The opioid crisis in America is nothing short of alarming.
According to the American Society of Addiction Medicine, roughly 2.6 million people had a substance use disorder involving opioids in 2015. Currently, drug overdose is the leading cause of death in the U.S. In 2015, 59.7 percent of drug overdose fatalities were caused by opioids, and the rate of death by opioids had risen 400 percent since 1999.
Clearly, there is an immense problem combating both substance use disorders and overdoses involving opioids. Fortunately, there is a new drug on the market. Available to the public as of June 21, Probuphine could be the answer that America is looking for.
What Is Probuphine?
Probuphine is an implant that delivers a constant dose of buprenorphine to people living with opioid addiction. Four of the one-inch rods that comprise the implant are inserted into the inside of the upper arm by a trained physician during an outpatient visit, and they last six months.
It is the first implant approved by the FDA to treat addiction to opioids, but buprenorphine itself is not a new drug; it has been approved to treat opioid dependence since October 2002. Buprenorphine is a partial opioid agonist, meaning that it acts on the same receptors in the brain as opioids do, but does not produce the same high or side effects. In addition, it creates a “ceiling effect,” so that you don’t crave getting high to the same extreme.
What Is Its History?
Probuphine has been in development since 2007–2008 when two studies — 805 and 807— were run. In 2009, the implant applicator and removal clamp were redesigned, the removal technique was changed, and training was developed that consisted of a manual, video, half-day class and hands-on training workshop. In 2010 and 2011, studies 806 and 811 were conducted, and in 2014, the final study (814) was completed. These studies were conducted by Titan Pharmaceuticals.
Clinical trials for Probuphine took place from 2007 to 2015 and were comprised of three phases:
- Phase I compared the urine tests of people with Probuphine implant to those of people with placebo implants. This phase found that an average of 40.4 percent of people with buprenorphine implants tested negative for opioids versus 28.3 percent of people with the placebo.
- Phase II compared buprenorphine implants to placebo implants and buprenorphine/naloxone tablets. This phase found that Probuphine was significantly more effective than a placebo, but its effects were comparable to those of the tablets.
- Phase III compared two groups of patients stable on 8 mg or less of buprenorphine/naloxone tablets. One group received placebo implants and continued to use the regular tablets, while the other received Probuphine implants and placebo tablets. This phase found that 88 percent of those with Probuphine tested negative for opioid use throughout the six-month study, compared to 72 percent of those on the buprenorphine/naloxone tablets.
Probuphine was FDA approved on May 26, 2016. Braeburn Pharmaceuticals (Probuphine’s license holder) had the capacity to train three thousand physicians on how to insert Probuphine rods in the six weeks afterward. By May 27, 2016, 2250 providers were already registered. Within a month, that number had risen to about four thousand and Braeburn acknowledged training capacity for 2016.
Probuphine is the first implant approved by the FDA to treat addiction to opioids, but buprenorphine itself is not a new drug; it has been approved to treat opioid dependence since October 2002. Buprenorphine is a partial opioid agonist, meaning that it acts on the same receptors in the brain as opioids, but does not produce the same high or side effects. In addition, it creates a “ceiling effect,” so that people who use it don’t crave its effects to the same extreme.
Who Should Use It?
Probuphine is indicated for people who:
- Are opioid-dependent
- Have been stable on transmucosal buprenorphine (a film dissolved between the cheek and the gums) for an extended period of time
- Take a low-to-moderate dose (no more than 8 mg per day) of buprenorphine
What Are the Benefits?
Some of the benefits of Probuphine include:
- Lower rates of illicit opioid use. In clinical trials lasting six months, Probuphine and sublingual buprenorphine were compared to each other. Probuphine always came out ahead, with over 90 percent cumulative negative opioid use in months 1–5 and over 80 percent cumulative negative opioid use in month six. In comparison, sublingual buprenorphine dropped from over 90 percent in month one to over 70 percent in month six.
- Ensuring that medication is taken as prescribed. According to the Centers for Disease Control and Prevention, only about half of people take their medications as prescribed, 20–30 percent never fill their prescriptions, and an unknown amount forget to take their medications or decide not to do so. If someone with an opioid use disorder lapses in their course of buprenorphine and then uses opiates, they could easily overdose and die. This scenario currently contributes to higher overdose rates, according to the National Institute on Drug Abuse.
- Ensure people can’t use buprenorphine to get high. Because buprenorphine is an opiate, it can be abused to get high. The Probuphine implant regulates the amount of buprenorphine a person receives in a day and has stringent guidelines so that it cannot be abused. Furthermore, the transmucosal form of buprenorphine can be given away or sold for illicit purposes, whereas the implant cannot.
- Eliminating dangers to children. Children can mistake other forms of buprenorphine for candy and experience drowsiness, vomiting, slowed breathing, quicker heart rate, agitation, coma and death.
- Potential access to sober living and halfway houses. These facilities generally have not taken people on medications thus far to avoid the risk of illicit substance use. Since Probuphine is an implant, this risk is mitigated.
- Strengthening your privacy. Many people living with substance use disorders would like that information to remain confidential due to fear of stigma. Without needing to take buprenorphine daily or fill a prescription every month, you can embark on recovery without worrying about judgment.
Are There Adverse Side-Effects or Risks?
There are some adverse side-effects that come with Probuphine. Out of people using the medication, 13 percent feel pain at the implant site, 12 percent develop redness at the implant site and 13 percent experience headaches. Less than 10 percent of people using Probuphine experienced back pain, constipation, depression, headaches, nausea, pain in the oropharynx (i.e. the base of the tongue, soft palate, tonsils, and the back and sidewall of the throat), toothaches and vomiting.
Other risks include:
- Fetal harm and neonatal withdrawal syndrome (if used while pregnant)
- Implant expulsion
- Implant protrusion
- Implant migration
- Nerve damage resulting from insertion
To combat these risks, all physicians must be trained in the Probuphine REMS (Risk Evaluation and Mitigation Strategy) program, which involves an implant training procedure, an insertion and removal procedure live practicum and a certification exam that must be renewed annually. Before receiving REMS training, the provider must also have performed a qualifying surgical procedure in the last three months.
You can also minimize risks by not trying to remove the implants yourself. This could lead to infection or immediate symptoms of withdrawal. If the implants come out on their own, follow these guidelines:
- Wash your hands if you touched the implants and do not allow anyone else to touch them
- Cover the area with a clean bandage
- Without directly touching the implants, put them in a plastic bag and keep them in a safe, secure place away from children
- Take the implants to your doctor as soon as possible
Cost and Insurance Coverage
Probuphine costs $4950 for the six-month course of treatment or roughly $825 per month — a big leap from buprenorphine pills, which cost between $130 and $190 per month. However, some insurance companies are willing to cover it:
- Some insurances like, Humana and MassHealth, require prior authorization to ensure that the indications listed above are met.
- Medi-Cal has designated Probuphine as “carved out,” meaning it is covered by the Fee-for-Service program and can be billed to the state by the pharmacy.
In case you’re intimidated by the cost, Braeburn has implemented two programs. The first is a program for insurers which would compare the cost of six months of Probuphine to the cost of six months of a different opioid addiction medication. If Probuphine costs more, Braeburn will give out a rebate for the difference. The second program is payment assistance for patients.
Should I Continue Other Treatments?
Just because you don’t have to go to the doctor as often to refill your buprenorphine prescription doesn’t mean you shouldn’t also be undergoing supplement treatment. Probuphine’s prescribing information provided by the FDA states that it should only be used in conjunction with counseling and other support, including rehabilitation, therapy and 12-step programs.
Remember that Probuphine is a medication like any other and should be treated that way. It can be one of many tools on the road to recovery.
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Medical Disclaimer: The Recovery Village aims to improve the quality of life for people struggling with a substance use or mental health disorder with fact-based content about the nature of behavioral health conditions, treatment options and their related outcomes. We publish material that is researched, cited, edited and reviewed by licensed medical professionals. The information we provide is not intended to be a substitute for professional medical advice, diagnosis or treatment. It should not be used in place of the advice of your physician or other qualified healthcare provider.