Initiating Brixadi (Buprenorphine Extended-Release) for Opioid Use Disorder
Brixadi can only be initiated in patients who have already been stabilized on transmucosal (sublingual or buccal) buprenorphine at doses of 8-24 mg daily for a minimum of 7 consecutive days. 1
Patient Selection Criteria
Before initiating Brixadi, you must confirm:
- DSM-5 diagnosis of opioid use disorder through formal assessment 2
- Demonstrated tolerance to buprenorphine to minimize precipitated withdrawal risk 1
- Stable or controlled medical/psychiatric comorbidities 3
- Safe, substance-free environment when possible 3
Required Stabilization Phase
You cannot skip directly to Brixadi. The patient must first complete:
- Minimum 7 days of sublingual/buccal buprenorphine at 8-24 mg daily 1
- Absence of withdrawal symptoms on their current oral dose 1
- Clinical stability demonstrated through supervised administration initially 4
The American Academy of Family Physicians recommends combination buprenorphine/naloxone formulations during this stabilization phase because naloxone prevents misuse by injection while being poorly absorbed sublingually 4.
Specific Dosing Protocol for Brixadi
Once stabilization is confirmed:
- First two monthly doses: 300 mg subcutaneous injection 1
- Subsequent maintenance doses: 100 mg monthly subcutaneous injection 1
This differs from standard oral maintenance where fixed dosages of at least 16 mg daily are clearly superior to placebo 3. Recent evidence suggests doses up to 32 mg daily improve outcomes including reduced opioid use (68.5% to 59.5%, P=0.02), decreased use frequency (1.58 to 1.15 times per week, P=0.0002), and better retention (78.7% vs 50%, P=0.02) 5.
Critical Pre-Initiation Considerations
For patients transitioning from full opioid agonists:
- Ensure they are in mild withdrawal before any buprenorphine initiation to avoid precipitated withdrawal 1
- Traditional induction requires existing opioid withdrawal, though low-dose initiation methods are emerging that allow continuation of full agonists during gradual buprenorphine titration 6, 7
Screen for contraindications:
- QT-prolonging agents (concomitant use is contraindicated) 1
- Other CNS depressants including benzodiazepines (avoid concurrent prescribing whenever possible) 2
- Pregnancy status (use buprenorphine without naloxone if pregnant) 2
Behavioral Therapy Integration
Medication-assisted treatment must combine buprenorphine with behavioral therapies 2. This is not optional—the CDC explicitly recommends "usually medication-assisted treatment with buprenorphine or methadone in combination with behavioral therapies" 2.
Provider Requirements
Historically, physicians needed a SAMHSA waiver to prescribe buprenorphine 2. While recent legal changes have modified these requirements 6, clinicians must still be knowledgeable about opioid use and risk mitigation 8.
If you cannot provide treatment yourself, you must arrange for the patient to receive care from a substance use disorder specialist or SAMHSA-certified opioid treatment program 2. Never dismiss patients from your practice due to substance use disorder—this represents patient abandonment and adversely affects safety 2.
Post-Initiation Monitoring
Monitor closely after the first Brixadi injection for:
- Signs of precipitated withdrawal, especially in patients recently using full opioid agonists 1
- Breakthrough cravings or withdrawal symptoms (indicates need for dose increase, not discontinuation) 4
- Continued opioid use (sporadic use in first few months is common; address with increased visit frequency and intensive behavioral therapy engagement) 3
Do not attempt to remove Brixadi after administration—risks include surgical complications, infection, and tissue damage 1.
Naloxone Co-Prescription
Prescribe naloxone for home use and ensure family/friends know how to administer it 4. This is a CDC recommendation for all patients on buprenorphine maintenance 4.
Critical Safety Warning
Stopping Brixadi suddenly dramatically increases risk of relapse, return to dangerous opioid use, and fatal overdose 4. If dose reduction is desired, work on a very slow taper over months to years with close monitoring 4.