal of Medicine, 367, 187–189. Retrieved from http://www.nejm.org/doi/full/10.1056/NEJMc1204141

U.S. Food and Drug Administration. (2013). Abuse-deterrent opioids—evaluation and labeling: Guidance for industry. Retrieved from https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm334743.pdf

Webster, L., St. Marie, B., McCarberg, B., Passik, S. D., Panchal, S. J., & Voth, E. (2011). Current status and evolving role of abuse-deterrent opioids in managing patients with chronic pain. Journal of Opioid Management, 7(3), 235–245. Retrieved from http://kolonline.com/

Woodcock, J. (2016). Public meeting on abuse deterrent formulations: Framing the issues. Silver Spring, MD: FDA Center for Drug Evaluation and Research. Retrieved from https://www.fda.gov/Drugs/NewsEvents/ucm509853.htm