At this year’s American Society of Addiction Medicine conference, researchers talked about innovative ways to dose buprenorphine (formerly known as Suboxone) that may be available in the future.
One of the new products doesn’t yet have a trade name. Researchers call it “CAM 2038.” It’s made by Camurus Pharmaceuticals, a small Swedish company that invented a nanoscale drug delivery system, as they say on their website. This “Fluidcrystal” injection containing buprenorphine comes in preparations of varying doses, and can be dosed once per week or once per month, depending on the preparation.
The liquid substance containing buprenorphine is injected subcutaneously (under the skin), where it forms a gel. Then a capsule-type substance surrounds it, allowing buprenorphine to be into the body over time. The capsulized gel makes the medication time release. Started weekly, the dose can be adjusted to meet patient needs. Eventually, the patient can move to once-monthly injections. The matrix of material is biodegradable, and eventually completely absorbed by the body.
This subcutaneous injection of medication has a very low viscosity, meaning it can be given with small needles that cause less pain to the patient. The medication is already pre-mixed, making it convenient for medical providers, and it is stable at room temperature for up to three years.
This form of buprenorphine is in Phase II trials in Germany now, so it will be some time before it’s even considered in the U.S. for FDA approval. Per the Drug Addiction Treatment Act of 2000, without this FDA approval, it can’t be used to treat opioid addiction. As we know, the buprenorphine implant (Probuphine) was turned down for approval by the FDA earlier this year, likely because the implants didn’t deliver a high enough dose of buprenorphine to patients.
Initial trials with CAM 2038 don’t appear to have this problem. The company’s initial studies show a fast delivery of medication, giving rapid onset and a steady blood level over one week or one month, depending on the preparation given. Safety data was pretty good; other than some headache and a low rate of inflammation at the injection site, it was well-tolerated. Because of the Fluidcrystal technology, if an addict attempts to inject into the vein, it will form a deposit at the injection site, blocking the vein.
Reckitt-Benckiser, the company who makes sublingual brand name Suboxone and Subutex, is developing a medication using a depot technology called Atrigel. Buprenorphine is put into the Atrigel preparation, a precipitation polymer that must be mixed before being injected. This delivery form of buprenorphine is also in Phase II trials now. RB apparently bought exclusive rights to use the Atrigel technology about four years ago.
These injectable depot forms of buprenorphine may be superior to sublingual forms of buprenorphine in the treatment of opioid addiction for several reasons:
First, with daily buprenorphine dosed sublingually, some patients relapse. They may decide to stop taking the buprenorphine for a few days so that they can use their opioid of choice and get high again. True, they have to do a little more planning to relapse than if they were not on buprenorphine, but relapse rates are still too high. The depot forms make relapse less likely, I think, because compliance is assured once the medication is injected.
Second, with the depot forms of buprenorphine, the patients don’t have to think about taking something to treat their addiction. They don’t have to think about their medication at all, and their addiction doesn’t have the chance to urge them to take more of their medication than prescribed. Thankfully with buprenorphine there is a ceiling to its opioid effect, so that patients already on a blocking dose of sublingual buprenorphine won’t usually feel any intoxication from taking more of their medication. But the disease of addiction is always telling the addict, “More!” so injectable forms thwart that urge completely.
Third, we’ve seen recent increases in the numbers of emergency department visits due to buprenorphine. Pediatric exposure remains a huge concern. Unlike pills which must be swallowed to have an effect, children who put the sublingual forms in their mouths will absorb the medication. Any pediatric exposure to buprenorphine is too much; unfortunately there have been a few pediatric deaths as well. With depot forms of buprenorphine, I don’t see how pediatric exposure would be possible.
Fourth, and probably politically most important, diversion of buprenorphine into the black market is getting much attention from press and law enforcement officials. More people are being arrested with illicit buprenorphine tablets and films, and law enforcement personnel believe buprenorphine is a desirable street drug. Of course, research shows most people using it illicitly are trying to prevent withdrawal and not trying to get high. The actual proportion of this medication getting into the black market hasn’t really risen; it’s being prescribed much more, so there’s more buprenorphine to be diverted. But diversion makes buprenorphine look like a desired street drug, and puts the DATA 2000 program at risk. I don’t see how a depot injection can be diverted, though I don’t doubt someone will try.
According to the Drug Addiction Treatment Act of 2000, the FDA must give approval to any form of buprenorphine that’s to be used to treat opioid addiction. At present, only the sublingual form of buprenorphine has that FDA approval. Other forms of buprenorphine in patch (Butrans) or injectable form are illegal for a doctor to prescribe to treat opioid addiction. If these new preparations of buprenorphine get approved, there will be a second delivery form that can be used in patients with addiction.
I like the idea of these depot injections. I’ve decided I don’t want to learn to do the minor surgery required to place Probuphine implants, but I can already do intramuscular and subcutaneous injections. Plus, I’d be seeing the patients once a week or once a month, rather than every six months with the implants. That’s more opportunity to keep track of what is happening with the patient’s addiction treatment counseling, a key component of recovery from addiction.
I’m looking forward to more research on these new forms of treatment.