We all know that Probuphine in now available. It’s a depot preparation of buprenorphine that can be implanted beneath the skin to release buprenorphine for six months. It finally came to market last year, and we are awaiting news of how well it is working.
Soon we may have another choice: weekly and monthly depot injections of buprenorphine. I blogged about this in an entry posted July 30, 2013.
In essence, this new subcutaneous injection of buprenorphine was invented by Camarus 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 released into the body over time. 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.
Initial trials of this medication have been intriguing; they 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 this substance into a vein, it will form a deposit at the injection site, blocking the vein.
I’m excited by this medication. 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.
Third, we’ve seen increases in the amount of buprenorphine being diverted to the black market, as the total amount prescribed has increased. Politically, this diversion threatens buprenorphine availability. One only need to look at regulations like what was passed by Virginia’s medical board to see the limits being placed on this life-saving medication, due to concerns about diversion. Law enforcement officials and politicians believe buprenorphine is a desirable street drug. Of course, research shows most people using illicit buprenorphine are trying to prevent withdrawal, and not using it to get high.
With this subcutaneous injection, I think it’s highly unlikely to be diverted, or at least much less likely that film or tablet to be diverted.
Because the dosing interval is every one week to every one month, medical providers can still see the patient once per month, and can provide counseling as a condition of continued treatment. With the six-month depot placement of Probuphine, it’s unlikely the patient will voluntarily return monthly for counseling visits, once they get the medication implanted. The more frequent and simpler administration of this form of buprenorphine appears ideal to me.
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, the sublingual form of buprenorphine and the implantable form of buprenorphine known as Probuphine have FDA approval. Other forms of buprenorphine in patch (Butrans) or injectable form are illegal for a doctor to prescribe to treat opioid addiction. this new subcutaneous injection of buprenorphine therefor must be approved by the FDA before it can be legally used to treat patients with opioid use disorder.
According to the manufacturer’s website, Phase 3 trials are concluded. According to a company press release, a double-blind, double dummy controlled trial of the weekly and monthly injections were found to be “non-inferior” to sublingual buprenorphine. That phrase is something drug manufacturers have to prove before a new drug is allowed to be approved by the FDA. The new drug must show it’s at least as good as the old drug. Additional data is rumored to show that it’s superior to sublingual buprenorphine, though I haven’t been able to find and read the original data yet.
This is a medication I would be excited to use in my practice. Instead of a surgical procedure, all I would need to do would be give a subcutaneous injection of this new product. How easy! My patient could see me as often as needed, and could see her counselor the same day she gets the injection, thus remaining established in a counseling program, too.
I am eager for the FDA to review this drugs study and approve it, if appropriate.