Opioids play an important and omnipresent role in the treatment of moderate to severe acute and chronic pain. The fact of the matter is that in patients with acute pain, such as postoperative pain, opioids are utilized as the first-line treatment at least 98% of the time. Opioids are also recognized as the cornerstone of managing moderate to severe sub-acute and chronic cancer pain. Although their long-term safety and efficacy in chronic non-cancer pain patients continues to be debated, they also frequently play a role in management of this type of pain as well.
Along with the unparalleled benefits that opioids provide in managing pain, is the issue that the rate of prescription opioid abuse continues to rise, and is approaching crisis levels. The possibility of abuse, misuse, addiction, or diversion of opioids is something that every clinician needs to consider when prescribing them. Regulatory agencies’ approach to dealing with these issues has consisted of monitoring prescriptions, and is in some cases pushing healthcare providers into a fearful corner when it comes to consideration of prescribing an opioid. This has often resulted in decreased comfort to prescribe opioids for the treatment of chronic pain despite the appropriateness, or public outcry for better management of pain.
Often fueled by media attention, the issue seems to be worthy of concern. Indeed, even in secondary school students, the numbers can be intimidating; 20% of 7th – 12th graders use prescription drugs non-medically1, with a significant amount of those medications being prescription opioids. The sources of abused or diverted opioids are quite varied, and can include:
- – Theft from the manufacturer, distributor, or pharmacy
- – Theft of prescription forms from clinicians
- – Theft or sale from the patient for whom the opioid was prescribed
- – The Internet
- – Drug dealers
Although opioids are often abused in the manner in which they were intended to be administered (e.g., oral), there is a significant amount of abuse after alteration (tampering) or extraction of the active ingredient has taken place. In light of these facts, along with the diverse routes of availability, pharmaceutical companies manufacturing opioids have invested a large amount of resources towards the development of a number of different approaches to resist or deter abuse and misuse.
These abuse-resistant or abuse-deterrent formulations especially target techniques that are devoted to doubling or tripling doses, by extracting active ingredients out of the original formulation, allowing either an alternate route of administration (i.e., intravenous, smoking, or snorting), or concentration and increased potency of the opioid. In fact, the ability to extract the opioid out of a sustained-release opioid formulation can yield a very significant amount of abusable substance.
The abuse-deterrent strategies generally work in one of two ways:
- – Combining the active opioid along with another compound, like an opioid antagonist, such as naloxone, which actually will counteract the opioid effects if taken in large enough quantities, and “block the high”, decreasing its attractiveness for abuse
- – Utilizing a number of different compounding approaches to thwart the “hacking” of the medication, by utilizing a physical barrier, or making it difficult to separate the delivery compounds from the active one, making the opioid unavailable for alternate forms of consumption, such as intravenous injection, smoking, or snorting
The solution to curbing abuse of prescription opioids is a multifaceted one. These include a concerted effort of clinician education about appropriate patient assessment and selection; improved dialogue between health care providers and regulatory agencies about opioid prescription; improved patient education about safe practices; and close monitoring of patients perceived to be at a higher risk of abuse, misuse or addiction.
Abuse-deterrent opioid formulations will likely play a significant role in the approach to curbing prescribed opioid abuse and misuse. They have the potential to provide opioids when appropriate, while limiting abuse and misuse, as well as its consequences. These abuse-deterrent formulations will help to reduce the public health burden of prescription opioid abuse, and also make it easier for clinicians to prescribe them when they are the appropriate choice for managing chronic pain. The Food and Drug Administration (FDA) has recently (January 2013) given guidance to manufacturers of opioids on evaluation and labeling for abuse-deterrent formulations. The purpose of the guidance is to “assist industry in developing new formulations of opioid drugs with abuse-deterrent properties.”Additionally, on April 16, 2013, the FDA approved updated labeling reformulated oxycodone hydrochloride controlled-release tablets. The new labeling indicates that the product has physical and chemical properties that are expected to make abuse via injection difficult and to reduce abuse via the intranasal route (snorting).
Clearly there seems to be regulatory movement in terms of abuse-deterrent formulations playing a role in combating abuse of opioids. After further validation of their ability to live up to expectations, they may become the “new generation” of opioids, and make non-deterrent formulations of opioids obsolete.
1Medical and Nonmedical Use of Prescription Drugs among Secondary School Students.McCabe, et al. Journal of Adolescent Health. Volume 40;76-83
1. Fischer, B. and Rehm, J. Nonmedical Use of Prescription Opioids: Furthering a Meaningful Research Agenda. The Journal of Pain, Vol 9, No 6 June, 2008: pp 490-493
2. Katz, N.P., et al. Challenges in the Development of Prescription Opioid Abuse-deterrent Formulations. Clinical Journal of Pain, Vol 23, No 8, October, 2007 648-660