Assessment of Extended-Release Opioid Analgesics for the Treatment of Chronic Pain

ABSTRACT

Approximately 3.8 million patients annually receive extended-release (ER) or long-acting opioid prescriptions in the outpatient setting, around half of which are written by primary care physicians. Compared with short-acting, immediate-release (IR) formulations, ER and oral long-acting opioid analgesics are associated with clinical advantages, such as extended periods of time during which drug plasma levels are within the therapeutic range, decreased peak-to-trough fluctuations, and prolonged analgesia over the dosing period. Additionally, ER opioids offer a more convenient, less frequent dosing regimen to chronic pain patients who are often taking several concomitant medications. The increased utilization of ER opioids has been accompanied by a rise in the misuse and abuse of these formulations. Certain pharmacokinetic parameters (e.g., longer time to maximum drug plasma concentration, lower maximum drug plasma concentration) may decrease the abuse potential of intact ER opioids by limiting the positive subjective and reinforcing effects relative to IR formulations. Putative abuse-deterrent formulations have also recently been introduced to impede physical manipulation of these formulations, or reduce the harm resulting from such behavior. Such formulations may represent an incremental advance to reduce non-oral forms of abuse. This article reviews the pharmacokinetic profiles and abuse-deterrent features of newer ER opioid analgesics for the treatment of moderate to severe chronic pain.

KEYWORDS :

• abuse
• abuse-deterrent
• extended-release
• opioid
• pharmacokinetics
• tamper-resistant

Notes

*These formulations have been referred to by various names, including “abuse-deterrent,” “abuse-resistant,” “tamper-deterrent,” “tamper-resistant,” and “crush-resistant.” Although some distinctions among them have been suggested,⁴⁹ there is not yet an agreed upon taxonomy, and the clinical implications of these terms are quite similar, if not the same.