Buprenorphine

Background

• Recommended as first-line treatment for opioid use disorder in Canadian guidelines
• Typically coformulated with naloxone (trade name Suboxone) at a dose of 2 mg buprenorphine to 0.5 mg naloxone
• Buprenorphine is partial μ-opioid receptor agonist
• Strong receptor affinity, displaces other opioids and can precipitate withdrawal
• Theoretical ceiling effect on side effects

Dosing

Standard Induction Protocol

• It's use can precipitate withdrawal, so wait 12-24h after short-acting opioids, 18-36h after long-acting, or after tapering methadone, before starting buprenorphine

Day	Buprenorphine	Opioid
—	—	stop to ensure withdrawal (COWS ≥12)
1	2 to 4 mg + 2 mg q1h prn (max 12 mg)	none
2	dose from yesterday + 2 mg q1h prn (max 16 mg)	none

Microdosing Protocols

• Suboxone combined with a short-acting opioid such as hydromorphone
• In general, all opioids can be stopped once at a dose of buprenorphine 12 mg daily

Short-Acting Opioids (Daily Dosing)

Day	Burprenorphine	Short-acting opioid
1	0.5 mg	maintain
2	1 mg	maintain
3	1.5 mg	maintain
4	2 mg	maintain
5	2.5 mg	maintain
6	3 mg	maintain
7	4 mg + 2 mg q1h prn (max 12 mg)	stop

Short-Acting Opioids (Twice-Daily Dosing)

Day	Burprenorphine	Short-acting opioid
1	0.5 mg daily	maintain
2	0.5 mg bid	maintain
3	1 mg bid	maintain
4	2 mg bid + 2 mg q1h prn (maximum of 12 mg)	stop

Long-Acting Opioids (Daily Dosing)

• Including fentanyl, fentanyl patches, and methadone

Day	Burprenorphine	Short-acting opioid
1	0.5 mg	maintain
2	1 mg	maintain
3	1.5 mg	maintain
4	2 mg	maintain
5	2.5 mg	maintain
6	3 mg	maintain
7	4 mg	maintain long-acting; stop any short-acting opioids
8	5 mg	maintain
9	6 mg	maintain
10	7 mg	maintain
11	8 mg	maintain
12	10 mg	maintain
13	12 mg	maintain
14	12 mg	stop all remaining opioids

Long-Acting Opioids (Twice-Daily Dosing)

Day	Burprenorphine	Short-acting opioid
1	0.5 mg daily	maintain
2	0.5 mg bid	maintain
3	1 mg bid	maintain
4	2 mg bid	maintain long-acting, stop any short-acting opioids
5	3 mg bid	maintain
6	4 mg bid	maintain
7	12 mg + 2 mg q1h prn (maximum 16 mg)	stop all remaining opioids

Extended-Release Monthly Injection (BUP-XR)

• Consider once stabilized on 8 to 24 mg buprenorphine for at least 7 days
• 300 mg SC monthly for the first 2 months, followed by 100 mg SC monthly maintenance

Perioperative Management

• Ideally, continue buprenorphine treatment without interruption and use higher doses of opioid analgesia
• If going to hold buprenorphine for surgery:
  • Consider tapering to 12 mg daily 2 to 3 days prior to surgery, or as low as 8 mg if a large or painful surgery
  • For the surgery itself, use NSAIDs, fentanyl, regional blocks, adjuncts, and non-pharmacologic options
  • Post-op, resume original dose as soon as possible, possibly split bid to tid to optimize for pain control, and continue non-buprenorphine pain management, including full agonist opioids if needed

Further Reading

• Management of opioid use disorders: a national clinical practice guideline. CMAJ. 2018;190(9):E247-E257. doi: 10.1503/cmaj.170958
• Opioid Enabler cheat sheet from Portico Network
• Use of microdoses for induction of buprenorphine treatment with overlapping full opioid agonist use: the Bernese method. Subst Abuse Rehabil. 2016; 7: 99–105. doi: 10.2147/SAR.S109919
• Buprenorphine/Naloxone Microdosing: The Bernese Method. A Brief Summary for Primary Care Clinicians. 2019. Available at https://www.metaphi.ca/wp-content/uploads/Guide_Microdosing.pdf