What is the recommended induction protocol and dosing schedule for Brixadi (buprenorphine weekly) and Sublocade (buprenorphine monthly), including short‑acting buprenorphine induction, breakthrough craving management, and steps to take if injection‑site complications occur?

Brixadi and Sublocade: Induction Protocols and Clinical Management

For patients not currently on buprenorphine, use Brixadi (weekly) with a 4 mg sublingual test dose when mild-to-moderate withdrawal appears, followed by 16 mg Brixadi within the same day, then 8 mg within 3 days to reach the target 24 mg weekly dose. For patients already stabilized on sublingual buprenorphine, both Brixadi and Sublocade allow direct switching based on established conversion tables 1.

Induction Protocol for Treatment-Naive Patients

Brixadi (Weekly) Induction

Step 1: Confirm withdrawal status

• Wait for objective signs of mild-to-moderate opioid withdrawal before initiating
• Administer a 4 mg sublingual buprenorphine test dose
• Observe for 1-2 hours to ensure no precipitated withdrawal occurs 1

Step 2: First injection

• If test dose is tolerated, administer 16 mg Brixadi (weekly) subcutaneously on the same day
• Inject into buttock, thigh, or abdomen (avoid upper arm until steady-state is achieved after 4 consecutive doses) 1

Step 3: Dose completion

• Administer an additional 8 mg Brixadi (weekly) within 3 days of the first dose
• This achieves the recommended 24 mg weekly target dose
• If needed during Week 1, an additional 8 mg dose can be given (minimum 24 hours between injections) for a maximum of 32 mg weekly 1

Step 4: Maintenance

• Continue weekly injections at 7-day intervals based on the total dose established in Week 1
• Maximum dose: 32 mg weekly
• Steady-state is reached after 4 weeks 1

Sublocade Induction

Sublocade is NOT indicated for treatment-naive patients 1. Patients must first be stabilized on sublingual buprenorphine before switching to Sublocade monthly injections.

Switching from Sublingual Buprenorphine

Conversion to Brixadi

Patients on sublingual buprenorphine can switch directly to either weekly or monthly Brixadi formulations 1:

Daily Sublingual Dose	Brixadi Weekly	Brixadi Monthly
≤6 mg	8 mg	Not recommended
8-10 mg	16 mg	64 mg
12-16 mg	24 mg	96 mg
18-24 mg	32 mg	128 mg

Key advantage: Brixadi allows same-day transition from sublingual formulations, including initiation with weekly dosing before transitioning to monthly 2, 3.

Conversion to Sublocade

Sublocade requires prior stabilization on sublingual buprenorphine. The standard protocol uses:

• 300 mg monthly for the first two months
• 100 mg monthly for maintenance thereafter

Sublocade offers only two dose options (100 mg and 300 mg monthly), providing less dosing flexibility compared to Brixadi's multiple weekly and monthly options 3.

Managing Breakthrough Cravings

During Induction (Week 1 with Brixadi)

• Administer additional 8 mg Brixadi (weekly) doses as needed
• Wait minimum 24 hours between injections
• Maximum total weekly dose: 32 mg 1

During Maintenance Phase

For Brixadi patients:

• Additional 8 mg weekly injections can be given based on clinical judgment
• Maximum: 32 mg/week or 128 mg/month 1
• Recent evidence suggests supplemental sublingual buprenorphine can address feelings of medication "wearing off" 4

For Sublocade patients:

• Supplemental sublingual buprenorphine is the primary option for breakthrough cravings
• Sublocade's limited dosing options (100 mg or 300 mg only) provide less flexibility 3, 4

Clinical pearl: A 2025 naturalistic study found that patients who experienced both formulations reported Brixadi wearing off less frequently than Sublocade, though individual responses varied 4.

Injection Site Complications

Prevention

• Use proper aseptic technique with gloves
• Inject slowly into subcutaneous tissue
• Rotate injection sites: buttock, thigh, abdomen, or upper arm (upper arm only after steady-state with Brixadi) 1
• Consider topical or subcutaneous anesthetics, particularly with Sublocade, which causes more injection site pain than Brixadi 4

Management of Complications

At each visit, examine injection sites for:

• Signs of infection (erythema, warmth, purulent drainage)
• Evidence of tampering or attempts to remove the depot 1

If infection occurs:

• Treat with appropriate antibiotics
• Consider temporary switch to sublingual buprenorphine if depot removal is necessary
• Resume injectable formulation using standard induction protocol once infection resolves 5

For injection site pain:

• Mild pain is common (reported in 18-22% of patients) and typically resolves spontaneously 6
• Sublocade causes more injection site discomfort than Brixadi 4
• Pre-treatment with topical anesthetics can reduce discomfort
• Rotate injection sites to minimize cumulative irritation

Key Differences: Brixadi vs Sublocade

Brixadi Advantages

• Can be used for treatment initiation (not just switching)
• Multiple dosing options: weekly (8,16,24,32 mg) and monthly (64,96,128 mg)
• Flexible transitions between weekly and monthly formulations
• Less injection site pain reported 4
• Faster plasma clearance after discontinuation (approximately 1 month for weekly, 4 months for monthly) 1

Sublocade Characteristics

• Requires prior sublingual stabilization
• Only two dose options: 100 mg and 300 mg monthly
• Standard protocol: 300 mg × 2 months, then 100 mg maintenance
• More injection site discomfort reported 4
• Longer plasma clearance after discontinuation (approximately 4 months) 1

Discontinuation Considerations

When stopping either formulation:

• Monitor patients for several months for withdrawal symptoms
• After steady-state, detectable plasma buprenorphine persists for:
  • Brixadi weekly: approximately 1 month
  • Brixadi monthly: approximately 4 months
  • Sublocade: approximately 4 months 1

If restarting buprenorphine after full agonist opioid use:

• Patient must be in mild opioid withdrawal before administering buprenorphine to avoid precipitated withdrawal
• Use standard induction protocol with sublingual test dose 5

Missed Doses

• Administer the next dose as soon as possible
• Maintain 7-day intervals for weekly dosing
• Maintain 28-day intervals for monthly dosing
• No specific guidance for extended delays; clinical judgment should guide whether to restart induction protocol 1

Special Populations

Recent evidence suggests rapid transition to long-acting injectable buprenorphine within 24 hours of last sublingual dose is feasible and well-tolerated, with short-term retention exceeding 60% and minimal withdrawal symptoms (4% requiring additional opioid support) 2. This approach may be particularly valuable for justice-involved individuals or those at high risk of treatment dropout 3.