February 2021

Getting under your skin: revolution in opioid treatment

Former heroin user ‘Jon’ (not their real name) has the highest possible praise for long-acting injectable buprenorphine (LAIB), the new kid on the block when it comes to pharmacotherapy: “In many ways, it’s saved my life.”

His story tells us a lot about how long-acting injectable buprenorphine could change treatment for opioid use disorder as we know it in this country.

In April 2020 – just as the initial wave of COVID-19 cases were unfolding in Australia – Jon was among the first clients referred to a pop-up LAIB clinic funded by St Vincent’s Hospital Melbourne.

“The requirement for frequent attendance at a pharmacy to receive sublingual [under the tongue] buprenorphine increased risk and stigma when we were all being asked by governments to isolate, and the possibility of prescribers and pharmacies being closed due to illness or quarantine also raised concerns,” Associate Professor Yvonne Bonomo, Director of the hospital’s Department of Addiction Medicine, says.

“We’d had a little bit of experience with LAIB already, and from putting in our application to having our first patients through the clinic took four weeks.”

Funding, initially granted for six months, was later extended by another three.

“This year, because we had to wrap up at the end of January, we went through transitioning many of our 100 clients to GPs.”

Brave new Product

At the time of the clinic’s launch, LAIB was still relatively new to Australia, the first of two formulations having been approved by the Therapeutic Goods Administration only six months earlier.

Both proprietary brands – Buvidal (from Camurus in Sweden) and Sublocade (from Indivior in the US) – are recognised by the Pharmaceutical Benefits Scheme as a treatment for opioid use disorder and can be prescribed by any accredited medical/ nurse practitioner or non-accredited medical practitioner.

Set doses are delivered in pre-filled syringes for injecting under the skin (“subcutaneous” injection). Once inside the body, LAIB forms a small gel mass, or ‘depot’, from which buprenorphine is released gradually over about a week or a month, depending on the product.

For Jon, visiting the St Vincent’s clinic once a week was ideal. “I tried monthly Buvidal but felt isolated because I’d had to cut myself off from friends who probably weren’t the best influence so I had no connection to anyone. I’m still on the weekly injection but wanting now to move to the monthly because I’ve just started a new job.”

Buprenorphine’s benefits

Buprenorphine prevents opioids engaging fully with the body’s Mu receptors. Because these receptors are largely responsible for controlling sedation and the ability to feel pain (analgesia), limiting opioids’ influence creates a ‘ceiling’ that stops overdose occurring, even when a large amount of an opioid-based substance is taken.

A person with sufficient buprenorphine in their system also does not experience the anticipated effects of a drug such as heroin or oxycontin. They are discouraged by this ‘blockade’ from using, and at the same time protected against the usual symptoms of opioid withdrawal.

It is estimated that 0.1–1 per cent of adult Australians have opioid use disorder (OUD) and 10–15 per cent of patients prescribed long-term opioid medication develop a dependence. Buprenorphine is used in Australia to treat OUD as part of medication-assisted treatment for opioid use disorder (MAT or MATOD) or pharmacotherapy programs.

This has been a major game-changer.

Professor Nicholas Lintzeris

Building momentum

In the not-too-distant future, LAIB will be Australia’s single biggest form of opioid pharmacotherapy, according to President of the Chapter of Addiction Medicine, Royal Australasian College of Physicians (RACP), Professor Nicholas Lintzeris.

“We’re on track to half of all opioid treatment in this country being depot,” Nick says.“Once the pandemic was declared, in NSW those services that in February 2020 had already been using depot rapidly escalated the amount they used.

“It’s a perfect response to COVID: rock up once a month, get your jab and go. Conversely, for any that weren’t ready, it wasn’t the time to learn new tricks in those first couple of months.”

Nick says responding to the virus monopolised the focus of some health professionals. “In many of the head offices, drug and alcohol [work] is done by the public or population health teams, and they’ve been doing nothing but COVID.”

Despite this, “in NSW, depot buprenorphine now accounts for more than a third of all opioid treatment in the public system”, he says. “That’s absolutely phenomenal.”

Sublocade: This image was supplied by Indivior

Nick says somewhere around 60 per cent of the nation’s LAIB is being used in NSW, although “NSW has only 30–40 per cent of the nation’s opioid treatment.”

Buvidal currently makes up the lion’s share of LAIB prescribed in Australia. “Buvidal hit the market first – about six months, roughly, before Sublocade,” he says. “Services started using whichever they could get.”

Nick says Australia’s acceptance of LAIB has positioned it as “the poster-child for depot buprenorphine in the world”.

“We’re the only country using both medications, the only country to have published guidelines, the only country providing online training for health advisors,” he says.

It’s a perfect response to COVID: rock up once a month, get your jab and go.

Professor Nicholas Lintzeris

Game-changer, inside and out

“This has been a major game-changer, including across our prison system,” Nick says.

“Prisons don’t like buprenorphine film because it’s easy to dope with [use illicitly] and administering it is time- consuming for staff: 30–60 minutes per patient every day.”

He says the absence of an illicit trade in LAIB has reassured law enforcement. “There isn’t that history of diversion of either depot. Yes, you can feel a little pea- or marble-sized lump at the injection site for a couple of weeks with Sublocade, but if someone did rip that open then what would they do with it?”

Professor Michael Levy AM, Honorary Professor at the ANU Medical School and, until last April, Chair of the National Prisoner Health Information Committee within the Australian Institute of Health and Welfare, concurs.

Michael, who also co-founded the Australian Council of Prison Health Services, says NSW and the ACT are both strong advocates of LAIB. “It’s a reality that prison health services are conducted within prisons. Custodials see their remit through a lens of security and control.”

Michael oversees 31 LAIB clients through the Canberra-based drug and alcohol service Directions. He says the treatments’ rollout to clients in Canberra has been smooth. “In fact, the big story is that there is no story. The process of receiving their medicine, which was once so institutionalised and regimented, has been normalised for many people.”

He calls monthly clients between injections to check up on them. “Especially when people are new to the program, I’ll call a week before appointments. Also, I want to pre-empt the dose they’re going to receive so we can have it waiting to make everything as seamless as possible.”

Michael says although Buvidal’s highest individual dose is 128mg, his clinic has given 160mg by combining 64mg and 96mg. “One fellow had been getting three-weekly 128mg and was still experiencing significant clinical withdrawal.”

It’s transformative for some people.

Professor Michael Levy AM

'This has worked wonders'

For many of his 36 years, the life Buvidal has “saved” hasn’t been an easy one for Jon.

After surviving a “troubled upbringing” he lived on the streets from a relatively young age before earning a place at university.

“As a part of that I did a placement overseas but while I was there I contracted HIV. I felt like I’d tried really hard to get myself on track but at that point, in my mind, I just gave up,” Jon says.

Feeling despondent, he was introduced to heroin – “very occasionally, recreationally, for a while”.

Jon’s double degree with honours in the health sciences led to work in a state government department. Eventually, though, trying to juggle a demanding job with chronic drug use that had by then become “unmanageable” took its toll and he resigned.

“The first thing I tried to get myself off heroin was methadone. I was on that for a long, long, long time but I found I could still use on top of it–and I did. It wasn’t really fixing the problem.”

He says 18 months ago, after experiencing a “counterproductive and shaming” period in a rehabilitation facility in northern NSW, he felt defeated.“I blamed myself for quitting rehab. I blamed myself for not being able to control my use more with methadone. Thoughts of suicide were really prominent.”

“Then, I found an organisation called PAMS (Pharmacotherapy, Advocacy, Mediation and Support) and they told me about a new treatment.”

Jon was referred to St Vincent’s Hospital Melbourne’s long-acting injectable buprenorphine (LAIB) clinic and within a week received his first dose.

“Initially it took some getting used to because I was so accustomed to heroin being such a significant part of my life,” he says. “Everything revolved around the drug – my friendship group, everything – so I had to more or less start from the beginning again, but I was also linked in with a therapist and she’s been wonderful.”

Jon says knowledge of LAIB is at best limited – or, more often, non-existent – within his social circle.

“Even my GP was completely unfamiliar with it – I found myself educating him,” he says.

“Traditionally, the only options people know about are Suboxone and methadone.”

However, he has been able to encourage one friend to try LAIB “ and she’s been really successful”.

“I was sceptical, but this has worked wonders for me,” he says. “The last time I used was about three months ago. I used once but it did absolutely nothing.”

“What works with Buvidal is that heroin doesn’t work.”

Buvidal: This image was supplied by Camurus

Freedom with stability

Many clients “like the stability” offered by LAIB, Michael says. “Some people, from total chaos, have started employment and held it down for a number of months.

“One patient was inducted in prison, came out into community and is now doing a course at tech college.

He presents for five minutes every 28 days to get his shot. We have the briefest of chats and he’s out the door.

“And one fellow in his late 40s, with terrible trauma and drug dependence, says his life’s been ‘transformed’. That’s his word. I hear that over and over again: it’s transformative for some people.”

In Melbourne, Gabby Cohen, Dr Adam Pastor, Dr Benny Monheit, Dr Danusia Pietrzak and nurse practitioner Rebecca Brereton of Alfred Mental & Addiction Health’s Southcity Clinic have been working with Buvidal and Sublocade since they were approved for use in Australia.

The clinicians cite three key benefits to clients: “cost, convenience and the psychological aspect of not being ‘reminded’ each day via a pickup that they’re opioid dependent.”

“One of the big unanswered questions is whether this is encouraging large groups of people to seek treatment who were previously deterred by having to visit the pharmacy on a daily basis,” Gabby says. “We’ve certainly had clients for whom that’s been the case.”

At Ballarat Community Health, nurse practitioner Brett Vallance has 10–12 LAIB clients.

“A few travel up to 90 minutes to come here,” Brett says. “I speak about it to patients I think it will be relevant to – anyone who’s looking at reducing or coming off the program.”

“The ones who’ve transferred over can’t speak highly enough of it. It’s moved them out of the pharmacy and provided them with a lot more freedom. “I always reassure people that if they do try it, it doesn’t have to be forever. They can go back.”

“It’s not for everyone, though. There’s reluctance, particularly among those who haven’t been injecting anything – the ones on codeine, for example. It’s a bit more foreign for them.”

“The injection itself stings so we talk about ice-packing the site prior to treatment. Quite a few bring their own packs now to use while they’re waiting in reception.”

Whatever works to help them feel the best they can and keep flourishing is what matters.

Associate Professor Yvonne Bonomo

Innovative thinking

Dr Hester Wilson, a Fellow of RACP’s Chapter of Addiction Medicine, says one of her clients devised an ingenious placebo to help herself through the transition from sublingual buprenorphine to LAIB.

“She said with the injection she didn’t feel she was receiving her medicine. So she decided to try taking Listerine film. She stayed on Buvidal and took Listerine daily for about three months. It was a great solution for her anxiety.”

Hester says while NSW offers daily dosing of standard pharmacotherapy treatments such as methadone and buprenorphine formulations free of charge at certain clinics, “the majority of people are still at pharmacy, so suddenly going from having a bill of $160 a month to nothing is a huge advantage.”

She says one area yet to be studied fully is using LAIB in pregnancy.“We know buprenorphine itself is safe but there’s also the matrix – the substance it’s in for the slow release. However, having people who are not in treatment or are unstable on another treatment is dangerous and withdrawal is dangerous. It’s balancing up those risks.”

Hester says the two LAIBs are equally effective.“The bottom line is that these formulations are just buprenorphine – not different, not scary, not new – but in a form targeted for people who don’t want to dose every day.

“It’s highly evidence-based and it’s great for a lot of patients but it’s not for everyone. I’m all about options, about choice, and about working through those with our patients.

Yvonne Bonomo echoes Hester’s message: “We don’t want people for whom it’s not suitable to feel bad.

It might suit them down the track, or it might not – whatever works to help them feel the best they can and keep flourishing is what matters.”

Rosalea Ryan