Experiences and Preferences of Opioid-Use-Disorder Patients Who Switched from Brand to Generic Buprenorphine/Naloxone Films: A Case Series.

PURPOSE: Differences in the suppression of withdrawal symptoms have been observed in opioid-use-disorder (OUD) patients who were switched from Suboxone (the brand name of buprenorphine/naloxone sublingual films) to either 1 of 2 generic versions. These descriptive observations evidence the need to further assess the use of these generics and its impact on the adherence to and outcomes of OUD treatments. The objective of this case series was to describe patient and provider experiences, perceptions, and preferences when said patients were abruptly switched from Suboxone to one of the generic versions manufactured by Sandoz or Alvogen. PATIENTS AND METHODS: A retrospective chart review of 24 Suboxone-maintained OUD patients from a single clinic who were forced to switch to a generic was performed to collect withdrawal and craving symptoms that occurred after the switch, as well as toxicology results and changes in dose (documented by the provider). RESULTS: The medical records of 9 (37.5%) of the 24 patients showed that they were suffering from withdrawal symptoms and/or cravings, had had their doses adjusted, and/or had had a positive urine toxicology screen. All 9 subjects communicated a preference for the brand formulation over that of either of the generic versions; few expressed a preference for one generic formulation over the other. None of patients were able to switch back to the brand formulation, nor were any of them able to choose the generic that worked best for them. Insomnia, muscle pain, and gooseflesh skin were the most common withdrawal symptoms reported by the patients using the generics. Better outcomes were observed in patients who received a buprenorphine dose increase (2 mg) to suppress the withdrawal symptoms experienced while using the generics. CONCLUSION: Our study serves as a reference to prescribers regarding approaches (eg, a small dose adjustment) that may potentially encourage OUD treatment adherence and even improve outcomes in patients who appear to be decompensating after the brand-to-generic switch.

Pharmacokinetic Characterization and External Evaluation of a Quantitative Framework of Sublingual Buprenorphine in Patients with an Opioid Disorder in Puerto Rico.

BACKGROUND: The aim of this analysis was to characterize the pharmacokinetics (PK) of sublingual buprenorphine (BUP) and its metabolites (buprenorphine glucuronide; BUP-g, norbuprenorphine; Nor-BUP, and norbuprenorphine glucuronide; Nor-BUP-g) in opioid use disorder (OUD) patients in Puerto Rico (PR) as a first step of evidence-based BUP dosing strategies in this population. METHODS: BUP and metabolites concentrations were measured from 0 to 8 h after the administration of sublingual buprenorphine/naloxone films in 12 stable OUD subjects. RESULTS: PK non-compartmental characteristics showed considerable variability in parameters between the subjects over the 8-h sampling time (tmax = 1.5 ± 0.7 h, Co = 1.6 ± 1.4 ng/mL, Cmax= 7.1 ± 6 ng/mL, and AUC0-8h = 26.8 ± 17.8 h·ng/mL). Subjects had a significantly higher tendency towards CYP-mediated N-demethylation, with the AUC0-8h ratios of the molar concentrations of [Nor-BUP + Nor-BUP-g] to BUP being (3.4 ± 1.9) significantly higher compared with BUP-g to BUP (0.19 ± 0.2). A two-compartment population-PK model with linear absorption (ka = 2.54 h-1), distribution (k12= 2.34 h-1, k14 = 1.29 h-1), metabolism (k24 = 1.28 × 10-1 h-1, k23 = 6.43 × 10-2 h-1, k35 = 1.23 × 10-1 h-1, k45 = 8.73 × 10-1 h-1), and elimination (k30 = 3.81 × 10-3 h-1, k50 = 1.27 × 10-1 h-1) adequately described the time-course of BUP and its metabolites, which has been externally validated using published data. CONCLUSIONS: Although limited in sampling time and number of recruited subjects, this study presents specific BUP PK characteristics that evidenced the need for additional PK studies and subsequent modeling of the data for the development of evidence-based dosing approaches in Puerto Rico.

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.

Opioid agonist treatment and the process of injection drug use initiation.

BACKGROUND: Opioid agonist treatment (OAT) is an effective biomedical intervention to manage opioid use disorder among persons who inject drugs (PWID). Preliminary evidence suggests that OAT may also disrupt the social communicability of injection drug use (IDU) practices by established PWID. We therefore aim to investigate the association between OAT enrollment and initiating others into IDU among PWID in Vancouver, Canada. METHODS: Preventing Injecting by Modifying Existing Responses (PRIMER; NIDA DP2-DA040256-01) is a prospective multi-cohort study seeking to identify structural interventions that reduce the risk that PWID initiate others into IDU. The present analysis was conducted using data from a participating cohort of PWID in Vancouver, Canada, between December 2014 and May 2017. Multivariable logistic regression models were built to assess the association between reporting active (i.e., within the past six months) OAT enrollment and assisting others in injection initiation. A final model was determined using a manual stepwise approach whereby covariates were excluded if their removal altered the coefficient of interest by <5%. RESULTS: Participants (n = 1740) were predominantly male (62.3%); 35.1% reported daily injecting (n = 611); 860 (49.4%) reported active OAT enrollment, and 80 (4.6%) reported recently providing injection initiation assistance. In a multivariable model, participants who reported active OAT enrollment had significantly lower odds of recently providing injection initiation assistance (Adjusted Odds Ratio = 0.52, 95% Confidence Interval: 0.31-0.87, P = 0.01). CONCLUSION: Results suggest a protective association between OAT and the expansion of IDU practices among vulnerable populations, suggesting its potential use as 'addiction treatment as prevention.'