Elsevier

Drug and Alcohol Dependence

Volume 136, 1 March 2014, Pages 21-27
Drug and Alcohol Dependence

The diversion and injection of a buprenorphine-naloxone soluble film formulation

https://doi.org/10.1016/j.drugalcdep.2013.12.005Get rights and content

Abstract

Background

We compared the diversion and injection of a new formulation of buprenorphine, a buprenorphine-naloxone film product (BNX film), with buprenorphine-naloxone tablets (BNX tablets), mono-buprenorphine (BPN) and methadone (MET) in Australia.

Methods

Surveys were conducted with people who inject drugs regularly (PWID) (2004–2012) and opioid substitution treatment (OST) clients (2012, N = 543). Key outcome measures: the unsanctioned removal of supervised doses, diversion, injection, motivations, drug liking and street price. Levels of injection among PWID were adjusted for background availability of medication using sales data. Doses not taken as directed by OST clients were adjusted by total number of daily doses dispensed.

Results

Among out-of-treatment PWID, levels of injection for BNX film were comparable to those for MET and BNX tablet formulations, adjusting for background availability; BPN injecting levels were higher. Among OST clients, recent injecting of one's medication was similar among clients in all OST types; weekly or more frequent injection of prescribed doses was reported by fewer BNX film clients (3%; 95% CI: 1–6) than BPN clients (11%; 95% CI: 3–17), but at levels similar to those observed among MET and BNX tablet clients. The proportion of BNX film doses injected was lower than that for BPN and BNX tablets, and equivalent to that for MET. The majority of BNX film doses injected by OST clients were unsupervised doses, although some injection of supervised doses of BNX film did occur. The median price of all buprenorphine forms on the illicit market was the same.

Conclusions

Non-adherence and diversion of the BNX film formulation was similar to MET and BNX tablet formulations; BPN had higher levels of all indicators of non-adherence and diversion.

Introduction

Methadone (MET) and buprenorphine are “essential medicines” in the treatment of opioid dependence (World Health Organization). Opioid substitution therapy (OST) has been long-established in Australia: MET has been prescribed with public subsidy since the 1970s, mono-buprenorphine (BPN) tablets (marketed as Subutex®) since 2001 and buprenorphine-naloxone tablets (BNX tablets, marketed as Suboxone®) since 2006. In October 2011, a newer buprenorphine formulation was introduced with public subsidy–buprenorphine-naloxone sublingual film (BNX film, marketed as Suboxone® Film).

Minimising the extent of diversion and injection of the pharmaceutical opioids used in opioid substitution therapy (OST) reduces harms to the individual (such as injection-related injuries and diseases, and overdose) and protects the reputation and integrity of OST programmes. Reports of OST medication diversion and/or injection can undermine public and clinical support for OST. This may in turn limit future investment and development, and hinder efforts to make OST more attractive and accessible. Understanding the extent of medical and extra-medical use of these important medications is relevant to policy and practice and confidence in the treatment system.

From 2006 to 2008, post-marketing surveillance studies of the diversion and injection of BNX tablets were required in Australia by federal regulatory authorities; the methodology and findings of which have been detailed elsewhere (Larance et al., 2011). These studies found that levels of BNX tablet injection among people who inject drugs (PWID) were lower relative to BPN, but comparable to those for MET, adjusting for background availability; and among OST clients, fewer BNX tablet clients reported recently injecting their medication, than BPN and MET clients (Degenhardt et al., 2009, Larance et al., 2011).

More recently (2011), BNX film was introduced in Australia and further post-marketing surveillance studies have been conducted. The manufacturer information states that the benefits of BNX film are: it is dissolved faster than BNX tablets; it has a more favourable taste; and doses are individually wrapped, more child resistant and more portable (Reckitt Benckiser Inc., 2013). However, there has been little published research on the safety and efficacy of BNX film (Soyka, 2012). One randomised-controlled trial found that BNX film adheres to the sublingual mucosa more rapidly and dissolves more quickly than BNX tablets, particularly at high doses (Lintzeris et al., 2013). Given these characteristics, we hypothesised that buprenorphine-naloxone film may be more difficult to remove from mouth than BNX tablets, resulting in less removal of supervised doses from the dosing site and subsequent diversion or injection of supervised doses in comparison to BNX tablets.

This paper examines the uptake of BNX film in Australia and presents the findings of surveillance studies of the diversion and injection of MET, BPN, BNX tablets and BNX film conducted during 2012. Where possible, the 2012 data are compared to those collected in earlier post-marketing surveillance studies (Degenhardt et al., 2009, Larance et al., 2011).

Specifically, this paper seeks to answer the following questions: (1) Is there less diversion and injection of BNX film, compared to methadone, mono-buprenorphine and buprenorphine-naloxone tablets, among OST clients and out-of-treatment people who inject drugs (PWID)? (2) Are there additional benefits of BNX film in the context of supervised dosing, for example less unsanctioned removal of supervised doses from the dosing site, compared to MET, mono-buprenorphine and BNX tablets? and (3) Is there less demand for diverted BNX film, compared to MET, mono-buprenorphine and BNX tablets?

Section snippets

Sales data

Background availability of medications is important in post-marketing evaluations of abuse liability: the more widely available a medication is, the more opportunity there may be for extra-medical use and/or diversion (Dart, 2009, McCormick et al., 2009). National sales data for BPN, BNX tablets and BNX film were provided by IMS Health (IMS)/Reckitt Benckiser, who also provided commercially available data on sales of methadone liquid (including brand names Methadone syrup® and Biodone®). Sales

Uptake of BNX film in Australia

From 2005 to 2012, MET retained the largest OST market share in Australia (68% in 2012). There was a modest increase in overall market share of any form of buprenorphine as an OST (from 25% in 2005 to 32% in 2012). Since the introduction of BNX tablets and BNX film, BPN tablet sales have steadily declined (Fig. 1). From March, 2007 to March, 2012, BNX tablets accounted for the largest market share of total buprenorphine sales. From April, 2012, BNX film became the predominant form of

Discussion

Although one clinical trial has found BNX film formulation to have faster dissolution and rapid mucosal adhesion than the BNX tablet formulation (Lintzeris et al., 2013), there has been no published research to date examining whether the BNX film formulation offers advantages in terms of non-adherence and diversion in real life settings. This is the first published study to provide post-marketing surveillance data on the diversion and injection of BNX film, making direct comparisons with MET,

Role of funding source

These studies were funded by Reckitt Benckiser by way of an untied educational grant. This study's design, conduct and interpretation of findings are the work of the investigators. The funder played no role in the conception or writing of this paper.

Contributors

BL undertook the analyses and wrote the first draft of the paper. All authors contributed to the manuscript and approved the final version.

Conflict of interest

BL, LD and RPM have received untied educational grants from Reckitt Benckiser for the post-marketing surveillance of buprenorphine-naloxone tablets (2006–2008), the development of an opioid-related behaviour scale (2010). PD, NL and RA have also received untied educational grants from Reckitt Benckiser. All such studies’ design, conduct and interpretation of findings are the work of the investigators; Reckitt Benckiser had no role in these.

Acknowledgements

LD and RPM are supported by an Australian National Health and Medical Research Council (NHMRC) Principal Research Fellowships. PD is supported by an ARC Future Fellowship (FT100100321). The National Drug and Alcohol Research Centre at the University of NSW is supported by funding from the Australian Government under the Substance Misuse Prevention and Service Improvements Grants Fund. These studies would not have been possible without the generous participation of people who inject drugs and of

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