Opioid Agonist Therapy (OAT)

Important Changes to Methadone Formulations Used as Opioid Agonist Therapy (OAT)

As of September 1, 2022, three commercially available methadone 10 mg/mL oral concentrates were added as listed benefits on the Saskatchewan (SK) Formulary of the SK Drug Plan and Extended Benefits Branch (DPEBB). These products were already listed on the Non-Insured Health Benefits (NIHB) Drug Benefit List.

After November 30, 2022, compounded methadone will not be a SK Formulary benefit of the DPEBB. Prescribers may submit additional clinical information that may be considered on a case-by-case basis for patients who experience severe allergic reactions to the commercially available products.

All people taking compounded methadone will require a new prescription to transition to commercially available products by November 30, 2022.

Click on the images below for details. 

Complete this form to request print copies of the education poster developed for people taking methadone.

Background & Reasons for the Change

• Methadone hydrochloride is used for pain management and/or as opioid agonist therapy (OAT) for opioid use disorder (OUD).
• When used for OUD, pharmacists in SK have traditionally compounded a stock solution from methadone powder and water, which was stored in the fridge. The prescribed dose of this solution was diluted with a suitable diluent (a liquid vehicle, such as Orange Tang™).
• As of September 1, 2022, three commercially available methadone 10 mg/mL oral concentrates were added as listed benefits on the SK DPEBB Formulary. These oral concentrates were also already on the NIHB Drug Benefit List.
• Compounded methadone will only be approved by the SK DPEBB in exceptional circumstances after November 30, 2022.

Reasons for this change include:

• Commercially available products are available that:
  • are consistently prepared and standardized products resulting in enhanced safety and quality control,
  • are recommended by the Institute for Safe Medication Practices Canada (ISMP Canada),
  • do not require refrigeration^[i],[ii] (before dilution),
  • may be associated with less wastage (due to the 14-day beyond-use date of the compounded stock solution if not preserved), and,
  • must be used rather than compounded solutions, per Health Canada Policy, whenever they are readily available^[iii].
• Regulatory changes to compounding standards in SK were implemented on August 31, 2022, which seek to ensure the safety of both patients and the personnel involved in compounding, as well as establish additional quality controls.  After this date, numerous pharmacies (i.e., those who have not declared as being Level B or C) are no longer authorized to compound complex non-sterile compounds, such as methadone.
• By removing the safety risks associated with compounding, and simplifying the preparation process for methadone, more pharmacies in Saskatchewan may begin dispensing OAT, reducing barriers to access for people taking methadone.
• All other jurisdictions in Canada have already transitioned away from using compounded methadone and are using the commercially available products as the preferred products.
  • Aligning the availability of products across provinces and territories, allows people taking methadone to maintain consistency of the product when they move between jurisdictions.
• The reasons for the change are believed to all be important and, ultimately, to be in the best interest of people taking methadone for improving safety.

Product Availability 

• As shown in Table 1, two brands of methadone concentrates (i.e., Metadol® and Methadose™) and three specific formulations (i.e., Metadol-D®, Methadose™ Sugar-Free, and Methadose™ Cherry-Flavoured) are listed benefits of the SK DPEBB for use as OAT on September 1, 2022. These are also already on the NIHB Drug Benefit list.

Table 1: Specifying the Methadone Brand and Formulation

Brand	Formulation
Metadol®	-D
Methadose™	Sugar-Free
Methadose™	Cherry-Flavoured

 

• In accordance with the SCPP OAT Standards, Methadose™ Cherry-Flavoured use should be limited to patient request due to the risk of contributing to destabilization.^[iv]
• To reduce the chance of dosing errors, pharmacies are required to dispense only the 10 mg/mL commercially available oral concentrates for OAT.
• It is important to recognize there is risk of potential error when pharmacies carry different products of the same medicinal ingredient. There is also risk to people taking methadone when they are not offered choice regarding their medication treatment.
  • Clinicians are encouraged to actively engage with people taking methadone and other providers involved in their care, to offer methadone-related information and recommendations (see Product Selection), while also not creating barriers to access to specific brands and formulations

Table 2: Commercially Available Methadone Concentrated Products Available on both the SK DPEBB and NIHB Drug Benefit Lists

Methadone 10 mg/mL Oral Concentrates a,b	Benefit of SK DPEBB	Benefit of NIHB	Preferred for OAT in SK	Rationale for Recommendation c
Metadol-D®	Yes	Yes	Yes	Person unlikely to notice a difference from compounded methadone.        May be preferred by people taking methadone
Methadose™ Sugar-Free	Yes	Yes	May use, but caution advised	Unknown if person will notice a difference (i.e., lack of effect) compared to compounded methadone. Published reports have been specific to the Cherry-Flavoured formulation; however, some anecdotal reports (low-quality evidence) suggest lack of effect with this formulation contributing to clinical destabilization.
Metadol®	Yes	Yes	No	Indicated for pain only.
Methadose™ Cherry-Flavoured	Yes	Yes	Nod	Documented serious risk of contributing to lack of effect and clinical destabilization.        Note: it also has a different colour, taste, and viscosity.

_{^a As of September 1, 2022.       
^b Other generic formulations of commercially available methadone concentrates are available on the Canadian market; however, they are not anticipated to be listed on the SK DPEBB Formulary and NIHB Drug Benefit Lists and should not be used at this time.       
^c Recommendation by medSask/Continuing Professional Development for Pharmacy Professionals (CPDPP) based primarily on observational studies and anecdotal reports of people taking methadone and clinicians experienced with these products at this time, given the lack of high-quality formal studies comparing the products. See Product Selection for more information.       
^d Not recommended as a first choice. SCPP OAT Standards indicate use should be limited to prescriptions written on the specific request of a person taking methadone.^[iv] Ensuring informed consent is documented is advised.}       
 

Product Selection

Considerations to support the decision regarding which product to select should include factors such as relative effect, safety, formulation properties, convenience, cost, as well as patient perceptions and preferences. Please see Characteristics of the Commercially Available Methadone 10 mg/mL Oral Concentrates for OAT on the SK DPEBB and NIHB Drug Benefit Lists, for an overview of the product characteristics, particularly those which compare the formulation properties and differences which people may notice.

medSask/CPDPP Recommendations

• Providers should collaborate with people taking methadone to discuss options for transitioning to a commercially available methadone product. Engaging people in their own health care decision-making can improve the outcomes associated with change.
• There are unfortunately no high-quality studies to direct the treatment choice at this time. In the absence of robust clinical trials to draw from, lower quality observational trials and anecdotal information provides the only information on which to base decision-making at this time. Lived experience is an important consideration.
• Metadol-D® may be preferred by people taking methadone and clinicians and is recommended by medSask/CPDPP as a first choice.
  • There are potentially serious safety concerns associated with Methadose™ related to lack of effect which have been anecdotally reported by some people taking methadone and clinicians in Canada. Given this risk, even though not yet clearly established in the scientific literature, alongside reports that Metadol-D® has been preferred by people and clinicians with experience, it may be prudent to use this product preferentially until further evidence becomes available.
  • Another benefit of Metadol-D® is that people are unlikely to notice a difference in the taste and appearance, as compared to compounded methadone.
  • From a logistical perspective, recommending this as a single methadone product may also improve safety, by simplifying processes in the steps relating to prescribing and dispensing, as well as supporting people taking methadone who may require "guest dosing".
• Methadose™ Cherry-Flavoured is not recommended as a first choice in SK when changing from compounded methadone. However, it may be appropriate to continue this product if a person has already been stabilized on it elsewhere and wishes to continue taking it. Use should be limited to prescriptions written on the specific request of a person taking methadone, after ensuring informed consent is provided and documented.^[iv]

medSask/CPDPP recommendations are based on these considerations:

Relative Effect and Safety

• The commercially available methadone products for OAT are not interchangeable in Saskatchewan.
• In 2020, Health Canada released a risk communication, which identified a potential risk of lack of effect (i.e., causing the person to experience opioid withdrawal symptoms) and clinical destabilization when switching between different methadone products.^[v] Reasons for this difference in effect are unclear. Health Canada did not indicate a specific brand or formulation of concern.
• The Methadose™ Cherry-Flavoured brand and formulation has been described in the literature as causing lack of effect and clinical destabilization (e.g., people taking methadone becoming “dope sick” or experiencing “withdrawals”), which can be a serious safety concern. (See Exploring the Reports of Clinical Destabilization for more information.)
  • For this reason, SCPP OAT Standards indicate use should be limited to patient request.^[iv]
• It is unknown whether the lack of effect associated with the Methadose™ Cherry-Flavoured formulation is similar with the Sugar-Free formulation.
  • The literature does not report on the Sugar-Free formulation and no randomized controlled trials or head-to-head analyses have been performed to compare the formulations.^[vi] Anecdotal reports suggest some people taking the Methadose™ Sugar-Free formulation have experienced lack of effect and clinical destabilization.
• Comparatively, in a Commentary written by clinicians in BC, it was reported that, “Fortunately, offering Metadol-D as an alternative to Methadose appears to be greatly beneficial.”^[vii]
• It may also be safer if clinicians preferentially recommend, prescribe, and dispense a single methadone product, to further reduce the chance of confusion and error in the prescribing and dispensing processes.

Formulation Properties

• Metadol-D® and Methadose™ Sugar-Free are most similar to compounded methadone in their taste and appearance.
• Methadose™ Cherry-Flavoured has a distinct taste, color, and thickness, which may decrease palatability.
• Metadol-D® contains dextrose while Methadose™ Sugar-Free does not.
  • Communication with the manufacturer indicates that Metadol-D® contains dextrose in a concentration of 125 mg/mL (Paladin Labs, personal communication, July 6, 2022). This concentration is low enough that it is unlikely to have clinical significance for people, such as those with diabetes or fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) intolerance. E.g., a Metadol-D® 100 mg PO daily dose = 10 mL = 1.25 g of dextrose = 4.25 calories.

Convenience 

• All products should initially be prescribed at the same dose and interval as the person previously received.
• If particular products do not last for twenty-four hours (e.g., “wear off” early), as has been described in the literature with the Methadose™ Cherry-Flavoured formulation, this may lead to clinical destabilization. Destabilization can result in the need for the person to make more frequent healthcare visits, lose authorization for take-home doses, and/or require split dosing at the pharmacy.
• Additionally, if a single product is used preferentially in SK, this will support people taking the product who might require “guest dosing” from a different pharmacy due to unexpected circumstances (e.g., travelling for a funeral, family emergency, rapidly changing living situations).

Cost

• At the time of initial product listing (September 1, 2022), there were no cost differences between the Metadol-D® and Methadose™ products. Subsequent listing prices may be modified by the manufacturers. Practitioners should consult current listing prices in circumstances when the cost becomes significant for people taking methadone (e.g., those not receiving provincial or federal drug plan benefits and without third party insurance).

Perspectives and Preferences of People Taking Methadone Alongside Clinical Experience

• Patient perspectives and experiences, particularly for structurally vulnerable individuals, are at times under-represented in the medical literature.
• Clinicians should be aware that the Methadose™ brand as a whole has been associated with negative experiences and public perception.
  • Board members from an advocacy group comprised of people with lived experience in British Columbia (e.g., the British Columbia Association for People on Opioid Maintenance) have advised to, “Avoid Methadose. Choose Metadol-D.” (L. Shaver, personal communication, June 21, 2022 and G. Mullins, personal communication, July 7, 2022).
  • A podcast by people with lived experience has supported the use of Metadol-D®, reporting that it, “… seems to work better” (than the Methadose™ Cherry-Flavoured) and, “…doesn’t have a dose-holding problem.”^{[viii], [ix]}
  • Regarding the reports of Methadose™ Cherry-Flavoured wearing off early, people have been quoted as describing it as, “It doesn’t haven legs!”^[ix]
  • Also anecdotally, some have suggested that the lack of documented reports in Canada outside of BC may be related to having fewer organized activist groups to speak to these issues.
• An electronic mailing list, META:PHI, composed of clinicians involved in addiction medicine, has provided a forum for some comments regarding experiences with the methadone products.
  • Some clinicians in Canada have described having patients experience withdrawal, particularly after switching to a Methadose™ product (reported with both the Cherry-Flavoured and the Sugar-Free formulations), often alongside a preference for Metadol-D®.
• Patients may prefer Metadol-D® because it has been reported more favourably by some people taking methadone and clinicians in other parts of the country, in terms of relative effect and safety, and because it has a comparable appearance and taste to the compounded methadone.

Characteristics of Commercially Available Methadone 10 mg/mL Oral Concentrate 

Brand Name & Formulation		Metadol-D®	Methadose™         Sugar-Free	Methadose™        Cherry-Flavoureda
DIN		02244290	02394618	02394596
Concentration         (All are oral concentrates)		10 mg/mLb	10 mg/mL	10 mg/mL
Package Size(s) Available		100 mL and 1000 mL	1000 mL	1000 mL
Properties	Flavour	Unflavoured	Unflavoured	Cherry-Flavoured
	Sweetener	Dextrose (125 mg/mL)c	None	Sucrose (400 mg/mL)
	Dye	Colourless	Colourless	Red (FD&C Red No. 40, D&C Red No. 33)
	Viscosity	No viscosity enhancers added	No viscosity enhancers added	Viscous/thickened (hypertonic, poloxamer 407 added)
Dilution – to decrease ability to inject the liquid and to mask the bitter taste of the methadone		Dilute to 100 mL with suitable diluent.	Dilute to 100 mL with suitable diluent.	Dilution not required for deterring injection but diluting to 100 mL is strongly recommended.d
Suitable Diluents		The same diluents used for compounded methadone solution (typically coloured, flavoured crystalline drink mix) may be used with these products. Examples: Orange Tang™, Grape Kool-Aid™, Grape/Lemonade/Tangerine-Grapefruit Crystal Light™.        Diluting with plain water is not acceptable, as per the SCPP OAT Standards.[iv]
Stability in Diluents		May be stored refrigerated in suitable diluent for up to 14 days.[iv]	The period of acceptable sterility for oral consumption under refrigeration is unknown. No information is provided in the product monograph (Professional judgement required).
Differences people may notice compared to compounded solution *Assuming the same diluent is used.		People are not expected to notice a difference in taste or appearance. People taking methadone have reported this product to be most similar to the compounded methadone product.[viii], [ix]	People are not expected to notice a difference in taste or appearance. May be a loss in effect associated with clinical destabilization, based on anecdotal reports, not well established.	The colour, flavour and viscosity will be different. Documented reports of the dose wearing off after 14-16 hours rather than 24 hours. See Exploring the Reports of Clinical Destabilization for more information
Interchangeability		These products are NOT interchangeable. If a lack of clinical effect occurs with one brand and formulation, this may resolve with a change to a different brand and/or formulation; however, a new prescription will be required.

_{^aMethadose™ Cherry-Flavoured is not recommended as a first choice for the switch from compounded methadone in SK.       
^b Metadol-D® is also available as a 1 mg/mL solution; however, only the 10 mg/mL concentrate is approved for use as OAT in SK.^[iv] Maintaining a consistent single concentration decreases the potential for dosing errors.       
^c This concentration is low enough that it is unlikely to have clinical significance for people, such as those with diabetes or fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) intolerance (e.g., a Metadol-D® 100 mg dose provides 1.25 g of dextrose).       
^d Dilute to retain consistent final volume among products and to reduce viscosity and “stickiness” (and therefore, potentially reduce adhesion to the vessel). The final diluted product will likely still be more viscous than the compounded and other available formulations of methadone. The dispensing cup should be rinsed and liquid consumed to ensure the full dose is given.}

Prescribing Information

• When converting from one methadone product to another, continue the same dose (e.g., 60 mg of compounded methadone = 60 mg of the commercial methadone concentrate).
• Prescriptions must be written in milligrams (mg).
• Since commercially available methadone products are not interchangeable, the product selected must be prescribed by brand and formulation.
  • E.g., If selecting Metadol-D®, ensure the prescription includes the “-D” (plain Metadol® is for pain only).
  • E.g., If selecting Methadose™, ensure the prescription specifies the Sugar-Free formulation (Methadose™ Cherry-Flavoured is not recommended as a first choice).
• Under the Section 56 Exemption, pharmacists are not authorized to prescribe for the change of prescription. A verbal order may only be accepted after every effort has been made to obtain a written or e-prescription.
• Collaboration, communication, and coordination between prescribers, pharmacists, and people taking methadone will be required to establish the best date on which to make the switch in order to facilitate a safe transition.
  • It is strongly recommended that prescriptions are coordinated to start the new brand and formulation on a day when the person receives a witnessed dose. This will allow for the pharmacist to discuss any concerns or questions the person has at the time of taking their first dose. It will also allow for the subsequent take-home doses (if applicable) to be prepared and dispensed as a single formulation.
  • Plan to start the new brand and formulation early in the week (e.g., Monday or Tuesday), whenever possible, to enhance access to providers for follow up or changes if needed.
• While it is not required, changes to take-home doses may be desired following the methadone switch to facilitate enhanced contact, monitoring, and communication with a pharmacist. This may be particularly relevant for those people who have very recently entered the maintenance phase of taking methadone.
• If there is particular concern, anxiety, or distress associated with making this change, people taking methadone may benefit from proactively having a prescription for pharmacological opioid withdrawal adjuncts logged on file at the pharmacy. This may include medications such as clonidine, loperamide, and non-steroidal anti-inflammatory drugs (note: see RxFiles “Prescription for Managing Opioid Withdrawal” available through SHIRP).
  • If opioid withdrawal occurs a few days after the methadone switch, this provides the person taking methadone an option to help manage their symptoms until the methadone prescription can be reassessed by the prescriber (See Responding to Clinical Destabilization). 

Sample Methadone Prescription - Note brand and formulation are specified

Responding to Clinical Destabilization

• There is a risk of destabilization with any change of OAT.
  • Serious destabilization has been associated with the Methadose™ Cherry-Flavoured product, though high-quality evidence to establish causality is not available. The best available evidence that speaks to this association includes a qualitative study (N=34), a survey (N=405), a cohort study (N=331), and anecdotal reports.^{[vii],[x],[xi],[xii]} All published reports have come out of British Columbia, and therefore the severity or extent of impact related to this change in other jurisdictions is also not well established.
  • It is unknown if there is a difference in destabilization risk between formulations.
  • Health Canada has identified a potential risk of lack of effect (i.e., causing the person to experience opioid withdrawal symptoms) and clinical destabilization when switching between different methadone products.^[v] Health Canada did not indicate a specific brand or formulation of concern.
• Validate, reassure, and address the concerns of people who report a lack of effect in the first few days after switching to a new methadone formulation.
• If withdrawal or destabilization occurs, the prescriber is encouraged to consider one of the following modifications to the methadone prescription as early as possible:
  • Switch to a different methadone brand and formulation (i.e., from Methadose™ Sugar-Free to Metadol-D®). Switching to Metadol-D® is the recommended approach by some people with lived experience. There are no reports to suggest benefit related to changing the brand if the person is already taking Metadol-D®. Alternative management strategies as below are advised.
  • Divide the methadone dose, such as to split the total daily dose to twice daily (e.g., methadone 100 mg PO daily could be divided to 50 mg PO BID). This approach may not be feasible if take-home doses are deemed unsafe in the clinical circumstance and/or the person is unable to attend the pharmacy twice in a day.
  • Trial an increase in the methadone dose (e.g., by 5-10 mg, no more often than every 5-7 days). There is concern that if the medication is wearing off in advance of 24 hours, a dose increase may not be sufficient to overcome this effect.
• If clinical stability cannot be achieved with these methadone adjustments, or if the person wishes to explore a different option, consider whether an alternate form of OAT, such as a buprenorphine product, might be appropriate (note: buprenorphine may be less effective than methadone for people who use high opioid doses, e.g., large amounts of fentanyl regularly). Consult with an expert in prescribing OAT and/or addiction medicine as required.
• All people experiencing withdrawal and/or destabilization will require closer follow up and possibly reassessment of the take-home dose authorization (if applicable), until re-establishment of clinical stability on OAT.
• Any changes in clinical response associated with a commercially available product, including withdrawal symptoms soon after the transition, or other serious or unexpected adverse reactions in people taking methadone should be reported to Health Canada to support ongoing monitoring of the safety of commercially available products.^[v]

Exploring the Reports of Clinical Destabilization

• High-quality clinical evidence to establish causality is not available; however, it is important to take reports of changes in effect seriously (i.e., getting “dope sick” or having “withdrawals”) since clinical destabilization can be life-threatening. Lack of effect may result in people “topping up” with opioids from the illicit drug supply which are often contaminated and potentially lethal.      
   
• In British Columbia, where this was primarily reported starting in the first few days after people were switched from compounded to the commercially available methadone in 2014, the lack of effect leading to opioid withdrawal was related to the Methadose™ Cherry-Flavoured concentrate.
• Researchers in British Columbia published a study in 2016, in which 405 people who had been switched to the Methadose™ Cherry-Flavoured product were surveyed. Of the respondents, 56% (202/358) reported feeling more dope sick and 54% (193/358) reported more pain after the formulation change. Also following the switch, 50% (181/360) of people surveyed reported supplementing with other opioids, and 33% (107/320) had an increase in their methadone dose.^[x]
• Another observational study quoted a participant as saying, regarding the switch to the Methadose™ Cherry-Flavoured concentrate, “It’s not agreeing with my body. I can feel a little bit of the effects of it [alleviation of withdrawal symptoms]. Other than that… the pain seems to be a lot more than it was when I was taking the regular methadone. I still don’t understand this [obscenity], but I don’t think I really wanna be on it [Methadose®]. In the middle of the night, I feel nauseated, whereas before I was always fine…I get my methadone at 6:30 [am] and by about eight or nine o’clock at night, my body aches a lot more.”^[xii]
• The exact reason for the difference in effect is not known.
  • Differences in viscosity and volume - This product is thicker and does not require dilution. As such, the smaller and “stickier” amount may adhere more readily to the dispensing container resulting in a partial loss of the more concentrated dose.
  • Potentially different ratio of enantiomers – Methadone is a chiral molecule. Given that its R- and S-enantiomers may not fit into the receptors in the same way, a change in their relative amounts could cause a change in effect.
  • Psychological effects - The smaller (undiluted) dispensed volume, feelings of loss of control secondary to imposed changes, and a disagreeable taste/consistency may all contribute to lack of effect of the medication.
• In consideration of the observational and anecdotal reports, Methadose™ Cherry-Flavoured is not recommended as a first choice when transitioning people to a new methadone formulation at this time.
  • Also, since the differences between the Sugar-Free and Cherry-Flavoured formulations are not known, and in keeping with what is recommended by some people with lived experience, people are encouraged to consider using Metadol-D preferentially at this time.
• Any change can be difficult, and it is important for providers to follow up with people who are making the transition. People who feel supported and are well-informed about this change along with the potential implications will be more likely to return to their prescriber early on to communicate any concerns.

Tips for Proactive Communication with People Taking Methadone

• Start the conversation early regarding the change itself and what differences and similarities to expect.
  • Reassure that the diluent and appearance of the product and bottle can stay the same.
  • Emphasize that the person will be prescribed the same initial methadone dose.
  • It may be helpful to reassure people taking buprenorphine products that they will not be affected by this change.
• Let people know the reason the change is happening - to help make it safer for both the person taking methadone and the dispensing pharmacy.
  • Examples of how these products are safer from a pharmacy perspective include:
    • Avoids compounding errors which may occur during the preparation process (such as preparing the incorrect concentration, which can result in unintentional over- or under-dosing of the methadone).
    • Commercially available products are manufactured with more stringent quality control measures to optimize sterility and stability of the products, which reduces the likelihood of the product being contaminated and increases the likelihood that the dose will be consistent from dose to dose.
    • Avoids exposure of pharmacy personnel and the pharmacy environment to the methadone powder, which is classified by WHMIS as a highly toxic substance.
    • Allows pharmacy software systems to utilize automated drug interaction checkers (important since methadone can have significant drug interactions with numerous other medications).
    • Aligns with what other provinces and territories are offering, so that the dispensed product can consistently be maintained when a person taking methadone moves between jurisdictions.
• Consider sharing the medSask/Continuing Professional Development for Pharmacy Professionals (CPDPP) information poster with them, and/or using it as a tool to support discussions. 
• Communicate the two products that are being offered, emphasize the person’s choice in the decision, and consider recommending Metadol-D® while acknowledging the strength of the recommendation is limited by low-quality evidence associated with the Methadose™.
• Acknowledge the difficulties that some people in other parts of the country had when methadone was switched (e.g., documented reports from British Columbia).
  • Reassure that the challenges experienced in British Columbia were associated with the Methadose™ Cherry-Flavoured product, and that this product is not being recommended as a first step for the change in SK.
  • Advise that members of an advocacy group comprised of people with lived experience in Canada (e.g., the British Columbia Association for People on Opioid Maintenance) have advised to, “Avoid Methadose. Choose Metadol-D." (L. Shaver, personal communication, June 21, 2022 and G. Mullins, personal communication, July 7, 2022).
  • Encourage that many people have switched in other parts of the country (SK is the last province to make this change), and numerous people have experienced a continued beneficial effect of the methadone.
• Remember to treat each person as an individual, with respect and dignity, and acknowledge that any changes directly impact their life.
• Emphasize the importance of continuity of care, that all pharmacies are making this change, and encourage the person to stay with the same methadone prescriber and pharmacist, whenever possible, through the transition.
• Commit to helping each person create a treatment plan that meets their own goals, values, and preferences.
• It may be helpful to explain the difference between compounded products and dilution, reiterate that diversion risks remain, and that people must safely store their medication and not share or sell it to others.
• Invite people to discuss any medication concerns early on with their care provider - including concerns before and after the change in methadone formulation – and offer reassurance that steps will be taken to partner with them to maintain and/or regain clinical stability after the formulation change.

References

 ⁱ Metadol-D Product Monograph. [cited May 3, 2022]. Paladin Labs Inc. Last revised February 25, 2021. Available from: https://www.paladin-labs.com/our_products/Metadol-D_En.pdf.

ⁱⁱ Methadose Product Monograph. [cited May 3, 2022]. Mallinckrodt Canada ULC. Last revised August 22, 2018. Available from: https://pdf.hres.ca/dpd_pm/00047060.PDF.

ⁱⁱⁱ Policy on Manufacturing and Compounding Drug Products in Canada (POL-0051). Health Canada. Issued January 26, 2009. Available from: https://www.canada.ca/en/health-canada/services/drugs-health-products/compliance-enforcement/good-manufacturing-practices/guidance-documents/policy-manufacturing-compounding-drug-products.html.

^iv Opioid Agonist Therapy (OAT) Standards. Saskatchewan College of Pharmacy Professionals. Last revised October 2020. Available from: https://www.saskpharm.ca/document/5871/REF_OAT_Standards.pdf.

^v Health Professional Risk Communication. Methadone treatment of opioid dependence and potential risk of lack of effect when switching between different products. Health Canada. July 17, 2020. Available from: https://recalls-rappels.canada.ca/en/alert-recall/methadone-treatment-opioid-dependence-and-potential-risk-lack-effect-when-switching.

^vi Metadol Liquid, Methadose, and Compounded Methadone in Patients Using Opioid Agonist Therapy: Comparative Clinical Effectiveness and Guidelines. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2018 Apr 12. (CADTH rapid response report: summary of abstracts). Available from: https://www.cadth.ca/sites/default/files/pdf/htis/2018/RB1208%20OAT%20Methadose%20Final.pdf.

^vii Raski M, Sutherland C, Brar R. From methadone to Methadose: Lessons learned from methadone formulation change in British Columbia. Can Fam Physician. November 2020;66(11):797-98.

^viii Mullins, G (Host). Change Intolerance (Episode 2). [Audio Podcast Episode]. In Crackdown. British Columbia. Feb 27, 2019. Available from: https://www.crackdownpod.com/episodes/c698nin092b486ji2hycfuf9gpo15v.

^ix Mullins, G (Host). Change Intolerance Part 2 (Episode 9). [Audio Podcast Episode]. In Crackdown. British Columbia. Oct 31, 2019. Available from: https://www.crackdownpod.com/episodes/pmbyiswxmpr3hxnbee3qjt1nz50ylm.

^x Greer AM, Hu S, Amlani A, et al. Patient Perspectives on Methadone Formulation Change in British Columbia, Canada: Outcomes of a Provincial Survey. Subst Abuse Treat Prev Policy. 2016;11(3). https://doi.org/10.1186/s13011-016-0048-3.

^xi Socias ME, Wood E, McNeil R, et al. Unintended impacts of regulatory changes to British Columbia Methadone Maintenance Program on addiction and HIV-related outcomes: an interrupted time series analysis. Int J Drug Policy. 2017;45:1-8. https://doi.org/10.1016/j.drugpo.2017.03.008.

^xii McNeil R, Kerr T, Anderson S, et al. Negotiating Structural Vulnerability Following Regulatory Changes to a Provincial Methadone Program in Vancouver, Canada: A Qualitative Study. Soc Sci Med. 2015;133:168-176. https://doi.org/10.1016/j.socscimed.2015.04.008.