Probuphine Update: Implantable Buprenorphine

At present, only the sublingual (under the tongue) forms of buprenorphine are approved to treat opioid addiction. But recently I’ve been reading more about the long-acting buprenorphine (active ingredient in Suboxone) implants that are undergoing Phase 3 tests. The brand name of this product is Probuphine and it’s marketed by Titan Pharmaceuticals.

This medication is composed of small cylinders consisting of ethylene-vinyl acetate and buprenorphine, to be implanted under the skin of the upper arm. The cylinders release buprenorphine slowly over six months, given a constant level of medication in the body. After six months the medication is depleted, so they must be replaced if the patient needs to stay on buprenorphine.

Last year we saw from study results published in the Journal of the American Medical Association (1) that Probuphine is superior to placebo, but the real question is this: how does it compare to sublingual Suboxone? (See my post from October 13, 2010)

From data obtained and recently released, in the drug’s Phase 3 trials, it appears implanted buprenorphine is “non-inferior” to sublingual buprenorphine. That’s doctor speak for saying implants appear to work at least as well as sublingual forms. In this study of 114 patients given Probuphine versus 119 patients given Suboxone, both groups had around 35% of their drug screens negative for illicit opioids. Additionally, both groups had the same amount of improvement on a scale of global severity of opioid dependence and overall patient improvement.

To me, 35% negative of urine drug screens negative for illicit opioids doesn’t sound all that great. I’d estimate at least 90% of my sublingual Suboxone patients have urine drug screens negative for illicit opioids, but I need to remember that most of them have been in treatment for quite some time. Many of them I “inherited” from another doctor, and these patients have been doing well for more than five years.

So if it appears that the implants work as well as sublingual Suboxone, what will this mean? I don’t know for sure, but I have a few predictions.

I don’t think patients will like the implants. Just look at the difficulty many had switching from the tablets to the film: go to any forum and read some of the very negative comments about the film. Plus, patients with addiction like to take drugs, particularly early in treatment. I try to get my patients to take their dose of Suboxone all at one time, and many say they prefer to divide the dose. Part of that, I believe, is the habit of taking drugs. With an implant, it may be easy for the disease of addiction to convince patients that the medication isn’t working, when it’s actually doing exactly what it should.

Some patients will love it, because they’ll like that it frees them from having to think about taking drugs. These folks may be further along in their recovery, or their addiction isn’t as bad.

Suboxone doctors will have to learn to do the minor surgical procedure to place the implants, or refer their patients to general surgeons. Then there will be great difficulty getting patients to make and keep follow up appointments with both doctors and therapists. If they already have the medication in their system, many won’t want to keep doctor and counseling appointments. That prescription is leverage to get the patient into the office.

Diversion will plummet, if we can get most patients on the implantable form of buprenorphine. How can you divert something that gets implanted into your arm? It’s not going to be impossible, but much more difficult. No more black market Suboxone.

There are other advantages. For patients on Suboxone who have to be incarcerated, they can’t be denied their medication since it will be implanted! No more jail house withdrawals. And no more awful taste in your mouth after the sublingual forms of medication.

As a way to force patients to get the implants rather than prescribed sublingual buprenorphine, I won’t be surprised if some states, or even the whole nation, reclassify sublingual buprenorhpine to a Schedule II drug, and allow buprenorphine implants to be Schedule III. Under the DATA 2000 Act, this would make sublingual forms only available at opioid treatment centers. This may not be a bad idea, given the rampant diversion of buprenorphine. You only need to read some of the posts on this blog by active addicts to see how addicts are misusing the present medication.

Doctors like me are wondering if we can remain in practice seeing only buprenorphine patients. Since we’ve only been allowed 100 buprenorphine patients anyway, I think most addictionologists already see other types of patients. For me,  the upcoming changes may mean going back into primary care, which I don’t enjoy nearly as much as addiction medicine.

  1. Ling, W et. al, “Buprenorphine implants for opioid dependence: A randomized controlled trial,” Journal of the American Medical Association, October 13, 2010, Vol 304, No. 14, pp 1576-1583.

7 responses to this post.

  1. Posted by carllee on September 2, 2011 at 6:48 pm

    Wouldn’t the implants increase the cost of treatment, because of the required minor surgery? And what would the implant itself cost? Wouldn’t there also be a risk of infection from the surgery? The implants sound a bit overboard to me, if the intent is to prevent diversion. I take subutex, because it comes in generic, therefore it’s more cost effective than the suboxone which I previously was perscribed. I wonder if they are conducting studies on implantable metadone also. Just a thought.


    • Yes, all of those are good questions. I don’t think we know the answers yet.
      For the cost, depending on how much the physician is charging for an office visit, it may be much cheaper for a once every six month procedure rather than every 2 to 4 week office visit. But patients still need the counselor. I hope we don’t see people get a six month implant and then they aren’t seen again for six more months, and have none of the necessary counseling.
      Infection is a risk, but minimal. It’s like the Norplant birth control.


  2. Posted by Josh gibson on January 20, 2012 at 1:20 am

    Don’t you think the real answer is to make these things for the true patients who need around the clock narcotics? Then, make it illegal for instant release, high dose preparation outside of monitored applications. This prevents the over-supply of high dose narcotics, or at best dramatically reduce the number of them available. Americans can handle drugs being out there, but they can’t handle them being in every cabinet in our homes. Evidence of this is the rapid increase in schedule II deaths over schedule I in the past few years.


    • I don’t understand what you are saying – to only allow opioids for “monitored applications?” What does that mean?
      And are you assuming that people with chronic pain don’t also develop addiction? It’s not so simple to divide people into groups & say, “These people have pain,” and “These have addiction.” In reality there’s a great deal of overlap, complicating the matter immensedly.


  3. Posted by ashley on April 6, 2012 at 6:08 am

    I agree there is a huge overlap. But the FDA groups us into those groups. I am an “addict” who got addicted to pain meds with my migrains. But they would never send me to a pain managment doctor for a scrip of methadone. I would have to go to the clinic and take liquid. To them I am an addict and they would never trust me with a bottle of methadone. Although they trust me with a bottle of subutex. I am very confused.


    • The reason you can get a bottle of subutex and not a bottle of methadone lies in th pharmacology of each. Methadone, as a full opioid, gives more opioid effect with more methadone ingested. This includes respiratory depression, which is how most people die from methadone overdoses. But with buprenorphine (Subutex, suboxone) there’s a limit to the opioid effect. Since it’s a partial opioid, once you take a blocking dose, you could take the rest of the bottle with little additional opioid effect. In other words, there’s a ceiling, a limit, to the opioid effect, including respiratory depression. Though it is still possible to overdose on buprenorphine if you aren’t opioid-tolerant, it’s less likely to cause a fatal overdose if you slip up and take too much. But with methadone, it takes very little extra medication to kill you.
      If you hae the disease of addiction, it’s not fair to you to give you a big bottle of a full opioid and tell you to take as directed, because the addiction interferes. Some people even take buprenorphine compulsively, even though they getno extra effect from it, due to the psychological part of addiction. this can sometimes be overcome by limiting each prescription to very small amounts until the person gets enough counseling.


  4. As a Subutex patient, I’m looking forward to the possibility of getting the Probuphine implant. I wouldn’t have a problem going in for Dr. visits throughout the 6 month period, or even paying the same amount I do now with only 1 visit every 6 months. I don’t look at this monthly Dr. fee as the cost of a Drs. visit but as an overall treatment plan (sort of like a tech support subscription for software) because I have a direct line to my Dr. 24/7, and can go in and see him anytime, i.e., 2 or 3 visits per month instead of 1, although I’ve never had a need for this. I don’t think most patients would agree with my perspective, given the overall costs of treatment.


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