What are the best practices and protocols for using buprenorphine (Suboxone) for opioid use disorder treatment?

Buprenorphine for Opioid Use Disorder: Best Practices and Protocols

Core Treatment Recommendation

Buprenorphine sublingual formulations (8-24 mg daily) should be initiated as part of a comprehensive treatment plan that includes counseling and psychosocial support, with patients stabilized on transmucosal formulations for at least 7 days before considering transition to long-acting injectable formulations (initial 300 mg monthly × 2 doses, then 100 mg monthly maintenance). 1, 2

Patient Selection and Assessment

• Confirm diagnosis of opioid use disorder through clinical evaluation before initiating buprenorphine treatment 2
• Assess the patient's risk of relapse, expected severity of opioid withdrawal symptoms, and presence of comorbid conditions (particularly psychiatric disorders and concurrent benzodiazepine use) 1
• Screen for concomitant benzodiazepine or CNS depressant use, as this significantly increases risk of respiratory depression and death—though this should NOT be a categorical barrier to treatment, as untreated opioid use disorder poses greater mortality risk 2
• Evaluate for QT-prolonging medications, as concomitant use with buprenorphine is contraindicated 1, 2

Standard Induction Protocol (Traditional Approach)

Traditional induction requires patients to be in mild opioid withdrawal before the first buprenorphine dose to avoid precipitated withdrawal. 3

• Wait until the patient demonstrates objective signs of withdrawal (typically 12-24 hours after short-acting opioids, 24-48 hours after methadone or long-acting opioids) 3
• Start with 2-4 mg sublingual buprenorphine, observe for 1-2 hours 2
• If no precipitated withdrawal occurs, give additional 2-4 mg doses to reach 8-12 mg on day 1 2
• Titrate to maintenance dose of 8-24 mg daily over subsequent days based on withdrawal symptoms and cravings 2

Critical Pitfall to Avoid

The traditional approach is increasingly problematic with fentanyl-contaminated opioid supply, as fentanyl's long half-life and lipophilicity make it difficult to achieve adequate withdrawal before induction, increasing precipitated withdrawal risk 4

Alternative Induction: Rapid Overlap Initiation (Micro-Dosing)

For patients using fentanyl or those unable to tolerate withdrawal, a rapid overlap initiation (micro-dosing) protocol allows buprenorphine initiation while continuing other opioid use, avoiding precipitated withdrawal. 5, 4

7-Day Micro-Dosing Protocol:

• Day 1: 0.5 mg sublingual once daily 5
• Day 2: 0.5 mg twice daily 5
• Day 3: 1 mg twice daily 5
• Day 4: 2 mg twice daily 5
• Day 5: 3 mg twice daily 5
• Day 6: 4 mg twice daily 5
• Day 7: 12 mg once daily, discontinue all other opioids 5
• Subsequently titrate to 12-32 mg daily as needed 5

3-4 Day Rapid Protocol:

• Use smaller, more frequent escalating doses reaching therapeutic levels (16-24 mg) by day 3-4 4
• Patients continue other opioid use during initiation 4
• This approach showed 92% success rate in fentanyl users 4

The micro-dosing approach is particularly valuable for fentanyl users and eliminates the need for a withdrawal period, though it requires more intensive monitoring. 5, 4

Long-Acting Injectable Formulations

After stabilization on sublingual buprenorphine (8-24 mg daily for minimum 7 consecutive days), transition to Sublocade with two initial 300 mg monthly subcutaneous injections, followed by 100 mg monthly maintenance doses. 1, 6

Key Considerations for Injectable Formulations:

• Patients must demonstrate tolerance to buprenorphine before first injection to minimize precipitated withdrawal risk 1, 6
• Monitor closely after first injection for signs of precipitated withdrawal 1
• Never attempt surgical removal of the depot injection—risks include infection, tissue damage, and surgical complications 1
• The depot provides sustained therapeutic levels, reducing diversion risk and improving adherence 7

Direct-to-Inject Approach (Emerging Practice):

Recent evidence suggests 7-day injectable buprenorphine can be initiated without prior sublingual stabilization in selected patients, with 77% retention at 7 days and 73% at 30 days, though some patients experience significant withdrawal symptoms 8

Integration with Behavioral Therapies

All buprenorphine treatment must be combined with counseling and psychosocial support—medication alone is insufficient. 1, 2

• Evidence-based treatment integrates medication-assisted treatment with behavioral therapies 1
• Address substance use disorders alongside other health issues through integrated care models 1

Managing Concomitant Benzodiazepine Use

Do not categorically deny buprenorphine treatment to patients taking benzodiazepines or CNS depressants—creating treatment barriers poses greater mortality risk than the opioid use disorder itself. 2

Specific Management Strategies:

• Educate patients about overdose risks from combined use as part of treatment orientation 2
• Cessation of benzodiazepines is preferred in most cases 2
• Consider higher level of care for supervised benzodiazepine taper if appropriate 2
• Alternatively, gradually taper prescribed benzodiazepines to lowest effective dose 2
• There is no evidence supporting arbitrary buprenorphine dose caps as a strategy to address benzodiazepine use 2
• If patient is sedated at time of buprenorphine dosing, delay or omit that dose 2
• Use toxicology screening for both prescribed and illicit benzodiazepines 2

Critical Drug Interactions

CYP3A4 Inhibitors (macrolides, azole antifungals, protease inhibitors):

• Increase buprenorphine plasma concentrations, causing increased sedation and respiratory depression risk 2
• Consider dose reduction of buprenorphine when starting inhibitors 2
• Monitor for respiratory depression and sedation frequently 2

CYP3A4 Inducers (rifampin, carbamazepine, phenytoin):

• Decrease buprenorphine levels, potentially causing withdrawal or treatment failure 2
• Consider increasing buprenorphine dose when inducers are present 2

Antiretrovirals:

• Atazanavir (with or without ritonavir) increases buprenorphine levels and may cause increased sedation—monitor and reduce buprenorphine dose if warranted 2
• Most protease inhibitors and NNRTIs have minimal clinically significant effects 3, 2

Special Populations

Pregnant Women:

• Buprenorphine medication-assisted therapy improves maternal outcomes 1
• Counsel about neonatal opioid withdrawal syndrome (NOWS) risk, which is expected and treatable 2
• The risk of NOWS must be balanced against the greater risk of untreated opioid use disorder, which results in poor pregnancy outcomes 2
• Ensure appropriate neonatal treatment will be available 2

Patients with Chronic Pain:

• For patients on buprenorphine maintenance with chronic pain, consider dividing daily dose into every 6-8 hours dosing to leverage analgesic properties 3
• Can add short-acting full opioid agonists (morphine, hydromorphone, fentanyl) at higher doses to compete with buprenorphine at μ-receptors 3
• Consider switching from sublingual to transdermal buprenorphine patch, which bypasses first-pass metabolism and may provide better analgesia 3
• If inadequate analgesia persists despite maximum transdermal buprenorphine, consider transitioning to methadone maintenance 3

Perioperative Management

Continue buprenorphine throughout the perioperative period—it is rarely appropriate to reduce or discontinue the dose, regardless of indication or formulation. 3

Specific Perioperative Strategies:

• Maintain buprenorphine at baseline dose to prevent withdrawal and preserve addiction treatment 3
• Use multimodal analgesia (NSAIDs, acetaminophen, ketamine, gabapentinoids, regional techniques) as foundation of pain management 3
• Add full μ-agonists (morphine, fentanyl, hydromorphone) at higher than typical doses for breakthrough pain while continuing buprenorphine 3
• Have naloxone available and monitor respiratory status frequently due to variable buprenorphine dissociation rates 3
• For patients on doses >12 mg daily, consider tapering to 12 mg over 2-3 days preoperatively only if absolutely necessary 3
• Discontinuing buprenorphine risks addiction relapse, which poses greater harm than the challenge of perioperative pain management 3

Provider Requirements and System Considerations

• Physicians must obtain a waiver from SAMHSA to prescribe buprenorphine in office-based settings (training requirement) 1
• Prescribers should identify community treatment resources and work to ensure sufficient treatment capacity 1
• Multiple refills should not be prescribed early in treatment without appropriate follow-up visits 2
• Clinical monitoring appropriate to patient's stability level is essential 2
• Implement appropriate precautions to minimize misuse, abuse, or diversion risk, including protection from theft 2

Safety Monitoring and Precautions

• Store buprenorphine safely out of reach of children—accidental pediatric exposure can cause fatal respiratory depression 2
• Instruct patients to destroy unused medication appropriately 2
• Use caution in patients with compromised respiratory function (COPD, cor pulmonale, decreased respiratory reserve) 2
• Ensure patients take medications as prescribed and are not diverting or supplementing with illicit drugs through toxicology screening 2
• Offer naloxone for overdose prevention to all patients with opioid use disorder 1