Opioid Agonist Therapy (OAT) guidelines

1.1 Stigma

Stigma is negative attitudes and beliefs about a group of people due to their circumstances in life. It includes discrimination, prejudice, judging, labelling, isolating, and stereotyping. Stigma matters because it can prevent people from getting help. Stigma creates barriers to accessing important health and social services.[1]

While stigma can certainly take the form of active negative treatment of individuals by healthcare providers, it can also be more insidious and unintentional. Regulated members need to understand that patient perceptions of stigma can lead to feelings of shame, guilt, and mistrust by the patient. This may contribute to reduced engagement that may lead to premature discontinuation of treatment and poorer health outcomes.

Regulated members can take steps to reduce stigma. These steps include

• identifying and recognizing their own biases;
• remembering that substance use disorder is a medical condition deserving of care and treatment; and
• changing the way staff talk about substance use and choosing respectful, person-centred language.

1.2 Trauma-informed care

Trauma-informed care is a set of guiding principles which takes into account the effects of trauma on an individual. Seventy-six per cent of Canadian adults report some form of trauma exposure in their lifetime and 9.2 per cent meet the criteria for PTSD[1].

Psychological trauma is often closely tied to substance use, mental health, stigma, health care access barriers, and other challenges. People who experience trauma can have varied responses; some will have minor disruptions to their personal life while others may have a debilitating response. Trauma-informed care means recognizing this link, making sure that people feel safe, and are not re-traumatized by their care.[2]

Disclosure of trauma is not necessary to implement trauma-informed care practices. Trauma-informed care is not counselling for trauma and, while it is not within the regulated member’s scope to directly address patient trauma, it is important that the impact of trauma is recognized and respected when providing patient care.

1.3 Harm reduction

Harm reduction means those policies, programs, and practices that aim primarily to reduce the adverse health, social, or economic consequences of the use of legal and illegal psychoactive substances without necessarily reducing consumption.[1]  It is about meeting people where they are and identifying the goals they wish to achieve based on their individual needs and circumstances at a particular moment in time.

Harm reduction principles recognize the inherent value of human beings and the importance of an inclusive community that can support people who use substances with compassion. People who feel supported and part of a community, rather than isolated, are more likely to seek help when they need it.^[2]

Regulated members must understand and accept, without applying moral judgements, that individuals with substance use disorders need to be treated with the same level of respect as any other patients.

1.4 Harm reduction services and take-home naloxone

For some individuals who use substances, engagement with their pharmacy team may be their most consistent connection to health care. These patients may present at different stages of change. Regardless of the patient’s stage of change or treatment intensity, regulated members should offer harm reduction information and services to minimize potential harms of substance use.

Various types of harm reduction services should be considered, including

• counselling on overdose prevention and treatment, including provision and training of take-home naloxone;
• education regarding safe use of substances;
• collaboration with community partners to provide supplies to support safe substance use;
• referral to an opioid/substance use disorder treatment provider or program;
• referral to other harm reduction services such as needle distribution programs or supervised consumption services;
• referral to other community agencies that can provide food, shelter, clothing, and other necessities of life;
• screening and offering immunizations for preventable illness (hepatitis A & B, influenza, etc.); and
• ordering laboratory tests (bloodwork) when appropriate.

Patients may benefit from harm reduction in numerous ways. Harm reduction may

• empower patients to have agency over how their health goals are met,
• reduce the risk of morbidity and mortality from overdose or non-medical use of opioids or other substances,
• reduce the transmission of blood-borne pathogens,
• reduce the need to engage in criminal activity to support a substance use disorder,
• reduce harm during pregnancy and breastfeeding to optimize neo-natal outcomes, and
• provide an opportunity to connect patients to other health services.

1.1 Treatment choices for opioid use disorder

OAT involves the substitution of opioids implicated in a patient’s OUD with a pharmaceutical-grade opioid in an effort to assist in stabilizing the patient’s opioid use. Several OAT options are currently used in Canada for treatment of OUD, the most prevalent being

• methadone (Metadol-D®, Methadose®, generics), and
• buprenorphine-naloxone (Suboxone®, generics).

For patients who have achieved stability of their OUD using sublingual buprenorphine, either buprenorphine depot (Sublocade®), or buprenorphine implants (Probuphine®) may be other options.

For patients unable to stabilize on methadone or buprenorphine-naloxone, expert-led options are available, such as

• slow-release oral morphine (Kadian®), and
• injectable hydromorphone, which is offered in specialized settings.

1.2 Factors in OAT medication choice

The choice of therapy between these options will depend on a number of factors including the patient’s

• preference, including past experiences with OAT;
• degree of opioid dependence and tolerance;
• risk of harm from the chosen therapy including the risk of non-adherence;
• concomitant health conditions and comorbidities;
• lifestyle and social history;
• potential to experience significant drug interactions with other concomitant therapies;
• ability to access the specialized services and expertise of an OUD program (e.g., iOAT);
• response to therapy; and
• ability to afford the chosen therapy.

2.1 Competence

Though there are no specific training or educational requirements for providing OAT, it is required that all regulated members will have the necessary competencies to support this unique patient population and complex medical condition.

Pharmacists must be aware of current, relevant, and evidence-based clinical practice guidelines including the resources available in Appendix 1.

Licensees are responsible to ensure all pharmacy team members are aware of their role and have the appropriate competencies to provide OAT services. Licensees must develop site-specific policies and procedures to support the safe and effective provision of OAT within their pharmacy.

2.2 Notification to ACP

Pharmacy licensees are required to inform the ACP registration department by email at pharmacy@abpharmacy.ca when their pharmacy begins providing OAT services to patients. Similarly, pharmacy licensees must notify the registration department as soon as possible if the pharmacy is no longer providing OAT services.

2.3 Pharmacy operating hours

Pharmacy operating hours must accommodate the needs of those requiring witnessed administration without compromising patient safety or causing undue hardship to the patient. Pharmacies that do not operate seven days a week must ensure that arrangements are made to enable the patient to access their medication on the days the pharmacy is closed. This may include

• collaboration with another pharmacy;
• opening at selected times on the day(s) the pharmacy is closed to provide care to pre-scheduled patients who require witnessed administration;
• authorization for a take-home dose on selected days that the pharmacy is closed, if safe and appropriate for the patient and approved by the prescriber; and
• on-call pharmacy personnel/services for emergencies and immediate need.

Considering the challenges associated with some of these options, it may be in the patient’s best interests to use another pharmacy altogether which is able to accommodate the patient seven days per week.

Changes made to pharmacy operating hours must consider the potential impacts to patients receiving OAT from that pharmacy.

2.4 Physical environment requirements for OAT

Suitable sound barriers to prevent unauthorized individuals from overhearing conversations and suitable visual barriers to maintain patient privacy are required at all pharmacies. However, regulated members  should be mindful of the potential stigma associated with witnessed administration and the sensitive nature of the conversations that may occur regarding the patient’s substance use.

2.5 Security

Licensees must consider security measures to address potential risks of robbery or burglary associated with storage of significant quantities of controlled substances, and the risks to the community that can result from theft of these products.

Licensees should review the ACP webpage for additional information on pharmacy robberies and burglaries.

4.1 Prescription requirements

Regulated members must only dispense OAT medications pursuant to receiving a prescription order that meets all of the requirements for an appropriate, current, authentic, and complete prescription. This may include, depending on the medication, additional requirements outlined in the TPP Alberta Program Guide. Furthermore, regulated members should ensure OAT prescriptions clearly outline the following OAT-specific information:

• the start and end date of the prescription, before and after which dispensing of OAT is not approved;
• the specific days or dates on which witnessed ingestion is to occur;
• the specific days or dates on which take-home doses are to be dispensed;
• indication for the OAT (e.g., opioid use disorder, analgesia, or both); and
• any special instructions.

4.2 Prescriber requirements

All healthcare professionals who prescribe or dispense OAT should be aware of the regulatory requirements and standards of practice that govern the prescribing and dispensing of such treatments.

In Alberta, prescribing physicians require approval from the College of Physicians and Surgeons of Alberta (CPSA) in order to prescribe OAT medications (other than buprenorphine-naloxone) for OUD, and the criteria may vary depending on the nature of their prescribing (e.g., initiating methadone therapy, maintenance of methadone therapy, slow release oral morphine, and injectable opioid agonist therapy).

While an authorization or approval is not provided by the College and Association of Registered Nurses of Alberta (CARNA), CARNA requires nurse practitioners to comply with the Prescribing Standards for Nurse Practitioners and meet all requirements for education and/or preceptorship to prescribe OAT for the category of prescribing applicable to their practice.

Where possible, regulated members must ensure that prescribers are eligible to prescribe OAT and can contact the prescriber’s regulatory body if verification is necessary.

For more information about physician OAT prescribing approval, refer to www.cpsa.ca.

4.3 Filling out-of-province prescriptions

Regulated members may dispense out-of-province, Canadian OAT prescriptions provided that they confirm that the out-of-province prescriber is eligible to prescribe the OAT in their jurisdiction and the  prescription complies with all requirements of the originating province. Out-of-province, Canadian OAT prescriptions do not need to be written on a TPP Alberta form.

4.4 Additional notes

• Pharmacists should discourage the use of abbreviations that may cause confusion or misunderstanding and should clarify abbreviated instructions with the prescriber as required (e.g., DWI or daily witnessed ingestion).
• Pharmacists should check that the last date for the OAT prescription falls on a day that the pharmacy is open for business to avoid missed doses or patient distress from seeking a new prescription and an alternate provider.

5.1 The role of pharmacists

Pharmacists are responsible for confirming that the medication and dosage prescribed is appropriate based on their assessment of a patient’s OUD and other factors such as concomitant medications that may pose a risk for drug interactions or other adverse effects. To facilitate this, pharmacists must have current knowledge of all applicable evidence-based clinical practice guidelines.

Pharmacists are also typically the front-line professional entrusted with witnessing ingestion of OAT, if required, and are therefore well positioned to assess the clinical effect of, and response to, the patient’s treatment. They play a key role in monitoring response and adherence to therapy and communicating to prescribers when they encounter potential problems that may compromise efficacy or safety of the therapy.

Pharmacists are required to communicate to the prescriber any signs and symptoms of intoxication, withdrawal, or other adverse effects, and they are required to inform and consult prescribers about concerns regarding adherence, including missed, lost, or vomited doses.

5.2 The role of pharmacy technicians

Pharmacy technicians are integral to the pharmacy team and play a role in caring for patients with OUD. It is important for pharmacy technicians to maintain competence with respect to treatment of these patients. This may involve

• identifying and prioritizing patients who require pharmacist assessment,
• processing and checking of prescriptions,
• preparation of medications for dispensing or administration, and
• facilitating communication with prescribers or other members of the healthcare team.

Pharmacy technicians may not witness ingestion of OAT because witnessed ingestion requires a clinical assessment that includes an assessment of the medication effectiveness, screening for intoxication, an evaluation of adverse effects, any adherence concerns/impact of missed doses, and a review of the use of other prescribed and non-prescribed substances.

5.3 Alberta Electronic Health Record (Netcare)

Pharmacists must review the Alberta Electronic Health Record (Netcare) every time the pharmacist assesses a patient that is prescribed OAT. This review should include consideration of

• adherence to prescribed treatment,
• relevant laboratory results,
• involvement of other pharmacies and/or prescribers, and
• use of other medications that may affect OAT.

Regulated members must also ensure that dispensing information is uploaded daily to Netcare, so that accurate records of missed doses are created and maintained.

5.4 Counselling and patient education - general

Pharmacists involved in dispensing OAT must provide sufficient information to enable the patient to receive the intended benefit of the therapy and to optimize the safety of the drug to both the patient and the public.

The need for counselling will be ongoing as the treatment plan changes over time and as the patient becomes ready for more information. Pharmacists must be able to assess the ability of their patient to understand the information provided and, wherever possible, provide supplementary written instructions to allow the patient to further review the information on their own time. Consider the literacy of the patient and provide appropriate literature that is clear and concise. Information provided, both verbally and written, should be evidence based, obtained from a reputable source, and culturally sensitive.

The environment and the manner in which information is provided are important factors to support understanding and retention of information by the patient. As opioid withdrawal can be extremely uncomfortable, patients may experience acute difficulties fully internalizing the information being provided to them when in withdrawal. It may be prudent in such cases to provide OAT prior to extensive counselling, particularly during the initiation phase of treatment. Counselling may need to be provided iteratively, or repeatedly, in such cases. Important counselling considerations for each OAT medication are provided within their respective sections.

The process of addressing and changing behaviours related to opioid use can be extremely difficult for patients. Regulated members should consider using resources and training to develop their counselling skills in areas such as motivational interviewing.

5.5 Pharmacy-patient agreements

During the initial counselling session, pharmacists should review and sign a two-way agreement with the patient. This provides an opportunity to highlight essential information unique to OAT. The document sets expectations by detailing what the pharmacy team is required to provide as well as the responsibilities for the patient. This agreement should be kept on the patient’s record, and revisited/updated regularly as treatment goals evolve. Pharmacists should consider a three-way agreement that includes the prescriber whenever possible to provide more complete information for the patient of what to expect and from whom. A sample agreement can be found in Appendix 3. All pharmacy team members assisting in the provision of OAT for a patient must be knowledgeable about the contents of the patient’s two-way or three-way agreement. These agreements are not intended to restrict patients from transferring their care to another pharmacy. The purpose is to support mutual understanding of patient and regulated member expectations.

It may be appropriate to delay signing an agreement if a client presents initially in active withdrawal until after they have received their initial medication doses and are more able to be attentive to the importance of the discussion.

5.6 Monitoring - general

Pharmacists are directly involved in the monitoring of patients who are prescribed OAT. Monitoring activities considered a priority for pharmacists are generally those to optimize the response and outcomes to therapy—in particular, activities to evaluate the efficacy and safety of the treatment and the patient’s adherence to the therapy. Pharmacists can play a key role in collaboration with the prescriber regarding the appropriateness of initiating carried doses.

Below are some of the monitoring activities performed by pharmacists:

• Monitor the patient’s understanding, engagement, and adherence to treatment.
• Assess for symptoms or evidence of intoxication to determine if the dose should be dispensed:
  • Intoxication from opioids: pinpoint pupils, drowsiness, slurred speech, unsteady gait, slow heart rate, low blood pressure.
  • Intoxication from alcohol: slurred speech, unsteady gait, uncoordinated movements, drop in blood pressure, alcohol smell on breath.
  • Intoxication from benzodiazepines: sedation, drooling, low blood pressure, loss of muscle coordination, slurred speech.
  • Intoxication from stimulants such as amphetamines: dilated pupils, pressured speech, hyperactivity, rapid heart rate, tremor, high blood pressure.
• Monitor daily response to administered doses, including signs of efficacy such as improvement in withdrawal symptoms, and signs of safety concerns such as symptoms of intoxication from the treatment that may require discontinuation of the medication or an adjustment of the dose.
• Monitor proper administration of ingested doses.
• Monitor for drug interactions with other concurrent therapies and for use of other opioids or substances that may contribute to increased risk of respiratory depression.
• Monitor for signs of diversion or use of the medication inconsistent with how it is prescribed.

It is important to note that some patients may exhibit signs consistent with intoxication due to other medical conditions. Pharmacists must always ensure they consider their observation in the context of the patient’s complete medical history to avoid stigmatizing them.

5.7 Urine toxicology testing

Urine toxicology testing (UTT) is a tool that may be used in the context of OAT by healthcare practitioners, usually prescribers, for various reasons. It is used at a baseline to establish or corroborate a patient’s recent opioid use and to screen for any drugs or substances which may increase the risk of harm to the patient who is prescribed OAT. As a monitoring tool, UTT can be used to assess adherence to treatment or may provide data to support efficacy or safety of treatment. Regulated members are frequently involved in notifying patients of upcoming urine tests ordered by their prescribers, administering point-of-care tests, or collecting specimens for laboratory analysis. Pharmacists may be involved in ordering UTT where appropriate. All these activities must occur in compliance with ACP’s Laboratory and Point-of-Care Testing Standards.

Regardless of their role in UTT, pharmacists are expected to collaborate with the patient’s prescriber to understand the role of UTT in their patient’s treatment plan, and to establish who is best to order, administer, interpret, and communicate the results of the tests. Duplication of testing is discouraged. If a pharmacist becomes aware of a UTT result and they are unsure of the implications of it on the patient’s treatment, or if a patient does not complete a required UTT that has been requested by the prescriber, they should collaborate with the prescriber prior to dispensing OAT.

While UTT may provide clinical value, it is also important to consider the impact that frequent screening may have on the lives and livelihoods of patients. It has the potential to contribute to untoward effects such as interference with work or other activities and may be interpreted by patients to be unnecessary and stigmatizing. All of this could lead to premature discontinuation of OAT by patients.

6.1 Introduction – buprenorphine-naloxone

Buprenorphine-naloxone is a medication for treatment of OUD which has gained popularity as a preferred treatment due to its enhanced safety profile as compared to methadone.

Buprenorphine-naloxone is most often available as sublingual tablets of buprenorphine in combination with naloxone in a 4:1 ratio.

Buprenorphine is a partial opioid agonist at the µ (mu) receptor. It is associated with a reduced risk of death in overdose compared to full opioid agonists such as methadone because it exhibits a ceiling effect. This means that higher doses or serum concentrations will not necessarily result in additional adverse effects such as respiratory depression. This is why many clinicians consider buprenorphine-naloxone to be a safer drug than methadone. However, buprenorphine’s ceiling effect may also result in limitations since its effectiveness plateaus once a certain serum level is reached.

Naloxone is an opioid antagonist that can displace opioids from their receptors, leading to withdrawal symptoms; however, it is not well absorbed orally and does not exert a pharmacologic response when administered sublingually. As such, buprenorphine-naloxone contains naloxone solely to deter diversion via the intravenous route, where naloxone is highly bioavailable and likely to cause immediate and significant withdrawal symptoms.

6.2 Counselling and patient education - buprenorphine-naloxone

Patients who are prescribed buprenorphine-naloxone for treatment of OUD require comprehensive education and information to ensure clear expectations and understanding of the treatment. Pharmacists should collaborate with prescribers to determine who is best positioned to deliver some, or all, of this information.

Counselling prior to initiation of buprenorphine-naloxone therapy is critical because of the

• risk of precipitated withdrawal following initial doses of buprenorphine-naloxone;
• importance of correct administration of the sublingual tablets;
• potential risks and toxicities when combined with other CNS depressants;
• common need for frequent monitoring, reassessment, and dose adjustments over the course of first few days of treatment;
• specific requirements for storage and handling to enhance safety; and
• considerations regarding time commitment (e.g., transportation) and cost of daily administration.

Due to the volume of important information that pharmacists need to discuss with patients during the initial counselling session, consider the use of an information sheet for patients to take home and review. There is the potential for repetition of material already provided by other health professionals caring for the patient; however, repetition positively reinforces the information. Pharmacists must ensure that they have made the patient aware of information pertaining to their own scope of practice.

A sample patient handout regarding buprenorphine-naloxone for treatment of OUD is provided in Appendix 9.

6.3 Buprenorphine-naloxone dosing

6.4 Administration – witnessed doses of buprenorphine-naloxone

6.5 Dispensing take-home buprenorphine-naloxone

Prescribers may consider offering take-home doses of buprenorphine-naloxone once the patient’s OUD has stabilized and/or when the benefits of offering take-home doses outweigh the risks. Due to the safety profile, patients may be offered take-home doses of buprenorphine-naloxone more quickly than other forms of OAT.

For patients prescribed buprenorphine-naloxone, regulated members should

• assess and document the social situation, environment, and arrangements in which the patient lives to determine safety and risk of take-home doses to others who cohabitate with the patient; and
• educate to ensure the patient understands how the product should be taken and stored to optimize efficacy and safety.

Based on the results of this assessment, regulated members may request that the patient pick up, transport to and from the pharmacy, and store their take-home doses in a locked box or secured container if they determine it is necessary for safety reasons.

Other considerations for buprenorphine-naloxone take-home doses are to

• Dispense take-home tablets in a manner that maintains their integrity, paying special care to avoid situations where the tablets are exposed to water or excess humidity. This may include dispensing in the original packaging.
• Dispense take-home tablets in a light-resistant and child-resistant bottle or vial.
• Dispense each tablet in individually labelled containers to support adherence.

Only permit deviations from the requirement for a child-resistant container at the patient’s request. If an exception is made

• document the rationale within the patient’s records,
• document the patient’s acknowledgement and acceptance of this deviation, and
• provide adequate counselling regarding the potential dangers and toxicity to children and the public from inadvertent ingestion of doses intended for the patient.

In addition to the items outlined in the label requirements for methadone, labels for take-home doses of buprenorphine-naloxone must include

• the instructions for administration, which can include the date(s) that individual tablets should be administered or, if not taken daily, the days of the week for administration by the patient; and
• one of the following cautionary warnings:
  • “Buprenorphine-naloxone may cause serious harm to someone other than the intended patient. Not to be used by anyone other than the patient for whom it was intended.”
  • “May be toxic or lethal if ingested by a child or adult other than the intended patient. Accidental ingestion is considered a medical emergency and requires immediate medical attention.”

Regulated members may consider instructing patients to return empty containers to the pharmacy for inspection and proper destruction (as applicable) as a tool to assess adherence. Returned containers may not be reused for the same or for another patient.

6.6 Managing missed buprenorphine-naloxone doses

As the inherent risks of missing doses of buprenorphine-naloxone are considered to be less harmful when compared to methadone, and because of buprenorphine-naloxone's long half-life, buprenorphine-naloxone may be considered a preferred treatment in patients who may experience challenges attending the pharmacy daily.

Due to the long half-life and safety profile of buprenorphine-naloxone, pharmacists should, in collaboration with the prescriber, consider options to minimize the risk of precipitated withdrawal. This may include delaying the next dose until at least 12 hours have passed since the time of opioid ingestion and confirming that the signs of opioid withdrawal are clearly evident before resuming doses. In deciding how long to withhold buprenorphine-naloxone, the pharmacist and prescriber should consider the half-life of the opioid taken by the patient, the patient’s clinical presentation, and the clinical judgement of the pharmacist and the prescriber.

Pharmacists must use their own professional judgement when withholding doses. Trusted clinical resources such as The British Columbia Centre on Substance Use (BCCSU) Opioid Use Disorder Guidelines[1] should be consulted in context with gathered patient information and in collaboration with the prescriber to determine the most appropriate treatment approach for the patient.

Pharmacists must

• document any missed doses on the patient’s administration record,
• clearly document the patient’s reason(s) for missing the doses,
• report all missed doses to the prescriber and collaborate on any treatment changes, and
• obtain a new prescription for any resulting dose changes.

Pharmacists should inactivate all old prescriptions to avoid errors.

Report missed doses to the prescriber and other relevant healthcare professionals who may be in the patient’s circle of care.

It is strongly recommended pharmacists develop a missed dose strategy/agreement with the prescriber in the event that the patient misses a dose(s) and the prescriber is unavailable for consultation.

6.7 Lost/stolen buprenorphine-naloxone doses

Patients reporting lost or stolen take-home buprenorphine-naloxone doses should be encouraged to report them to the authorities. Even if the patient does not report their lost or stolen buprenorphine-naloxone to the authorities, it is the responsibility of pharmacists and other health care professionals to report this to the proper authorities if it is deemed to be a risk to the community/public.

Pharmacists may not replace a buprenorphine-naloxone dose without consulting with the prescriber and obtaining a new prescription for the replacement dose. In consultation with the prescriber, the pharmacist should assess the potential benefits of replacing the dose(s) against the potential risks to the patient or the public.

6.8 Vomited buprenorphine-naloxone doses

Buprenorphine is absorbed sublingually within one to 10 minutes, bypassing the gastrointestinal tract. Vomited doses generally do not require a replacement dose.

6.9 Managing buprenorphine-naloxone overdose

The partial agonist properties of buprenorphine may contribute to a reduced overdose potential when compared to methadone. Buprenorphine has a lower potential for respiratory depression and standard doses are well below the threshold lethal dose for opioid-naïve adults compared to standard methadone doses, which often exceed the threshold lethal dose.

Regardless, overdose of buprenorphine-naloxone must be taken seriously, and if the patient is exhibiting any symptoms consistent with overdose, especially CNS or respiratory depression, naloxone should be administered immediately (by the patient, if possible, or by a pharmacist), and 911 should be called.

While naloxone is still recommended in the event of an overdose of buprenorphine-naloxone, patients could be less responsive to naloxone due to the pharmacodynamics of buprenorphine (i.e., high affinity for opioid receptors, long duration of action). This underscores the importance of calling 911 for ongoing assistance.

As buprenorphine is absorbed sublingually, induced vomiting will likely be ineffective to reverse the course of the overdose.

7.1 Buprenorphine subcutaneous injection

Buprenorphine extended-release depot injection (Sublocade®) is a long-acting formulation of buprenorphine available for the treatment of OUD. The product is administered to the patient subcutaneously on a monthly basis. Patients must be stabilized on buprenorphine-naloxone sublingual tablets for a minimum of seven days prior to being initiated on the injectable product.

7.2 Buprenorphine subdermal implant

Buprenorphine implants (Probuphine®) must be surgically implanted by healthcare professionals who are appropriately trained to do so and are acting within their professional scope of practice. Pharmacists and pharmacy technicians have a limited role in management of this therapy; should they become aware of it, they should document this in the patient record of care.

8.1 Introduction - methadone

Though methadone has a large body of evidence to support its use in OUD, like other opioids, it can present significant risk to the individual and the community. Methadone must be dispensed, administered, and monitored by trained health professionals. Evidence suggests that patients are at highest risk of morbidity and mortality during the initiation phase, typically the first two weeks, of methadone maintenance treatment. Close monitoring and support are required to ensure patient safety and retention in care.

Methadone is a full opioid agonist and, as such, has no ceiling effect. This means, relative to other treatment options, methadone poses an increased risk of harm from overdose, drug interactions, or other circumstances which can lead to elevated serum methadone levels.

There can be significant variability in the response to methadone among patients. Peak plasma levels following oral administration range from one to five hours, and the elimination half-life can range from 15 to 60 hours.

Blood levels of methadone continue to rise during initial daily dosing until steady state is achieved which may take several days; careful dose titration and monitoring for efficacy and toxicity are crucial, particularly during the initiation phase. During the maintenance phase of treatment, blood levels are typically relatively stable with few fluctuations minimizing the likelihood of withdrawal symptoms. Regardless, pharmacists must continue to be diligent about assessing the patient and ensuring they are aware of any new medications or medical conditions which may affect the patient’s response to methadone.

Pharmacists and prescribers must be vigilant in assessing the risk of exposure to others, particularly in patients authorized for self-administration of take-home doses of methadone (carries). Improper handling and storage of methadone within the patient’s home can result in unintended ingestion. This is especially of concern where children may be inadvertently exposed to the medication. Methadone can harm adults as well. Doses as low as 40 mg can be lethal to an adult who is opioid naïve.

8.2 Counselling and patient education - methadone

Patients who are prescribed methadone for treatment of OUD require comprehensive education and information to ensure that they are fully aware of what they can expect when therapy begins. Pharmacists should collaborate with prescribers to determine who is best positioned to deliver some, or all, of this information.

Counselling prior to initiation of methadone therapy is critical because of

• a delayed efficacy which can be uncomfortable or frustrating for a patient experiencing opioid withdrawal;
• potential side effects that, if the patient is unprepared for them, may lead to discomfort or early discontinuation of therapy;
• a requirement for careful and gradual titration requiring patience;
• the inherent risks and potential for toxicity including overdose or death if patients consume excessive doses or supplement with additional opioids or other CNS depressants;
• specific requirements for storage and handling to enhance safety; and
• considerations regarding time commitment (e.g., transportation) and cost of daily administration.

Due to the volume of important information that needs to be reviewed with patients during the initial counselling session, consider the use of an information sheet for patients to take home and review. There is the potential for repetition of material already provided by other health professionals caring for the patient; however, repetition positively reinforces the information. Pharmacists must ensure that they have made the patient aware of information pertaining to their own scope of practice.

A sample patient handout regarding methadone for treatment of OUD is provided in Appendix 8.

8.3 Selection of product - methadone

Commercially available methadone liquids are approved by Health Canada for treatment of OUD. Unless in the case of a drug shortage during which Health Canada-approved products are not available, or a clinical reason such an allergy to a component of the commercially available product, compounded methadone must not be dispensed as OAT.

Some patients including those who have been stable for years, have reported symptoms of opioid withdrawal after being switched from one methadone formulation to another. Regulated members should be aware that

• Some patients may experience withdrawal symptoms after being switched from one formulation to another; these patients should be clinically managed and monitored regularly.
• If patients are stable on their methadone treatment and can be maintained on that product, it is advisable to avoid switching products.
• Early withdrawal symptoms can lead to a failure to remain in treatment and subsequent problematic substance use, which may lead to serious harms.[1]

8.4 Measuring methadone

Even small variations in the dispensed volume of methadone can result in increased risk or decreased efficacy for the patient. Both scenarios could result in serious harm. Pharmacists, pharmacy technicians, and other pharmacy team members involved in the measuring and preparation of methadone doses must ensure that accurate, calibrated equipment with an error rate of no greater than +/- 0.1mL is used. Additional guidance for measuring methadone includes the following:

• For any devices used to measure methadone, including oral syringes, obtain documentation from the manufacturer that supports the accuracy of the measurements.
• Oral syringes may not be re-used.
• Graduated cylinders are not recommended.
• Equipment used to measure methadone should be dedicated for this purpose and labelled as such to avoid possible cross-contamination with other preparations.
• Equipment used to measure methadone should be cleaned, used, and maintained according to manufacturer specifications.

8.5 Diluting methadone

Commercially available methadone products indicated for treatment of OUD are available in 10mg/mL concentrations. Some products (e.g., Methadose® Sugar-Free) are isotonic solutions and require dilution with a crystalline liquid (e.g., Tang®) to a total volume of 100mL, to minimize risk of diversion and administration via the intravenous route. While hypertonic solutions (e.g., Methadose® Cherry-Flavoured) do not specifically require dilution with a crystalline liquid, pharmacists may decide to do so at their discretion. Considerations include

• when dispensing small volumes, surface adhesion of the concentrate to the dispensing device or bottle may result in inaccurate or variable dose delivery; and
• risk of potential misuse and/or diversion.

When diluting methadone solution, regulated members should record

• the date of dilution,
• the lot number, and
• the expiry date of both the commercially available methadone solution and the diluent based on the expiry of the product or opened bottle, whichever is shorter.

This information should be documented on the dilution record (see sample in Appendix 6), the patient’s electronic profile, or directly on the prescription, whichever is most feasible, and it must be available to audit or track the diluted preparation.

In general, dispensing methadone in fruit juices, water, or diluents not identified in Appendix 7 or within a product monograph is discouraged due to the lack of sufficient evidence for stability and sterility upon extended storage of the mixture, especially beyond immediate ingestion upon dilution.

8.6 Stability and potential for microbial growth – methadone

The stability and potential for microbial growth of commercially available methadone solutions diluted with a crystalline liquid such as Kool-Aid®, Tang®, or Crystal Light® is not well understood. Dispensing guidelines within many provincial jurisdictions have identified the duration of stability of methadone in various diluents from a collection of past literature (see Appendix 7); however, available literature does not address the issue of microbial growth in the prepared solution stored under refrigerated or unrefrigerated conditions. The information in Appendix 7 is provided as best existing guidance to allow professional judgement when assigning a beyond-use date (BUD) for diluted methadone preparations.

Pharmacists are required to use best judgement to determine the BUD for diluted products. All diluted methadone products must be refrigerated, and take-home (carried) doses are permitted a maximum BUD date of 14 days from the date of dilution. A pharmacist must determine a BUD based on the earliest expiry of the ingredients used or 14 days refrigerated, whichever comes first. Dilution with fruit juices may require a shorter dating as an opened juice bottle may have a best before date that is earlier than 14 days. Pharmacy technicians may assign a BUD if that data is available from reputable sources.

To avoid the potential for mix-ups during dosing, and to optimize the stability and sterility of dispensed carries, diluted methadone doses should not be prepared far in advance of the anticipated date of consumption.

8.7 Methadone dosing

There are many individual considerations for dose initiation and maintenance treatment with methadone. Methadone has been used for many years for treatment of OUD, and dosing guidelines are available in most jurisdictions. Pharmacists should collaborate with the prescriber to ensure the patient’s treatment plan follows relevant, current, evidence-based clinical practice guidelines.

8.8 Administration - witnessed doses of methadone

Daily witnessed administration of methadone by a pharmacist is typically required for all patients during the initiation phase of treatment with methadone for OUD. If patients are prescribed take-home doses, witnessed doses will be required less frequently.

Witnessed administration of OAT requires an assessment by a pharmacist including observation prior to, during, and after administration of the medication. For this reason, pharmacy technicians or other pharmacy staff must not witness the administration of OAT.

8.9 Dispensing take-home methadone doses

Take-home methadone doses, sometimes referred to as “carries” or “carried doses,” are doses of methadone that the patient is authorized to take home for self-administration. Take-home doses are typically only prescribed once a patient demonstrates a consistent, high degree of stability including a stable dose, which can take months. Before authorizing them, prescribers must ensure that take-home doses are safe for both patients and the public, as unsafe storage, non-prescribed use, and diversion of methadone may result in mortality or serious morbidity to a child, pet, or other individual for whom the medication was not prescribed. Pharmacists must also assess this risk prior to dispensing take-home doses and communicate any concerns to the prescriber.

Take-home doses of methadone must be authorized by the prescriber. A valid prescription with updated instructions regarding take-home doses is preferred, but prescribers may also provide instructions regarding take-home doses verbally or in written form to the pharmacist, as long as the patient’s dose has not changed, and the current methadone prescription still has doses remaining. Any verbal or written changes to the instructions must be documented by the pharmacist on the patient’s record of care. If any dose or quantity changes are required, the prescriber must issue a new TPP Alberta prescription.

Take-home doses must be picked up by the patient personally and not by an agent on their behalf. In extenuating circumstances, where it is not possible or practical for the patient to attend the pharmacy in person and the pharmacist determines that the benefits of providing the doses to the patient agent outweigh the risks to the patient and the public, the take-home dose may be picked up by the patient’s agent.

As mentioned, take-home doses can pose a risk that doses may be lost, misplaced, stolen, or improperly stored such that accidental exposure by someone for whom the methadone is not prescribed may occur. Pharmacists must assess this risk each time methadone is dispensed. They are also strongly encouraged to maintain a signed agreement with the patient to acknowledge the expectations and obligations of both the patient and the pharmacy in the dispensing of take-home doses (see Appendix 3 for the relevant section of the pharmacist-patient agreement).

Pharmacists must

• Ensure they determine if the patient has a take-home naloxone kit at home and provide a replacement or new kit if required or requested.
• Ensure the prescription authorizing take-home doses is appropriately written to identify ingestion days and dispensing intervals.
• Assess the stability of the patient.
• Assess the social situation, environment, and arrangements in which the patient lives to determine safety and risk of take-home doses to others who cohabitate with the patient.
• Educate to ensure the patient understands how the product should be taken and stored, to optimize efficacy and safety.
• Prepare all take-home doses to their final formulation; further dilution or manipulation by the patient should not be necessary.
• Package and label to optimize safety and adherence with proper administration.
• Dispense take-home methadone as single-use doses (i.e., each dose must be in its own container).
• Dispense take-home methadone doses in a child-resistant container. Deviation from this standard should only be permitted at the patient’s request and when assessed as appropriate by the pharmacist. Document the rationale within the patient record and include the patient’s acknowledgement and acceptance of this deviation. Provide adequate counselling on the potential dangers and toxicity to children and the public from inadvertent ingestion of doses intended for the patient.
• Monitor adherence with take-home doses.
• Instruct patients to return all used/empty take-home methadone containers to the pharmacy for proper disposal prior to receiving additional take-home doses.
• NOT reuse take-home methadone containers, even for the same patient. All used containers must be discarded appropriately with all confidential labelling removed.
• Communicate with prescribers if issues and concerns arise. Patients who experience challenges with the management of take-home doses, or who frequently request replacement for lost, stolen, or spoiled doses, may require re-evaluation of their treatment plan in the interests of safety and efficacy.
• Maintain a record when preparing diluted take-home doses to enable the tracking of products and diluents used to prepare the final product.

Pharmacists may

• request that patients return take-home bottles to the pharmacy for inspection at any time as a tool to assess patient adherence;
• ask that the patient present to the pharmacy during the take-home dose period for an unscheduled witnessed ingestion if required for patient reassessment; and
• request that the patient pick up, transport to and from the pharmacy, and store their take-home doses in a locked box or secured container if they determine it is necessary for safety reasons.

8.10 Withholding the medication dose

Pharmacists can withhold the medication if the patient’s presentation causes the pharmacist to question if the risks of administering the dose at that time may outweigh the benefits. The pharmacist must contact the prescriber if they withhold a dose.

It may be appropriate to allow the patient to stay in the pharmacy until their symptoms resolve or suggest that the patient return to the pharmacy later that day for their dose.

If a patient reports unanticipated sedation with their dose particularly during the induction phase or with dose increases, regulated members should advise the prescriber and could consider withholding the dose until collaboration with the prescriber has occurred.

It is valuable to, at the onset of treatment, outline potential reasons for withholding medication in the pharmacy-patient agreement.

8.11 Managing missed methadone doses

Because missing methadone doses can result in rapid and unpredictable loss of tolerance to opioids, it can be harmful to administer methadone to a patient who has missed several doses. Pharmacists must communicate all missed doses to the prescriber in a timely fashion and prior to any future doses being dispensed. If a pharmacist identifies that a patient has missed any number of recent methadone doses, especially consecutive doses, the pharmacist should conduct an assessment to determine whether it is safe and appropriate to administer the next prescribed dose.

Trusted clinical resources such as The British Columbia Centre on Substance Use (BCCSU) Opioid Use Disorder Guidelines[1] should be consulted in context with gathered information and in collaboration with the prescriber to determine the most appropriate treatment approach for the patient.

Pharmacists must

• document any missed doses on the patient’s administration record,
• clearly document the patient’s reason(s) for missing the doses,
• report all missed doses to the prescriber and collaborate on any treatment changes, and
• obtain a new prescription for any resulting dose changes.

Regulated members should inactivate all non-current prescriptions to avoid errors.

Report missed doses to the prescriber and other relevant healthcare professionals who may be in the patient’s circle of care.

It is strongly recommended pharmacists develop a missed dose strategy/agreement with the prescriber in the event that the patient misses a dose(s) and the prescriber is unavailable for consultation. This may be outlined in a three-way agreement with the prescriber, and it is important to be aware that expectations regarding handling of a missed dose may be different during the initiation phase of treatment as compared to the stabilization phase.

8.12 Lost/stolen methadone doses

Patients reporting lost or stolen take-home methadone doses should be encouraged to report them to the authorities. Even if the patient does not report their lost or stolen methadone to the authorities, it is the responsibility of pharmacists and other healthcare professionals to report this to the proper authorities if it is deemed to be a risk to the community/public.

Pharmacists may not replace a methadone dose without consulting with the prescriber and obtaining a new TPP Alberta prescription for the replacement dose. In consultation with the prescriber, the pharmacist should assess the potential benefits of replacing the dose(s) against the potential risks to the patient or the public.

8.13 Vomited methadone doses

The decision to replace a methadone dose following vomiting must be made on a case-by-case basis, in collaboration with the prescriber. The pharmacist and prescriber should consider the time the original dose was ingested, the time of vomiting, whether the vomiting was witnessed by the pharmacist, and other relevant clinical information including any symptoms being experienced by the patient. Replacement of any part of the dose must only occur when accompanied by a new TPP Alberta prescription for the replacement.

To prevent this situation, pharmacists should screen patients for nausea prior to administering methadone and, if needed, offer strategies to minimize risk of vomiting. Strategies may include pre-dosing with an anti-nauseant, sipping methadone slowly, or returning to the pharmacy later when the patient is feeling less nauseous. Pharmacists should recommend that nauseous patients who receive methadone in the pharmacy remain under direct observation for at least 15 minutes after they take their methadone; this way, in the event vomiting does occur, the pharmacist will be able to verify the timing.

Vomited doses and the subsequent actions taken must be documented on the patient’s administration record.

8.14 Managing methadone overdose

Methadone overdose can be fatal if not managed appropriately.

If a regulated member becomes aware that a patient received a higher dose of methadone than prescribed, the regulated member should advise the patient to use their naloxone kit (if they have one) and call 911 immediately.

If the poisoning occurs in the pharmacy a regulated member should administer naloxone and call 911 immediately.

9.1 Slow-release oral morphine – SROM

Slow-release oral morphine refers to a 24-hour slow-release formulation of morphine (Kadian®). Other formulations of oral morphine, such as twice-daily, 12-hour sustained- or extended-release formulations (e.g., M-Eslon®), have not been empirically studied in this context and are not recommended for treatment of opioid use disorder. Morphine, like methadone, is a full opioid agonist and exhibits no ceiling effect. SROM in OUD has less evidence to support its use compared to methadone or buprenorphine-naloxone. Because of the limited evidence available, SROM is not considered a first-line therapy and pharmacists dispensing SROM to patients should work collaboratively with the prescriber and other members of the healthcare team to mitigate the risks of harm associated with this medication.

9.2 Supervised injectable opioid agonist therapy

Injectable Opioid Agonist Therapy (iOAT) involves the use of prescribed injectable hydromorphone to treat OUD. There is evidence to support the use of iOAT in individuals with OUD who have a history of injecting opioids and have not responded optimally to first-line oral OAT therapies.

Because treatment of OUD with iOAT is complex and multifaceted, iOAT is currently only delivered to patients within structured, multi-disciplinary iOAT programs. Pharmacists practising within such programs must collaborate closely with the other members of the patient’s healthcare team and must follow all relevant legislation and standards.

It is not appropriate for pharmacists to dispense or facilitate iOAT outside of an Alberta Health sanctioned iOAT program.

If regulated members become aware that their patient is receiving iOAT, they should collaborate with the iOAT program to minimize errors, optimize patient outcomes, and support continuity of care.

9.3 Naltrexone

Naltrexone is an opioid receptor antagonist that blocks the euphoric effects of opioids at adequate doses. Potential benefits of naltrexone include ease of administration, lack of induced tolerance during long-term treatment, and lack of potential for dependence or misuse. However, as an opioid antagonist, naltrexone can block the effects of opioids, including opioid analgesics prescribed for pain. The reduced tolerance to opioids resulting from the use of naltrexone may increase the risk of overdose for patients who stop taking the medication and resume opioid use.

There is limited evidence for the efficacy of naltrexone in the context of OUD, and risks may outweigh benefits. If involved in dispensing naltrexone for treatment of OUD, pharmacists must be familiar with the clinical evidence, understand the risks, educate the patient, and collaborate with the prescriber.

9.4 Non-conventional opioid substitution therapy

Regulated members may encounter prescriptions for opioids for unclear indications, or multi-factorial indications such as pain with a substance use disorder component. Pharmacists should collaborate with the prescriber on the patient’s treatment plan to minimize risks to the patient and provide harm reduction education and resources where appropriate.

10.1 Transitioning from one form of OAT to another

Switching between medications used for treatment of OUD can be a useful approach to maximize clinical outcomes or address changes to the patient’s circumstances or preferences. This activity can be nuanced and should be person-centred, considering the unique pharmacology of the medications involved. Pharmacists should consult appropriate clinical guidelines and collaborate with the prescriber and the patient to clearly outline the treatment plan and address any potential challenges.

10.2 Off-site witnessed administration of OAT

If a pharmacist delivers OAT to another facility or location where witnessed administration is to occur, they may witness the dose ingestion outside of the pharmacy premises, provided they are able to meet all standards of practice and all requirements for witnessed ingestion, including assessment of the patient. After witnessing the dose administration, the pharmacist must comply with the documentation requirements for witnessed administration.

10.3 Delegated administration of OAT

Only a pharmacist can supervise and witness the daily administration of OAT by a patient. When appropriate a prescriber may request the pharmacist delivers a dose to another regulated health professional acting within their scope for a delegated witnessed administration. Pharmacists may refuse these requests if they have concern for the security of the medication and/or the safety and risk to the patient or the public. However, pharmacists must clearly communicate these concerns and discuss them with the prescriber to resolve issues and facilitate continuity of care in the best interest of their patient.

Document the request and final decision in the patient record. If the patient requires delivery, make every effort to ensure the dose reaches the intended individual(s). Use a reliable, secure, and confidential method of transportation and follow-up to ensure that the dose has been delivered untampered. Receipt must be documented, including the date of receipt, intended date of administration, drug, dose, and name and signature of the individual delegated to witness the dose. A locked container is advisable to transport the medication to the intended recipient, along with packaging and labelling consistent with that used for take-home doses of OAT. Transportation of controlled substances must comply with the requirements outlined in Health Canada’s Controlled Drugs and Substances Act.

It is the delegated individual’s responsibility to record the ingestion. The pharmacist must confirm that the dose has been ingested as intended.

10.4 Voluntary patient discontinuation of treatment

If a patient wishes to discontinue their OAT, regulated members must respect their decision. However, a pharmacist must discuss with the patient any potential consequences including risk of relapse to disordered substance use. Inform other members of the healthcare team of the patient’s decision and status. Abrupt discontinuation should be discouraged to prevent a rapid loss of tolerance creating a high risk for overdose morbidity and mortality. Sudden cessation of therapy can also result in severe and lasting withdrawal symptoms. If applicable, the pharmacist should collaborate with the prescriber to develop a taper schedule for the individual and/or prescribe medications to provide symptomatic relief. Pharmacy staff should continue to support the patient until the patient no longer requires the pharmacy’s services.

10.5 Involuntary discontinuation of treatment

At the onset of therapy, a regulated member should discuss potential scenarios that may lead to discontinuation of pharmacy services with the patient. These scenarios can be outlined in the patient-pharmacy agreement. If discontinuation of pharmacy services is necessary, regulated members must assist the patient in receiving care from another pharmacy to ensure continuity of care. The pharmacist must also inform the other members of the treatment team. As in the case of voluntary discontinuation of OAT, the pharmacist should consider collaborating with the prescriber to develop a taper schedule for the individual and/or prescribe medications to provide symptomatic relief.

10.6 Transfer of care

If a patient requires a transfer of care, it is the obligation of regulated members to assist the patient and to maintain continuity of care. This may require regulated members to facilitate the transfer of records and patient information to a new pharmacy or care provider. It may also require regulated members to support the patient in locating a new pharmacy or care provider.

A key piece of information to provide to the new care provider are the details of the patient’s last confirmed ingested dose.

Note that only licensed dealers with appropriate permits are authorized to import or export narcotics across international borders; patients transferring out of country will have to secure a prescriber and comply with the applicable rules and regulations within their new country.

All take-home doses required to facilitate a transfer of care must be approved by the prescriber and documented by the pharmacist. A pharmacist is not required to provide take-home doses if they deem it unsafe for either the patient or the public.

10.7 Incarceration

OAT should continue if a patient is incarcerated. OAT services are often available in provincial correctional facilities, remand centres, and federal prisons.

Pharmacies providing medication-assisted treatment services that become aware of the incarceration of a patient should notify the patient’s prescriber to facilitate a seamless and coordinated transition of care. Pharmacists should also collaborate with the correctional facility to share any pertinent clinical information at the time of intake, and to discuss discharge planning to ensure a smooth transition of care when the patient is released from incarceration.

Individuals leaving incarceration may have a reduced tolerance to opioids due to discontinuation of opioid use while incarcerated or disruption to their OUD treatment plan. This may lead to higher risk of adverse effects and mortality due to overdose even at previously tolerated doses of OAT or other opioids. Pharmacists should be aware of this and take steps to educate the patient about these increased risks as they transition their care back to the community.

10.8 Hospitalization

Regulated members providing OAT services who become aware that a patient is hospitalized, must notify the patient’s prescriber to facilitate a seamless and coordinated transition of care. Community pharmacists should also collaborate with the hospital pharmacist to share any pertinent clinical information at the time of admission, and to discuss discharge planning when the patient is being released. Regulated members working in the hospital must ensure the patient’s community pharmacist is advised of the hospitalization and the need to hold or discontinue the community pharmacy OAT prescription while the patient is in hospital. Where appropriate, regulated members working in a hospital must ensure that OAT therapy continues uninterrupted for the duration of the hospital visit and at discharge.  The patient should be closely monitored for any adverse effects.

Hospital physician prescribers do not require CPSA approval to maintain patients on methadone, SROM, or iOAT. If changes are required to any OAT dose, these prescribers are required by CPSA to consult with the initiating prescriber or their delegate.

Some hospitals may have limited access to OAT medications based on their location or resources. Community pharmacies and prescribers who provide OAT should collaborate with hospitals to facilitate continuity of treatment where such gaps exist, and this may include the provision of interim OAT doses at the time of admission or ongoing as required.