Sequestered naltrexone in sustained release morphine or oxycodone - a way to inhibit illicit use?

Under the growing concern about prescription opioid misuse, abuse, addiction, tampering and diversion, stakeholders (e.g, governments, pharmaceutical companies and health care providers) are developing opioid formulations that they hope are less attractive to those seeking to misuse or abuse pain medications. However, these products must maintain their therapeutic effectiveness and safety. Many abusers tamper with formulations in an effort to convert the active ingredient into a form suitable for alternative and more abuse-desirable routes of administration, such as snorting, inhaling or injecting.

A tamper-deterrent strategy is to embed opioid antagonists into the opioid agonist formulation. Upon tampering, the opioid antagonist is released and binds to the opioid receptors in sufficient amount to impede access of the agonist. This approach is intended to reduce the opioid subjective rewarding effects such as euphoria which are prominent following swallowing the dosage form without tampering. Sequestered naltrexone in sustained-release morphine or oxycodone is an example of this. We performed a comprehensive literature search using available databases to identify clinical studies utilizing an opioid agonist in combination with naltrexone. Efficacy, safety and abuse potential studies were identified for the developed products containing morphine and naltrexone as well as oxycodone and naltrexone.

The clinical impact of such combined formulations on tampering for abuse/misuse potential has not yet been determined, but long-term epidemiological studies are currently being conducted in order to answer these questions. Until these studies are complete, it seems prudent to remain cautious and assume that all formulations of prescription opioids might be abusable and that, similar to other opioids, the best current practice is to adhere to the principles of opioid risk management.