Revolutionizing Opioid Use Disorder Treatment: Long-Acting Injectables

The opioid crisis continues to strain healthcare systems nationwide, with millions struggling with opioid use disorder (OUD) each year. As the epidemic evolves, so do the tools available to combat it. One of the most promising advancements? Long-acting injectables (LAIs). These medications are changing the game—providing consistent dosing, minimizing diversion risk, and helping patients maintain recovery without the daily reminder of a pill or film.

Below, we’ll walk through the major LAI options, how they work, and what to consider when integrating them into clinical practice.

Why Long-Acting Injectables Matter for Opioid Use Disorder

Traditional treatments like daily sublingual buprenorphine can work well—but also come with challenges. Adherence issues, stigma, and the logistics of daily dosing can get in the way of recovery.

LAIs remove some of those barriers. They provide steady medication levels, help reduce misuse, and support better continuity of care—especially in outpatient, carceral, and hospital-to-community transitions. Many patients also report higher satisfaction and improved quality of life with LAIs. That makes these meds a valuable addition to our toolkit in responding to the opioid crisis.

Extended-Release Naltrexone (Vivitrol®)

Mechanism and Administration

Approved by the FDA in 2010, XR-naltrexone is a mu-opioid antagonist delivered as a monthly 380 mg intramuscular injection. By blocking opioid receptors, it reduces cravings and prevents euphoria from opioid use.

Key Considerations

• Initiation Protocols: Initiating XR-naltrexone requires complete opioid detoxification, typically over 7–15 days. A recent JAMA study highlighted a rapid initiation protocol using minimal doses of buprenorphine followed by oral naltrexone titration, cutting the start time to 5–7 days.

• Safety Profile: Common side effects include nausea, headaches, and injection site reactions. However, overdose risks may increase during treatment gaps, as seen in a survival analysis of the X:BOT trial.

• Patient Suitability: Ideal for patients who prefer initiating medications that do not result in physical dependence/withdrawal (e.g., methadone, buprenorphine) or struggle with daily medications.
  

Buprenorphine LAIs: Sublocade® and Brixadi®

Sublocade®

This monthly subcutaneous buprenorphine formulation has been available since 2017 and requires patients to stabilize on SL buprenorphine for a week before initiation.

• Dosage: Starts with 300 mg monthly, with some individuals transitioning to 100 mg monthly as maintenance.

• Advantages: Improved treatment satisfaction and quality of life compared to daily SL buprenorphine. It must be administered abdominally and refrigerated (can be left at room temp for up to 12 weeks) under a REMS program.

Brixadi®

FDA-approved in 2023, Brixadi offers weekly and monthly dosing flexibility

• Key Features: Can be injected into various sites, doesn’t require refrigeration, and uses a binder that enables different dosing volumes.

• Scheduling Flexibility: Weekly doses can vary by ±2 days, while monthly doses have a ±7-day window, helpful for patients with inconsistent schedules.

Buprenorphine Implant (Probuphine)

Although limited in use, this FDA-approved implant involves four rods placed in the upper arm, delivering buprenorphine continuously for six months. It’s an option for patients stabilized on ≤8 mg of SL buprenorphine daily.

• Challenges: High cost and surgical requirements limit its adoption, but it may benefit patients seeking long-term maintenance without frequent visits.
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Practical Challenges and Solutions for LAIs

Cost and Coverage

Insurance coverage varies. Some manufacturers offer patient assistance programs, but inconsistent Medicaid coverage remains a major barrier—especially for vulnerable populations. Advocacy at the state and payer level is essential to expand access.

Storage and Administration

Both buprenorphine LAIs are Schedule III substances. They must be stored securely and dispensed according to REMS protocols. Make sure your clinic is set up for this before prescribing.

Person-Centered Care

Don’t underestimate the importance of preference and autonomy. Some patients prefer daily oral meds; others are ready to try injectables. Coercion has no place in opioid use disorder treatment. Offering options and engaging in shared decision-making goes a long way.

What This Means for Your Practice

The opioid crisis demands innovative solutions, and LAIs stand out as powerful tools in our arsenal. By addressing adherence, reducing diversion, and offering flexibility, they bring hope for better patient outcomes and mitigating this crisis. As healthcare professionals, staying informed about these evolving therapies is our responsibility to ensure every patient receives the care they deserve.