Mohammed Fessal looks at the evolving role of buprenorphine in medication-assisted treatment in the UK and how it has benefitted Change Grow Live’s service users Mohammed Fessal is chief pharmacist at Change Grow Live People seeking medication-assisted treatment (MAT) for management of opioid dependence have two primary options – methadone and buprenorphine. Maintenance treatment with methadone was commonplace in the late 1980s into the 1990s, with buprenorphine introduced as an additional option under the brand name Subutex in 1998 and later becoming available as a generic preparation. Since 2006, a combination product called Suboxone containing naloxone in addition to buprenorphine has also been available, which has a place in treatment where there is a risk that buprenorphine alone may be misused through intravenous or intranasal use. Both methadone and buprenorphine are effective in achieving positive outcomes in opioid-dependent individuals and are recommended in national guidelines, including the Drug misuse and dependence guidelines and NICE. Decisions relating to medication choice are made on a case-by-case basis, taking into account the person’s dependence history, their commitment to a long-term treatment plan, their personal medication preference and an evaluation of the risks and benefits of each drug. There is evidence that buprenorphine is associated with reduced risk of fatal overdose during treatment initiation – however there is also evidence that methadone is more effective at retaining people in treatment, and therefore may reduce risk in the long-term. Buprenorphine may be a preferable treatment option for those with children in the home as it presents less risk than methadone due to the different routes of administration. All but three of the 110 UK deaths in under-18s from ingestion of medications used in MAT between 2003 and 2013 were related to methadone. Buprenorphine has historically been available for use in substance misuse treatment solely as a sublingual tablet, and long-term experience with its use, cost-effectiveness, better safety profile and ready availability has made it the ideal choice to support thousands of individuals. Espranor In 2015, a new oral lyophilisate formulation of buprenorphine, Espranor, was launched. A formulation that dissolves on the tongue in 15 seconds, its intended benefits include service user convenience and reduced risk of diversion. In 2017, Change Grow Live conducted a pilot study in four services across the country with Espranor to evaluate its place in treatment, which demonstrated the following outcomes: \tEspranor was preferable for service users compared to sublingual buprenorphine as it dissolves more quickly on top of the tongue. This results in a faster administration time and reduced waiting time in the pharmacy for those receiving supervised consumption. \tPharmacy teams also preferred it to sublingual buprenorphine as it reduced the time they spent observing MAT doses, particularly in pharmacies where they observe a lot of people receiving MAT each day. \tAnecdotal evidence that Espranor was associated with reduced risk of misuse and diversion. In the UK, supply issues saw the market price of generic buprenorphine increase unexpectedly by more than 700 per cent in early 2018, putting unanticipated strain on prescribing budgets. The positive information gathered from the Espranor pilot combined with the impact of this price increase on already limited prescribing budgets – as well as unpredictability in supply of medicines not manufactured in the UK as a result of Brexit – meant that a decision was made to move people taking buprenorphine onto Espranor where appropriate to ensure continuity of treatment. The positive feedback about Espranor from service users, staff and other stakeholders provided assurance that this would be a positive adjustment for service users, and Espranor became the first-line buprenorphine treatment on the Change Grow Live formulary. Changing people from sublingual buprenorphine to Espranor In August 2018, just 2 per cent of clients were taking Espranor (a continuation of treatment from the pilot study) with all other people taking buprenorphine being prescribed the sublingual formulation (Figure 1). Those taking buprenorphine who were identified as suitable for moving over to Espranor were contacted individually and the change discussed with them. By April 2021, 78 per cent of people who were taking a buprenorphine formulation were prescribed Espranor (Figure 1). Of note is that 1,932 people remained on prescribed generic buprenorphine – Espranor is not for everyone because of licensed dose limitations, clinical parameters, side effects, religious beliefs or dietary reasons. A significant benefit of this national switch to Espranor prescribing was that it provided the opportunity to optimise MAT doses in line with the ‘Orange Book’ to a minimum of 12mg buprenorphine daily. Optimising the dose is a huge challenge for individuals who have in many cases been on the same dose for a long period – however with this medication switch the average dose increased from 9.7mg to 10mg between August 2018 and April 2021, and 44 per cent (3,886) of people taking a buprenorphine preparation are now on a dose of 12mg and above, compared with 41 per cent in August 2018. Bioavailability differences between generic buprenorphine and Espranor mean that the two medications are not directly interchangeable. However some studies suggest that Espranor is no more likely than equivalent doses of buprenorphine to cause respiratory depression – this is due to Espranor resulting in a higher buprenorphine to norbuprenorphine ratio, which is associated with a reduced risk of respiratory depression. With a safety first and learning- based approach, each person was reviewed individually, and their medication and dose adjusted as appropriate, with careful monitoring during the transition period. More than half of the people who changed from buprenorphine to Espranor remained on the same dose at the point of switching (Figure 2), and a large proportion of people remained on the dose they started Espranor on after 28 days of treatment (Figure 3). A larger proportion of people required a dose change within 28 days of starting Espranor treatment if they changed dose at the point of switching from sublingual buprenorphine, and if people needed to change dose after starting Espranor they were more likely to need a dose increase than decrease. The feedback received about Espranor from both service users and the people involved in delivering their treatment has generally been positive. \t‘It’s easier to take and tastes better .’ \t‘I really feel good being on Espranor. I feel this has really helped in me being able to fully stop illicit drug use.’ \t‘I wish I’d been given this years ago.’ For example, one individual has been able to reduce their medication dose from 16mg to 6mg since starting treatment with Espranor. This positive outcome has also been experienced by another person who requested to change from methadone to Espranor, and is since fully engaged in group sessions and proud that they are able to no longer use heroin which they have put down to the change in medication. An outreach worker reports that people find Espranor less intrusive when doses are being supervised, and that Espranor feels more dignified as people do not have to stand in the pharmacy for a long time waiting for the dose to dissolve. They also echo service user feedback that Espranor tastes better. Staff report reduced diversion risk as a key benefit, and they are more assured that people are taking their prescribed dose. Buvidal Drug development in recent years also led to the introduction of Buvidal in 2018, which is a prolonged-release buprenorphine injection administered either weekly or monthly. Buvidal may offer benefits such as reduced diversion or misuse risk, and prolonged partial agonist effect in the event of abrupt treatment cessation – for example, unexpected prison release or hospital discharge – which may lessen overdose risk. Other benefits may include convenience for the service user, and assurance of adherence to treatment for the prescriber. The safety of Buvidal is similar to oral buprenorphine with the exception of injection site reactions, although long-term safety data is limited to a 48-week long study. Change Grow Live has conducted a pilot study in two locations to evaluate Buvidal’s place in treatment and has introduced Buvidal across the country to further evaluate the benefits this treatment option has for supporting service users, many of whom may previously have struggled to engage and remain in treatment. The benefits and outcomes need to be weighed against the cost of this treatment, which is much higher than for the more ‘traditional’ MAT options. Treatment with buprenorphine in specific populations Prisons Historically, buprenorphine has not been routinely offered as an MAT option in prisons due to risk of diversion and misuse, and the length of time it takes to supervise sublingual buprenorphine until it has fully dissolved. Espranor may be an appropriate alternative due to its quicker dissolution time, and Buvidal may also have a place in custodial settings where there can be challenges around supervising medicines safely. Prisons in Scotland have offered Buvidal as an alternative to daily supervised MAT, and have found positive effects on wellbeing, reduced illicit drug use, and freeing up of healthcare resources. Pregnancy Buprenorphine is not licensed for use during pregnancy, and transfer onto buprenorphine during pregnancy is not recommended due to risk of precipitated withdrawal or inducing withdrawal in the foetus. However, if a woman is stabilised on buprenorphine and becomes pregnant, then therapy should be continued. Buprenorphine does not have adverse effects on pregnancy or neonatal outcomes, and there is some evidence that buprenorphine results in less severe neonatal abstinence syndrome (NAS) than methadone. Prescription and OTC dependence People seeking treatment for prescription or over-the-counter (OTC) opioid dependence may respond differently to treatment with buprenorphine (or methadone) than those dependent on heroin, and the evidence base to determine practice is weak. However, it is appropriate to suggest a period of substitution treatment with either buprenorphine or methadone, recognising the benefits and limitations of each. The evolving role of buprenorphine means people now have a wider range of formulations available to them, making it a suitable medication choice for many people who present for treatment and who previously may not have been an appropriate candidate for buprenorphine. This allows more people to be supported in a way that is optimal for them, and ultimately contributes to their successful treatment and recovery. This online article is intended for medical professionals and does not recommend one medication over another. If you are a member of the public, always speak to your GP or medical advisor who will recommend the best treatment options available to you.