Charlotte Boone, RPh, PharmD1,2
Mark Barnes, RPh, BScPhm1
Maria Zhang, RPh, BScPhm, PharmD, MSc.2,3
Beth Sproule, RPh, BScPhm, PharmD2,3
1 Respect Rx Pharmacy, Ottawa, Ontario.
2 Centre for Addiction and Mental Health, Toronto, Ontario.
3 Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario.
In 2020 there were 6,214 opioid-related deaths across Canada , with 2,426 (39%) taking place in Ontario.  Over the course of the COVID-19 pandemic, there was an almost 80% increase in opioid-related deaths in Ontario when comparing rates in February and December 2020. 
“IN 2020 THERE WERE 6,214 OPIOID-RELATED DEATHS ACROSS CANADA”
These deaths are overwhelmingly accidental and preventable, with fentanyl and fentanyl analogues directly contributing to almost 90% of the deaths.  Opioid agonist treatment (OAT; e.g., methadone, buprenorphine, slow-release oral morphine) is an evidence-based intervention that consistently demonstrates effectiveness in reducing mortality in individuals with opioid use disorder, even in the fentanyl era. [3,4] However, barriers to treatment access, engagement and retention exist, therefore, complementary harm reduction strategies are also essential. Harm reduction services that prevent opioid-related deaths include safe consumption sites, drug checking services and take-home naloxone kit provision. Safer opioid supply (SOS) programs have expanded over the past year in efforts to prevent overdoses and overdose deaths secondary to an unknown and increasingly toxic illegal drug supply, by providing low barrier access to pharmaceutical opioids of known doses and quantities to people at high risk of opioid-related harms. Safer supplies can also include stimulants or benzodiazepines; however, this article focuses on 5 things pharmacists should know about SOS programs in the context of the opioid crisis.
1. Safer supply aims to offset the toxic illegal drug supply and reduce harm.
The primary goal of providing safer opioid supplies is to offset the use of illegal toxic drug supplies, thereby possibly reducing the risk of death. It is important to acknowledge that in SOS programs individual client goals may vary over time with respect to their substance use and desire to transition to OAT. “SOS is a low-barrier model intended to reach people who are alienated from other models of health care delivery as a result of structural barriers that prevent those impacted by homelessness, poverty, mental health issues, racism and stigma from accessing needed care
.”  This approach can have a beneficial stabilizing effect, particularly when provided in the context of other health services (e.g., primary health care, hepatitis C treatment, HIV management, mental health care) and social services (e.g., housing support). Pharmacists are well positioned to support the primary care needs of marginalized people and promote complementary harm reduction approaches. When dispensing safer opioid supplies every client should be trained on the use of naloxone and offered a kit.  Pharmacists can also guide clients to approved sites
that offer drug checking services and supervised consumption sites. 
2. Safer opioid supply is different from opioid agonist treatment.
Opioid agonist treatments are taken orally or sublingually, and have favourable pharmacokinetic profiles (i.e., delayed peaks and long durations of action) to minimize euphoric effects and provide sustained attenuation of opioid withdrawal symptoms. These medications have decades of research supporting their place as first-line therapy for individuals with opioid use disorder. Injectable opioid agonist treatment (iOAT) is dispensed for observed safe injections of pharmaceutical grade hydromorphone or diacetylmorphine multiple times a day. It also has a strong and positive evidence base for individuals with severe opioid use disorder and ongoing illicit injection opioid use or other significant risks , however, access to iOAT is very limited due to funding.
In contrast, for individuals participating in safer supply programs there is a focus on providing short-acting opioid tablet formulations for self-regulated take-home consumption. A common approach is to provide a daily dose of sustained-release oral morphine (SROM) with observed administration in the pharmacy, combined with take-home hydromorphone immediate-release tablets.  However, safer supply may take many forms involving other combinations of opioids. Safer opioid supply is overseen by healthcare providers and generally offers more regimen flexibility than OAT.  This is still an emergent practice and evidence of the benefits and risks to the individual and their local communities continues to be collected. An overview of opioid use disorder treatment guidelines and safer supply related resources can be found here.
3. Dispensing guidance is currently based on clinical experience.
As a newer approach, there is limited peer-reviewed evaluative evidence upon which to base safer supply practice. An Ontario community of practice has developed a guidance document for safer opioid supply practice based on clinical experience.  The following guidance is based on this and good pharmacy practice standards.
Safer opioid supply prescriptions and dispensing practices must follow all provincial controlled substance regulations.  Upon receiving a new safer opioid supply prescription, the pharmacist or pharmacy manager should reach out to the prescriber if a relationship has not yet been established. Introducing the pharmacy and expressing a willingness to support the client will create a collaborative interprofessional relationship that benefits clients. Since this is a new approach for individuals at highest risk of opioid overdose, a clear mutual understanding of individual needs and the management plan is essential. Expectations and requirements should be discussed with the client upon initial intake – providing written information or using signed agreements can be considered. Pharmacy opening hours should be clearly communicated. Opening 365 days per year for clients to maintain access, educating pharmacy staff on all procedures and ensuring adequate time for pharmacists to dispense and observe dosing is recommended. Safer opioid supply prescriptions may be billed as any other prescription, with all Ontario Narcotics Monitoring System requirements followed.
The approach to initial dosing can vary, however, people with high tolerance levels due to fentanyl use may start with 30-60 mg daily of slow-release oral morphine (daily observed by pharmacist) plus 6-8 tablets of hydromorphone 8mg (daily dispensed to take away).  Both are then titrated up based on responses (e.g., decrease in withdrawal symptoms, ongoing illegal supply use), with maximum doses determined by the potency of the illegal opioid supply in the area. As an example, the maximum daily doses ranged from 16 to 24 hydromorphone 8 mg tablets per day based on experience at the time.  Pharmacists may see doses outside this range. A collaborative relationship with the prescriber is imperative to ensure safe titration and dosing for all safer opioid supply clients. It is recommended that clients be reassessed by the prescriber after 2 or more days of missed hydromorphone dispenses.  For missed slow-release oral morphine doses OAT guidelines should be followed. 
The pharmacist is responsible for dispensing and observing safer opioid supply doses. Slow-release oral morphine capsules should be opened by the pharmacist and the pellets given to the client to swallow with water under observation, as recommended as by the OAT guidelines. Crushing, chewing or dissolving SROM pellets should be avoided as it can cause an overdose. Using a motivational approach, clients should be advised to take hydromorphone orally due to the risks associated with injecting tablets. If clients still choose to inject tablets, they may be directed to harm reduction programs or supervised consumption sites that can offer sterile injection equipment, including different types of filters. It is important to ensure a physical environment that maintains client safety and dignity.
4. Pharmacists have a key role in supporting participants of safer opioid supply programs.
As clients attend the pharmacy regularly, ongoing assessments should take place. Prompting clients to discuss any withdrawal symptoms at their current dose, ongoing use of other drugs, functional status changes, side effects and infections should all be part of ongoing care. When clients miss any doses of safer opioid supply, the pharmacist should discuss any relapse to use of illegal supplies, overdoses, or challenges in making it to the pharmacy. Importantly, pharmacists should adopt an open dialogue with clients surrounding overdoses. Using open-ended questions and assuring clients that the pharmacy is a judgement-free environment can facilitate the relationship. Private counselling areas may be beneficial for client safety, comfort and to minimize distractions during these discussions. Clinical documentation of these discussions, as well as actions taken and communications with prescribers should be explicit and available to all pharmacists providing care to safer opioid supply clients in the pharmacy.
5. Transitions in care must be managed carefully.
Transitions in care increase the risk of medication errors and pharmacists are best positioned to prevent these by:
- Communication between pharmacists for clients transferring pharmacies or when admitted to hospital.
- Having accurate, complete and easily retrievable clinical documentation to facilitate communication, particularly for managing opioid dosing to reduce the risk of withdrawal symptoms or overdose.
- Discussing management options with the client to help meet their goals and acknowledging these goals may evolve and change over time.
- Getting as accurate a determination as possible on their total daily opioid intake (including recently missed visits to the pharmacy for observed and take-home doses, amounts of take-home tablets used or other opioids accessed).
- For hospital admissions, options include maintaining the outpatient opioid dosing regimen during admission or converting the total daily dose to a single opioid accounting for incomplete cross-tolerance, or some reasonable combination. If it is not possible to obtain an accurate account then careful titration will be necessary. Opioid formulation choices depend on the clinical situation (e.g., parenteral needs) and availability. This could also be an opportunity to discuss the option of engaging in opioid agonist treatment. Early planning is needed between the hospital team and the community prescriber and pharmacist to ensure a smooth transition upon discharge.
In caring for all clients, and in particular those who continue to experience systemic oppression, pharmacists must aim to provide clients with a non-judgmental, compassionate, respectful and safe environment that is free of stigma. It is highly recommended that all pharmacists undertake training in opioid use disorder to ensure an understanding of the nature of addiction and to reflect on their own biases and stigmatizing behaviours. There are several resources available, for example, the CAMH Opioid Use Disorder Treatment course  and the ‘Overcoming Stigma – Online Learning’ provided by the Canadian Centre on Substance Use and Addiction.  Safer supply programs provide people with a safer avenue to obtain opioids. Ultimately, clients should guide their goals of care and pharmacists should provide a supportive, inclusive environment. Research evaluating this harm reduction approach is underway and will help develop the evidence-base needed to guide future practice.
- Special Advisory Committee on the Epidemic of Opioid Overdoses. Opioid and Stimulant-related Harms in Canada. Ottawa: Public Health Agency of Canada; June 2021. https://health-infobase.canada.ca/substance-related-harms/opioids-stimulants/
- Gomes T, Murray R, Kolla G, Leece P, Bansal S, Besharah J, Cahill T, Campbell T, Fritz A, Munro C, Toner L, Watford J on behalf of the Ontario Drug Policy Research Network, Office of the Chief Coroner for Ontario and Ontario Agency for Health Protection and Promotion (Public Health Ontario). Changing circumstances surrounding opioid-related deaths in Ontario during the COVID-19 pandemic. Toronto, ON: Ontario Drug Policy Research Network; 2021. https://odprn.ca/research/publications/opioid-related-deaths-in-ontario-during-covid/
- Santo T, Clark B, Hickman M, Grebely J, Campbell G, Sordo L, Chen A, et al. Association of Opioid Agonist Treatment With All-Cause Mortality and Specific Causes of Death Among People With Opioid Dependence: A Systematic Review and Meta-Analysis. JAMA Psychiatry, June 2, 2021. https://doi.org/10.1001/jamapsychiatry.2021.0976
- Pearce LA, Min JE, Piske M, Zhou H, Homayra F, Slaunwhite A, Irvine M, McGowan G, Nosyk B. Opioid Agonist Treatment and Risk of Mortality during Opioid Overdose Public Health Emergency: Population Based Retrospective Cohort Study. BMJ, March 31, 2020, m772. https://doi.org/10.1136/bmj.m772
- Hales J, Kolla G, Man T, O’Reilly E, Rai N, Sereda A. (2019). Safer Opioid Supply Programs (SOS): A Harm Reduction Informed Guiding Document for Primary Care Teams-April 2020 update. Available online: https://bit.ly/3dR3b8m
- Tsuyuki RT, Arora V, Barnes M, Beazely MA, Boivin M, Christofides A, Patel H, Laroche J, Sihota A, and So R. Canadian National Consensus Guidelines for Naloxone Prescribing by Pharmacists. Canadian Pharmacists Journal / Revue Des Pharmaciens Du Canada, August 26, 2020. https://doi.org/10.1177/1715163520949973
- Interactive map: Canada’s response to the opioid crisis. 2021; Available from: https://health.canada.ca/en/health-canada/services/drugs-medication/opioids/responding-canada-opioid-crisis/map.html
- Canadian Research Initiative in Substance Misuse (CRISM). National Injectable Opioid Agonist Treatment for Opioid Use Disorder Clinical Guideline. Published September 23, 2019. Available at: https://crism.ca/projects/ioat-guideline/
- Health Canada. Safer Supply. Available from: https://www.canada.ca/en/health-canada/services/opioids/responding-canada-opioid-crisis/safer-supply.html
- Prescription Regulation Summary Chart. 2020, Ontario College of Pharmacists. https://www.ocpinfo.com/wp-content/uploads/2019/05/Prescription-Regulation-Summary-Chart-Summary-of-Laws.pdf
- CAMH. Centre for Addiction and Mental Health. Opioid Agonist Therapy: A Synthesis of Canadian Guidelines for Treating Opioid Use Disorder. May 2021. https://www.camh.ca/en/professionals/treating-conditions-and-disorders/canadian-opioid-use-disorder-guideline
- CAMH. Opioid Use Disorder Treatment Course. https://www.camh.ca/en/education/continuing-education-programs-and-courses/continuing-education-directory/opioid-use-disorder-treatment-course
- CCSA Overcoming Stigma: Online Learning. https://www.ccsa.ca/overcoming-stigma-online-learning