Precipitated withdrawal during maintenance opioid blockade with extended release naltrexone
ABSTRACT Background There has been increasing interest in the use of extended release injectable naltrexone for the treatment of opioid dependence. Case description We report a case of precipitated withdrawal in a 17-year-old adolescent female receiving extended release naltrexone (Vivitrol) for opioid dependence, following her third serial monthly dose of the medication, several days after using oxycodone with mild intoxication. Conclusions This case suggests that, in some circumstances, the opioid blockade may be overcome when naltrexone levels drop towards the end of the dosing interval, producing vulnerability to subsequent naltrexone-induced withdrawal. This may provide cautionary guidance for clinical management and dosing strategies.
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- "An abuser may attempt to override naltrexone’s receptor blockade with higher doses of opioid agonists, or by taking opioids at the end of naltrexone’s dosing interval, a time when plasma levels are decreasing and the blockade is diminishing.49,62 None of the studies presented in this review indicated any overdose cases, but there have been reports of opioid overdose in patients after discontinuation of oral naltrexone maintenance.63,64 "
ABSTRACT: The United States Food and Drug Administration (FDA) approved naltrexone, a synthetic competitive antagonist at opioid receptors, in oral form in 1984 for use in the management of opioid abuse and addiction. Because naltrexone and its major metabolite, 6-β-naltrexone, are both competitive antagonists at opioid receptors - and thereby inhibit opioid agonist-induced effects including those desired by abusers - it was hypothesized that once maintained on naltrex-one, opioid-induced desirable effects would be diminished to the point that relapse to illicit use would decline because it was no longer rewarding. However, good medication compliance is a requisite for such a strategy to be effective and a systematic review of oral naltrexone concluded that this method of treatment was not superior for any outcomes measured (ie, retention, abstinence, or side effects) to placebo, psychotherapy, benzodiazepines, or buprenorphine treatment. In addition, the retention rate on oral naltrexone was very low (less than 30%). Recently, the FDA approved an extended-release formulation (intramuscular depot injection) of naltrexone for prevention of relapse to opioid dependence following opioid detoxification and to be used along with counseling and social support. Since it needs to be administered only monthly, as opposed to the daily administration required for the oral formulation, naltrexone injection has the potential for increasing adherence and retention rates. Concerns include liver damage at high doses (oral formulation) and possible opioid overdose if an attempt is made to surmount receptor antagonism by taking higher doses of an opioid agonist or if opioid receptors become "sensitized" under long-term antagonism. The focus of the present review is the current information regarding the safety and efficacy of naltrexone extended-release therapy.12/2011; 2:219-226. DOI:10.2147/SAR.S17920
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ABSTRACT: The major problem with the oral formulation of naltrexone for heroin dependence is poor compliance (adherence). Long-acting sustained release formulations of naltrexone (implantable and injectable) might help to improve compliance and, thus, increase the efficacy of abstinence-oriented treatment of heroin dependence with naltrexone. There have been several implantable and injectable formulations of naltrexone developed within the last decade. It was demonstrated that some of them are effective and relatively well tolerated medications for relapse prevention in heroin addicts. However, advantages and disadvantages of these new medications have never been systematically analyzed. Long-acting sustained release formulations of naltrexone are well tolerated and more effective for relapse prevention in heroin addicts than the oral ones.Current opinion in psychiatry 03/2010; 23(3):210-4. DOI:10.1097/YCO.0b013e3283386578 · 3.94 Impact Factor
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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 ofa 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.Journal of opioid management 07/2010; 6(4):300-3. DOI:10.5055/jom.2010.0028