Opioid Replacement Therapy basics

Aaron D’Souza BPharm

As a young pharmacist, I attended a session at APP twelve years ago held by speaker, Tony Trimingham.

For those of you who haven’t heard his story, it’s one that makes you break down and cry.

I, and many other pharmacists in the room that day, certainly did.

Tony recounted the background, events and circumstances of the tragic heroin overdose death of his son Damien; at the time aged only 23.¹

A pharmacist colleague of mine from university, Stacey, was co-presenting and narrated how she had implemented an Opioid Replacement Therapy program in her pharmacy.

Almost seven years later, I came good on a promise I made that day and implemented an ORT program in the pharmacy I owned — and it was one of the most rewarding programs my team and I implemented.

I have never forgotten Tony’s story and, during interactions with my ORT clients, kept in mind Damien’s death and how, as a pharmacy team, we could contribute positively to our community.

ORT plays a critical role in the community and there is no better placed health professional to help people through the journey away from opioid addiction than the pharmacist. That statement is backed by data in Figure 1.

Success in pharmacy ORT programs is pinned to a knowledge of the drugs, a robust, fair and clear relationship with clients, collaboration with prescribers and clinics, and good infrastructure and training to maintain the program.

ORT and pharmacy

Statistics from the AIHW show that up to 50,000 clients receive ORT in Australia per year.

Of those, approximately 60% receive methadone, 20.8% buprenorphine-naloxone and 14.3% receive buprenorphine.

These patients are served by 3,074 prescribers and 2,732 dosing points around the country.²

88.7% (2,424) of ORT dosing points are pharmacies. This quantifies the importance of pharmacists being attuned to this area of practice.

The graph below shows that even across pharmacotherapy options, different dosing points deliver varying ORT therapy proportions. The reasons for this will become clear as we explore the different ORT options and their purpose in therapy.

Figure 1: %ORT dispensed by dosing point sites

ORT options

There are three ORT options available:

(Note: Naltrexone is not covered in this article due to its indications)

The federal Department of Health’s 2014 National Guidelines for Medication-Assisted Treatment of Opioid Dependence provides a thorough body of information for any health professional wanting a complete picture of opioid dependence. An electronic copy can be obtained if you email aaron@pharmacy.com.au.

Mechanism of action

As a refresher, it is recommended to view the short videos available on opioid agonists/antagonists and how partial opioid agonists work.

Opioid agonists/antagonists visualised: QR: https://youtu.be/W2kL0nPPbII

Partial opioid agonists: QR:  https://youtu.be/qeVNcNf8orE

Firstly, it is important to note that all opioids (including partial agonists) have abuse potential.³ The pharmacological agents must be placed within a framework that includes medical, social and psychological treatment, as stated in the PBS.⁴

Methadone⁵

Methadone is a synthetic compound which is an agonist at µ-opioid receptors. It has a long half-life, is quickly absorbed, has 75% oral bioavailability and only requires single-day dosing.

The benefits of methadone therapy are that it is:

• slowly absorbed, which results in less intoxication and withdrawal symptoms
• cross-tolerant with other opioid drugs.

Purpose of therapy: Helps patients experience µ-opioid receptors stimulatory effects, leading to a reduction opioid dependence and a gradual dose reduction.

Drawback of therapy: Risk of overdose — especially in the first 3–4 days of initial therapy. 

ORT using methadone requires effective management, especially at the start of therapy when other pharmacological therapies are being co-prescribed.

Buprenorphine⁵

Buprenorphine is a ‘mixed’ agonist/antagonist, or ‘partial opioid agonist with high receptor affinity’.

It has a higher affinity for the µ-opioid receptor than full opioid agonists, leading to a blockade at the receptor site of other opioid agonists.

It saturates receptor sites at approximately 16mg dosing after which there is little or no effect, even after consumption of other opioids.

Buprenorphine has a long duration of action, allowing once-a-day to three-times-per-week dosing.³

Purpose of therapy: Block other opioids and provide reduced µ-opioid receptors stimulatory effects.

Drawback of therapy: It can precipitate withdrawal symptoms after the first dose as it displaces opioid agonists from receptors. This requires careful patient monitoring upon therapy initiation.    

Buprenorphine-Naloxone³

The combination therapy of buprenorphine-naloxone aims to limit the potential of a patient to abuse buprenorphine. As stated above, all opioids, including partial agonists, have abuse potential. As discussed in ITK Feb/March 2017, naloxone is a competitive antagonist at µ-opioid receptors. Upon entering the brain, naloxone displaces opioids bound to µ-opioid receptors.⁶

When naloxone is combined with buprenorphine and taken sublingually, there is no apparent effect of naloxone. If that same dose was injected, the naloxone would have a substantial effect on the effectiveness of buprenorphine due to its competitive antagonist activity. The extent is a likely opioid withdrawal event in patients using full agonist opioids.³

Purpose of therapy: Reduces the abuse potential of buprenorphine because naloxone mitigates the agonist effects of buprenorphine if the dose is injected.

Drawback of therapy: It can precipitate withdrawal symptoms if the patient injects the dose and has been using opioids.

Diversion of ORT

A 2012 observational study by Andrew Smirnov and Robert Kemp from the School of Population Health at the University of Qld provides an Australian context on the diversion of ORT.

The authors studied diversion and misuse of ORT and they noted key points of interest that:

• diversion and misuse of ORT occurs only 5% of the time
• buprenorphine-naloxone has the lowest diversion/misuse
• single formulation buprenorphine and methadone have higher diversion/misuse than buprenorphine-naloxone
• single formulation buprenorphine had higher diversion/misuse than methadone.

This observational study highlights the powerful outcomes from the combination formulation buprenorphine-naloxone. For pharmacy, it reaffirms this combination as an impactful clinical option and may help to explain why buprenorphine-naloxone has a higher client% dispensing in pharmacy as per Figure 1.

In short, buprenorphine-naloxone use leads to less diversion/misuse, which alludes to greater patient trust and safety as a take-home dose.

Pharmacist considerations

When we first discussed implementing an ORT program in our pharmacy, I was challenged to think through the risk and impact on the business.

Our pharmacy had a large fragrance and beauty section — raising the concern of increased theft. There was also valid concern about losing regular customers due to the perception of ‘druggies’ in the pharmacy.

Upon discussion with other pharmacies successfully offering the program, my team — lead by my fearless pharmacists Kieran and Niny — created patient agreements, protocols, processes and procedures; implemented a dosing robot and dosing software; and engineered a space for convenient, confidential and secure dosing. We implemented a camera system to help monitor and reduce dose diversion.

When diversion happened (once), it was immediately seen on camera and the patient was promptly removed from our service as per the patient agreement.

We visited local clinics to encourage referral to us and made connections with medical practitioners.

The program provided us with excellent patient interactions — the basis being a firm but fair approach with patients; especially for payments, prescriber rules and script availability.

The most important aspect of the program was the convenient service we provided to a number of patients who, incidentally, did not fit the preconceived societal stereotype of a ‘druggie’.

The patients we served were full of hope, determination and a desire to change their lives. It is this important social function where buprenorphine-naloxone can play a very impactful role.

The reduced diversion/misuse as seen in the Smirnov and Kemp study (one result of mechanism of action) means patients can create concordant relationships with their medical practitioners and set up boundaries for their treatment goals as they overcome the psychological aspects of their rehabilitation.

Following prescribed treatments can often be hard for patients when daily dosing is required.

When forced to visit a pharmacy daily, successful therapy outcomes are threatened due to simple regimen adherence challenges. This adds to the benefit profile of buprenorphine-naloxone as a longer-term ORT option for patients.

For pharmacies wanting to help the 50,000 patients per year needing assistance with opioid addition, they are encouraged to reach out to professional bodies, such as the Guild in their state.

If there are patients and families in your community who are in need of support, a 24-hour support line is available from Family Drug Support on 1300 368 186. The CEO of FDS is Tony Trimingham, who continues to do great work in memory of his son for the Australian community.

As an owner who implemented an ORT program, I’d encourage anyone to reach out if you’re unsure about, or planning to offer, the service in your pharmacy: aaron@pharmacy.com.au.

References

1. Tony Trimingham: Why the worst thing that could happen to Andrew Chan and Myuran Sukumaran is their execution | Bali 9 [Internet]. [cited 2018 Dec 12]. Available from: https://www.news.com.au/lifestyle/real-life/true-stories/tony-trimingham-why-the-worst-thing-that-could-happen-to-andrew-chan-and-myuran-sukumaran-is-their-execution/news-story/9fde5a4959056145da9b52099a98b7b9 
2. National opioid pharmacotherapy statistics (NOPSAD) 2017, Summary [Internet]. Australian Institute of Health and Welfare. [cited 2018 Dec 12]. Available from: https://www.aihw.gov.au/reports/alcohol-other-drug-treatment-services/nopsad-2017/contents/summary 
3. Lintzeris N, National Expert Advisory Committee on Illicit Drugs (Australia), Australia, Department of Health and Ageing, National Drug Strategy (Australia). National clinical guidelines and procedures for the use of buprenorphine in the treatment of opioid dependence. Canberra: Dept. of Health and Ageing; 2006.
4. Health AGD of. Pharmaceutical Benefits Scheme (PBS) | [Internet]. Australian Government Department of Health; [cited 2018 Dec 13]. Available from: https://www.pbs.gov.au/medicine/item/6308B
5. Gowing L, Ali R, Dunlop A, Farrell M, Lintzeris N. National guidelines for medication-assisted treatment of opioid dependence. Commonw Aust Canberra. 2014;38–39.
6. Sponsor Phebra. Narcan Product Information [Internet]. 2013. Available from: https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-02490-3&d=2017121816114622483