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Lisa Bromley, MD, CCFP(AM), FCFP, Robert Cooper, MD,
CCFP(AM), FCFP, CCSAM, DABAM, DFASAM, Maire Durnin, MD, PhD, MSc,
Mel Kahan, MD CCFP FRCPC, Sharon Koivu, MD MCFP PC AM, Vincent Lam,
MD, CCFP (AM), Michael Lester, MD , Jenny Melamed, MBChB, B.Sc., FASAM,
DABAM, FIAIME, Lori Regenstreif, MD, CCFP(AM), FCFP, MScCH(AMH),
CISAM, Clement Sun, MD.
Developed by Addiction Medicine Canada
January 22, 2025
1. Introduction:
Recently, a number of methadone/buprenorphine maintenance prescribers (commonly referred to as community Opioid Agonist Therapy or OAT) and primary care prescribers in Canada have begun prescribing immediate-release (IR-HM) hydromorphone tablets to patients with opioid use disorder, often in combination with methadone or Slow Release Oral Morphine. The clinics are sometimes, but not always, calling this practice “Safer Supply;” it is also called “methadone plus,”
This briefing note reviews the potential risks of prescribing hydromorphone in community OAT clinics, and makes recommendations about minimizing these risks.
This briefing note was prepared by members of Addiction Medicine Canada. It is
based in part on previous writings by the authors on Safer Supply and opioid
agonist treatment (Kahan 2023).
2. Background: “Safer Supply” (SS) programs:
Safer Supply programs are intended for high risk opioid users with severe, unstable opioid use disorder who have repeatedly dropped out of methadone or buprenorphine treatment, or those who have declined OAT treatment. Hydromorphone is prescribed to give high risk opioid users an opioid alternative to illicit fentanyl. SS programs typically prescribe between ten and forty 8mg tablets of IR-HM daily for use away from the pharmacy or clinic. This is referred to as “take-home” dosing. Many SS programs have also been funded to provide “wrap-around services” such as housing, support services, access to food and clothing, psychological counselling and other social service supports.
3. Effectiveness of Safer Supply programs
To date, evaluations of SS programs have been mainly qualitative. A few observational studies have been published, but no controlled trials.
One retrospective cohort study found that patients in the London SS program had reduced emergency department visits compared to before program entry and compared to matched controls who were not in treatment (Gomes 2022). It is not possible to determine from this study whether the prescribed opioids, or the wraparound services (or both) were responsible for the outcomes identified.
An observational study conducted in British Columbia found that patients who received “Risk Mitigation Guideline” (RMG) medications (another term for “safer supply”), in addition to methadone, had lower mortality than those who received methadone alone in a subsequent week (Slaunwhite, 2024). The authors only published outcome survival data for the first 7 days of SS treatment.
In another observational study, patients on OAT and SS medications (primarily hydromorphone) had considerably higher treatment retention rates than those on SS medications alone (Selfridge, 2022).
These observational studies have major limitations. SS was compared to no treatment, rather than OAT, even though OAT is the standard of care and has been shown to reduce overdose deaths, hospitalization from injection-related infections and all-cause mortality (Lee, 2023; Santo, 2021; Wakeman, 2020). The Slaunwhite study controlled for methadone dispensation as a binary variable, but did not control for the dose of methadone or its frequency of dispensation. Thus the observed effect on mortality cannot be attributed to hydromorphone alone, as it is possible that the Risk Mitigation group also received more frequent and higher doses of methadone, Nor did any of the studies account for the effects of wraparound services, separate from the hydromorphone prescribing itself.
4. Harms of take-home hydromorphone
The prevalence of diversion of SS medications has not been formally studied, but research indicates that diversion of prescription opioids was a major driver of previous opioid epidemics. Diversion by pain patients fuelled the OxyContin epidemic in North America in the 1990s up until 2012 (Humphreys 2022). Retrospective cohort studies conducted in British Columbia and the United States prior to the fentanyl era have found that, compared to youth who use nonopioid substances, youth who use diverted prescription opioids are at high risk for transitioning to heroin use and to injection use. (Cerda, 2015; DeBeck, 2016; Goldman, 2019).
Unfortunately, Canadian harm reduction researchers have not attempted to study the harms of diversion. Instead they have conducted qualitative studies, in which SS patients were interviewed about diversion. In one recent study (Olding 2024), the SS patients interviewed stated that they gave or sold their hydromorphone tablets only to fentanyl users. This could reflect ‘social desirability bias”; subjects would be reluctant to admit that they sold to youth. Yet, diversion to youth certainly occurs, based on multiple reports from clinicians, families, youth, and the media. Currently there is a class action lawsuit against the BC and federal governments by two families whose children overdosed on opioids after repeatedly accessing hydromorphone tablets diverted from SS programs (DeRosa 2024).
Unsupervised injection of take-home hydromorphone tablets, whether prescribed or diverted, can result in serious bacterial infections. In a national case control study from France, people with Opioid Use Disorder who received take-home morphine had a much higher rate of hospitalization for bacterial infection than those on methadone or buprenorphine (Bertin, 2019; Bertin, 2022).
5. Hydromorphone prescribing in community OAT clinics in Canada: Risks
and harms
While we do not know the prevalence of this practice, we are aware that some community OAT clinics and primary care clinicians are prescribing hydromorphone to patients with Opioid Use Disorder, in a manner similar to SS clinics, ie large quantities of tablets are dispensed as take-home doses. Unlike SS clinics, this practice is not intended mainly for high risk opioid users but for patients who are, or were, relatively stable on OAT. This puts these patients at risk for relapse and the public at risk for harms associated with diversion and unsupervised injection. The authors, and other clinicians we have spoken to, have had stable patients who have left OAT to go to a clinic which prescribes hydromorphone; often, these patients have experienced poor outcomes.
6. Differences between SS programs and community OAT programs that prescribe take-home hydromorphone.
SS programs are explicitly intended for high risk opioid users who have failed at or declined OAT. In contrast, community OAT programs that prescribe take-home hydromorphone appear to be enrolling patients who are stable on OAT, putting these patients at risk of harm. Furthermore, this practice creates pressure on other OAT clinics to prescribe take-home hydromorphone, in order to retain patients and remain viable. If many OAT clinicians begin to prescribe take-home hydromorphone, this could cause serious harm to communities across Canada. Widespread diversion of take-home tablets will put youth at risk, destabilize OAT patients, increase injection-related infections, and increase the demand for fentanyl, methamphetamine and other drugs. To prevent this, it is critical that community OAT clinics follow evidence-based principles when prescribing hydromorphone or other short-acting opioids.
7. Recommendations for Community OAT Clinics:
We put forward the following recommendations for community OAT providers who are considering prescribing hydromorphone or other short-acting opioids to patients with OUD:
- Without exception, all doses of short-acting opioids should be observed by a healthcare professional, e.g. a pharmacist or nurse. Observed dosing has been shown reduce diversion and its harms. For example, overdose deaths in the UK declined markedly following the introduction of observed dosing of methadone (Srrang 2010).
- Hydromorphone prescriptions should be reserved exclusively for patients who meet both criteria below:
- High-risk opioid users (patients who inject or inhale opioids such as fentanyl)
- Repeatedly dropped out of OAT, or are unable to achieve a therapeutic dose of methadone because of missed doses, or who have experienced overdoses or injection-related infections, even while on OAT.
- Hydromorphone should only be prescribed during titration to therapeutic doses of OAT, in order to retain patients in treatment.
- The OAT clinician should contact the patient’s previous OAT provider before prescribing hydromorphone. If the patient had stopped or markedly reduced highrisk opioid use during their past OAT treatment, then the clinician should encourage the patient to return to their previous clinic. If the transfer is accepted, then the clinician should restart with the patient’s previous OAT medication, with dose adjustment as necessary. Sub-therapeutic doses of OAT are a common cause of patients dropping out of treatment. Patients who were unable to reach a therapeutic dose of methadone 80 mg should be given a trial of SROM and methadone, before hydromorphone is prescribed.
- Hydromorphone should be prescribed as follows:
- All doses of hydromorphone tablets should be supervised to avoid diversion and unsupervised injection.
- Methadone should be titrated quickly and safely to an optimal dose, which is generally considered to be 80 mg or more,
- The hydromorphone dose should be carefully titrated to provide immediate relief of withdrawal symptoms and cravings, without causing sedation. A maximum dose of five tablets of 8 mg per day (200 mg morphine equivalents) is suggested. Doses above five tablets per day are difficult to supervise, are not necessarily safe if taken all at once, and are easy to divert by holding in them in the mouth for later use.
- As the methadone or SROM medication approaches an optimal dose, the hydromorphone dose should be tapered and stopped.
- Wrap-around services should be provided to high risk opioid users, on-site wherever possible. Such services should include mental health support, social services, and acute primary care services such as management of injection related infections, including HIV and Hep B and C.
- Clinics that currently prescribe take-home hydromorphone tablets should inform patients that this practice will be discontinued, because it is not safe for patients or the public. If the number of tablets dispensed is large, then 5 tablets can be dispensed under observation in the morning, while the remaining take home doses should be tapered at a fixed rate.
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