SUBLOCADE: A Very, Very Extended Release Version of Buprenorphine

SUBLOCADE: A Very, Very Extended Release Version of Buprenorphine

SUBLOCADE: A Very, Very Extended Release Version  of Buprenorphine





“After steady-state has been achieved (4-6 months), patients discontinuing SUBLOCADE may have detectable plasma levels of buprenorphine for twelve months or longer. “


The new kid on the block is SUBCLOCADE. If you haven’t heard about this, it’s basically an extended once a month injection of Buprenorphine, by Indivior, the makers of Suboxone.

Why would a once a month injection of buprenorphine be a good idea? What problem is this the solution to? Let me explain. One very real problem currently with transmucosal buprenorphine products like Subutex, Suboxone, and Zubsolv is diversion. Diversion is when a patient misuses their medications. This could mean they sell some, trade some, or overtake their prescription so it doesn’t last the entire month. The worst case is they’re just selling their prescription altogether and using heroin or pain pills.  There is a black market for Suboxone.  Buprenorphine, off the street,  is used by opiate-dependent patients when they can’t get what they really want and have a fear of going into withdrawal.

I think that’s really the only benefit. There will be less buprenorphine on the street to divert. Not entirely a bad thing.

I’ve only spoken to my regional representative and reviewed the prescribing information. I have not yet used SUBLOCADE, so please take what I have to say with a grain of salt. I think patient selection here is vitally important. A good patient for SUBLOCADE is someone stable on the oral product who has no desire for a dose reduction and is not looking to discontinue buprenorphine at any time in the near future.  They should be on at least 12mg/day (8mg if you ask the company). Also, they would have already proven themselves stable in recovery with good evidence that buprenorphine is working well, has prevented relapse, controlled cravings and has not been associated with any intolerable adverse effects.

I need to admit my biases and put them out on the table so you know where I’m coming from. I don’t have a lot of faith in data and other information provided by drug manufacturers. Don’t forget, these are the people who told us long-acting opiates for pain weren’t addictive and created the opiate epidemic we’re dealing with today.

I’ve known some Suboxone prescribers who were of the mindset that patients on buprenorphine for a history of Opiate Use Disorder would always need to stay on it. I would call them ” Life’ers”. They simply believed that the opiate dependent brain is changed and the only way for those folks to feel normal and deal with cravings and withdrawal is to keep them medicated. It’s a valid perspective and it may work for some, but I think it’s wrong. It’s true that many patients will prefer to be on maintenance medications for a long time, possibly indefinitely. But most people don’t. Most patients gradually reduce their dose at some point. In fact, studies out of Europe that followed heroin users at legal use centers showed many patients eventually stopped using as they were able to fill their lives with relationships, community, and responsibility.

I”m always encouraging my patients to try dose reductions. Most of them are successful and feel better as their dose comes down. Even a slight dose reduction monthly or every few months builds self-confidence and hope. Lastly, I emphasize that if the goal is to get off it, you’ve got to be stable and successful on your last reduction before reducing more. Even long-term patients can get to doses in the sub 4mg range. This brings up the next problem. Unless you effectively want to go up on your dose, you’ll need to be on 12mg of buprenorphine or more for equal bioequivalence of the injectable product.

Using Indivior’s data,  they compared patients who were stable at 12mg and 24mg of buprenorphine to both 300mg/month or 100mg/month at steady state levels of SUBLOCADE The average serum concentrate at 12mg/day of buprenorphine was 1.7ng/ml, compared to the lowest SUBLOCADE maintenance dose of the 100mg/ injection which was 3.21ng/ml, almost twice as much. So I’m not sure why Indivior says to use Sublocade for patients stable on as little as 8mg/day of buprenorphine. It seems to me patients should be on at least 12mg/day. They didn’t look at 16mg/day which is a much more common dose. Most of my patients are either on 16mg/day or on 8mg or less.

Even patients who are on a very high dose of buprenorphine at 24mg/day have a steady state concentration of 2.91ng/ml compared with the monthly 300mg injection which provides a level of 6.54ng/ml. Given that we know almost 100% of the opiate receptors are bound by a 16mg/day dose I have no idea what blood concentrations mean when they show levels obtained by the injection that are twice as high as patients who are doing fine on what’s considered a full dose of Suboxone. Since there isn’t any meaningful difference in opiate free weeks by participants in the study going out 10 weeks, serum concentrations may not mean anything at all.

Interestingly, the adverse reaction data is significant. 25% of patients on SUBLOCADE had significant GI problems like constipation, nausea or diarrhea compared to 12% of the placebo (so twice as much). 10% of patients experienced elevated liver function studies compared to just 2% of the placebo patients (5 fold increase).

It turns out patients who stop receiving the once a month shot of SUBLOCADE have a therapeutic level for up to “2-5 months on average”. That’s right, once you’re stable on this product and stop using it, you have therapeutic levels for up to 5 months. That’s crazy!. Furthermore, buprenorphine levels were detected in the urine for 12 months after discontinuing treatment. Wow!. That is a very long-acting formulation of buprenorphine.

Despite the medication taking a year to fully metabolize, aggravating your liver, and giving you GI upset, what I’m really afraid of is that it’s going to keep people out of recovery. In the current system, I get to see my patients monthly and check-in. I can get a urine drug screen and evaluate their progress. Ideally, this will also happen with SUBLOCADE,  which can be administered every 26 days, however therapeutic levels exist for up to 5 months after steady state is achieved. The opiate dependence patients I know who feel fine for 5 months aren’t going to come in and see me, I can promise you that. They’re going to come in when they’re in withdrawal. Are we going to be seeing patients every 5 months?

I don’t want to be the first or the last to use an effective medication. The current problems that patients report to me are the awful taste and palatability of these products, losing medications, stolen medications, or taking too much medication. SUBLOCADE could be an answer to these concerns. But we may be trading it for higher drug levels which in the long run may be more difficult to taper off of, tapering down in general, injection site reactions, skin infections, increased side effects, and unfortunately, it may allow patients to go even longer without doing any real work of recovery.   Does Indivior have an interest in maintaining levels of buprenorphine a little higher than then they need to be?  With a variety of strip strengths (2mg, 4mg, 6mg, 8mg, 12mg) I think we can do a better job of meeting patients where they’re at and helping them find the least amount of medication possible. Switching to the monthly injectable version from the daily strip gives patients higher buprenorphine levels then they made of had previously and would make tapering and eventual discontinuation more difficult.

Let’s keep this option on the table for the right patients, but let’s be aware of the cost of our decisions

Ken Starr MD




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