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Six-month, open-label study of hydrocodone extended release formulated with abuse-deterrence technology: Safety, maintenance of analgesia, and abuse potential

Martin E. Hale, MD, Yuju Ma, MS, Richard Malamut, MD


Objective: To evaluate long-term safety, maintenance of analgesia, and aberrant drug-related behaviors of hydrocodone extended release (ER) formulated with CIMA® Abuse-Deterrence Technology.

Design: Phase 3, multicenter, open-label extension.

Setting: Fifty-six US centers.

Patients: Adults with chronic low back pain completing a 12-week placebo-controlled study of abuse-deterrent hydrocodone ER were eligible. One hundred eighty-two patients enrolled and received 1 dose of study drug, 170 entered open-label treatment, and 136 completed the study.

Interventions: Patients receiving hydrocodone ER in the 12-week, placebo-controlled study continued their previous dose unless adjustment was needed; those previously receiving placebo (n = 78) underwent dose titration/adjustment to an analgesic dose (15-90 mg every 12 hours). Patients received 22 weeks of open-label treatment.

Main outcome measures: Safety: adverse events (AEs). Maintenance of analgesia: worst pain intensity (WPI) and average pain intensity (API) at each study visit. Aberrant drug behavior: study drug loss and diversion.

Results: AEs were reported for 65/182 (36 percent) patients during dose titration/adjustment and 88/170 (52 percent) during open-label treatment. No treatment-related serious AEs were reported. There were no clinically meaningful trends in other safety assessments, including physical examinations and pure tone audiometry. One patient receiving hydrocodone ER 30 mg twice daily experienced a severe AE of neurosensory deafness that was considered treatment related. Mean WPI and API remained steady throughout open-label treatment. Six (3 percent) patients reported medication loss, and 5 (3 percent) reported diversion.

Conclusions: Abuse-deterrent hydrocodone ER was generally well tolerated in patients with chronic low back pain, maintained efficacy, and was associated with low rates of loss and diversion.


hydrocodone, opioid analgesics, chronic pain, narcotic abuse

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Institute of Medicine Committee on Advancing Pain Research, Care, and Education: Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. Washington, DC: National Academies Press, 2011. Available at Accessed December 10, 2015.

Moore RA, Derry S, Taylor RS, et al.: The costs and consequences of adequately managed chronic non-cancer pain and chronic neuropathic pain. Pain Pract. 2014; 14(1): 79-94.

Hoy D, March L, Brooks P, et al.: The global burden of low back pain: estimates from the Global Burden of Disease 2010 study. Ann Rheum Dis. 2014; 73(6): 968-974.

Chaparro LE, Furlan AD, Deshpande A, et al.: Opioids compared with placebo or other treatments for chronic low back pain: an update of the Cochrane Review. Spine. 2014; 39(7): 556-563.

Passik SD: Issues in long-term opioid therapy: unmet needs, risks, and solutions. Mayo Clin Proc. 2009; 84(7): 593-601.

Brennan MJ, Stanos S: Strategies to optimize pain management with opioids while minimizing risk of abuse. PM R. 2010; 2(6): 544-558.

Spitz A, Moore AA, Papaleontiou M, et al.: Primary care providers’ perspective on prescribing opioids to older adults with chronic non-cancer pain: a qualitative study. BMC Geriatr. 2011; 11: 35.

Mahowald ML, Singh JA, Majeski P: Opioid use by patients in an orthopedics spine clinic. Arthritis Rheum. 2005; 52(1): 312-321.

IMS Institute for Healthcare Informatics: The Use of Medicines in the United States: Review of 2011. Parsippany, NJ: IMS Institute, April 2012. Available at ehs/news/2013/pdf-links/IHII_Medicines_in_U.S_Report_2011-1.pdf. Accessed December 10, 2015.

Barkin RL: Acetaminophen, aspirin, or ibuprofen in combination analgesic products. Am J Ther. 2001; 8(6): 433-442.

CIMA LABS, Inc.: OraGuard Tamper Deterrent Alcohol Resistant Technology. Brooklyn Park, MN: CIMA, 2013. Available at Accessed January 19, 2016.

Hale ME, Zimmerman TR, Eyal E, et al.: Efficacy and safety of a hydrocodone extended-release tablet formulated with abuse-deterrence technology in patients with moderate-to-severe chronic low back pain. J Opioid Manag. 2015; 11(6): 507-518.

Hale ME, Zimmerman TR, Ma Y, et al.: Twelve-month, open-label assessment of long-term safety and abuse potential of hydrocodone extended-release formulated with abuse-deterrence technology in chronic pain patients. J Opioid Manag. 2015; 11(5): 425-434.

Friedman RA, House JW, Luxford WM, et al.: Profound hearing loss associated with hydrocodone/acetaminophen abuse. Am J Otol. 2000; 21(2): 188-191.

Ho T, Vrabec JT, Burton AW: Hydrocodone use and sensorineural hearing loss. Pain Physician. 2007; 10(3): 467-472.

Krashin D, Murinova N, Trescot AM: Extended-release hydrocodone—Gift or curse? J Pain Res. 2013; 6: 653-657.

Yorgason JG, Kalinec GM, Luxford WM, et al.: Acetaminophen ototoxicity after acetaminophen/hydrocodone abuse: evidence from two parallel in vitro mouse models. Otolaryngol Head Neck Surg. 2010; 142(6): 814-819.

Reddy A, Yennurajalingam S, Desai H, et al.: The opioid rotation ratio of hydrocodone to strong opioids in cancer patients. Oncologist. 2014; 19(11): 1186-1193.

Brush DE: Complications of long-term opioid therapy for management of chronic pain: the paradox of opioid-induced hyperalgesia. J Med Toxicol. 2012; 8(4): 387-392.



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