Potentially better treatment retention, particularly in patients with higher-intensity opioid use disorder (e.g., long history of opioid use, injection heroin use, high tolerance and frequent use), or at high risk of dropping out18,22,23
May be more effective for withdrawal-symptom control in chronic, severe opioid use disorder22,23
Treatment initiation may be easier
No maximum dose
Approved in Canada for the indication of pain control
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Health Canada exemption is not required to prescribe buprenorphine–naloxone in most provinces and territories (Appendix 1)
Lower risk of overdose due to partial agonist properties and ceiling effect for respiratory depression (in the absence of benzodiazepines or alcohol)19,24,25
Lower risk of public safety harms if diverted26,27
Milder adverse effect profile22,23
Easier to transition from buprenorphine–naloxone to methadone if treatment is unsuccessful22,23
Shorter time to achieve therapeutic dose (1–3 d)28–30
Lower risk of toxicity and drug–drug interactions31
Milder withdrawal symptoms when discontinuing treatment; may be a better option for individuals with lower-intensity opioid dependence (e.g., oral opioid dependence, infrequent or no injection use, short history of opioid use disorder), and individuals planning to taper off opioid agonist treatment in a relatively short period22,23
Optimal for rural and remote locations where access to care is limited, methadone prescribers are lacking, or daily witnessed ingestion at a pharmacy is not feasible
More flexible dosing schedules (e.g., alternate-day dosing, earlier provision of 1- to 2-week take-home prescriptions, and unobserved home inductions) support patient autonomy and can reduce costs32–35
Easier to adjust and retitrate following missed doses, owing to its partial agonist properties
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Health Canada exemption is required to prescribe methadone in all provinces and territories
Higher risk of overdose19,24,25,36
More often prescribed as witnessed doses; prescription of take-home doses typically use slow graduated schedule (e.g., increase of 1 take-home dose per week about every 4 weeks), which can be inconvenient or not feasible for some patients
More severe adverse effect profile (e.g., somnolence, erectile dysfunction, cognitive blunting)22,23
Longer time to achieve therapeutic dose (several weeks)36
Can be more challenging to transition from methadone to buprenorphine–naloxone if treatment is unsuccessful22,23
Higher risk of public safety harms if diverted26,27
Higher potential for adverse drug–drug interactions (e.g., antibiotics, antidepressants, antiretrovirals)31
Associated with QTc prolongation and increased risk of cardiac arrhythmia in patients prescribed higher doses, with pre-existing risk factors or taking other medication(s) that prolong QTc interval22,23
Can be more expensive if prescribed as daily witnessed doses, mainly owing to fees associated with dispensing and witnessed ingestion34,35
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Potentially lower treatment retention, particularly in higher-intensity opioid use disorder with low-dose buprenorphine–naloxone18
May cause precipitated withdrawal if appropriate dose-induction protocols are not followed30
Suppression of withdrawal symptoms may be inadequate for individuals with high opioid tolerance22,23
Reversing effects of overdose can be challenging because of the pharmacology of buprenorphine (i.e., high affinity for opioid receptors and long half-life)31
Patients require education on how to take sublingual doses correctly (i.e., hold under tongue until dissolved — up to 10 minutes; do not drink or smoke, and minimize swallowing)
Nonadherence to treatment may require frequent reinductions
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