Buprenorphine/naloxone sublingual (SL) tablet, buprenorphine subdermal implant and buprenorphine extended-release (ER) injection
Indication(s)
Buprenorphine/naloxone sublingual (SL) tablet (Suboxone®, generics): substitution treatment in adults with problematic opioid drug dependence.
Buprenorphine subdermal implant (Probuphine®): management of opioid dependence in patients clinically stabilized on no more than 8 mg of SL buprenorphine in combination with counselling and psychosocial support.
Buprenorphine extended-release (ER) injection (Sublocade®): management of moderate to severe opioid use disorder (OUD) in adult patients who have been inducted and clinically stabilized on a transmucosal buprenorphine-containing product.
Formulary status
The Drug Advisory Committee (DAC) recommended that generic buprenorphine/naloxone (2/0.5 mg and 8/2 mg) SL tablets, buprenorphine (80 mg) subdermal implant (Probuphine®), and buprenorphine (100 mg and 300 mg) ER injection (Sublocade®) be listed on the Musculoskeletal Injury (02WS), Central Nervous System/Peripheral Nervous System Injury/Disorder (03WS), Facial/EENT (04WS), Burn (05WS), Cancer (19WS), Psychotraumatic Disorder (22WS), Chronic Pain Disability (23WS) and Serious Injury (27WS) formularies, with the following criteria:
Generic buprenorphine/naloxone:
(i) For the treatment of opioid use disorder and/or;
(ii) For the purposes of opioid tapering for patients currently taking high dose opioids (morphine equivalent dose [MED] ≥90/day)
Buprenorphine subdermal implant:
(i) For the management of opioid dependence
(ii) For patients clinically stabilized on a dose of no more than 8 mg per day of SL buprenorphine in the preceding 90 days
Buprenorphine ER injection:
(i) For management of moderate to severe OUD
(ii) For patients induced and stabilized on an equivalent of 8 mg to 24 mg per day of transmucosal buprenorphine for a minimum of seven days.
The WSIB accepts the Drug Advisory Committee recommendations for listing.
Recommendation highlights
- Buprenorphine is a partial opioid agonist that exhibits reduced withdrawal symptoms compared to full agonists. Naloxone, an opioid antagonist with negligible oral and SL absorption, is included in the SL tablet formulation as a deterrent for abuse.
- An external, independent review completed in 2009 concluded that, while Suboxone® may be better tolerated and safer in overdose, it may not be as effective as methadone and is much more expensive. Since then, numerous systematic reviews have been published concluding that the efficacy of buprenorphine is equivalent to methadone for OUD. In addition, patent loss resulted in significant price reduction of generic buprenorphine/naloxone.
- Canadian Research Initiative on Substance Misuse 2018 National Guidelines for the Clinical Management of Opioid Use Disorder classifies buprenorphine/naloxone as a first-line agent for opioid agonist therapy.
- The McMaster 2017 Guideline for Opioids for Chronic Non-Cancer Pain suggests buprenorphine/naloxone may be used as a tapering strategy for patients on high dose opioids (MED ≥ 90/day).
- Buprenorphine has a superior safety profile compared to methadone, including lower risk of overdose, milder side effects, and fewer drug interactions.
- Buprenorphine/naloxone can be dispensed as multiple take-home doses more safely than methadone; this facilitates access to OUD treatment, especially in the return-to-work setting.
- Buprenorphine subdermal implant and ER injection were reviewed by the Canadian Agency for Drugs and Technologies in Health in 2018/2019, with a recommendation to reimburse with clinical criteria and/or conditions, based on phase III randomized-controlled trials and network meta-analyses. Despite higher drug cost, removal of barriers to access with more convenient injection/implants and potentially less interaction with the health care system are important to address the stigma and improve outcomes of persons with OUD.
- The Ontario Drug Benefit program covers generic buprenorphine/naloxone SL tablets, as well as buprenorphine subdermal implant and ER injection.
- Based on published evidence and current guidelines, the DAC recommended that buprenorphine/naloxone SL tablets, buprenorphine subdermal implant, and buprenorphine ER injection be listed with criteria on WSIB formularies.
- The buprenorphine products discussed in this listing decision are not indicated for use in pain treatment.
Products available in Canada:
- Buprenorphine/naloxone 2/0.5 mg and 8/2 mg SL tablets (Suboxone® and generics)
- Buprenorphine/naloxone 12/3 mg and 16/4 mg SL tablets (Suboxone® only)
- Buprenorphine 80 mg subdermal implant (Probuphine®)
- Buprenorphine 100 mg/0.5 mL and 300 mg/1.5 mL extended-release solution (Sublocade®)