Category Principle Examples Physical/chemical barriers Physical barriers that prevent chewing, crushing, or grinding (e.g., tablet hardness). Chemical barriers that resist extraction and injection (e.g., gelling in water). OxyContin®, Nucynta®, Exalgo®, Opana® ER Agonist/antagonist combinations Addition of an opioid antagonist (e.g., naloxone, naltrexone) that reduces or eliminates euphoria or drug “high”. Embeda™, Suboxone Aversion Addition of a substance (e.g., niacin, SLS) that produces an unpleasant effect. Oxecta® Delivery system Drug depots and implants Probuphine Prodrug An opioid prodrug that lacks opioid activity and must be transformed in the body to produce activity   Combination Multiple methods incorporated into the formulation Oxecta® *Abbreviation: SLS = Sodium Lauryl Sulfate.

Table 1: Formulation Changes that may Reduce Misuse/Abuse of Opioids (FDA, 2013).