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Probuphine Implant For Opioid Addiction Treatment

Written by Thomas Christiansen

& Medically Reviewed by Dr. Davis Sugar, MD

Medically Reviewed

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Last Updated - 12/28/2022

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Updated 12/28/2022

Key Takeaways

  • The implant must be inserted via a minor surgical procedure by a certified medical personnel
  • Once inserted, the implant can last up to six months
  • The implant requires minimal office visits (once per month) and eliminates the need for daily medications
  • The implant is proven to be effective in the treatment of opioid dependence
  • The implant carries minor risks including dangers associated with implantation and removal, such as migration, protrusion and expulsion

Probuphine is an implant medication used in the maintenance treatment of opioid dependence. It is part of a complete program that includes therapy and psychosocial support.

As a form of buprenorphine, Probuphine is an implant medication approved for the treatment of opioid dependence. Opioid dependence could arise from prescription medications such as hydrocodone codeine, or illicit substances such as heroin.

Probuphine is used in the treatment of opioid dependence as part of a complete medication-assisted treatment program (MAT), which includes counseling and psychosocial support.

What is Probuphine?

Probuphine is a partial opioid agonist, which means it activates the brain’s opioid receptors. It is deemed “partial” because at low doses it can improve withdrawal symptoms, but at high doses it saturates the opioid receptors, rendering them ineffective. This partial activity reduces the potential for a drug overdose.

By binding to opioid receptors, Probuphine prevents the reinforcing effects of opioids and works to decrease the intensity and duration of opioid withdrawal symptoms.

It should be noted that the implant is only used in individuals who have already achieved clinical stability on low-to-moderate doses (less than 8 mg per day) of transmucosal or sublingual forms of buprenorphine.

History of Probuphine

As it contains the active ingredient buprenorphine, Probuphine is a Schedule III controlled substance. This Drug Enforcement Administration classification is because although therapeutic when used accordingly, buprenorphine has the potential to be abused if used inappropriately.

As a sublingual (under the tongue) tablet, buprenorphine was initially approved by the FDA in 2002. Since then, many studies have shown substantial benefit of using buprenorphine in supporting recovery from opioid addiction.

Probuphine is the implant formulation of buprenorphine created by Titan Pharmaceuticals. It was FDA approved for the treatment of opioid dependence in 2016 and is eligible for use in individuals between the ages of 16 and 65.

Probuphine is the only implant medication approved in the treatment of opioid dependence. The implant formulation was designed to allow for the continuous and stable release of buprenorphine without the associated clinic visits or risk of inconsistent dosing.

The benefits of using Probuphine over other formulations include:

  • Lower risk of diversion compared with daily formulations
  • Sustained release of medication leading to non-fluctuating blood levels
  • Greater adherence in comparison with oral and transdermal formulations
  • Convenience (no need for daily treatment because implant is every six months)
  • Fewer office visits (required only once per month to inspect implant area)
  • Less possibility of misuse or incorrect use

Probuphine for Opioid Addiction

Probuphine is used for the maintenance treatment of opioid-dependent patients already on a maintenance dose of 8 mg or less of submucosal or sublingual buprenorphine.

Probuphine is not appropriate for individuals new to opioid treatment plans. Individuals who have not yet achieved a sustained, prolonged clinical stability on oral formulations are not eligible for Probuphine treatment. Clinical stability with submucosal or sublingual buprenorphine is required prior to the commencement of Probuphine.

Probuphine Dosing and Administration

The Probuphine implant procedure proposed by the FDA involves administering four soft and malleable rods underneath the skin. The rods are an ethylene-vinyl acetate capsule that house the buprenorphine medication. The small rods are implanted subdermally (beneath the skin, also called subcutaneously) on the inside of an individual’s upper arm.

Each of the four rods are 26 mm long and 2.5 m in diameter, about the size of a matchstick. The implant contains 74.2 mg of buprenorphine which is released at a steady rate.

One of the significant benefits of the implant is that it lasts up to six months. After six months, certified medical personnel must remove the implant.

The implant can be prescribed twice, once in each arm. After two rounds of implant medication (one in each arm), the treatment regimen may be converted back to the sublingual or submucosal forms, at the previously held dose.

Probuphine Insertion and Removal

As Probuphine is an implant medication, it must be inserted beneath the skin of the upper arm via a minor surgical procedure. This procedure must be done under aseptic (sterile) conditions, conducted by trained medical personnel.

Certified providers include medical staff and healthcare personnel who have successfully completed a live training program on the insertion and removal procedures inherent of subcutaneous implants. The FDA utilizes a step-by-step procedure for the insertion and removal of Probuphine.

The following medical personnel are certified to insert and remove the implant:

  • Medical Doctor (MD)
  • Doctor of Osteopathic Medicine (DO)
  • Physician Assistant (PA)
  • Nurse Practitioner (NP)

After the procedure is completed, avoid touching the area of the implant which may inadvertently introduce infection. If the area must be touched (to change a bandage for example), be sure to thoroughly wash hands with soap and water prior. This will help prevent the development of an implant-site skin infection.

How Does Probuphine Work?

Probuphine works to provide people with a sustained and regulated dose of medication throughout the entirety of the six-month treatment period. It eliminates the need for daily medication and ensures the most effective dose is received on a constant basis.

6-Month Treatment Regimen

The implant works by providing a consistent dose of buprenorphine, released at a constant rate for up to six months. The implant provides the advantage of avoiding daily medications and frequent physician visits. Additionally, the implant allows for significantly improved efficacy and compliance rates.

Check-ups Once per Month

It is recommended that individuals with the Probuphine implant see their health care provider once a month to ensure the implant rods remains stationary and the surrounding area is infection-free.

Who Should Use It?

Probuphine is recommended for the treatment of opioid dependence in individuals currently taking low dose buprenorphine.

  • Individuals with Opioid Dependence. It is recommended for people diagnosed with opioid dependence who are currently stable on low dose buprenorphine.
  • Clinically Stable on Low Dose Buprenorphine (less than 8 mg per day). Probuphine is only used in individuals who are already taking low dose buprenorphine (sublingual or submucosal), and have achieved clinical stability. It is not used in the initial management of opioid dependence.

Who Should Avoid It?

There are a few patient populations that should avoid using Probuphine. Individuals who should avoid Probuphine include:

  • Patients with moderate to severe liver disease. The implant is not recommended in individuals with moderate or severe liver impairment. There is no dosage adjustments for mild liver impairment.
  • Those who have had a previous allergic reaction. Individuals who have had a previous allergic reaction to any buprenorphine-containing products or ethylene vinyl acetate should not use Probuphine.
  • Lactating patients. Buprenorphine passes into the mother’s milk.
  • Geriatric patients. If Probuphine is used in this population, they should be monitored for sedation and respiratory depression.

Probuphine Side Effects

The Probuphine implant is well tolerated when used appropriately. However, some side effects have been reported from using Probuphine.

Common side effects include:

  • Headaches
  • Local pain or itching (at implant site)
  • Nausea or vomiting
  • Constipation
  • Back pain
  • Tooth pain
  • Fatigue or CNS depression
  • Dizziness
  • Depression

Uncommon, but serious side effects include:

  • Opioid withdrawal
  • Infection
  • Allergic reaction
  • Hepatic (liver) injury
  • QT prolongation
  • Low Blood Pressure

Individuals should always consult their health care practitioner regarding any potential side effects and interactions with other medications.

Individuals should contact their health provider immediately if:

  • The implant changes location on their arm
  • The implant bulges out more than usual under the skin
  • The implant penetrates the skin and starts to come out
  • The implant starts to bleed excessively
  • The implant area (inner arm) has associated signs of infection such as redness, swelling, or pus production
  • The implant causes arm weakness or numbness, which could signify nerve injury
  • They experience shortness of breath, which could signify the implant has migrated to the lung. This occurrence is a rare but serious complication in which pieces of the implant relocate to the blood vessels of the lung, causing blockage and potential lung collapse.

Drug Interactions

Some medications may interact with Probuphine or the CYP enzyme system in which it is metabolized. It is important to be aware of the following drug interactions:

  • Benzodiazepines: post-marketing reports of coma and death have been associated with the concomitant use of buprenorphine and benzodiazepines.
  • CYP3A4 Inhibitors/Inducers: the liver enzyme that breaks down buprenorphine is also used by several other medications. Interactions may occur that alter the effective concentration.
  • Serotonergic Medications: medications affecting the serotonin system in the body may be affected by buprenorphine and should be used with caution.

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Benefits & Effectiveness

randomized, double-blind study demonstrated the equal efficacy of Probuphine in treating opioid dependence in comparison with other buprenorphine formulations such as the transdermal patch or sublingual tablets. One of the big advantages of Probuphine stems from the method of administration. By providing a regulated dose at a steady rate, the implant provides more effective results than oral formulations. Due to the nature of the medication, the implant also provides substantially higher compliance rates.

Another randomized control study demonstrated its standalone effectiveness. The use of Probuphine resulted in less opioid use over 16 weeks in comparison with a placebo.

How Much Does Probuphine Cost?

The implant contains a total of 74.2 mg, distributed evenly throughout four rods. Each of the four rods costs $1,485. The average wholesale price of a six-month course of Probuphine is $5,940.

View Sources

Barnwal, Pretti; et al. “Probuphine (Buprenorphine Implant): A Promising Candidate In Opioid Dependence”. Therapeutic Advances in Psychopharmacology, 2017. Accessed July 23, 2019.

Food and Drug Administration. “Probuphine (Buprenorphine Hydrochloride Subnormal Implant) For Maintenance Treatment of Opioid Dependence.” January 12, 2016. Accessed July 23, 2019.

Itzoe, Maria; Cuarnieri, Michael. “New Developments in Managing Opioid Addiction: Impact of a Subdermal Buprenorphine Implant”. Journal of Drug Design, Development and Therapy, May 10, 2017. Accessed July 23, 2019.

Ling, Walter; et al. “Buprenorphine Implants for Treatment of Opioid Dependence: A Randomized Controlled Trial.” Journal of the American Medical Association, October 13, 2010. Accessed July 23, 2019.

Ling, Walter; Mooney, Larissa; Torrington, Matthew. “Buprenorphine For Opioid Addiction”. Pain Management, July 2012. Accessed July 23, 2019.

Rosenthal, Richard; et al. “Effect of Buprenorphine Implants on Illicit Opioid Use Among Abstinent Adults With Opioid Dependence Treated With Sublingual Buprenorphine: A Randomized Clinical Trial”. Journal of the American Medical Association,  July 19, 2016. Accessed July 23, 2019.

Smith, Lillian; et al. “Probuphine (Buprenorphine) Subdermal Implants for the Treatment of Opioid-Dependent Patients”. Journal of Pharmacy and Therapeutics, August 2017. Accessed July 23, 2019.