Webster Lynn, Gudin Jeffrey
Dr. Vince Clinical Research, Overland Park, KS, USA.
Department of Anesthesiology and Pain Management, University of Miami, Miller School of Medicine, Miami, FL, USA.
J Pain Res. 2024 Jun 5;17:1989-2000. doi: 10.2147/JPR.S457982. eCollection 2024.
The misuse and abuse of opioid analgesics continue to pose a serious public health concern, but for some patients, opioids remain an important analgesic option. Extended-release (ER) opioid formulations are effective for treating chronic pain and are supported by multiple 12-week efficacy studies. ER opioids often contain a high opioid content, and similar to immediate-release (IR) formulations, are subject to abuse, misuse, and diversion. Unintentional misuse may also occur when ER formulations are manipulated for medicinal administration, such as crushing a dose for easier oral intake. As part of a multipronged strategy designed to fight the opioid epidemic, abuse-deterrent formulations (ADFs) were developed to deter misuse, abuse, and diversion of opioids by making manipulation more difficult and nonoral routes of administration less rewarding. Although ADF opioids have been shown to decrease rates of abuse and diversion, they are not equally effective in terms of deterring manipulation for abuse or misuse. Xtampza ER utilizes DETERx technology, which allows it to retain ER characteristics when chewed or crushed, making it the only ER opioid without a boxed warning against these types of manipulation. OxyContin was also developed as an ADF but uses RESISTEC technology, making the tablet hard to crush and viscous in aqueous solutions. ADF utilization has been hampered by patient access issues, including high prices due to lack of insurance coverage. Postmarket real-world studies demonstrate lower rates of abuse, misuse, and diversion for ADF ER opioids compared with non-ADF formulations. However, similar studies comparing abuse-related effectiveness and health care costs for ADF opioids are warranted if clinicians are expected to utilize these potentially safer opioid formulations. These studies would support further education surrounding the benefits and utilization of ADFs and manipulation potential of different ADFs.
阿片类镇痛药的误用和滥用仍然是严重的公共卫生问题,但对一些患者来说,阿片类药物仍是重要的镇痛选择。缓释(ER)阿片类制剂对治疗慢性疼痛有效,并有多项为期12周的疗效研究支持。ER阿片类药物通常含有高剂量的阿片成分,与即释(IR)制剂一样,容易被滥用、误用和转移用途。当为便于给药而对ER制剂进行处理时,如碾碎剂量以便于口服,也可能发生无意的误用。作为旨在抗击阿片类药物流行的多管齐下战略的一部分,开发了具有滥用威慑作用的制剂(ADF),通过增加操作难度和降低非口服给药途径的获益来防止阿片类药物的误用、滥用和转移用途。尽管ADF阿片类药物已被证明可降低滥用和转移用途的发生率,但在阻止为滥用或误用而进行的操作方面,它们的效果并不相同。Xtampza ER采用了DETERx技术,使其在咀嚼或碾碎时仍能保持缓释特性,成为唯一一种没有针对此类操作的盒装警示的ER阿片类药物。奥施康定也是作为一种ADF开发的,但使用的是RESISTEC技术,使片剂难以碾碎且在水溶液中具有粘性。ADF的使用受到患者获取问题的阻碍,包括由于缺乏保险覆盖导致的高价格。上市后真实世界研究表明,与非ADF制剂相比,ADF ER阿片类药物的滥用、误用和转移用途发生率较低。然而,如果期望临床医生使用这些潜在更安全的阿片类制剂,那么进行类似的比较ADF阿片类药物与滥用相关有效性和医疗保健成本的研究是有必要的。这些研究将支持围绕ADF的益处和使用以及不同ADF的可操作性进行进一步教育。