Acute opioid withdrawal precipitated by ingestion of crushed Embeda (morphine extended release with sequestered naltrexone): Case report and the focused review of the literature

Xiulu Ruan, MD; Tao Chen, MD, PhD; Jeff Gudin, MD; John Patrick Couch, MD; Srinivas Chiravuri, MD

doi:10.5055/jom.2010.0028

Authors

Xiulu Ruan, MD
Tao Chen, MD, PhD
Jeff Gudin, MD
John Patrick Couch, MD
Srinivas Chiravuri, MD

DOI:

https://doi.org/10.5055/jom.2010.0028

Keywords:

morphine, naltrexone, opioid withdrawal, Embeda

Abstract

Background: The introduction of newly formulated extended release (ER) morphine with sequestered naltrexone (Embeda) has provided another treatment option for moderate to severe persistent pain. Embeda was designed to be an abuse-deterrent opioid formulation. Naltrexone is a centrally acting opioid receptor antagonist that blocks the action of opioid. When taken as directed, insignificant amount of sequestered naltrexone would reach systemic circulation, but upon tampering, the released naltrexone may blunt the euphoria of opioids, and possibly precipitate opioid withdrawal in opioid-dependent patient.
Objective: To describe a case report of a 50-year-old opioid-dependent male who developed acute opioid withdrawal after taking crushed Embeda.
Case report: A 50-year-old male with severe, chronic low back pain due to degenerative disc disease was referred to our clinic for pain management. He was taking ER oxycodone 80 mg tid and Roxicodone 30 mg qid prn, with inadequate pain relief. A trial of ER oxymorphone was decided, at 40 mg 1-2 doses bid. The patient returned to the clinic 1 week early, out of his ER oxymorphone. At this time, the decision to switch him to Embeda was made, at 80 mg/3.2 mg, 1-2 doses bid. The patient and his family members were counseled about risk involved with tampering with Embeda. A few hours later, our clinic was informed that the patient was brought to emergency room by ambulance, in severe opioid withdrawal. He was treated with IV fluid, antiemetics, clonidine, and IV hydromorphone. His condition improved and he was discharged home the next morning. Later on, the patient admitted that he took two prescribed Embeda within half an hour, the 1st one whole and the 2nd one crushed. He further admitted that he did so against our medical advice.
Conclusion: Taking tampered Embeda may precipitate opioid withdrawal in opioid-tolerant patient. To the best of our knowledge, this is the first report of induced opioid withdrawal following consumption of crushed Embeda.

Author Biographies

Xiulu Ruan, MD

Associate Medical Director, Physicians’ Pain Specialists of Alabama, Mobile, Alabama; Adjunct Assistant Professor of Neurology, College of Medicine, University of South Alabama, Mobile, Alabama.

Tao Chen, MD, PhD

Clinical Fellow, Interventional Pain Medicine, Physicians’ Pain Specialists of Alabama, Mobile, Alabama.

Jeff Gudin, MD

Director of Pain and Palliative Care, Englewood Hospital and Medical Center, a Mt Sinai University School of Medicine affiliate, Englewood, New Jersey.

John Patrick Couch, MD

Medical Director, Department of Neurology, Physicians’ Pain Specialists of Alabama, Mobile, Alabama; Adjunct Assistant Professor of Neurology, College of Medicine, University of South Alabama, Mobile, Alabama.

Srinivas Chiravuri, MD

Pain Fellowship Director, Assistant Professor of Anesthesiology, Department of Anesthesiology, University of Michigan Health System, Ann Arbor, Michigan.

References

Embeda (Package Insert). Bristol, TN: King Pharmaceuticals, Inc, 2009.

Stauffer J, Setnik, B, Sokolowska M, et al.: Subjective effects and safety of whole and tampered morphine sulfate and naltrexone hydrochloride (ALO-01) extended-release capsules versus morphine solution and placebo in experienced non-dependent opioid users: A randomized, double-blind, placebo-controlled, crossover study. Clin Drug Investig. 2009; 29(12): 777-790.

Katz N, Sun S, Johnson F, et al.: ALO-01 (morphine sulfate and naltrexone hydrochloride) extended-release capsules in the treatment of chronic pain of osteoarthritis of the hip or knee: Pharmacokinetics, efficacy and safety. J Pain. 2009; 11: 303-311.

Sloan P: Review of oral oxymorphone in the management of Pain. Ther Clin Risk Manag. 2008; 4(4): 777-787.

Pergolizzi J, Boger RH, Budd K, et al.: Opioids and the management of chronic severe pain in the elderly: Consensus statement of an international expert panel with focus on the six clinically most often used World Health Organization Step III opioids (buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone). Pain Pract. 2008; 8(4): 277-313.

Manchikanti L: National drug control policy and prescription drug abuse: Facts and fallacies. Pain Physician. 2007; 10: 399-424.

Kuehn BM: Opioid prescription soar: Increase in legitimate use as well as abuse. JAMA. 2007; 297: 249-251.

Caudill-Slosberg MA, Schwartz LM, Woloshin S: Office visits and analgesic prescriptions for musculoskeletal pain in US: 1980 vs 2000. Pain. 2004; 109: 514-519.

Olsen Y, Daumit GL, Ford DE: Opioid prescriptions by US primary care physicians from 1992 to 2001. J Pain. 2006; 7: 225-235.

The American Academy of Pain Medicine, The American Pain Society: The use of opioids for the treatment of chronic pain: A consensus statement from the American Academy of Pain Medicine and American Pain Society. Clin J Pain. 1997; 13: 6-8.

Center on Addiction and Subtance Abuse: Substance Abuse and Federal Entitlement Programs. New York: Columbia University, 1995.

Office of Applied Studies: Substance Abuse and Mental Health Service Administration: Results from the 2004 National Survery on Drug Use and Health. Rockville, MD: Department of Health and Human Services, 2005.

Webster L: Update on abuse-resistant and abuse deterrent approaches to opioid formulations. Pain Med Suppl. 2009; 2: S124-S133.

Wick JY: Drug-abuse deterrent formulations. Consult Pharm. 2009; 24(5): 356-362, 365.

Boyce SH, Armstrong PAR, Stevenson J: Effect of inappropriate naltrexone use in a heroin misuser. Emerg Med J. 2003; 20: 381-382.

Armstrong J, Little M, Murray L: Emergency department presentations of naltrexone-accelerated detoxification. Acad Emerg Med. 2003; 10(8): 860-866.

Manelli P, De Risio, Possi G, et al.: Serendipitous rapid detoxification from opiates: The importance of time dependent processes. Addiction. 1999; 94: 589-591.

Quigley MA, Boyce SH: Unintentional rapid opioid detoxification. Emerg Med J. 2001; 18: 494-495.

Drug Information Online: http://www.drugs.com/pro/naltrexone.html. Accessed July 2009.

RxList: The Internet Drug Index. Available at http://www.rxlist.com/revia-drug.htm. Accessed July 2008.

Fishman M: Precipitated withdrawal during maintenance opioid blockade with extended release naltrexone. Addiction. 2008; 103(8): 1399-1401.