What are the indications, dosing schedule, contraindications, and safety considerations for the 300 mg Sublocade (buprenorphine) injection in adults with opioid use disorder?

Sublocade 300mg: Indications and Clinical Considerations

Primary Indication

Sublocade 300mg is FDA-approved exclusively for moderate-to-severe opioid use disorder (OUD) in patients who have already been stabilized on sublingual or buccal buprenorphine (8-24 mg daily) for at least 7 consecutive days. 1 This is not a first-line treatment—patients must demonstrate tolerance to transmucosal buprenorphine before receiving the depot injection to minimize precipitated withdrawal risk. 1

Standard Dosing Protocol

• Initial phase: Administer 300 mg subcutaneously monthly for the first two doses 1, 2
• Maintenance phase: After two 300 mg doses, transition to either 100 mg or 300 mg monthly depending on patient characteristics 2, 3
• Higher-risk populations: Patients who inject opioids or use high-dose opioids require the 300 mg maintenance dose rather than 100 mg, as this population shows clinically meaningful improvements in treatment retention and opioid abstinence with the higher dose 3
• Standard-risk populations: Non-injecting patients achieve comparable efficacy with either 100 mg or 300 mg maintenance doses 3

Injection Site Options

• Approved sites: Abdomen (original FDA-approved site), upper arm, thigh, or buttocks 4
• Pharmacokinetic differences: Upper arm and thigh injections produce 39% and 52% higher peak concentrations (Cmax) respectively compared to abdomen, though these higher peaks do not increase adverse events 4
• Therapeutic levels: All injection sites maintain buprenorphine plasma concentrations at or above 2 ng/mL (therapeutic target) throughout the monthly dosing interval 4

Critical Safety Considerations

Contraindications and High-Risk Combinations

• Absolute contraindication: Concomitant use with QT-prolonging medications 1
• Black-box warning: Combining Sublocade with benzodiazepines dramatically increases risk of respiratory depression, coma, and death—avoid this combination whenever possible 5, 6
• If benzodiazepine co-prescription is unavoidable: Use lowest effective doses, obtain documented informed consent discussing death risk, and schedule weekly monitoring initially 6

Pre-Treatment Requirements

• Stabilization period: Minimum 7 days on 8-24 mg daily sublingual/buccal buprenorphine 1
• Withdrawal status: Patient must NOT be in withdrawal at time of Sublocade injection—confirm they are comfortable on oral dose 1
• Tolerance verification: Ensure patient tolerates transmucosal buprenorphine without precipitated withdrawal before depot administration 1

Post-Injection Monitoring

• Immediate monitoring: Watch closely after first injection for signs of precipitated withdrawal, especially in patients recently using full opioid agonists 1
• Injection site reactions: Most common adverse events are injection-site related (13.2% of patients), typically mild-to-moderate in severity 7
• Temporal pattern: Incidence of treatment-emergent adverse events decreases in the second 6 months compared to first 6 months of treatment 7
• Long-term safety: 66.8% of patients report at least one treatment-emergent adverse event over 12 months, with no clinically meaningful changes in safety assessments 7

Special Clinical Situations

Perioperative Management

• Major concern: Sublocade's high mu-opioid receptor binding affinity may interfere with perioperative pain management 1
• Planning requirement: Discuss surgical plans in advance with anesthesia team to develop pain management strategy 1

Depot Removal

• General principle: Do NOT attempt surgical removal except in extreme circumstances 1, 8
• Removal risks: Surgical complications, infection, and damage to surrounding tissue 1
• Documented case: One patient required surgical removal due to refractory nausea/vomiting, tachycardia, hyperglycemia, and elevated anion gap unresponsive to pharmacotherapy 8
• Clinical implication: Sublocade is essentially irreversible once administered—ensure appropriate patient selection 8

Treatment Retention and Efficacy

• 12-month retention: Approximately 50% of patients remain in treatment at 12 months 7
• Abstinence rates: After 12 months, 61.5% of patients who rolled over from prior buprenorphine treatment and 75.8% of de novo patients achieve opioid abstinence 7
• Maintenance therapy priority: Buprenorphine should never be discontinued once started, as discontinuation precipitates withdrawal and dramatically increases relapse risk to more dangerous opioids 6
• Duration of treatment: No maximum recommended duration—patients may require treatment indefinitely 6

Common Pitfalls to Avoid

• Premature initiation: Never give Sublocade to buprenorphine-naive patients or those not stabilized for at least 7 days 1
• Underdosing high-risk patients: Opioid-injecting patients specifically require 300 mg maintenance doses, not 100 mg 3
• Benzodiazepine continuation: Actively work to taper and discontinue benzodiazepines rather than accepting chronic co-prescription 6
• Treating as reversible: Unlike sublingual buprenorphine, Sublocade cannot be easily stopped—counsel patients that effects persist for weeks after injection 2, 8
• Ignoring drug interactions: Screen for QT-prolonging medications, serotonin syndrome risk, and other significant interactions before each injection 1