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.

Comparison of Treatment Retention of Adults With Opioid Addiction Managed With Extended-Release Buprenorphine vs Daily Sublingual Buprenorphine-Naloxone at Time of Release From Jail.

Importance: Extended-release buprenorphine (XRB), a monthly injectable long-acting opioid use disorder (OUD) treatment, has not been studied for use in corrections facilities. Objective: To compare treatment retention following release from jail among adults receiving daily sublingual buprenorphine-naloxone (SLB) vs those receiving XRB. Design, Setting, and Participants: This open-label, randomized comparative effectiveness study included 52 incarcerated adults in New York City observed for 8 weeks postrelease between June 2019 and May 2020. Participants were soon-to-be-released volunteers from 1 men's and 1 women's jail facility who had OUDs already treated with SLB. Follow-up treatment was received at a primary care clinic in Manhattan. Data were analyzed between June 2020 and December 2020. Interventions: XRB treatment was offered prior to release and continued monthly through 8 weeks after release. SLB participants continued to receive daily directly observed in-jail SLB administration, were provided a 7-day SLB supply at jail release, and followed up at a designated clinic (or other preferred clinics). Main Outcomes and Measures: Buprenorphine treatment retention at 8 weeks postrelease. Results: A total of 52 participants were randomized 1:1 to XRB (26 participants) and SLB (26 participants). Participants had a mean (SD) age of 42.6 (10.0) years; 45 participants (87%) were men; and 40 (77%) primarily used heroin prior to incarceration. Most participants (30 [58%]) reported prior buprenorphine use; 18 (35%) reported active community buprenorphine treatment prior to jail admission. Twenty-one of 26 assigned to XRB received 1 or more XRB injection prior to release; 3 initiated XRB postrelease; and 2 did not receive XRB. Patients in the XRB arm had fewer jail medical visits compared with daily SLB medication administration (mean [SD] visits per day: XRB, 0.11 [0.03] vs SLB, 1.06 [0.08]). Community buprenorphine treatment retention at week 8 postrelease was 18 participants in the XRB group (69.2%) vs 9 in the SLB group (34.6%), and rates of opioid-negative urine tests were 72 of 130 tests in the XRB group (55.3%) and 50 of 130 tests in the SLB group (38.4%). There were no differences in rates of serious adverse events, no overdoses, and no deaths. Conclusions and Relevance: XRB was acceptable among patients currently receiving SLB, and patients had fewer in-jail clinic visits and increased community buprenorphine treatment retention when compared with standard daily SLB treatment. These results support wider use and further study of XRB as correctional and reentry OUD treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT03604159.

A cross-sectional survey on buprenorphine-naloxone practice and attitudes in 22 Canadian emergency physician groups: a cross-sectional survey.

BACKGROUND: Buprenorphine-naloxone (BUP) initiation in emergency departments improves follow-up and survival among patients with opioid use disorder. We aimed to assess self-reported BUP-related practices and attitudes among emergency physicians. METHODS: We designed a cross-sectional physician survey by adapting a validated questionnaire on opioid harm reduction practices, attitudes and barriers. We recruited physician leads from 6 Canadian provinces to administer surveys to the staff physicians in their emergency department groups between December 2018 and November 2019. We included academic and community non-locum emergency department staff physicians. We excluded responses from emergency department groups with response rates less than 50% to minimize nonresponse bias. Primary (BUP prescribing practices) and secondary (willingness and attitudes) outcomes were analyzed using descriptive statistics. RESULTS: After excluding 1 group for low response (9/26 physicians), 652 of 798 (81.7%) physicians responded from 22 groups serving 34 emergency departments. Among respondents, 64.1% (95% confidence interval [CI] 60.4%-67.8%, emergency department group range 7.1%-100.0%) had prescribed BUP at least once in their career, 38.4% had prescribed it for home initiation and 24.8% prescribed it at least once a month. Overall, 68.9% (95% CI 65.3%-72.4%, emergency department group range 24.1%-97.6%) were willing to administer BUP, 64.2% felt it was a major responsibility and 37.1% felt they understood people who use drugs. Respondents most frequently rated lack of adequate training (58.2%) and lack of time (55.2%) as very important barriers to BUP initiation. INTERPRETATION: Two-thirds of the emergency physicians surveyed prescribed BUP, although only one-quarter did so regularly and one-third prescribed it for home initiation; wide variation between emergency department groups existed. Strategies to increase BUP initiation must address physicians' lack of time and training for BUP initiation and improve their understanding of people who use drugs.

Sublingual Buprenorphine-Naloxone Compared With Injection Naltrexone for Opioid Use Disorder: Potential Utility of Patient Characteristics in Guiding Choice of Treatment.

OBJECTIVE: Sublingual buprenorphine-naloxone and extended-release injection naltrexone are effective treatments, with distinct mechanisms, for opioid use disorder. The authors examined whether patients' demographic and clinical characteristics were associated with better response to one medication or the other. METHODS: In a multisite 24-week randomized comparative-effectiveness trial of assignment to buprenorphine-naloxone (N=287) compared with extended-release naltrexone (N=283) comprising inpatients planning to initiate medication treatment for opioid use disorder, 50 demographic and clinical characteristics were examined as moderators of the effect of medication assignment on relapse to regular opioid use and failure to initiate medication. Moderator-by-medication interactions were estimated using logistic regression with correction for multiple testing. RESULTS: In the intent-to-treat sample, patients who reported being homeless had a lower relapse rate if they were assigned to receive extended-release naltrexone (51.6%) compared with buprenorphine-naloxone (70.4%) (odds ratio=0.45, 95% CI=0.22, 0.90); patients who were not homeless had a higher relapse rate if they were assigned to extended-release naltrexone (70.9%) compared with buprenorphine-naloxone (53.1%) (odds ratio=2.15, 95% CI=1.44, 3.21). In the subsample of patients who initiated medication, the interaction was not significant, with a similar pattern of lower relapse with extended-release naltrexone (41.4%) compared with buprenorphine (68.6%) among homeless patients (odds ratio=0.32, 95% CI=0.15, 0.68) but less difference among those not homeless (extended-release naltrexone, 57.2%; buprenorphine, 52.0%; odds ratio=1.24, 95% CI=0.80, 1.90). For failure to initiate medication, moderators were stated preference for medication (failure was less likely if the patient was assigned to the medication preferred), parole and probation status (fewer failures with extended-release naltrexone for those on parole or probation), and presence of pain and timing of randomization (more failure with extended-release naltrexone for patients endorsing moderate to severe pain and randomized early while still undergoing medically managed withdrawal). CONCLUSIONS: Among patients with opioid use disorder admitted to inpatient treatment, homelessness, parole and probation status, medication preference, and factors likely to influence tolerability of medication initiation may be important in matching patients to buprenorphine or extended-release naltrexone.

Buprenorphine Microdose Induction for the Management of Prescription Opioid Dependence.

Prescription opioid dependence remains a major source of morbidity and mortality in the United States. Patients previously on high-dose opioids may poorly tolerate opioid tapers. Current guidelines support the use of buprenorphine therapy in opioid-tapering protocols, even among patients without a diagnosis of opioid use disorder. Buprenorphine microinduction protocols can be used to transition patients to buprenorphine therapy without opioid withdrawal. From November 2019 to April 2020, we transitioned 8 patients on high-dose prescribed opioids for pain to sublingual buprenorphine-naloxone using a microdose protocol without any evidence of precipitated withdrawal. Six of these patients remain on buprenorphine-naloxone and report improved analgesia. Because of its simplicity, the buprenorphine microinduction protocol can be easily adapted for telemedicine and may help to prevent unnecessary clinic visits and opioid-related admissions in the setting of social distancing regulations during the coronavirus 2019 pandemic.

Comparing rapid micro-induction and standard induction of buprenorphine/naloxone for treatment of opioid use disorder: protocol for an open-label, parallel-group, superiority, randomized controlled trial.

BACKGROUND: Buprenorphine/naloxone (Suboxone) is a current first-line treatment for opioid use disorder (OUD). The standard induction method of buprenorphine/naloxone requires patients to be abstinent from opioids and therefore experience withdrawal symptoms prior to induction, which can be a barrier in starting treatment. Rapid micro-induction (micro-dosing) involves the administration of small, frequent does of buprenorphine/naloxone and removes the need for a period of withdrawal prior to the start of treatment. This study aims to compare the effectiveness and safety of rapid micro-induction versus standard induction of buprenorphine/naloxone in patients with OUD. METHODS: This is a randomized, open-label, two-arm, superiority, controlled trial comparing the safety and effectiveness of rapid micro-induction versus standard induction of buprenorphine/naloxone for the treatment of OUD. A total of 50 participants with OUD will be randomized at one Canadian hospital. The primary outcome is the completion of buprenorphine/naloxone induction with low levels of withdrawal. Secondary outcomes are treatment retention, illicit drug use, self-reported drug use behaviour, craving, pain, physical health, safety, and client satisfaction. DISCUSSION: This is the first randomized controlled trial to compare the effectiveness and safety of rapid micro-induction versus standard induction of buprenorphine/naloxone. This study will thereby generate evidence for a novel induction method which eliminates substantial barriers to the use of buprenorphine/naloxone in the midst of the ongoing opioid crisis. Trial registration ClinicalTrials.gov, NCT04234191; date of registration: January 21, 2020; https://clinicaltrials.gov/ct2/show/NCT04234191.

Does XR injectable naltrexone prevent relapse as effectively as daily sublingual buprenorphine-naloxone?

YES. MONTHLY EXTENDED-RELEASE INJECTABLE NALTREXONE (XR-NTX) TREATS OPIOID USE DISORDER AS EFFECTIVELY AS DAILY SUBLINGUAL BUPRENORPHINE-NALOXONE (BUP-NX) WITHOUT CAUSING ANY INCREASE IN SERIOUS ADVERSE EVENTS OR FATAL OVERDOSES. (STRENGTH OF RECOMMENDATION: A, 2 GOOD-QUALITY RCTS).

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.

Use of a novel prescribing approach for the treatment of opioid use disorder: Buprenorphine/naloxone micro-dosing - a case series.

INTRODUCTION AND AIMS: Buprenorphine/naloxone is an evidence-based treatment for opioid use disorder, but an identified limitation is the period of required opioid abstinence prior to induction on the medication. 'Micro-dosing', or using incrementally increasing doses of buprenorphine/naloxone over time, may be a way to overcome this challenge as it can be done in parallel with the ongoing use of other opioids (either illicit or prescribed). DESIGN AND METHODS: A retrospective case series (January to December 2018) was completed of seven participants who underwent buprenorphine/naloxone induction using micro-dosing at two outpatient addiction clinics in Vancouver, Canada. RESULTS: Seven participants completed a 7-day buprenorphine/naloxone micro-dosing protocol. Prior to and during the induction, one participant was prescribed methadone, three were prescribed slow release oral morphine and three used only illicit fentanyl. Participants were prescribed sublingual buprenorphine/naloxone: 0.5 mg once daily (day 1), 0.5 mg twice daily (BID; day 2), 1 mg BID (day 3), 2 mg BID (day 4), 3 mg BID (day 5), 4 mg BID (day 6) and 12 mg once daily (day 7). On day 7, all prescribed or illicit full opioid agonists were discontinued. Buprenorphine/naloxone was subsequently titrated to a daily dose of between 12 and 32 mg. All patients reported success with buprenorphine/naloxone induction with no precipitated withdrawal. DISCUSSION AND CONCLUSIONS: Buprenorphine/naloxone micro-dosing may offer a promising alternative approach for successful induction for individuals with opioid use disorder who desire treatment with buprenorphine/naloxone, and further research to determine effectiveness is warranted.

Towards a common metric for assessing heroin-dependent patient satisfaction with medications: Testing methadone and buprenorphine-naloxone.

BACKGROUND: Patient satisfaction with methadone or buprenorphine-naloxone can be multidimensionally and specifically assessed by using, respectively, the Scale to Assess Satisfaction with Medications for Addiction Treatment-Methadone for Heroin addiction (SASMAT-METHER) or the SASMAT-Buprenorphine-Naloxone for Heroin addiction (SASMAT-BUNHER). The factor structures of the SASMAT-METHER and SASMAT-BUNHER show substantial commonalities. The objective of the present study is to evaluate the replicability of the SASMAT-METHER factor structure using data from the SASMAT-BUNHER development study in order to obtain an instrument that can be used to compare patient satisfaction with methadone vs. buprenorphine-naloxone. METHOD: Secondary analysis of SASMAT-BUNHER data provided by 205 participants in the original validation study of that scale (Pérez de los Cobos et al., 2018). Using the SASMAT-METHER component solution (17 items, 3 factors) as the target structure, a principal component analysis was performed on the data set comprised of the corresponding 17 SASMAT-BUNHER items using an oblique semi-specified Procrustean rotation. Additionally, Tucker congruence coefficients were computed to examine the correspondence between the two solutions. RESULT: The factor structures of SASMAT-METHER and the 17-item version of the SASMAT-BUNHER can be considered equal given that the overall Tucker's congruence coefficient of factorial similarity was 0.972, with individual component congruencies ranging from 0.960 to 0.995. CONCLUSIONS: The SASMAT-METHER component solution can serve as a single common tool to compare methadone vs. buprenorphine-naloxone in terms of patient satisfaction. This finding supports the feasibility of using a common metric to specifically assess satisfaction with medications to treat heroin dependence.

A Case Report: Rapid Micro-Induction of Buprenorphine/Naloxone to Administer Buprenorphine Extended-Release in an Adolescent With Severe Opioid Use Disorder.

BACKGROUND AND OBJECTIVES: Buprenorphine extended-release (BUP-XR) is a monthly injectable form of opioid agonist therapy. Before its administration, a minimum 7-day induction period with a transmucosal buprenorphine-containing product is recommended. METHODS: Case report (n = 1). RESULTS: A 16-year-old female with active, severe opioid use disorder (OUD) and stimulant use disorder, hepatitis C virus, co-occurring mental health disorders, and complex social stressors had five recent overdoses requiring naloxone. She had previously been treated with methadone and several trials of sublingual buprenorphine/naloxone, but would quickly discontinue the treatment. Using a rapid micro-induction protocol, buprenorphine/naloxone was administered for 3 days. On day 4, 300 mg BUP-XR was administered subcutaneously. Minimal withdrawal symptoms occurred, despite recent fentanyl use. DISCUSSION AND CONCLUSIONS: A rapid sublingual buprenorphine/naloxone micro-induction was successfully used to initiate BUP-XR, thereby eliminating the abstinence period prior to buprenorphine/naloxone administration, shortening the induction period, and minimizing withdrawal. SCIENTIFIC SIGNIFICANCE: This is the first reported case of using rapid micro-induction as a bridge to initiate BUP-XR. By reducing the length of induction to 4 days and minimizing withdrawal, this induction method can make BUP-XR more accessible to patients who would otherwise refuse the medication due to concerns of enduring withdrawal. (Am J Addict 2020;29:531-535).

Rapid Induction Therapy for Opioid-Use Disorder Using Buprenorphine Transdermal Patch: A Case Series.

INTRODUCTION: Opioid dependency is a major epidemiologic problem with profound morbidity and mortality. Despite the availability of effective treatments, there are often overwhelming barriers to those treatments. CASE PRESENTATIONS: We present a case series involving a novel approach to the induction phase of buprenorphine or buprenorphine-naloxone therapy using transdermal buprenorphine. This approach has been demonstrated in inpatient settings but has not been widely explored in the outpatient setting. We demonstrated that a range of patients, from the highly medically complex to relatively straightforward cases, benefited from this approach. DISCUSSION: We believe that this approach can be used in a wide range of patients to transition from opioid use to buprenorphine therapy without the patient having to experience withdrawal or wait to start treatment. This should reduce the risk of lack of return for follow-up as well as decrease the dropout rate caused by patients being unable to tolerate withdrawal symptoms.

Transitioning a patient from injectable opioid agonist therapy to sublingual buprenorphine/naloxone for the treatment of opioid use disorder using a microdosing approach.

In the wake of North America's opioid crisis, access to evidence-based treatment for opioid use disorder (OUD) is of critical importance. While buprenorphine/naloxone and methadone are currently indicated as first-line medications for the treatment of OUD, there are a proportion of individuals who do not benefit from these therapies. Recent Canadian guidelines suggest the use of alternate therapies, including slow-release oral morphine or injectable opioid agonist therapy (iOAT) for individuals unsuccessful with either methadone or buprenorphine/naloxone. While the guidelines highlight the need to intensify OUD treatment as disease severity increases, equally important is the consideration for deintensification of treatment (eg, from iOAT to an oral opioid agonist treatment (OAT) option) following successful stabilisation. Literature addressing how best to accomplish this, however, is currently lacking. Accordingly, the case presented here describes a patient that successfully transitions from iOAT to oral buprenorphine/naloxone using a novel induction approach termed microdosing.

Case report: Successful induction of buprenorphine/naloxone using a microdosing schedule and assertive outreach.

BACKGROUND: The requirement for moderate withdrawal prior to initiation can be a barrier to buprenorphine/naloxone induction. CASE PRESENTATION: We aimed to use a microdosing regimen to initiate regular dosing of buprenorphine/naloxone in a high-risk patient with a history of failed initiations due, in part, to withdrawal symptoms. Using an assertive outreach model and a buprenorphine/naloxone microdosing schedule, we initiated treatment of an individual's opioid use disorder. There was a successful buprenorphine/naloxone microdosing induction as the team reached a therapeutic dose of buprenorphine/naloxone. Including the induction period, the medication was used consistently for 4 weeks. CONCLUSIONS: A microdosing schedule can be used to induce a patient onto buprenorphine/naloxone with no apparent withdrawal; gradually reducing illicit substance use. This case report builds on previous literature, highlighting ways to minimize barriers to induction of buprenorphine/naloxone, using a microdosing schedule and assertive outreach. Given the safety profile of buprenorphine and its potential to be a lifesaving intervention, a larger study of microdosing is indicated.

Rapid Induction of Buprenorphine/Naloxone for Chronic Pain Using a Microdosing Regimen: A Case Report.

Buprenorphine is an effective treatment for chronic pain and may reduce opioid-induced hyperalgesia. However, its pharmacological properties make its induction challenging, time-consuming, and can precipitate opioid withdrawal. We present the case of a 66-year-old woman with inadequately controlled postoperative pain despite escalating doses of oxycodone and methadone, who was successfully transitioned to buprenorphine/naloxone using a rapid microinduction technique without precipitating opioid withdrawal. Rapid induction provides an alternative method for transitioning patients from other opioids to buprenorphine/naloxone and facilitates transition of patients with chronic pain to buprenorphine therapy within a shorter window compared to currently existing protocols.

Longitudinal analysis of HIV-risk behaviors of participants in a randomized trial of prison-initiated buprenorphine.

BACKGROUND: It has been estimated that approximately 15% of people who are incarcerated in the US have histories of opioid use disorder. Relapse to opioid use after release from prison poses a serious risk of HIV infection. Prison-initiated buprenorphine may help to reduce HIV infection given the association between opioid use and HIV-risk behaviors. METHODS: The present study is a secondary analysis of longitudinal data gathered from a randomized controlled trial of buprenorphine-naloxone for people who were incarcerated (N = 211) between 2008 and 2012. It compares the impact of assignment to initiate buprenorphine in prison (N = 106 randomized, N = 104 analyzed) versus in the community (N = 107 randomized, N = 107 analyzed) and whether or not participants entered community treatment on the frequency of HIV-risk behaviors in the 12 months following release from prison. Data were analyzed hierarchically and for each outcome variable, a multilevel, over-dispersed Poisson model was fit to the data. Outcome variables were the number of times the following behaviors occurred in the last 30 days: (1) having sex without a condom (2) injecting drugs (3) using unsterilized needles, and (4) sharing injection paraphernalia. RESULTS: Participants assigned to begin buprenorphine in the community experienced a greater decrease in injection drug use over time compared to participants assigned to begin buprenorphine in prison. There were no significant associations between treatment assignment or community treatment entry and instances of having sex without a condom, sharing injection paraphernalia, or using unsterilized needles. CONCLUSIONS: Overall, the present study did not find support for the initiation of buprenorphine in prison (as opposed to the community) as a means to reduce incidences of HIV-risk behaviors. Avenues for future research in the nexus of HIV-risk reduction, criminal justice, and pharmacotherapy are discussed. Trial registration This study was supported by the National Institute on Drug Abuse (NIDA), Buprenorphine for Prisoners (PI: Kinlock; R01DA021579). ClinicalTrials.gov identifier: NCT00574067.