Opioid Formulations Designed to Resist/Deter Abuse

Abstract

Physicians who prescribe opioid analgesics for patients with moderate to severe chronic pain face a balancing act in the wake of the current publicity regarding abuse (nonmedical use) of prescription pain killers. There is a spectrum of opioid abuse ranging from those who misuse the drug by not following doctor's orders to those who take the drugs to achieve a high or divert the drugs to the street market for profit. Formulations of opioid analgesics designed to resist or deter abuse have been proposed, and are now either on the market or in the pipeline. These are innovative formulations that make the drug less convenient or less desirable to abusers. This article examines three such new products along with clinical studies that report on their safety and effectiveness. These drugs include extended-release morphine with sequestered naloxone (Embeda), controlled-release oxycodone in a high-viscosity hard gelatin capsule (Remoxy) and an immediate-release oxycodone tablet with subtherapeutic niacin as an aversive agent (Acurox with niacin tablets). Extended-release morphine with sequestered naltrexone offers a pharmacological barrier in that pellets of morphine surround an internal core of naltrexone (ratio 100 : 4 of morphine : naltrexone), which is released if the tablet is compromised by chewing or crushing. The hard gelatin capsule of controlled-release oxycodone was designed to resist tampering and the drug cannot be extracted with a needle. The immediate-release oxycodone formulation with subtherapeutic niacin uses a gel-forming ingredient designed to inhibit inhalation and prevent extraction of the drug for injection. The subtherapeutic niacin is intended to induce flushing and other unpleasant effects if the drug is taken in an excessive quantity. While these drugs hold individual promise, it remains undetermined if they can truly prevent abuse. Drug-seeking individuals are extremely resourceful and show little loyalty to a particular drug when other drugs are available. It is possible that abuse-deterring formulations may divert such individuals to find other drugs that are easier to compromise. Nevertheless, these formulations are important innovations and warrant further study to assess their appropriate role as analgesics.