Introduction
Sublocade (buprenorphine extended-release) is a subcutaneous injectable formulation indicated for the treatment of moderate to severe opioid use disorder. As the first once-monthly buprenorphine product approved by the FDA, it represents a significant advancement in medication-assisted treatment by providing continuous opioid receptor blockade while eliminating the need for daily dosing.
Mechanism of Action
Sublocade contains buprenorphine, a partial agonist at mu-opioid receptors and an antagonist at kappa-opioid receptors. Its partial agonist activity provides:
- Lower intrinsic activity than full agonists (e.g., heroin, oxycodone)
- Ceiling effect on respiratory depression at higher doses
- High receptor affinity that displaces full opioid agonists
- Prevents withdrawal symptoms while reducing craving
The ATRIGEL® delivery system creates a solid depot upon subcutaneous injection that slowly releases buprenorphine over approximately one month.
Indications
FDA-approved for the treatment of moderate to severe opioid use disorder in patients who have initiated treatment with a transmucosal buprenorphine-containing product, followed by dose adjustment for a minimum of 7 days.
Dosage and Administration
Initial dosing:- 300 mg monthly for first 2 months
- Maintenance: 100 mg monthly (may increase to 300 mg if needed)
- Administered subcutaneously in the abdominal region by healthcare provider
- Rotate injection sites between monthly administrations
- Must be administered using the provided syringe and safety needle
- Hepatic impairment: Use with caution in severe impairment
- Renal impairment: No dosage adjustment needed
- Elderly: Limited data available
- Pediatrics: Not approved for patients under 18
Pharmacokinetics
Absorption: Slow release from subcutaneous depot with mean Tmax of 24 hours post-injection Distribution: Volume of distribution 99-157 L, 96% plasma protein bound Metabolism: Primarily hepatic via CYP3A4 and CYP2C8 Elimination: Terminal half-life approximately 43-60 days; fecal elimination (major route) Steady-state: Achieved after 4-6 months of monthly dosingContraindications
- Hypersensitivity to buprenorphine or ATRIGEL® components
- Concurrent use of benzodiazepines or other CNS depressants without careful medical supervision
- Significant respiratory insufficiency
- Acute alcoholism or delirium tremens
Warnings and Precautions
Boxed Warning:- Serious life-threatening respiratory depression and death have occurred
- Risk of accidental injection or self-injection
- Potential for diversion and misuse
- Risk of injection site reactions including pain, erythema, and pruritus
- Hepatic events including cytolytic hepatitis and hepatitis with jaundice
- Precipitation of opioid withdrawal in physically dependent patients
- QTc interval prolongation at high doses
- Orthostatic hypotension
- Use in patients with head injury or increased ICP
Drug Interactions
Major interactions:- CYP3A4 inhibitors (ketoconazole, clarithromycin): May increase buprenorphine levels
- CYP3A4 inducers (rifampin, carbamazepine): May decrease buprenorphine levels
- Benzodiazepines and other CNS depressants: Additive CNS depression
- Opioid antagonists (naloxone, naltrexone): May precipitate withdrawal
- Serotonergic drugs: Possible serotonin syndrome
- MAO inhibitors: Potential enhanced effects
Adverse Effects
Common (≥5%):- Constipation (12%)
- Headache (10%)
- Nausea (8%)
- Injection site reactions (pain 16%, erythema 14%, pruritus 11%)
- Vomiting (7%)
- Fatigue (6%)
- Respiratory depression
- Severe injection site reactions
- Allergic reactions
- Hepatic toxicity
- Adrenal insufficiency
- Androgen deficiency
Monitoring Parameters
Baseline:- Complete opioid use history
- Liver function tests
- Renal function
- Pregnancy test if indicated
- ECG if cardiac risk factors present
- Injection site assessment
- Signs of withdrawal or overmedication
- Liver function monitoring (periodically)
- Respiratory status
- Constipation management
- Adherence to comprehensive treatment plan
Patient Education
Key points:- This is a monthly injection administered by healthcare providers only
- Continue treatment as part of comprehensive management program
- Report any signs of injection site reactions promptly
- Avoid alcohol and other CNS depressants
- Notify all providers about Sublocade treatment
- Keep medication out of reach of children
- Understand potential for withdrawal if treatment stopped abruptly
- Use caution when driving or operating machinery
- Report any symptoms of allergic reaction
- Stored refrigerated at 2°C to 8°C (36°F to 46°F)
- Allow to warm to room temperature for 15 minutes before administration
- Discard if left at room temperature for >7 days
References
1. FDA Prescribing Information: Sublocade (buprenorphine extended-release injection). 2022 2. Haight BR, et al. Efficacy and safety of a monthly buprenorphine depot injection for opioid use disorder: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2019;393(10173):778-790 3. Lofwall MR, et al. Long-term safety of a weekly and monthly buprenorphine depot injection in the treatment of opioid use disorder: A phase 3 randomized, multicenter, open-label study. Drug Alcohol Depend. 2021;218:108315 4. Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Use Disorder. SAMHSA, 2020 5. NICE Guidelines [NG115]: Drug misuse in over 16s: opioid detoxification. 2017