Navigating Changes to Opioid Agonist Therapy and How to Support Patients

Jennifer Wyman, MD, FCFP, DABAM, MPH¹
Maria Zhang, BScPhm, PharmD, MSc^2,3

¹Women’s College Hospital, META:PHI
²Centre for Addiction and Mental Health
³Leslie Dan Faculty of Pharmacy, University of Toronto

Ontario continues to struggle with an epidemic of deaths related to toxicity of the unregulated drug supply. Recent statistics indicate that up to 85% of drug-related deaths in Canada involve fentanyl or fentanyl analogues from the unregulated supply, often mixed with benzodiazepines and other contaminants.

Opioid agonist therapy (OAT) is the first-line treatment for opioid use disorder (OUD). Multiple studies have demonstrated reduced mortality and OAT prevents overdose even in people who continue to use unregulated opioids. There is evidence of improvements in mental and physical health, including engagement in treatment for hepatitis C and HIV for people on methadone and buprenorphine/naloxone.

However, treatment engagement and retention on OAT has remained low. The former guidelines of the College of Physicians and Surgeons of Ontario (CPSO) mandated prolonged daily witnessed dosing of methadone, which many patients experienced as “liquid handcuffs”. Furthermore, people with very high opioid tolerance may not derive sufficient benefit from buprenorphine/naloxone or from standard approaches to methadone dosing and titration.

In an effort to improve treatment retention in the fentanyl era and reduce lives lost, OAT prescribing guidance has evolved. Since the rescinding of the CPSO’s methadone maintenance therapy guidelines in 2021, several new OAT prescribing documents have been released, including new guidance on methadone initiation, titration, and take-home doses, the use of slow-release oral morphine (24-hour formulation; Kadian ®) as OAT, combined OAT, and new approaches to buprenorphine initiation and injectable buprenorphine.

Below is a summary of some key changes to OAT prescribing and dispensing from META:PHI’s recent resources.

Higher initial & ‘target’ methadone doses

Recent Ontario guidance suggests starting methadone at higher doses (30 mg) for people with very high opioid tolerance, including for people on benzodiazepines. Doses can be increased by 10–15 mg every 3–5 days until about 80 mg, and thereafter typically by 10 mg increments. This is intended to help people reach an optimal dose of methadone safely and quickly, since people who remain on methadone have lower rates of overdose even if they continue to use unregulated opioids.

The recently released BCCSU Guideline for the Clinical Management of Opioid Use Disorder suggests that starting doses up to 40 mg/day may be used for people with previous experience of methadone, known very high opioid tolerance, and very low risk of toxicity. With this document in circulation, practice may begin to include starting doses up to 40 mg for select patients in Ontario as well.

People who use fentanyl often need doses of methadone above 120 mg to address both withdrawal symptoms and cravings. People on higher doses should be monitored for sedation and side effects. If the patient is experiencing sedation, severe constipation, or sweats, the dose should be held or lowered, and slow-release oral morphine (SROM) can be added if the methadone dose is subtherapeutic.

Starting methadone along with slow-release oral morphine (SROM 24-hour formulation)

As 30 mg of methadone is often too low to be effective for people with high opioid tolerance, co-prescribing SROM (24-hour formulation) with methadone can achieve effective OAT doses more rapidly. SROM can be initiated on the same day as the first methadone dose at doses of 100–300 mg. It can be continued or tapered once the person reaches an effective methadone dose.

SROM as OAT

Historically, treatment with SROM was reserved for people who had “failed” buprenorphine/naloxone or methadone or had contraindications to either of the first-line OAT medications. New guidance in Ontario and British Columbia suggests that all three medications can be considered for people seeking OAT. Starting doses for SROM range from 30–50 mg for people with low opioid tolerance or high risk for toxicity, to 200–400 mg for people with high tolerance. Capsules can be swallowed whole for observed doses, followed by a swallow of liquid to ensure that the whole dose has been ingested.

Adjustments for missed methadone doses

Repeated missed doses present a barrier to reaching a therapeutic dose of OAT. Previous recommendations suggested reducing the dose of methadone after three consecutive missed doses, and of SROM after two consecutive missed doses. Clinicians should consider the individual’s ongoing substance use, the impact of a reduced dose, and medical and social factors.

For example, people who continue to use unregulated opioids regularly have more ongoing tolerance than those who are not supplementing their OAT with other opioids and may also be at greater risk of discontinuing treatment if doses are reduced. In these circumstances, doses can be maintained for up to 4 missed doses. If the person presents on day 5, they can receive 50% of their usual dose or a typical starting dose, whichever is higher.

More flexible methadone and SROM take-home doses

Several studies have explored the impact of more flexible approaches to take-home doses implemented during the COVID-19 pandemic. In Ontario, among 5,852 people who previously had daily observed doses of methadone, transitioning to carries was significantly associated with lower risks of opioid-related overdose, treatment discontinuation, and treatment interruption. Rather than focusing exclusively on the risks of carries and requiring abstinence for all take-home doses, current guidance encourages clinicians to consider the person’s ability to store and manage carries safely and their overall stability. Carries are usually not given during the first four weeks of treatment with methadone or SROM but can be started as 1–3 non-consecutive carries per week after a month, if the person is stabilizing, able to store their carries safely, and not using substances in high-risk ways. A locking device is required for storage.

Patient Examples

Patient 1: Jenny

Case scenario: Jenny has been on methadone for two weeks and is still at a dose of 30 mg because of multiple missed doses. Her prescriber sees her on Tuesday. She missed her methadone on Sunday but had her methadone on Thursday, Friday, Saturday and Monday. The prescriber increases her dose to 45 mg for Tuesday even though she hasn’t had three consecutive doses. Is it safe to dispense 45 mg?

Patient 2: Chris

Case scenario: Chris is on 650 mg of SROM. He had been doing quite well and reported a significant reduction in his use of unregulated opioids. Due to a crisis in the family, he had to go out of town and missed his doses on Friday, Saturday, and Sunday. The prescriber can’t reach Chris for a conversation, but wants to avoid treatment disruption or discontinuation. In light of Chris’s recent low substance use, the prescriber decides to reduce his dose to 400 mg (the high end of SROM starting doses) and increase by 100 mg/day back to 600 mg. The pharmacist is asked to assess Chris for sedation and hold the dose if he looks sleepy or impaired. Is this an appropriate dose adjustment strategy?

Patient 3: Tanya

Case scenario: Tanya is on 80 mg of methadone. She has been receiving two carries per week, for Tuesdays and Fridays. She comes into the clinic on Thursday looking intoxicated; her speech is slurred and her behaviour is atypical. She wants her observed methadone dose and her carry. How should the pharmacist proceed?