Methadone and

Buprenorphine/Naloxone
Toolkit for Pharmacists
Part A: Methadone

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Table of Contents

Introduction to Opioid Agonist Treatment (OAT) ............................................................ 3

Methadone Dispensing at a Glance………………………………………………………….5

Methadone Drug Interactions ................................................................................................................................................. 8

Initiating a Methadone Program in Your Pharmacy………………………………..……..11

Initiating MMT Services: a Brief Overview…………………………………………………14

Methadone Maintenance Dosing Guide............................................................................................................................... 17

Resources ............................................................................................................................................................................ 20

Disclaimer

These tools have been developed by the Ontario Pharmacists Association for pharmacists in Ontario as a general guide to support those wishing to
initiate a methadone program in their pharmacy setting. The resource materials provided in this toolkit are for general information purposes only and are
NOT meant to be used as a sole tool for clinical decisions.

This toolkit is complementary and is not inclusive of all recommendations and considerations. The information provided is not a substitute for sound
clinical judgement from the health care professional. Pharmacists are to exercise their professional judgment in accordance with the Ontario College of
Pharmacists (OCP) Standards of Pharmacy Practice. This tool is not a substitute for established clinical practice guidelines or regulatory requirements. It
is not intended to supersede or replace guidelines, practice standards, policies or procedures issued by OCP, the Ministry or corporate employers. It is
also not intended, and should not be construed, as legal or professional advice or opinion.

While OPA strives to ensure the accuracy of the information provided in this document, information may be subject to change, and it is the responsibility
of the user of this document to ensure they have the most up-to-date and complete information from available resources.

Note: During the COVID-19 pandemic, modifications to the standard guidelines have been made in order to reduce community transmission. Please
refer to the CAMH document “COVID-19 Opioid Agonist Treatment Guidance” for further information on these modifications to treatment delivery.

Acknowledgement

Compilation of this toolkit required the dedicated effort of many individuals. The Ontario Pharmacists Association would like to thank the following for
their tireless work in revising and reviewing the toolkit for the benefit of all Ontario pharmacists and the patients they serve: Rose Fitzgerald, B.Sc.Phm;
Satinder Sanghera, BScPhm, RPh; Andrew Tolmie, RPh, BScPhm; Shamim Rajan; Dr. Alice Ordean, MD, CCFP, MHSc, FCFP; Mohammad-Usman
Imran, B.Sc.Phm., RPh; and the Ontario College of Pharmacists.

The Ontario Pharmacists Association wishes to acknowledge the Ministry of Health for funding this initiative.

Full update: March 2023

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Opioid Agonist Treatment (OAT)
OAT involves the prescribing of methadone buprenorphine or sustained-release oral morphine as part of a comprehensive
program which includes counselling to help the person in treatment reduce or stop the harmful use of opioids. (Kleber,
2008).

Pharmacotherapy is the most effective treatment for opioid use disorder (OUD), and opioid agonist therapy (OAT) saves
lives. The mortality risk is significantly reduced for people with OUD while in OAT treatment compared to out of OAT
treatment.

Currently, methadone and buprenorphine are the most prescribed treatment options. Methadone is the most studied and
longest used pharmacological treatment for opioid dependence.

A third option, oral slow-release morphine OSRM (e.g., Kadian®) may be used as OAT in individuals who have not
benefited from treatment with first line and second line treatment options (i.e., buprenorphine/naloxone and methadone).
Kadian may also be used in combination with methadone during the initiation phase for people who use fentanyl.
Guide_MethadoneForFentanyl.pdf (metaphi.ca) In Canada, this use is considered off-label, and requires careful review
of the risks and benefits, fully informed consent of the patient and rigorous clinical documentation.

The approach to providing OAT services is evolving in Ontario. The CPSO Methadone Maintenance Treatment Program
Standards and Guidelines from 2011 was rescinded in March 2021. It was perceived that the exceptional status of
methadone and the high degree of oversight, disincentivized physicians to offer OAT, thus limiting access for patients. As
well, in 2018, Health Canada removed the Section 56 exemption requirement for methadone prescribers – to improve
access to treatment,

Recent practice changes for OAT can be reviewed at:

https://pharmacyconnection.ca/update-on-opioid-use-disorder-treatment/

OAT as a Harm Reduction Approach

Any program or policy designed to reduce drug-related harm without requiring the cessation of drug use. Interventions
may be targeted at the individual, the family, community or society (Erickson et al, 2002).

Harm reduction includes both strategies that focus on reducing drug use and those that focus on reducing the harm of
drug use.

OAT has been shown to reduce:

• Use of other opioids (Brand et al., 2003; Davioli et al., 2007; Gibson et al., 2008)
• Criminal activity (Lind et al, 2005) as OAT is legal and may keep patients away from the harmful consequences of
acquiring and possessing illicit opioids and prescription opioids
• Patient mortality rates (Degenhardt et al., 2011; Gibson et al., 2008; Soyka et al., 2011) compared to people who
continue to use opioids
• Injection-related risk (including behaviours and transmission of HIV and sexually transmitted infections (Hart,
2007)
• Cost of law enforcement, health care and social services for patients who are unemployed, homeless or in other
difficulties (Hart, 2007)

OAT improves (Brands et al., 2002):

• Physical and mental health
• Social functioning
• Quality of life
• Pregnancy outcomes

In contrast to many short-acting opioids (e.g., heroin), long-acting opioids used for OAT:

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 • Are well absorbed and effective orally (methadone, morphine), sublingually (buprenorphine) or subcutaneously
(buprenorphine XR injection)
• Take longer (e.g., 30 minutes vs. instantaneously) to produce an effect than opioids that are injected, smoked or
snorted
• Are longer acting than other opioids (24 to 36 hours or longer vs. three to six hours) and are administered less
frequently
• Do not cause drowsiness or euphoria in patients on an appropriate dose
• Do not cause significant impairment in thinking, behaviour or functioning when taken at an appropriate dose
• Do not dull normal emotions and physical sensations
• Diminish opioid craving
• Decrease drug-seeking behaviour
• Reduce the likelihood of euphoria from other opioids in stable patients
• Continue to be effective with long-term use without dose increases

Limitations to the use of OAT

• Methadone is a high-risk medication with a narrow therapeutic range that can result in opioid overdose, especially
at the beginning of treatment. It may prolong QT interval, leading to an increased risk of fatal arrhythmias.
• Buprenorphine has a lower overdose mortality risk but can still have severe health consequences including death
– especially, if misused or combined with other CNS depressants including alcohol.
• People (including health professionals) may inadvertently or inappropriately label patients as ‘still addicted’, thus
stigmatizing them further.
• Program practices may be experienced by patients as demeaning (e.g., observed urine collection, waiting in line
at the pharmacy for their dose).
• OAT requires regular visits to the pharmacy, physician, and counsellor.
• Cost may be a barrier for some patients.
• Both buprenorphine and methadone can produce adverse side-effects and may interact with other medications.
• OAT practices may limit patient’s ‘flexibility’ for work or travel.
• There may be limited availability of physicians and pharmacies that offer OAT in some areas
• Pharmacists can aid their patient’s recovery by supervising drug administration, monitoring their dosage,
communicating with the treatment team, dispensing take-home doses in accordance with established guidelines
and providing encouragement and support.

CAMH Opioid Agonist Maintenance Treatment: A pharmacist’s guide to methadone and buprenorphine for opioid use
disorder. Third edition 2015

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Methadone Dispensing at a Glance
For Methadone Maintenance Therapy (MMT)

Prescription must include:

• Registration number of the certificate of registration for the prescriber (specific to each province’s college)
• Name of the person for whom the methadone is prescribed
• Name and dose of methadone
• Directions for use of methadone
• Name and address of the prescriber
• Date the methadone is prescribed
• ID number of the patient and the type of ID used

As per CAMH Guidelines:

• Start and stop dates (use the word ‘inclusive’ to minimize ambiguity)
Total quantity is not required as this can be clearly and exactly calculated based on start and stop dates
• Best practice for Prescribers – specific days methadone doses are to be ingested/observed; and days that
dose(s) can be given as take-home/carry doses
• Dose spelled out in words, as well as in numbers
• Instructions to ‘dispense in drink/juice’
• Name of the dispensing pharmacy (the patient has a choice, but the physician needs to know to ensure physician-
patient communication)
• Best practice – information about changes in dose (i.e., cancel previous prescription, dose change, carry change
etc.)
• Other instructions as needed

Confirm Narcotic Monitoring System (NMS) requirements and evaluate NMS alerts
https://www.ocpinfo.com/library/practice-related/download/Narcotics%20Monitoring%20System.pdf

Process and prepare the prescription using the DIN for one of the commercially available methadone solutions 10mg/ml
indicated for opioid agonist treatment.

Prescription label should make the following clear:

• The drug product (name, manufacturer) and amount in the bottle
• The total dose of methadone in milligrams contained in the bottle
• A notation that the drug product has been diluted (i.e., ‘in orange drink’)
• The date for ingestion (for take-home/carry doses)

For take-home/carry doses, include:

• Child resistant safety cap
• Tamper-proof tape/cap (best practice)
• ‘Keep in Refrigerator’ label
• Methadone auxiliary label which reads-
‘Methadone 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 FATAL TO CHILD OR ADULTS’
OR
‘Methadone may cause serious harm to someone other than the intended patient. MAY BE FATAL TO CHILD
OR ADULTS’

Compounded methadone is only permitted in the following:

• Therapeutic need* – patient is unable to tolerate all commercially manufactured products
NB: ODB requires the physician to submit a request to the Exceptional Access Program along with a completed
Adverse Drug Reaction form
• Lack of product availability
• A concentration less than the commercially manufactured 10mg/ml solution is required
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 • It is not a patient choice based on preference.

Where a compounded product is prescribed and dispensed, the pharmacist shall label with the expiry date and
concentration in accordance with NAPRA Model Standards for Pharmacy Compounding of Non-sterile preparations.
https://www.napra.ca/publication/model-standards-for-pharmacy-compounding-of-non-sterile-preparations/

Take-home/carry doses

• Do not dispense methadone take home doses unless authorized by prescriber

• May only be given to the patient.
NB: During this time of COVID-19, the pharmacist may consider delivering a small number of carries/take-home doses
at one time to enhance patient safety.
covid-19-modifications-to-opioid-agonist-treatment-delivery-pdf.pdf (camh.ca)
• Lock box and return of take-home bottle(s) can be considered best practices - this process should be established with
the prescriber and explained to the patient.
https://www.camh.ca/-/media/files/camh-covid-19-oat-guidance-for-pharmacists-
pdf.pdf?la=en&hash=ECEB406CEB7E973EE4A3B637520AAAA974D642B7
• Use of tamper evident tape, caps or seals is best practice to enhance safety and monitoring
• Once patient qualifies, the take home dose schedule is determined by the prescriber.

Minimizing risk

• Use tamper evident-tape or self-sealing bottles

• Best practice is to have all measurements checked by at least two pharmacy staff (one of whom must be registered
with the College)
• Positively identify all patients; call them by name and verify with picture ID
• Confirm the dose with the patient by asking them their dose before it is consumed
• If a patient is receiving methadone from two different pharmacies, have an effective communication system to confirm
last dose or missed doses.

Pharmacology of Methadone

• Readily absorbed, onset of effect is within 30 minutes

• Usual peak plasma levels: two to four hours after ingestion
• Elimination half-life is 22-48 hrs
• Steady state levels in 5-7 days
• Metabolism: primarily by cytochrome P450-3A4 in liver; minor roles for CYP1A2, 2B6, 2C8, 2C9, 2C19 and 2D6.
Primary metabolite is EDDP which is inactive and is used as a marker in urine drug screens

Methadone Adverse Effects

Note: This is a list of the more common side effects or symptoms and is not intended to be all-inclusive

Common with All Opioids:

• sweating (dose related) is exacerbated by heat and social situations (can be misinterpreted as withdrawal)
• constipation
• sexual dysfunction and neuroendocrine effects
• weight changes (usually weight gain)
• drowsiness/sedation (slurred speech, cognitive impairment, ‘nodding off’ or ataxia) sleep disturbances-insomnia (may
also be related to other causes such as depression, anxiety, PTSD or rumination of past trauma) or sleep apnea
• Dental problems caused by or related to dry mouth (there may be other medications, such as anti-depressants, used
by a methadone client that may also cause increased dryness of the mouth). With low saliva, generalized bacterial
plaque accumulates as a result of poor oral health

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Less Common-Methadone specific:
• psychoactive changes (mood or cognitive impairment)
• cardiovascular effects (QTc prolongation and cases of TdP-torsades de pointes)
• urinary hesitancy or retention

Rare-Methadone specific:
• cutaneous effects (flushing, itchiness, skin rash)
• peripheral edema (swelling of feet or ankles)

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Methadone Drug Interactions
Methadone can interact with other medications. Pharmacists should always ask about all other drugs the patient is taking
including prescription medications and herbal remedies.

Mixing methadone with other drugs that depress the central nervous system ca be extremely dangerous. Other opioids,
alcohol and benzodiazepines should be avoided. This is especially risky when you first start OAT. Using other drugs
while taking methadone can also cause your dose of methadone to affect you differently.

Pharmacists are encouraged to regularly access the most up-to-date information on drug interactions from reliable drug
information sources as part of their clinical assessment and new information is becoming known daily.

Pharmacists and Methadone Drug Interactions

• Keep an accurate, updated medication profile, including OTC, herbal and illicit drugs
• Develop a working knowledge of methadone drug interactions
• Watch for additive toxicity, particularly with CNS depressants and drugs known to increase QT interval
• Need quick access to a current list of interactions
• Determine clinical significance of drug interaction.
• Use alternative, non-interacting drugs when possible
• If potentially interacting drug must be used, adjust methadone dose based on patient response
• Make dose adjustments slowly and in small increments to avoid toxicity or symptoms of withdrawal. Severity of
signs/symptoms of withdrawal or over sedation may help determine extent of dose change required
• If potential increase in methadone levels, advise patient in advance of signs or symptoms to watch for and what to do
• When possible, avoid concurrent administration of drugs with overlapping side effect profiles
• Consider pre-existing disease states as an alternative cause for symptoms, other than a drug interaction.
• Consider complexity of prescribed regimens on patient adherence
• Patients should be carefully monitored when starting or discontinuing a medication that may interact with methadone.
• Many interactions can be managed by monitoring for symptoms (e.g., Opioid withdrawal symptoms or excess sedation)
and making dose adjustments as needed.

Patients and Methadone Drug Interactions

• Provide all health care providers with an updated list of all medications used (including OTC, herbal and illicit)
• Carry a list of all medications (Best Possible Medication Record)
• Consult with their doctor or pharmacist before taking any new prescription, OTC, herbal or dietary supplements.
• Be advised of hazards of using illicit substances or drugs intended for someone else
• Patients who are on an interacting medication should be educated about the importance of adhering to their medication
regimen.
• Counselled to quickly report any sudden or unexpected signs/symptoms of methadone withdrawal or overmedication
• If potential increase in methadone levels, advise patient in advance of signs or symptoms to watch for and what to do.
• Verbally instructed on what the drug is for, how to take it, and how to reduce risk of side effects or interactions
• Adherence to prescribed medications emphasized
• Special consideration for patients with liver or kidney disorders, pulmonary or heart ailments, pregnancy
• Instructed in advance on what to do in an emergency if their supply of methadone and/or other medications runs out

Pharmacodynamic Interactions of Methadone

Additive Effects: When methadone is combined with a medication or illicit drug that has similar pharmacological profile,
the effects may be additive – e.g., Potentiation of CNS or respiratory depressant effects, constipation, nausea or urinary
retention. CNS depressant effects of alcohol and benzodiazepines are additive when combined with methadone – putting
patients at increased risk of respiratory depression and sedation. This can result in death.

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OTC medications containing dimenhydrinate and diphenhydramine can be abused and are problematic when used by
patients on methadone. They also have CNS depressant effects.
Anticholinergic medications can potentiate the effects on the bowel, causing increased risk of severe constipation,
possibly leading to paralytic ileus. It can also increase the risk of urinary retention.

Pharmacokinetic Interactions

Many of the interactions with methadone occur through involvement of the microsomal P450 system – especially those
that are also metabolized by CYP3A4. Methadone may also be metabolized to a lesser extent by the CYP1A2, 2B6, 2C8,
2C9, 2C19 and 2D6 enzymes.

Effects of induction of methadone metabolism tend to occur slowly. Maximal effects generally occur at one to two weeks
and can result in methadone withdrawal symptoms.

Inhibition of methadone metabolism occurs rapidly, and toxic effects (sedation, respiratory distress) can present in 1-2
days – patients need to be monitored for a longer time.

Chronic use of alcohol can enhance hepatic metabolism of methadone through enzyme induction. However, acute alcohol
use reduces methadone metabolism by competing for metabolic enzyme activity. Patients presenting as intoxicated or
smelling of alcohol must be refused their dose and referred to the prescriber.

Theoretically, grapefruit juice could cause elevated plasma levels of methadone – clinical significance is unknown

Medications that can decrease Medications that can increase Medications that may be affected
plasma levels/effects of Methadone plasma levels/effects of Methadone by Methadone

Amprenavir Amitriptyline Abacavir

Barbiturates Benzodiazepines Amprenavir
Efavirenz Cimetidine Desipramine
Fusidic acid Ciprofloxacin Didanosine
Indinavir Clarithromycin MAOI’s
Lopinavir Delavirdine Nifedipine
Nelfinavir Disulfiram Stavudine
Nevirapine Erythromycin AZT
Phenytoin Fluconazole
Primidone Fluoxetine
Rifampin Fluvoxamine
Risperidone Indinavir
Ritonavir Ketoconazole
Somatostatin Paroxetine
St. John’s Wort Sertraline
Urinary acidifiers Etc.

Check with your Drug Information Centre or an online reference for current, up to date information.

Resources:

CAMH Opioid Agonist Treatment: A pharmacist’s guide to methadone and buprenorphine for opioid disorder 3rd edition
NB: Appendix 2 is not exhaustive.
To order- https://www.camh.ca/en/camh-news-and-stories/get-the-latest-on-opioid-agonist-guidelines

Drugs.com
https://www.drugs.com/drug-interactions/methadone.html

Addiction Treatment Forum 2005

https://atforum.com/documents/Drug_Interactions.pdf

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Initiating a Methadone Program in Your Pharmacy
Ontario College of Pharmacists Opioid Policy, 2018
(Formerly Methadone Maintenance Treatment (MMT) and Dispensing Policy June 2014)
http://www.ocpinfo.com/regulations-standards/policies-guidelines/opioid-policy/

Abbreviations: Ontario College of Pharmacists (OCP); College of Physicians and Surgeons of Ontario (CPSO); Centre for
Addiction and Mental Health (CAMH); Designated Manager (DM)

Information to provide to OCP:

Notify OCP within seven days of initiating methadone dispensing practice (for MMT) by submitting completed Methadone
Dispensing Notification Form – send by email to pharmacyapplications@ocpinfo.com, or fax to 416-847-8399, or mail to
the attention of Pharmacy Applications & Renewals at 483 Huron St. Toronto, ON M5R 2R4

http://www.ocpinfo.com/library/forms/download/Methadone%20Dispensing%20Form.pdf

•
Hours and days of operation for your pharmacy (including holidays)
•
Does pharmacy accept new patients?
•
Date(s) that DM and staff pharmacist(s) trained (or will be trained) to dispense methadone
•
Does the pharmacy transfer custody of methadone doses to an exempted physician or his/her delegate
for administration at a clinic?
NB: OCP must be notified of any changes to the information specified above (e.g., change in hours)

Training Requirements

Designated Manager must take the CAMH Opioid Use Disorder Treatment (OUDT) Course (or comparable course) within
6 months of beginning methadone dispensing.
https://www.camh.ca/en/education/continuing-education-programs-and-courses/continuing-education-directory/opioid-
use-disorder-treatment-oudt-course

In addition to the DM, within one year, at least one staff pharmacist must take the CAMH OUDT Course (or comparable
course) within one year.

Training must be updated every five years. One of the following would be acceptable as a training update:
OPA one-day live program
or
OPA opioid addictions and substitution therapy online modules - completion of 5 online modules including
Policies Guiding Methadone Dispensing in Ontario module
https://opatoday.com/product/opioid-substitution/

Although not mandatory, OPA methadone training courses would be beneficial for all pharmacists involved with
methadone dispensing.

All pharmacists (regular and casual) who dispense methadone must be familiar with the principles and guidelines outlined
in the current CAMH Opioid Agonist Maintenance Treatment: A pharmacist’s guide to methadone and buprenorphine for
opioid disorder 3rd edition

Required Documentation

Pharmacists should record relevant and pertinent details with regards to opioid therapy in an accessible and standardized
manner in accordance with OCP Documentation Guidelines.

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https://www.ocpinfo.com/regulations-standards/practice-policies-guidelines/documentation-guidelines/

Documentation of any decisions that requires professional or clinical judgment involving a change in therapy (holding
dose, what to do when dose vomited etc.), Documentation should include: the decision, the rationale for the decision,
expected patient outcome and plan for monitoring and follow up.

Treatment Agreement

A written two-way (pharmacist-patient) OR three-way (prescriber-pharmacist-patient) agreement serves as best practice

to outline expectations and prevent miscommunication.
CAMH Opioid Agonist Treatment 3rd edition – Appendix 4

Items to be addressed in agreement may include:

• Expectations of all parties involved (hours of operation, consequences of inappropriate behaviour of patient)
• Patient’s consent to access and share personal health information with other health professionals involved in
their care
• Notice to the patient that methadone dose will be withheld if the patient appears to be intoxicated or under the
influence of other substances
• Patient’s acknowledgement that, if requested, they will be required to provide photo ID before receiving their
dose
• Signature of Designated Manager (or delegated pharmacist) and the patient
NB: This agreement should be reviewed and re-signed when the pharmacy makes substantial changes to their
policies or procedures regarding methadone

Record of dispensing of daily observed/witnessed and take-home/carry doses. This record of administration for MMT to
include patient’s name, daily dose, date, time, and place of observed administration.

When a physician or delegate administers the methadone in a clinic/treatment location (i.e., if transferring custody of
doses), the dispensing pharmacist must be provided with copies of the daily administration record. Record of daily
reconciliation of methadone dispensed to and received from a clinic/treatment location under transfer of custody
agreements.

Record of destruction of unused doses in accordance with applicable laws and standards of practice.

If applicable, written institution1-specific policies for dispensing methadone (e.g., hospital, licensed nursing homes,
correctional facilities)
1 Institution is a facility that is licensed, approved or designated by a province in accordance with the laws of that
province to provide care or treatment to persons or animals suffering from any form of disease or illness; or is owned
or operated by the Government of Canada or the government of a province that provides health service. This would
include correctional facilities-both federal and provincial.

Note: these are not to be considered transfer of custody scenarios

Dosage Form

All doses (observed/witnessed and take-home/carry doses) must be prepared using a manufactured product (10mg/mL
solution) diluted to at least 100mL with a vehicle that does not lend itself to injection (e.g., Tang®)

Equipment Needed

• An appropriate measuring device (e.g., calibrated pump) that can accurately deliver 0.1 mL increments.
Note that graduated cylinders are not suitable.
• Disposable cups (approx.100ml) for observed doses,
• 100mL bottles for carry doses
• Childproof safety caps are required; tamper proof caps are recommended.

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 • A lock box is recommended for take home/carry doses. The necessity for a lockbox should be discussed in
collaboration with the prescriber and patient. Consideration should be given to the risks. Unsecured methadone
doses may pose a risk while under the patient’s custody – both in transit and at home.

Required auxiliary labelling for take home doses

• “Methadone 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 FATAL TO CHILD OR ADULT.”
OR “Methadone may cause serious harm to someone other than the intended patient. MAY BE FATAL TO CHILD OR
ADULT.”
• “Keep Refrigerated” auxiliary label for take home doses (may be typed as part of the prescription label)

Required References

The pharmacy must have access to the current text:

CAMH Guide Opioid Agonist Maintenance Treatment, 3rd edition

• To order - https://store-camh.myshopify.com/products/p6500

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Initiating MMT Services: A Brief Overview
Things to Consider Before Starting to Dispense Methadone

Pharmacy hours of operation – hours for methadone administration? Open seven days per week?
Pharmacy layout and workflow – private area for preparing methadone doses without distraction
A private area/alcove for counseling and witnessing methadone dose self-administration
Staffing Impact - adequate personnel, training and competency, professional satisfaction
Business Impact -impact on new clients, current patients and clientele
Impact on the surrounding community
Collaborations with methadone prescribers
Reimbursement

Develop policies on:

• Hours when methadone is dispensed
• Number of methadone clients
• Number of methadone clients in pharmacy at one time
• Service to methadone clients who are regularly serviced by other facilities (i.e., guest dosing)
• Assess staff competence to deliver methadone services in a non-stigmatizing environment
• Procedures to minimize dosing errors and optimize work processes
• Appropriate equipment (e.g., dispensing tools, measuring equipment, labels and labeling as regulated, child proof
liquid bottles, tamper evident caps or seals [best practice])
• Documentation logs with information as regulated
• Establish patient care process for patient assessment, dispensing, witnessed administration, and management of
difficult situations

Role of Pharmacist in MMT Program

• Assess patient care issues for the safe dispensing of observed/witnessed and carry/take-home doses.
• Monitor for signs and symptoms of withdrawal, intoxication and/or overdose.
• Observe for changes in patient’s appearance or behaviour
• Aware of social and housing issues that may require special dispensing needs
• Ensure a process is in place for handling missed, lost, stolen or vomited doses
• Identify and address drug interactions
• Positive identification of the patient
• Observe ingestion of witnessed/observed doses
• Provide carry/take-home doses
• Awareness of when methadone doses must be withheld and physician immediately contacted (e.g., 3 or more
missed doses in a row or as pre-established with prescriber; symptoms of intoxication such as slurred speech,
stumbling gait, confusion, disorientation)
• Provide patient advice and information as necessary (e.g., signs and symptoms requiring immediate attention at
various phases of methadone treatment and dosing, harm reduction education)
• Diversion alertness
• Determine physician’s preferred method of communication (e.g., email, cell phone, etc.) especially after office
hours
• Be familiar with the required guidelines for methadone dispensing
• Ensure all regulations are met in accordance with the pharmacist’s assigned role
• Dispensing and billing roles pending staffing

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Role of Pharmacy Technician in MMT Program

• Enter/process prescriptions pending staffing

• Check prescriptions for technical accuracy
• Prepare individual patient doses
• Monitor return of empty bottles from carry doses
• Report discrepancies to supervising pharmacist (e.g., missing patient documentation, patient identification
discrepancies, interaction codes, discoloration of solutions, unusual patient behaviour etc.)
• Billing/administrative issues as assigned by the pharmacy
• Maintain stock and required supplies

Methadone Label Requirements

(in addition to DPRA requirements for all prescriptions)

• Directions for use: “Drink entire contents of bottle”

• Dose in mg.
• A notation that the drug product has been diluted (i.e., “in orange drink”)
• Date of ingestion for carry/take-home doses

Required auxiliary labels as per OCP Policy

• Methadone 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 FATAL TO CHILD OR ADULT.”
OR “Methadone may cause serious harm to someone other than the intended patient. MAY BE FATAL TO CHILD
OR ADULT.”
• “Keep Refrigerated” auxiliary label for take home doses (may be typed as part of the prescription label)

Preparing Methadone Dose

• Accurately measure commercially available methadone solution using an appropriate measuring device accurate
to 0.1ml increments
• Diluents for methadone doses (witnessed/observed and take home/carry) may include Tang®, Crystal Light®,
Kool-Aid®, and other brands of artificially sweetened crystals. It is important to note that stability data is lacking
for the mixture of Methadose® or commercially prepared methadone 10mg/ml liquids in these drinks. The vehicle
component will develop microbial contamination; therefore, it is recommended to refrigerate take home doses. In
the absence of clinical stability and sterility data, USP 795 recommends a maximum beyond use date of 14 days
for oral non-sterile preparations containing water, when stored at controlled cool temperature (i.e., Temperature
thermostatically maintained between 2 and 8 degrees Celsius)
• Take-home/carry doses prepared in these diluents must be protected from extremes in temperature when
transferring custody to a physician’s clinic using delegation

Initiating a New Patient

• Copy of picture identification

• Current contact information (keep regularly updated)
• Two or three-way treatment agreement signed by all parties
• Explain hours of operation and usual process/procedure
• Lock box and take-home/carry dose bottle return policy (as necessary)
• Counsel on safety and harm reduction

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Physician - Pharmacist Collaboration

• Pharmacy and clinic hours of operation

• After hours contact information for physician and pharmacist
• Consistency in patient messaging and counseling for patient care issues
• Is a lock box required by the prescriber
• Tamper proof caps/seals required by the prescriber/clinic?
• Return take home dose bottles?
• Procedures for missed appointments and missed doses?
• How to notify prescriber of missed doses?

Patient Treatment Agreement

2-way (pharmacist-patient) or 3-way (prescriber-pharmacist-patient)

Expectation of all parties and consequences may include:
• Consent to access and share personal health information among health care professionals involved in their care
• Pharmacy and clinic hours of operation
• Consequences of inappropriate behaviour
• Need for lock box and returned take home dose bottles (if applicable)
• Inability to have methadone dose if patient appears to be intoxicated and/or under the influence of other
substances
• Notice to the patient that missed, lost, stolen or wasted doses will not be replaced without a prescription
• Patient’s acknowledgement that, if requested, they will be required to provide photo ID before receiving their dose
Sample patient-pharmacist agreement can be found in references pages of
CAMH Guide Opioid Agonist Maintenance Treatment, 3rd edition - Appendix 4

Witnessing a Dose

• Positive identification of patient (photo ID)

• Only the pharmacist can assess the patient in order to safely administer the dose
• Confirm the dose with the patient
• Prepare the dose and administer it in a container that will hold at least 100 mL of liquid (disposable cup or bottle)
• Ensure total volume is consumed and converse with patient to ensure dose was swallowed
• Cup is to be disposed of in the pharmacy
• Pharmacist and/or patient sign the record of administration

Documentation

Documentation of methadone ingestion must include the patient’s name, daily dose, date, time and place where the
administration was observed
All ‘No-shows’ (missed doses) communicated to prescriber
Patient receipt given, with dose documented- especially important when a patient is guest-dosing at another pharmacy.

Provision of Naloxone kits:

Naloxone is a Schedule II medication that can be provided by a pharmacist through funding from the Ontario Ministry of
Health and Long-Term Care for ‘emergency use’ to temporarily prevent overdoses from opioids including methadone.
Pharmacists must do a patient assessment and get the appropriate training to provide patient/agent education.
https://www.ocpinfo.com/practice-education/practice-tools/support-materials/naloxone-guidance/?hilite=naloxone

Resources

https://www.ocpinfo.com/library/practice-related/download/Methadose%20Article.pdf

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Methadone Maintenance Dosing Guide
Methadone is prescribed in a way that balances the risk of adverse effects to the patient and people in their environment
while optimizing the benefits, including retention in treatment and decreased health and quality-of-life harms related to
substance abuse.

Methadone Pharmacokinetics

• Methadone is a long-acting, orally effective full mu-opioid receptor agonist – it exhibits no ceiling effect. Ceiling effect
is the point at which the increasing effects of partial agonists reach maximum levels and do not increase further, even if
doses continue to rise. Therefore, dosing must be managed in a manner to always minimize risk of overdose.
• Administration once per day mixed with orange drink (e.g., Tang®) or another suitable drink which does not lend itself
to injection - QS to 100mL
• Note: Split daily dosing may be beneficial to patients with the following conditions: chronic pain, pregnancy,
rapid metabolism (due to genetics or drug interactions)
• Onset of Action: 30 minutes
• Time to peak plasma concentration after ingestion: 2 to 4 hours
• Steady state: 5 to 7 days
• Elimination half-life 22-48 hrs.

Some important dosing facts about Methadone Maintenance Therapy

• Most deaths with methadone treatment occur during the initiation phase or within the first two weeks as the dose is
adjusted.
• Accidental overdoses in adults of as little as a starting dose of 40 mg have led to deaths after 3 days of treatment.
• For non-tolerant adults, a single day’s maintenance dose as low as 50-100 mg can be lethal.
• For children, an accidental overdose of 10 to 20 mg can be fatal.
• The effectiveness of methadone maintenance therapy is tied to adequacy of methadone dosing. Adequate dosing can
result in treatment retention and reduction in illicit opioid use.
• Patients should be on same dose for at least three consecutive days; although the frequency of dose adjustment
ranges are based on various clinical parameters (stage of titration, base dose, risks of toxicity etc.). There should be no
missed dose before a dose increase.
• The META-PHI fentanyl guidelines specify patients should have had 4 of the 5 previous doses (not necessarily 3
consecutive doses) for dose to be increased.
http://www.metaphi.ca/wp-content/uploads/Guide_MethadoneForFentanyl.pdf
• All missed doses must be communicated to the prescriber.

Phases in Methadone Dosing

Induction (or Initiation) Doses ‘Start Low’

Goal is to reduce withdrawal or abstinence symptoms safely.

An initial dose of 10mg or less should be prescribed; then doses increased by no more than 5mg every 5 days (as
necessary) for patients who:
• Are recently abstinent or use intermittently
• Have unknown tolerance to opioids due to unclear history or lack of collateral information
• Use low-potency opioids (e.g., codeine)

An initial dose of 5-20mg should be prescribed; then doses increased by 5-10mg every 3-5 days (as necessary) for
patients who:
• Have established tolerance via patient history or collateral information (e.g., UDT results)
• Have risk factors that include:
o High or multiple CNS depressant use (e.g., alcohol, antipsychotic, benzodiazepine, gabapentoid)
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 o Medical illness involving respiratory compromise (e.g., chronic obstructive pulmonary disease)
An exception would be if a patient uses fentanyl. See META PHI fentanyl guidelines r- starting dose recommended is 30
mg, including for those with risk factors listed.
• Have changes in drug metabolism

An initial dose of 5-30mg should be prescribed; then increase doses by 5-15mg every three to five days (as necessary) for
patients who both:
• Have high tolerance of high-potency opioids from daily use and have UDT confirmation of recent opioid use
• Do not have risk factors for excessive CNS depression (as listed above)

Reassess patients frequently during the first two weeks of treatment because they are at the highest risk of fatal overdose
during this period. Discuss the risks and strategies to reduce it (e.g., use only small amounts of additional opioids; do not
use alone; have a naloxone kit available).

Reassess the patient with every subsequent dose increase.

Titration and stabilization Phase

The dose should be increased 5-10mg every five to seven days to manage withdrawal symptoms and cravings.

Maintenance Phase
An appropriate maintenance dose is determined through clinical judgment i.e., one which provides 24hours without opioid
withdrawal and reduction of opioid cravings while not causing sedation or toxicity.

Consideration should be given to tapering down the dose for patients experiencing opioid-induced side effects (e.g.,
sweating, hypogonadism, severe constipation, adrenal insufficiency. Also, collaborate with the patient to balance the
benefits, disadvantages and risks of methadone treatment.

Rapid metabolism is confirmed with serum methadone levels and/or observing emergence of withdrawal after an observed
dose.

There is no consensus on the best way to assess the need for split dosing. Consideration should be given to clinical stability
before offering split dosing. It often requires providing evening doses as take-home doses as most patients are unavailable
to attend a pharmacy for witnessed dosing.

Assessment of post-dose sedation at peak serum levels should be done for patients on high doses of methadone.

Missed doses
• One or two doses: the dose is not reduced unless there are concerns about loss of tolerance or adverse events
• Three doses: the dose should be decreased by 50 percent
• Four or more doses: the dose should be decreased to 30mg or less
NB: Guidelines for patients who use fentanyl--decrease dose by 50% after four missed doses; to 30 mg after five missed
doses

A stable methadone dose should be re-established after several missed doses. This may not be the same as the previous
dose,
One replacement dose of methadone (no more than 50 percent of the regular dose) should be offered if the patient has
emesis witnessed by a health care professional occurring withing 15 minutes of an observed dose. If emesis occurs during
pregnancy, the dose should be spread over 30 minutes and consider observing for 15-20 minutes after dosing.
https://www.ocpinfo.com/library/practice-related/download/Importance%20of%20Missed%20Doses.pdf

Signs of Opioid Intoxication

• Sedation (‘nodding off’)
• Slowed or slurred speech
• Motor retardation
• Euphoria
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 • Dysphoria
• Pinpoint pupils

Opioid intoxication occurs when opioids are taken in excess of the individual’s level of tolerance and may progress into
overdose. Medical attention is required if patients exhibit signs of sedation, motor retardation or slurred speech

Signs of Overdose
• Respiratory depression – infrequent or shallow breathing, change in skin colour
• Circulatory collapse – slow pulse and low blood pressure
• Severe sedation, including stupor and coma
• Cardiac arrest
• Death

Opioid overdose is considered a medical emergency as it can be fatal.

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Resources
OCP Opioid Policy
https://www.ocpinfo.com/regulations-standards/practice-policies-guidelines/opioid-policy/

OPA Methadone and Buprenorphine/Naloxone Toolkit for Pharmacists

https://opatoday.com/methadone-and-buprenorphine-toolkit/

OPA Opioid Addictions and Substitution Therapy Online Modules (FREE)

https://opatoday.com/product/opioid-substitution/

CAMH Methadone Maintenance Treatment: Recommendations for Enhancing Pharmacy Services-2009

https://www.porticonetwork.ca/documents/77404/475940/mmt_enhancing_pharmacy_services.pdf/52d1a5d9-
8a42-4b23-964c-c0bba6ccc8ae

The 2017 Canadian Guideline for Opioids for Chronic Non-Cancer Pain
https://www.cmaj.ca/content/cmaj/suppl/2017/05/03/189.18.E659.DC1/170363-guide-1-at-updated.pdf

Naloxone dispensing and training resources

http://www.ocpinfo.com/regulations-standards/policies-guidelines/naloxone-guidance/

Canada’s Mental Health & Addiction Network

https://www.oha.com/about-oha/Ontario-Hospitals/mental-health-and-addiction-network-(2)

OCP Update on Opioid Use Disorder Treatment

https://pharmacyconnection.ca/update-on-opioid-use-disorder-treatment/

Addiction Treatment Forum

http://atforum.com/

Connex Ontario: Addiction, Mental Health, and Problem Gambling Treatment Services
https://www.connexontario.ca/en-ca/

OPA Opioid Substitution Therapies Discussion Forum

http://methadoneforum.opatoday.com/

CAMH Making the Choice, Making It Work, Treatment for Opioid Addiction 2nd edition
(Formerly Methadone Maintenance Treatment: Client Handbook)
https://www.porticonetwork.ca/web/knowledgex-archive/amh-specialists/mmt-client-handbook

CAMH Opioid Agonist Maintenance Treatment 3rd edition 2015. Available for purchase at-
https://store-camh.myshopify.com/products/p6500

CAMH Primary Care Addiction Toolkit

https://www.porticonetwork.ca/tools/toolkits/pcat

CRISM National Guideline for the Clinical Management of Opioid Use Disorder
https://crism.ca/projects/opioid-guideline/

NAPRA Model Standards for Pharmacy Compounding of Non-sterile Preparations

https://napra.ca/general-practice-resources/model-standards-pharmacy-compounding-non-sterile-preparations

CAMH Opioid Agonist Therapy: A Synthesis of Canadian Guidelines for Treating Opioid Use Disorder May 2021
https://www.camh.ca/-/media/files/professionals/canadian-opioid-use-disorder-guideline2021-pdf.pdf

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Live Telephone Resources

CAMH Addiction Clinical Consultation Service

• 416-535-8501, press 2
• (M-F 8:30AM - 5PM)

OPA Opioid Substitution Therapy Drug Information Line

• 1-888-519-6069 (M-F 9AM-5PM)
• Email: methadone@opatoday.com

CPSO Methadone Infoline (for prescribing)

• 416-967-2600

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The Ontario Pharmacists Association wishes to acknowledge the Ministry of Health and Long-term care for funding this initiative.