Archive for the ‘Probuphine’ Category

Probuphine Update

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About a month ago, the FDA accepted the re-submission of Probuphine, an implantable preparation of buprenorphine, for review. New Phase III studies apparently showed this form of buprenorphine to be “non-inferior” to existing products presently on the market.

As you may recall from my previous blog entry from May 21, 2013, Probuphine is an implantable form of buprenorphine that releases the medication over six months. The FDA rejected this form of buprenorphine in 2013 because the implanted rods impregnated with buprenorphine didn’t produce an adequate blood level of buprenorphine. The FDA also wanted more information about how physicians would be trained to implant the medication.

A double-blind, double-dummy phase 3 trial was completed in May of 2015 which apparently showed Probuphine did as well as the present sublingual buprenorphine products now available. I’ve searched the internet for this information but haven’t found the actual data. I’ve seen some information saying the Probuphine implant was compared to sublingual buprenorphine patients dosing at 8mg per day or less. If so, this would mean the company set the bar lower than the last study, when it was compared to patients on 16mg or less.

The process of Probuphine implantation may be cumbersome; doctors who wish to do this procedure must have a DATA 2000 waiver, and most of these doctors are not surgeons. Will general medicine doctor and psychiatrists presently prescribing buprenorphine want to learn this surgical procedure? I don’t know.

Unless the regulations are changed, if DATA 2000-waived physicians prefer to let surgeons implant the rods, we still must be physically present with the surgeon during both implantation, and explanation six months later. Will the patient’s insurance pay for the time and expertise of two doctors? I don’t see that happening.

What do I think about Probuphine? I think it’s an excellent method to reduce diversion. I think it would probably reduce opioid overdose deaths. However, I think it will make it more difficult to get patients to engage in the psychosocial counseling that’s so necessary for long-term change and recovery.

At present, the need to get new buprenorphine prescriptions keeps patients coming back to healthcare providers. We can, in a way, hold the prescription hostage until our patient engages in counseling. With an implantable form, we have no such leverage.

Probuphine could be an ideal treatment for incarcerated patients. If opioid-addicted patients are sent to jail, they could agree to have Probuphine implanted in order to reduce opioid craving and withdrawal symptoms. These patients would still need the psychosocial counseling for the treatment of addiction, but the Probuphine would be a humane comfort measure for these pateints.

If any of my readers have more information about Probuphine, please chime in.

And buprenorphine patients, what do you think about getting buprenorphine implanted every six months? Would this be something you’d be interested in, if it were covered by insurance?

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.