Dental adverse effects of sublingual buprenorphine and naloxone.

Overview of: Etminan M, Rezaeianzadeh R, Kezouh A, et al. Association between sublingual buprenorphine-naloxone exposure and dental disease. JAMA. 2022;328:2269-71.

Weight change among patients engaged in medication treatment for opioid use disorder: a scoping review.

Background: Medication treatment for opioid use disorder (MOUD) is an instrumental tool in combatting opioid use and overdose. Excess weight gain associated with MOUD initiation is a potential barrier that is not well understood.Objectives: Conduct a scoping review of available studies investigating the effect of MOUD on weight.Methods: Included studies consisted of adults taking any type of MOUD (e.g. methadone, buprenorphine/naloxone, naltrexone) with data on weight or body mass index for at least two time points. Evidence was synthesized using qualitative and descriptive approaches, and predictors of weight gain including demographics, comorbid substance use, and medication dose were examined.Results: Twenty-one unique studies were identified. Most studies were uncontrolled cohort studies or retrospective chart reviews testing the association between methadone and weight gain (n = 16). Studies examining 6 months of methadone treatment reported weight gain ranging from 4.2 to 23.4 pounds. Women appear to gain more weight from methadone than men, while patients using cocaine may gain less. Racial and ethnic disparities were largely unexamined. Only three case reports and two nonrandomized studies examined the effects of either buprenorphine/naloxone or naltrexone, and potential associations with weight gain were not clear.Conclusion: The use of methadone as an MOUD appears to be associated with mild to moderate weight gain. In contrast, there is little data supporting or refuting weight gain with buprenorphine/naloxone or naltrexone. Providers should discuss the potential risk for weight gain with patients as well as prevention and intervention methods for excess weight gain.

Association Between Sublingual Buprenorphine-Naloxone Exposure and Dental Disease.

This study examines the association of sublingual buprenorphine/naloxone and dental adverse events using the IQVIA health claims database.

Buprenorphine/naloxone (Suboxone®) withdrawal may facilitate antipsychotic-induced priapism. A case report.

INTRODUCTION: Priapism is defined as a prolonged penile erection in absence of sexual arousal, leading also to serious sexual and urological problems such as erectile dysfunction and penile fibrosis. Amongst many different etiologies, priapism may be caused by a wide range of antipsychotic medications, mainly due to the α1-adrenergic receptor antagonism. On the other hand, only a couple of cases of opioid compounds have been linked to the onset of priapism, with evidence coming only from methadone and buprenorphine. Here we describe the case of a patient treated with antipsychotics who developed priapism four times following rapid discontinuation of buprenorphine/naloxone (Suboxone®). CASE PRESENTATION: S.C. is a 30-year-old Caucasian man suffering from chronic buprenorphine/naloxone (Suboxone®) abuse, borderline personality disorder, antisocial traits, and multiple suicide attempts. During the acute and the first part of post-acute Suboxone® withdrawal, four episodes of priapism developed while he was treated with clotiapine, clozapine, and chlorpromazine. However, after the last episode of priapism, despite he was either on haloperidol or zuclopenthixol and chlorpromazine, no other urological event occurred during the following 6 months of observation. CONCLUSIONS: As opioids may have dampened the patient's sexual function due to chronic consumption, a rapid drug suspension coupled with an antipsychotic therapy might have created the conditions to facilitate the occurrence of close clustered priapism events.

Prescribing the Buprenorphine Monoproduct for Adverse Effects of Buprenorphine-Naloxone.

Buprenorphine-naloxone (BNX) reduces the risk of mortality from untreated opioid use disorder by 50% or more. However, adverse effects of BNX can be a cause of inconsistent use or discontinuation. The buprenorphine monoproduct (BUP) is effective and is sometimes tolerated better, but practice guidelines and insurance restrictions discourage its prescription due to concerns about diversion and injection. An idiopathic reaction of bilateral flank pain reported by three patients is used as an example to show how to assess the success of a BUP trial. Sublingual absorption of naloxone is discussed as a potential cause of adverse effects of BNX in sensitive individuals. Issues in clinical decision-making are presented to help prescribers assess the risk-benefit ratio of a BUP trial for the individual patient, the prescriber, and society. This commentary may serve as a stimulus for changes in practice guidelines and insurance coverage policies to allow greater flexibility in the prescribing of BUP.

Comparison of naltrexone implant and oral buprenorphine-naloxone in the treatment of opiate use disorder.

OBJECTIVE: We aimed to compare the effectiveness of extended-release naltrexone (XR-NTX) implant and sublingual buprenorphine-naloxone (BUP-NX) in relapse prevention in opiate use disorder (OUD). METHODS: Medical records of 400 patients who were treated for OUD between 2016 and 2020 were retrospectively evaluated concerning sociodemographic and clinical characteristics and abstinence duration with either BUP-NX (192 patients) or XR-NTX (208 patients) as maintenance treatments. RESULTS: The median age of patients using BUP-NX was 25.00, and the median age of patients using XR-NTX was 25.50 (p = .785). The ratio of female patients in the BUP-NX group and the XR-NTX group was 7.3% (n = 14) and 6.7% (n = 14), respectively. A significantly higher abstinence time was observed in the BUP-NX group (median = 4 months) than in the XR-NTX group (median = 3 months) (p = .015). Liver function tests were within the normal ranges at the three time points, which were just before the beginning and in the first and third months of treatment. CONCLUSIONS: These findings suggest that BUP-NX might be more effective than XR-NTX in preventing relapse in OUD and both drugs are safe for the liver. Prospective randomized studies are needed to replicate our results.

Methadone and suboxone® mentions on twitter: thematic and sentiment analysis.

BACKGROUND: According to the latest medical evidence, Methadone and buprenorphine-naloxone (Suboxone®) are effective treatments for opioid use disorder (OUD). While the evidence basis for the use of these medications is favorable, less is known about the perceptions of the general public about them. OBJECTIVE: This study aimed to use Twitter to assess the public perceptions about methadone and buprenorphine-naloxone, and to compare their discussion contents based on themes/topics, subthemes, and sentiment. METHODS: We conducted a descriptive analysis of a small and automatic analysis of a large volume of microposts ("tweets") that mentioned "methadone" or "suboxone". In the manual analysis, we categorized the tweets into themes and subthemes, as well as by sentiment and personal experience, and compared the information posted about these two medications. We performed automatic topic modeling and sentiment analysis over large volumes of posts and compared the outputs to those from the manual analyses. RESULTS: We manually analyzed 900 tweets, most of which related to access (15.3% for methadone; 14.3% for buprenorphine-naloxone), stigma (17.0%; 15.5%), and OUD treatment (12.8%; 15.6%). Only a small proportion of tweets (16.4% for Suboxone® and 9.3% for methadone) expressed positive sentiments about the medications, with few tweets describing personal experiences. Tweets mentioning both medications primarily discussed MOUD broadly, rather than comparing the two medications directly. Automatic topic modeling revealed topics from the larger dataset that corresponded closely to the manually identified themes, but sentiment analysis did not reveal any notable differences in chatter regarding the two medications. CONCLUSIONS: Twitter content about methadone and Suboxone® is similar, with the same major themes and similar sub-themes. Despite the proven effectiveness of these medications, there was little dialogue related to their benefits or efficacy in the treatment of OUD. Perceptions of these medications may contribute to their underutilization in combatting OUDs.

Use of Sublingual Nitrates for Management of Limb Ischemia Secondary to Inadvertent Intra-Arterial Buprenorphine/Naloxone (Suboxone®) Film Injection.

Multiple case reports have signaled a rise in buprenorphine abuse in the US, particularly among inmates. We present the case of limb ischemia secondary to accidental intra-arterial buprenorphine/naloxone film injection successfully treated with sublingual nitroglycerin. A 39-year-old man with history of intravenous drug use presented sudden severe left hand pain since three days prior to evaluation. Pain was preceded by self-injection of dissolved buprenorphine/naloxone sublingual film onto the affected arm. An arteriogram suggested severe vasoconstriction in the absence of frank thrombosis. Patient was initially treated with continuous heparin infusion and nifedipine. Forty-eight hours later, due to poor response, sublingual nitroglycerin was added to therapy. Digits regained color, sensation, and pain resolved within 15 minutes of administration of sublingual nitroglycerin. The presence of acute limb ischemia caused by prolonged vasospasm is a very rare complication. A normal angiogram should raise suspicion regarding vasospasm as the mechanism of ischemia, and prompt nitroglycerin therapy.

Therapeutic Drug Monitoring in Buprenorphine/Naloxone Treatment for Opioid Use Disorder: Clinical Feasibility and Optimizing Assay Precision.

INTRODUCTION: Compliance with sublingual buprenorphine/naloxone (SL-BUP/NX) is associated with higher abstinence from illicit opioid use. Therapeutic drug monitoring (TDM) has been recommended for adherence monitoring of buprenorphine (BUP) maintenance treatment for opioid use disorder (OUD), but to date there have been no reported clinical applications. In this TDM feasibility study, we investigated BUP assay precision in 15 adults with OUD who had been stabilized on buprenorphine/naloxone. METHODS: Using solid phase extraction, BUP recovery was contrasted at 100 mMol and 1 Molar of acetic acid wash solution. Precision was determined by applying the condition generating highest recovery using 0.2 ng/mL and 10 ng/mL standards. Four blood samples were drawn to examine the BUP peak and trough plasma concentrations, and BUP elimination rate was estimated. BUP recovery was examined again in a random sample and contrasted with the concentration predicted applying first-order kinetics. RESULTS: Higher BUP recovery was achieved with 1 Molar wash (94.3%; p=0.05). Precision ranged from 15-20%. The estimated limit of detection (LoD) and limit of quantitation (LoQ) were 0.02 and 0.069 ng/mL, respectively. BUP peak and trough concentrations were successfully examined, and BUP trough concentrations were replicated confirming steady state. BUP concentrations were predicted at a variance of -7.20% to 1.54 %. CONCLUSIONS: TDM for BUP maintenance treatment of OUD is feasible, and simple adjustment of the assay conditions enhances BUP recovery.

Overdose Risk and Client Characteristics Associated With the Injection of Buprenorphine at a Medically Supervised Injecting Center in Sydney, Australia.

Background: Buprenorphine and buprenorphine/naloxone (BNX) were developed to improve the safety profile of opioid substitution treatment (OST) and reduce diversion and injection, yet continue to be injected, despite the risk of harm. Previous studies examining injection of these substances have relied on self-reported injection and overdose. Using data from the Uniting Medically Supervised Injecting Center (MSIC) in Sydney, this study aimed to assess the overdose risk associated with the use of buprenorphine and BNX and identify factors associated with injecting. Methods: Client data routinely collected from MSIC, a drug consumption room where clients can legally inject drugs under supervision, was used. Odds ratios (OR) to assess the risk of overdose and their associated 95% confidence intervals (95%CI) were calculated and compared to other substances. Univariate analysis using χ-square and multivariate logistic regressions were used to determine characteristics associated with buprenorphine and BNX injection. Results: Data from 1,020,782 injections by 15,832 individuals were analyzed. Risk of overdose was low for buprenorphine compared to other substances (OR 0.16; 95%CI: 0.07-0.19) and no overdoses occurred when BNX was injected. Injection of both buprenorphine and BNX was associated with male gender, homelessness, no income/reliance upon government payments, and prior imprisonment. Conclusions: Buprenorphine and BNX continue to be injected, albeit in small numbers. This is the first study to report on injection and overdose risk using direct observation, and has confirmed the lower overdose risk. MSIC clients who inject buprenorphine and BNX tend to be marginalized and may benefit from targeted harm reduction measures.

No increased pain among opioid-dependent individuals treated with extended-release naltrexone or buprenorphine-naloxone: A 3-month randomized study and 9-month open-treatment follow-up study.

BACKGROUND AND OBJECTIVES: It is presently unclear whether extended-release naltrexone hydrochloride treatment induces pain or aggravates existing pain among individuals with opioid use disorders. We assessed changes in pain among individuals receiving treatment with either extended-release naltrexone hydrochloride or buprenorphine-naloxone hydrochloride. METHODS: This randomized prospective open-label clinical study included 143 participants (aged 18-60 years) with opioid dependencies, recruited from outpatient addiction clinics at five urban hospitals in Norway. After in-patient detoxification from opioids, patients were randomized to 12-week treatment with either long-acting naltrexone (380 mg intramuscularly injected every four weeks) or buprenorphine-naloxone (flexible 4-16 mg sublingual doses daily). This phase was followed by a 9-month open-treatment study with the participant's choice of either naltrexone or buprenorphine-naloxone. Changes in pain were assessed every 4 weeks using the Norwegian Short-Form of McGill Pain Questionnaire. RESULTS: Throughout the study period, we found no increase in mean sensory pain, affective pain, or present pain intensity on the McGill Pain Questionnaire, in either treatment group, including the subgroups of participants with chronic pain. Participants who switched from buprenorphine-naloxone to extended-release naltrexone treatment after week 12 reported no increase in pain intensity during longer-term treatment. Women experienced significantly more affective pain symptoms than men (p = .01). DISCUSSION AND CONCLUSIONS: Among individuals with opioid use disorder, switching from daily opioid use to long-acting naltrexone did not induce pain, or aggravate mild-to-moderate chronic pain. SCIENTIFIC SIGNIFICANCE: In opioid-dependent individuals, mild-to-moderate chronic pain was not influenced by opioid agonist or antagonist treatment. TRIAL REGISTRATION: Clinicaltrials.gov #NCT01717963, first registered: Oct 28, 2012. Protocol version # 3C, June 12th 2012. (Am J Addict 2018;XX:1-9).

The effects of buprenorphine/naloxone maintenance treatment on sexual dysfunction, sleep and weight in opioid use disorder patients.

Opioid use disorder is a growing social problem. Different agents are used in the treatment of this disorder. One of these agents is buprenorphine / naloxone combination that includes buprenorphine and naloxone in a ratio of 4:1. Although used successfully in opiate maintenance treatment, buprenorphine / naloxone could have some side effects that might affect the treatment. The present study aimed to examine the effects of buprenorphine /naloxone opiate maintenance treatment on sexual dysfunction, sleep and bodyweight in patients diagnosed with opioid use disorder and to draw the attention of clinicians to the adverse effects of the treatment. The study group included 107 inpatients who were diagnosed based on The Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) and received treatment for opioid use disorder. On admission to the hospital and at the end of the 4th month, a Sociodemographic and Clinical Data Form, the Pittsburgh Sleep Quality Index (PSQI) and the Arizona Sexual Life Scale (ASEX) were applied to all patients. Patients were weighed, and their weight was recorded on the day of admission to the hospital and at the end of the 4th month. The data recorded at the beginning and during the treatment of the same group were compared. The mean age of 107 patients was 24.55 ±â€¯4.27. Overall ASEX scores were 12.98 ±â€¯4.33 before treatment and 15.03 ±â€¯6.61 at 4 months (p < 0.001). The mean patient bodyweight was 63.86 ±â€¯8.78 kg before the treatment and 68.49 ±â€¯8.65 kg at the 4th month of the treatment (p < 0.001). Total PSQI scores were 8.87 ±â€¯3.53 before the treatment and 6.85 ±â€¯3.29 at the 4th month of the treatment (p < 0.001). The study findings demonstrated that after 4 months of buprenorphine /naloxone treatment, total ASEX scores and bodyweight of the patients increased and total PSQI scores decreased. These results demonstrated that sexual problems and bodyweight of the patients increased after the buprenorphine /naloxone treatment and sleep-related problems decreased, albeit still prevalent. These potential side effects should be included with other information about buprenorphine that is given to patients as they may influence interest in starting or continuing treatment.

Intravenous Misuse of Methadone, Buprenorphine and Buprenorphine-Naloxone in Patients Under Opioid Maintenance Treatment: A Cross-Sectional Multicentre Study.

BACKGROUND: The act of intravenous misuse is common in patients under opioid maintenance treatment (OMT), but information on associated factors is still limited. OBJECTIVES: To explore factors associated with (a) intravenous OMT misuse, (b) repeated misuse, (c) emergency room (ER) admission, (d) misuse of different OMT types and (e) concurrent benzodiazepine misuse. METHODS: We recruited 3,620 patients in 27 addiction units in Italy and collected data on the self-reported rate of intravenous injection of methadone (MET), buprenorphine (BUP), BUP-naloxone (NLX), OMT dosage and type, experience of and reason for misuse, concurrent intravenous benzodiazepine misuse, pattern of -misuse in relation to admission to the addiction unit and ER -admissions because of misuse. According to inclusion/exclusion criteria, 2,585 patients were included. RESULTS: Intravenous misuse of OMT substances was found in 28% of patients with no difference between OMT types and was associated with gender, age, type of previous opioid abuse and intravenous benzodiazepine misuse. Repeated OMT misuse was reported by 20% (i.e., 71% of misusers) of patients and was associated with positive OMT misuse experience and intravenous benzodiazepine misuse. Admission to the ER because of misuse complications was reported by 34% of patients, this outcome being associated with gender, employment, type of previous opioid abuse and intravenous benzodiazepine misuse. OMT dosage was lower than the recommended maintenance dosage. CONCLUSIONS: We offered new information on factors associated with intravenous OMT misuse, repeated misuse and ER admission in Italian patients under OMT. Our data indicate that BUP-NLX misuse is not different from that of BUP or MET. Choosing the more expensive BUP-NLX over MET will likely not lead to the expected reduction of the risk of injection misuse of the OMT. Instead of prescribing new and expensive OMT formulations, addiction unit physicians and medical personnel should better focus on patient's features that are associated with a higher likelihood of misuse. Care should be paid to concurrent benzodiazepine and OMT misuse.

Treatment of opioid dependence with buprenorphine/naloxone sublingual tablets: A phase 3 randomized, double-blind, placebo-controlled trial.

INTRODUCTION: The purpose of the study is to evaluate the efficacy and safety of buprenorphine/naloxone sublingual tablets for the treatment of opioid dependence in Chinese adults. METHODS: This multicenter, double-blind, placebo-controlled study included four periods: induction (3-5 days), stabilization (7-21 days), randomization/treatment (6 weeks), and postmedication follow-up (1 week). A total of 442 participants with opioid dependence were enrolled; 260 were randomized to buprenorphine/naloxone or placebo. The primary outcome was retention in treatment, defined as the time from randomization to treatment completion or treatment failure. Secondary outcomes included maximum consecutive days of abstinence from opioids, self-reported craving and opioid withdrawal symptoms, and urine drug screen results. Safety assessments included adverse event reporting, electrocardiograms, clinical laboratory tests, vital signs, and prior/concomitant medications. RESULTS: The median treatment retention time (95% confidence internal) with buprenorphine/naloxone was 32 days (26-38) versus 6 days (5-8) for placebo, with a Cox hazard ratio of 0.28 (95% confidence interval, 0.21-0.38; P < 0.0001). The median maximum consecutive days of abstinence (95% confidence interval) was: buprenorphine/naloxone, 21 days (26-38); placebo, 5 days (5-8) with a Cox hazard ratio of 0.38 (95% confidence interval, 0.25-0.60; P < 0.0001). Withdrawal and craving symptoms were significantly milder with buprenorphine/naloxone versus placebo (P < 0.001). Urine drug screen results indicated significantly lower opioid usage in the buprenorphine/naloxone group compared with placebo (P < 0.001). The most commonly reported adverse events in the buprenorphine/naloxone group during treatment were aspartate aminotransferase increased and nasopharyngitis. DISCUSSION: Efficacy and safety results from this clinical trial support a positive benefit-risk ratio for buprenorphine/naloxone sublingual tablet use in the treatment of an opioid-dependent Chinese population.

The LASSO Program in Oslo: Harm Reduction Using Buprenorphine-Naloxone (Suboxone®) in a Low Threshold Setting.

BACKGROUND: This is a 6-year retrospective quality control study of the LASSO Program (Low Threshold Substitution Treatment in Oslo), using exclusively Suboxone® (buprenorphine-naloxone [BPNX]) in out-patient settings. Adequate abstinence prior to induction is necessary to avoid acute onset opioid withdrawal symptoms; thus, its use in low threshold settings is far less common than methadone. OBJECTIVES: The aim of this study was to determine if BPNX is a safe and feasible medication to use in a low threshold setting. METHODS: The analysis is based on daily supervised BPNX medication. The standardized induction regime started with 4-mg BPNX increasing by 4 mg daily until 16 mg, with individual adjustments based on clinical status. Treatment effect was evaluated by the number of medication induction attempts, treatment length and lag time between initial contact and medication start. Statistical computations were performed with SPSS®. RESULTS: There were 331 out of 394 registered patient inquires that started on BPNX. Two hundred fifty-three patients (76.4%) completed induction on first attempt with 95% Wilson score CIs of (0.716-0.807). The accumulated percentage increased to 85.2% during successive inductions. No significant association was found between lag time and (i) the number of days on medication during the first induction; or (ii) total treatment length. Patients had a median lag time of 5 days, remained in treatment a median of 52.0 days with an average of 3.9 inductions. There were no cases of severe precipitated withdrawal and only 2 cases of adverse reactions among the 1,293 inductions and 25,544 administered dosages. CONCLUSION: This study shows that BPNX is highly effective in treating marginalized heroin addicts in low threshold settings. Even during their first attempt, 76.4% completed induction. There were no cases of severe precipitated withdrawal. Prolonged lag time affected neither the length of first treatment nor the total treatment length. Individualized induction readiness approach and motivation were central to the above results.

Dissatisfaction with opioid maintenance treatment partly explains reported side effects of medications.

BACKGROUND: Drop-out is a core problem in opioid maintenance treatment (OMT), but patients' reactions to and acceptance of the various OMT medications are insufficiently investigated. In Norway, there has been vocal patient resistance to the newest medication, buprenorphine-naloxone (BNX), and complaints have focused on the side effect profile. There has been no comparison of patient satisfaction and side effects of the three most common OMT medications. AIM: To compare patient satisfaction with OMT and side effects of BNX, buprenorphine monopreparate (BUP), and methadone (MET) as reported by patients. METHODS: Data were drawn from a national peer-to-peer survey developed by a patient advocacy group. The survey engaged more than 1000 OMT patients, corresponding to one seventh of OMT patients in Norway. The associations between side effects, treatment satisfaction, and patient characteristics were tested in multinomial logistic regressions. RESULTS: High patient satisfaction with OMT overall was reported despite lower satisfaction with medication itself and widely prevalent side effects. Among each medication group, dissatisfaction with medications or OMT in general along with poor health status increased the relative risk ratio of reporting the heaviest side effect burden. MET users reported the highest side effect burden and BNX users the lightest, but BNX users were more dissatisfied with their medication. CONCLUSIONS: Side effects are a concern for nearly all OMT patients, and they do not appear to accumulate with age or length of treatment. BNX users' dissatisfaction with their medication is of particular concern, and expectations and preferences of medication may be influencing their dissatisfaction.

Treating women with opioid use disorder during pregnancy in Appalachia: Initial neonatal outcomes following buprenorphine + naloxone exposure.

BACKGROUND AND OBJECTIVES: Rising concerns regarding diversion and misuse of mono-buprenorphine for treatment of pregnant women with opioid use disorders have sparked interest in the use of buprenorphine + naloxone to reduce misuse and diversion rates. Examined the relationship of prenatal buprenorphine + naloxone exposure to neonatal outcomes. METHODS: This is a retrospective chart review of 26 mother infant dyads in comprehensive medication-assisted treatment with buprenorphine + naloxone during pregnancy. RESULTS: All neonatal birth outcome parameters were within normal ranges, albeit on the lower side of normal for gestational age and birth weight. Only 19% of neonates required morphine pharmacology for NAS. CONCLUSIONS: Use of buprenorphine + naloxone shows relative safety in pregnancy. SCIENTIFIC SIGNIFICANCE: These findings can help better guide prescribing practices for pregnant patients at risk for misuse or diversion of buprenorphine. (Am J Addict 2018;27:92-96).

Buprenorphine alone or with naloxone: Which is safer?

To address concerns regarding the intravenous diversion of buprenorphine, a combined buprenorphine-naloxone (BUP-NLX) preparation was developed. The aim of this study is to compare health outcomes in opioid dependent patients treated with BUP and BUP-NLX. All patients treated with BUP and/or BUP-NLX in Western Australia between 2001 and 2010 were included in the study ( N = 3455). Patients were identified via State prescribing records and matched against the State mortality, hospital, and emergency department records. Rates of health events were examined and compared using Cox Proportional Hazard Models and Generalized Estimating Equations. While on treatment there was no significant difference between mortality rates in the two groups, mortality rates following the cessation of treatment were significantly higher in patients treated with BUP-NLX (adjusted hazard ratio: 1.59). Rates of hospitalization were significantly elevated in BUP-NLX patients (adjusted odds ratio: 1.17) compared with BUP treated patients; however, rates of hospitalization with a skin/subcutaneous diagnosis were significantly lower in BUP-NLX treated patients (adjusted odds ratio: 0.65). Off-treatment rates of both all-cause hospital admissions (adjusted odds ratio: 1.53) and hospital admissions with an opioid poisoning diagnosis (adjusted odds ratio: 1.59) were significantly elevated in BUP-NLX treated patients compared with BUP treated patients. The addition of naloxone does not appear to improve the safety profile of buprenorphine.