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- Hepatotoxicity in a 52-week randomized trial of short-term versus long-term treatment with buprenorphine/naloxone in HIV-negative injection opioid users in China and Thailand. [JOURNAL ARTICLE]
- Drug Alcohol Depend 2014 Jun 19.
Buprenorphine/naloxone (BUP/NX), an effective treatment for opioid dependence, has been implicated in hepatic toxicity. However, as persons taking BUP/NX have multiple hepatic risk factors, comparative data are needed to quantify the risk of hepatoxicity with BUP/NX.We compared rates of alanine aminotransferase (ALT) elevation≥grade 3 (ALT≥5.1 times the upper limit of normal) and graded bilirubin elevations in HIV-negative opioid injectors randomized to long-term (52 weeks) or short-term (18 days) medication assisted treatment (LT-MAT and ST-MAT, respectively) with BUP/NX in a multisite trial conducted in China and Thailand. ALT and bilirubin were measured at baseline, 12, 26, 40 and 52 weeks, times temporally remote from BUP/NX exposure in the ST-MAT participants.Among1036 subjects with at least one laboratory follow-up measurement, 76 (7%) participants experienced ALT elevation≥grade 3. In an intent-to-treat analysis, the risk of ALT events was similar in participants randomized to LT-MAT compared with ST-MAT (adjusted hazard ratio 1.25, 95% confidence interval 0.79 to 1.98). This finding was supported by an as-treated analysis, in which actual exposure to BUP/NX was considered. Hepatitis C seroconversion during follow-up was strongly associated with ALT events. Bilirubin elevations≥grade 2 occurred in 2% of subjects, with no significant difference between arms.Over 52-week follow-up, the risk of hepatotoxicity was similar in opioid injectors receiving brief and prolonged treatment with BUP/NX. These data suggest that most hepatotoxic events observed during treatment with BUP/NX are due to other factors.
- Opioid substitution treatment in New Zealand: a 40 year perspective. [JOURNAL ARTICLE]
- N Z Med J 2014; 127(1397):57-66.
We provide an overview of the history and philosophy of the treatment for opioid dependence, which has been dominated by methadone substitution treatment for the past 40 years in New Zealand. Although changes in approach have occurred over this time, influenced by various sociopolitical events and changing ideologies, opioid substitution treatment has still "not come of age". It remains undermined by stigma and risk concerns associated with methadone and has struggled to be accessible and attractive to illicit opioid drug users, comprehensive and integrated into mainstream health care. However, the introduction in 2012 of Pharmac-subsidised buprenorphine combined with naloxone (Suboxone) in the context of an emerging trend towards a broader recovery and well-being orientation could signal a new era in treatment. The availability of buprenorphine-naloxone may also facilitate a further shift in treatment from primarily siloed specialist addiction services to integrated primary care services. This shift will help reduce stigma, promote patient self-management and community integration and align opioid substitution treatment with treatment for other chronic health conditions such as diabetes and asthma.
- Sublingual Buprenorphine as an Analgesic in Chronic Pain: A Systematic Review. [JOURNAL ARTICLE]
- Pain Med 2014 Jul 4.
There is growing interest in the use of sublingual buprenorphine for the treatment of chronic pain due to the unique pharmacology of buprenorphine, widespread use of the transdermal buprenorphine patch for chronic pain, and recent availability of sublingual buprenorphine tablets for the treatment of opioid dependence. The aim of this systematic review was to evaluate the evidence from clinical trials that have assessed the effectiveness of sublingual buprenorphine for chronic pain analgesia.Electronic searches of MEDLINE, Embase, CINAHL, Web of Science, and the Cochrane Database of Systematic Reviews were used to identify clinical trials of sublingual buprenorphine for the treatment of chronic pain.Ten trials involving 1,190 patients were included in the review. Due to heterogeneity of studies, pooling of the results and meta-analysis were not possible. All studies reported that sublingual buprenorphine demonstrated some effectiveness as a chronic pain analgesic. The majority of studies were observational and of low quality.Preliminary trials suggest a plausible role; however, due to a paucity of high-quality trials, the current evidence is insufficient to determine the effectiveness of sublingual buprenorphine for the treatment of chronic pain. Rigorous further trials are warranted.
- Clinical factors associated with sexual dysfunction among men in methadone maintenance treatment and buprenorphine maintenance treatment: a meta-analysis study. [JOURNAL ARTICLE]
- Int J Impot Res 2014 Jul 3.
Methadone maintenance treatment is proven to be effective treatment for opioid dependence. Of the many adverse events reported, sexual dysfunction is one of the most common side effects. However, there may be other clinical factors that are associated with sexual dysfunction among methadone users. We conducted a meta-analysis to examine the clinical factors associated with sexual dysfunction among male patients on methadone and buprenorphine treatments, of which eligible studies were selected using prior defined criteria. A total of 2619 participants from 16 eligible studies, published from inception till December 2012, were identified from the PubMed, OVID and EMBASE databases. The included studies provided prevalence estimates for sexual dysfunction among methadone users with a meta-analytical pooled prevalence of 52% (95% confidence interval (CI), 0.39-0.65). Only four studies compared sexual dysfunction between the two groups, with a significantly higher combined odds ratio in the methadone group (odds ratio=4.01, 95% CI, 1.52-10.55, P=0.0049). Our study shows that eight clinical factors are associated with sexual dysfunction among men receiving opioid substitution treatment, namely age, hormone assays, duration of treatment, methadone dose, medical status, psychiatric illness, other current substance use and familial status, and methadone versus buprenorphine treatment. Despite the methodological limitations, the findings of this meta-analysis study may offer better insights to clinicians in dealing with both sexual dysfunction and its related problems.International Journal of Impotence Research advance online publication, 3 July 2014; doi:10.1038/ijir.2014.18.
- [Injectable extended-release naltrexone for the prevention of relapse to opioid dependence following opioid detoxification.] [JOURNAL ARTICLE]
- Zh Nevrol Psikhiatr Im S S Korsakova 2014; 114(5 Vypusk 2 Addiktivnye rasstroistva):64-72.
Opioid dependence is a growing, worldwide public health concern. In contrast to opioid ?-agonist (or 'substitution') maintenance treatments, injectable extendedrelease naltrexone (XR-NTX), approved in the USA and Russia, is an opioid antagonist, formulated to address nonadherence, which limits the utility of oral naltrexone for opioid dependence. This article reviews the clinical trial data underlying the approval of XR-NTX for opioid dependence and the agent's clinical use. XR-NTX met all primary and secondary end points in a multicenter, placebo-controlled trial (n=250) conducted in Russia, with two discontinuations in each group because of adverse events. Cost-effectiveness analysis of claims data found that 6-month total healthcare costs following XR-NTX (US$8582 per patient) were not significantly different from oral naltrexone (US$8903; p=0.867) or buprenorphine (US$10,049; p=0.414), and were 49% lower than with methadone (US$16,752; p<0.0001). Future research should address induction and duration of treatment with XR-NTX.
- Perioperative management of a patient undergoing Clagett window closure stabilized on Suboxone(®) for chronic pain: a case report. [JOURNAL ARTICLE]
- Can J Anaesth 2014 Jul 2.
Buprenorphine is a semisynthetic opioid with both agonist and antagonist activity at the opioid receptor. Currently, buprenorphine is commonly available in sublingual preparations combined with naloxone (e.g., Suboxone(®), Subutex(®)). There has been increased use of buprenorphine derivatives in the areas of substance addiction and chronic pain. Nevertheless, there is limited and conflicting information in the literature pertaining to the optimal management of buprenorphine-stabilized patients presenting for surgery. We present our experience with a chronic pain patient on buprenorphine presenting for thoracic surgery.A 47-yr-old female with a history of a Clagett window procedure for pulmonary aspergillosis and subsequent chronic pain presented to our institute for a window closure procedure. Preoperatively, her pain regimen included Suboxone 16 mg bid, which was continued perioperatively. Postoperatively, her course was complicated by suboptimal pain at the surgical site requiring in excess of 70 mg/24 hr of intravenous hydromorphone. Liberal addition of long-acting oral opioids was ineffective in improving pain management. Eventually, concern was raised regarding opioid receptor blockade by her long-acting Suboxone, and the decision was made to taper her Suboxone. Following this, her pain control improved dramatically and her opioid requirements were markedly reduced. By discharge, her Suboxone was discontinued and she was managed on oral hydromorphone.In a chronic pain patient continued on Suboxone perioperatively, significant improvement in control of postoperative pain was observed following tapered doses, and eventually her use of Suboxone was discontinued. This case highlights the potential for opioid receptor blockade by Suboxone, which can interfere with acute pain management.
- Factors contributing to the rise of buprenorphine misuse: 2008-2013. [JOURNAL ARTICLE]
- Drug Alcohol Depend 2014 Jun 18.
The purpose of the present study was to examine the motivations underlying the use of buprenorphine outside of therapeutic channels and the factors that might account for the reported rapid increase in buprenorphine misuse in recent years.This study used: (1) a mixed methods approach consisting of a structured, self-administered survey (N=10,568) and reflexive, qualitative interviews (N=208) among patients entering substance abuse treatment programs for opioid dependence across the country, centered on opioid misuse patterns and related behaviors; and (2) interviews with 30 law enforcement agencies nationwide about primary diverted drugs in their jurisdictions.Our results demonstrate that the misuse of buprenorphine has increased substantially in the last 5 years, particularly amongst past month heroin users. Our quantitative and qualitative data suggest that the recent increases in buprenorphine misuse are due primarily to the fact that it serves a variety of functions for the opioid-abusing population: to get high, manage withdrawal sickness, as a substitute for more preferred drugs, to treat pain, manage psychiatric issues and as a self-directed effort to wean themselves off opioids.The non-therapeutic use of buprenorphinehas risen dramatically in the past five years, particularly in those who also use heroin. However, it appears that buprenorphine is rarely preferred for its inherent euphorigenic properties, but rather serves as a substitute for other drugs, particularly heroin, or as a drug used, preferable to methadone, to self-medicate withdrawal sickness or wean off opioids.
- Evaluation of the perioperative analgesic efficacy of buprenorphine, compared with butorphanol, in cats. [JOURNAL ARTICLE]
- J Am Vet Med Assoc 2014 Jul 15; 245(2):195-202.
Objective-To compare the analgesic effects of buprenorphine and butorphanol in domestic cats. Design-2-phase positive-controlled randomized masked clinical trial. Animals-39 healthy female cats (10 in phase 1 and 29 in phase 2). Procedures-Cats admitted for ovariohysterectomy received buprenorphine (4 in phase 1; 14 in phase 2) or butorphanol (6 in phase 1; 15 in phase 2). In phase 1, cats were premedicated with buprenorphine (0.02 mg/kg [0.009 mg/lb], IM) or butorphanol (0.4 mg/kg [0.18 mg/lb], IM), in combination with medetomidine. Anesthesia was induced with propofol (IV) and maintained with isoflurane in oxygen. After extubation, medetomidine was antagonized with atipamezole. A validated multidimensional composite scale was used to assess signs of pain after surgery starting 20 minutes after extubation and continuing for up to 360 minutes, and pain score comparisons were made between the 2 groups. Phase 2 proceeded similar to phase 1 with the following addition: during wound closure, cats from the butorphanol and buprenorphine groups received butorphanol (0.4 mg/kg, IM) or buprenorphine (0.02 mg/kg, IM), respectively. Results-Phase 1 of the study was stopped after 10 cats were ovariohysterectomized because 9 of 10 cats required rescue analgesia at the first evaluation. In phase 2, at the first pain evaluation, pain scores from the buprenorphine group were lower, and all cats from the butorphanol group required rescue analgesia. None of the cats from the buprenorphine group required rescue analgesia at any time. Conclusions and Clinical Relevance-Buprenorphine (0.02 mg/kg, IM) given before surgery and during wound closure provided adequate analgesia for 6 hours following ovariohysterectomy in cats, whereas butorphanol did not.
- CYP2D6-Inhibiting Drugs and the Increased Risk of Fall-Related Injuries due to Newly Initiated Opioid Treatment - a Swedish, Register-based Case Cross-over Study. [JOURNAL ARTICLE]
- Basic Clin Pharmacol Toxicol 2014 Jun 30.
It has been shown that newly initiated opioid therapy increases the risk of fall-related injuries. Yet, it remains to be determined whether drug-drug interactions can affect this negative effect, for instance with drugs inhibiting cytochrome P4502D6 (CYP2D6) that metabolizes codeine, and also has a partial effect on tramadol and oxycodone. Our aim was to investigate how CYP2D6-inhibiting drugs contribute to explaining the risk of fall-related injuries for newly initiated opioid treatments with codeine, tramadol or oxycodone. Data from a Swedish national case cross-over study were revisited. This study identified a total of 167,257 fall-related injuries leading to hospitalization that occurred between 1 May 2006 and 31 December 2009 and linked information about dispensed drugs to them. Use of newly dispensed opioids in the 28 days before fall-related injury with and without CYP2D6-inhibiting drugs was compared with an earlier control period. For codeine, there was a two-fold elevated risk with concomitant CYP2D6-inhibiting drug use (OR, 1.76; 95% CI 1.40-2.20) and a three-fold risk increase without (OR, 3.17; 95% CI 2.88-3.50). For tramadol, the risks were doubled when CYP2D6-inhibiting drugs were used (OR, 2.19; 95% CI 1.84-2.60) and tripled without their use (OR, 3.04; 95% CI 2.82-3.27). The risks were about the same for oxycodone, morphine, fentanyl and buprenorphine irrespective of CYP2D6-inhibiting drug use. In newly initiated opioid therapies, drug-drug interactions from concomitant use of CYP2D6-inhibiting drugs are associated with a lower risk of fall-related injury for codeine and tramadol that undergo metabolism via CYP2D6, but not for other opioids. This article is protected by copyright. All rights reserved.