Maximum Daily Dose of Buprenorphine

Hser et al., 2014, Addiction

 

 

 

 

 

I’d like to thank my readers for their patience during my recent break from blogging. Now that I’m rested, it’s time to start barbequing some sacred cows.

First on my list: limiting the dose of sublingual buprenorphine to 16mg per day.

Recently I’ve heard from physicians who have been told 16mg of sublingual buprenorphine is the highest daily dose that should be prescribed, because studies show that opioid receptors in a human brain are saturated at that dose in most people. While this is true, limiting all patients to 16mg or less neglects research from real life patients.

Some governmental agencies have gone as far as forbidding daily doses higher than 16mg. For example, the Virginia Board of Medicine passed a regulation earlier this year that the highest dose that physicians could prescribe was 16mg per day. In Tennessee, patients can’t go above 16mg per day unless they are seen by an addiction specialist physician.

However, the FDA has approved doses up to 24mg SL per day. Who is right? Did the FDA get it wrong? Are patients who want to go higher than 16mg all drug seekers? Or do all such patients plan to sell their excess medication?

If you read the REMS document created by the manufacturer of Suboxone film, it says the target dose should be no higher than 16mg per day, and that doses higher than 24mg haven’t been shown to provide additional benefit. That leaves a question mark about dosing between 16 and 24mg.

The American Society of Addiction Medicine (ASAM) issued a statement addressing the tendency of state prescription monitoring programs to assign MME (morphine milligram equivalents) values to buprenorphine doses. In that statement, issued earlier in 2017, they said, “The US Food and Drug Administration (FDA) approves dosing to a limit of 24 mg per day. There is some evidence regarding the relative efficacy of higher doses.” [1]

If ASAM says 24mg is OK for some patients, and the FDA has already approved that dose, that’s good enough for me…assuming the patient truly needs a higher dose.

Some patients do better on a dose of 24mg than on 16mg. I work at an opioid treatment program where we observe the patients taking their doses on site, and we pay close attention to any attempt at diversion of the dose. Therefore, we have no question about whether a patient is taking less than the dose I’m prescribing.

When I see new patients within a week or two of admission, I ask how they are feeling. Some patients dosing at 16mg per day of buprenorphine describe symptoms consistent with opioid withdrawal by late evening. I increase their dose above 16mg when I also see physical signs of withdrawal, like large pupils, sweaty palms, and the like. Many patients feel improvement to the point we don’t have to consider switching to methadone.

I increase these patients’ doses because I am sure they are getting their full dose each day, and because I see signs of withdrawal with my own eyes. I know experts say a dose of 16mg is “supposed” to block all the opioid receptors according to studies of this drug, and I believe that is true for many patients. I also think there are patients for whom increasing the dose above 16mg provides benefit, and can eliminate the need to switch to methadone.

Not that there’s nothing wrong with methadone. It has a proven track record, but it does have more medication interactions than buprenorphine, and is more dangerous with certain medical problems.

Methadone patients were under-dosed for years, when physicians had the misperception that no patient needed more than 70mg per day to treat withdrawal. With further studies and information, we know that’s not true, and best evidence shows most patients need between 80-120mg, and sometimes much more than that.

I think in years to come, we will see that by limiting patient doses to 16mg, we are under-dosing some buprenorphine patients.

Why are so many agencies trying to keep buprenorphine doses low?

First, the U.S. has a “less is more” attitude regarding medication-assisted treatments for opioid use disorder. Given the existing bias against these medications, of course some peoples’ attitudes will be grudging acceptance of the medications, but trying to limit the doses to be as low as possible.

Second, there’s the very real concern about diversion of buprenorphine. The more buprenorphine that’s being prescribed and dispensed, the more that may end up being diverted to the black market. I know this is true.

However, opinions can differ regarding the potential harm of providing more buprenorphine to the black market. Some experts might think since buprenorphine is one of the safest opioids manufactured, increased black market access could help save lives. Though many more people embrace harm reduction now than ten years ago, we are not yet in a place where the law-and- order types would allow a serious conversation about this.

Third, I’m worried that some decisions about dose maximums for buprenorphine may be driven by cost. In a state where many patients prescribed buprenorphine products are on Medicaid, higher doses would cost the state more. The same would be true for managed care organizations and the insurance companies and the like. I hate to sound cynical, but financial concerns often drive medical decisions.

By now you know my opinion; if a patient dosing with buprenorphine 16mg SL per day reports withdrawal symptoms and has physical signs that match these symptoms, I’m willing to increase the dose to 20 to 24mg per day. We have a pretty good study, by Hser et al., 2014, that shows higher treatment retention rates with higher doses. Plus, the FDA has already approved doses up to 24mg per day. [2]

I’m cautious about take home dose in patients at the opioid treatment program. If the patient has a history of injecting drugs, I’d like them to have more time in stable recovery before granting take homes. For patients on 24mg per day, I may do more frequent pill counts and bottle recalls, as a precaution against drug diversion. But I’m not sure a patient on 16mg is any less likely to sell part of her prescription than a patient dosing at 24mg.

  1. https://www.asam.org/advocacy/find-a-policy-statement/view-policy-statement/public-policy-statements/2016/10/11/public-policy-statement-on-morphine-equivalent-units-morphine-milligram-equivalents
  2. Hser et al., “Treatment Retention among Patients Randomized to Buprenorphine/naloxone Compared to Methadone in a Multi-site Trial,” Addiction, 2014, Jan; 109(1) 78-87.

 

29 responses to this post.

  1. In my opinion, state legislators who mandate dose limits and define who may be prescribed the mono product are practicing medicine without a license. I also believe that they are killing people with that malpractice. If a patient cannot receive an adequate blocking dose of a very safe treatment (buprenorphine) or who refuse to take the combo product because of intolerable side effects, their only alternative is to continue using whatever illicit substances they can obtain. And a high percentage of those patients will eventually die of a polypharmacy overdose. I just pray that the NC legislator does not follow the irrational precedent of the KY, WV, TN, and VA legislatures.

    Reply

  2. Posted by Craig on October 9, 2017 at 3:20 am

    Yes I agree 100%,here in ky we have a bunch of jackazzes telling drs how to pfescribe buprenorphine,how much to prescribe,and only pregnant women are to be prescribed buprenorphine only without naloxone,totally stupid and costing thousands more dollars to get suboxone vs subutex,total jackazzes.

    Reply

  3. Posted by William F. Taylor, MD on October 9, 2017 at 3:11 pm

    From the pain side: “Mounting evidence from clinical studies and conclusions drawn by a panel of experts strongly support superior safety and efficacy profile of buprenorphine vs. marketed opioids. NO CEILING ON ANALGESIC EFFECT HAS BEEN REPORTED IN CLINICAL STUDIES.”

    Khanna and Pillarisetti, J. Pain Res 2015; 8: 859-870.

    Reply

  4. Posted by Heather on October 10, 2017 at 3:39 am

    I’ve been on 20mg buprenorphine for something like 4 years now. It works, and has been the only thing to help me abstain from illicit drug use. I hope NC doesn’t decide to enforce a 16mg limit. I might do okay on that dose, but I’d rather not have to find out unless I’m the one making the decision.

    Reply

  5. Posted by Chelle McKinney on October 10, 2017 at 4:44 am

    I agree with you 110%!!! I’ve been following your blog for nearly a year now, and I wish to God that I had access to a physician like you here in my home state of Georgia! I’ve been addicted to opioids since 2002. I was able yo go cold turkey several times, but was never able to stay clean for more than 8 or 10 months straight. It was o my recently that I was able to find a local doctor who did in office, private, suboxone therapy. I was on the treatment for 3 months straight and Omg! It was a God sent, MIRACLE!!! I just couldn’t believe the difference! It was amazing! I felt “normal” and didn’t have any withdrawal or cravings for the first time in over a decade!!!
    My fiance and I were doing so much better financially that we were able to.move our small family into a much better and bigger home. And of course with that came.all of the “deposits” and down payments and other moving expenses. As a result I had to reschedule my monthly appointment with my doctor, which the unfortunately considered a “missed appointment”. As a result they insisted that I start over as a “new patient” with all of the added expenses of a “first appointment cost”, new lab work, and other “firsts” expenses, even though I had all of the receipts to prove to them that I wasn’t lying about why I had to reschedule. As a result, I ended up falling off the wagon BIG TIME!!!
    Its caused DO MANY problems with my fiance and home life, and as a result I’m back where I was 2 years ago!!
    Why is there no lea way??? Because of treatment we’re financially able to do better for ourselves and our family, but when there’s a bit.of extra cost, that can be PROVEN, to better ourselves, there’s seems to be absolutely no leeway to help us stay on track.
    As an addict, with NO insurance,, who is a full time, stay home mom to a 3 year old with down syndrome, and who so desperately WANTS to be a better mother and wife, what am I to do??? Suboxone was a GOD SEND for me and my family!
    An office visit is $200, lab work is $150, and my monthly script is $396. It’s SO HARD to come up with that much at one time, and it’s far easier to come up with the $60-$80 a day to pay a dealer to just NOT BE SICK.
    I WANT HELP! I WANT A NORMAL LIFE!
    I’m so PUSSED at big pharma for creating this addiction, and for making that addictive addiction so much more affordable than the TREAMENT for the addiction that they encouraged!
    If anyone has ANY advice or info that can help me be able to get back on suboxone PLEASE EMAIL ME!!!! chellega74@gmail.com

    Reply

    • Posted by Craig on October 16, 2017 at 1:52 pm

      You can’t blame big pharma or drs or anyone but yourself alone for your situation that you are in,it pisses me off when people want to blame anything or anybody for their addiction.i promise you no dr prescribed you to take 4-6 pills at a time nor did they tell you to take more than prescribed,we are the ones that made the decision to abuse these medications,and now thanks to us lowlifes the people that really need pain medication cannot get it unless they go thru a lot of useless nonsense,so don’t blame anyone for your addiction unless you are looking in a mirror

      Reply

      • Posted by Brad Hood on February 23, 2019 at 3:38 am

        i myself had been administered suboxeone at 24ml each day. That shood answer that question. FDA had it wright again.

      • Posted by Manager on July 11, 2019 at 4:37 pm

        While this may have been true in the beginning for her, I think it’s pretty safe to say she now has a chronic disease called addiction.

  6. Posted by Julia Reddy on October 10, 2017 at 1:09 pm

    Welcome back! I’m glad to have your blog in my inbox again!

    Reply

  7. Reblogged this on My Sharing Blog.

    Reply

  8. Posted by Martin on October 16, 2017 at 10:58 pm

    Regarding receptor saturation: Buprenorphine receptor binding has been studied in just a few small PET studies by dr Greenwald’s group. This was first studied at 4 h post dose, and at that time point, a 16 mg buprenorphine dose almost fully saturates the receptors with ~70-80% receptor binding which does not increase much if the dose is doubled to 32 mg (https://www.ncbi.nlm.nih.gov/pubmed/12902992). However, from a treatment perspective, trough values are probably more relevant as you want to suppress cravings until your next dose.

    A subsequent study indicated trough values of only 46% receptor binding at 28 hours after steady state dosing of 16 mg buprenorphine (https://www.ncbi.nlm.nih.gov/pubmed/16950210 note that the reported 54% “receptor availability” reported in this study corresponds to 100-54=46% receptor binding). So in addition to the potential for individual treatment responses (PET studies are usually very limited in size and may not be fully representative of the entire patient population), the available data does not even appear to support full receptor saturation around the clock from a 16 mg daily buprenorphine regimen. (This is likely a conclusion based on the comparison only 4 hours after dose in the first publication…)

    Reply

  9. Posted by David on April 1, 2018 at 4:56 am

    I realise that I am very late to the discussion. I came across this as I was looking for something regarding the science behind maximum dosing. I was surprised by the maximum of 16mg, or even 24mg. I live and practice in Australia, and I often prescribe 32mg of buprenorphine/naloxone. This is the maximum recommended dose in our country. I have no qualms about increasing dosing to this level if patients describe feeling a need for it. Most don’t, but I do think that potential risks of 32mg vs 16mg or 24mg are negligible. So if there is a chance that the patient will be more comfortable, more likely to find being on the medication rewarding, I will prescribe 32mg.
    Thanks for the references above re: trough levels. That makes a lot of sense.
    With regard to diversion, I personally am unconcerned by this; however, as in your case, I have to take account of the risk in my prescribing, as there is no chance of an open discussion about the risks and benefits of being relatively lenient about this.

    Reply

  10. I do agree that people who legally have the need for pain medication have to jump theew so many hoopes to get it it is bull shit. And the you have phamacist questioning a doctor giving a patient a certial dosing when the pharmacist is not an addiction spesialist. A farmacist tech. Was asking me if i was sure if i was suppose to get 1 8ng tab of bupronorphine plus 4 two 2 milligram a day. So that is to take 1- 8mg plus 1- 2mg tablet 4 times a day as needed for pain . Because I have a L4 nerve being compressed at the nerve root in my lower back. This pharmacist act like your a junkie even when you are on subutex. Makes me laugh

    Reply

  11. Posted by Tommy Thompson on October 31, 2018 at 8:42 pm

    It isn’t true that Virginia restricts dosing to 16 mg. I live in Virginia, see a Virginia Dr. and have my med filled in Virginia — I am prescribed 24 mg./day, as of 10/2018. Now, I DO know that Insurance providers in Virginia won’t cover anything > 16 mg./day, *unless* they get a simple PA from the doctor, which is easy to get.

    Reply

  12. I practice in California. I judge the dose for the individual patient to be that dose that completely suppresses craving. It’s simple: Craving = relapse potential. The few studies that have been done on the effect of dose on relapse support this belief. I suspect that dose is a proxy for control of craving. I suspect also that the metabolism of buprenorphine can vary 4-5-fold, so it stands to reason that the dose required to suppress all craving varies similarly. Why not just ask the patient whether they have persistent craving or not and, if they do, increase the dose until the craving is controlled? Is it that we believe PET scans more than we believe our patients? How often have we gone astray basing our treatment on crude tests rather than listening to the patient? And, as one commenter stated, and it is true, according to the data we have, 32 mg. is probably about as safe as 16 mg., especially in the tolerant patient. Yes, there may be more diversion at 32 mg than at 16, but if it is being diverted, it is saving lives in the midst of a deadly epidemic! Get real, people.

    Reply

    • You make excellent points! From a completely harm reduction point of view, we should be handing out buprenorphine with few barriers. Unfortunately, this country has a long history of ignoring harm reduction principles & science in favor of criminalizing drug use.

      Reply

  13. Posted by Ken on February 4, 2019 at 1:37 am

    Your site has been an inspiration as well as a guide to get it correct! I’ve been on 580 mme for over 20 years went as high as 1200 long acting morphine. The doctor I’m going to wants me to be below or at 16 mg and I find that 25.6 of zubsolv does the trick.
    But they push for 16 mg what’s up with that? At 16 I’m sick a mess at just one more tablet I’m normal and feeling perfect? Any thoughts to tell the doc.?

    Reply

    • Just tell your doctor what you are telling me. Clearly there are some patients who do better at higher doses than they are “supposed” to take. With Zubsolv, 25.6mg is far over the highest dose that the manufacturer recommends. Is it possible you may do better on methadone, which does not have that ceiling at 16-24mg of Suboxone, or 17.1mg of Zubsolv? Maybe buprenorphine just isn’t strong enough for you at this point.

      Reply

  14. So have a issue I’ve been seeing my doc for 4 months now and he’s had me on 1 8mg sub a day.. when I first saw him I clearly stated that I was taking narcotics and recently buying subs and was used to taking 3 a day .. so what he do he started me on 1 and said that’s all he would prescribe.. so at this time I’m already withdrawing so I took the script and I run out in half the time because I feel like I need at least 2 a day to stop withdraw… I. Got new insurance that was reason I was stuck with him before … I’ve found other doctors in my area was wondering if it should be problem switching doctors …

    Reply

  15. Posted by robert f cooper,md on March 6, 2019 at 8:57 pm

    I am a suboxone/methadone physicianincentralvalley of calif. doses of suboxone at 16mg cover 87% of mu r4ceptors in brain. Therre are 95% of pts within 2 SD of norm. You will have a few people who will need above 16mg up to 20-24mg sl. In higher doses of suboxone you are not worried about torsades de pointes that concerns one when the methaone dose is above 150mg and qtc is 500 msec. Until we are Portugal the suffering will continue under these govt regulations.

    Reply

  16. Nice to see you out there. Hope to run into you sometime at a meeting!

    Reply

  17. Posted by Working Man on February 26, 2020 at 3:52 am

    I am 55 year old male who works full time. I maintain on 24 mg per day because 16 mg/day still left me with string cravings (later in the day). At one point I switched over to Sublocade 300/300 & was on that for about 9 months. But, I had to take 1 supplemental 8 mg strip in the evening — every day — for the Sublocade 300 to be fully effective. At some point, the insurance said “no more supplemental strip” every day. So without it, I was getting strong cravings again. Because of this, I simply went right back on 24 mg. day Suboxone, discontinuing the Sublocade. I am better again. One thing interesting to note: I take my entire 24 mg dose at once and (now) in the late evening, before bed. That covers me great for each 24 hours.

    Reply

    • Thank you for writing in with your experience with Sublocade. I wondered if insurers would pay for sublingual supplementation for patients on the monthly Sublocade injection.

      Reply

    • Posted by Sparky on February 26, 2020 at 9:03 pm

      Sub locale is useless,nothing but a patented moneymaker is reason it was invented,no one is using sublocade,no one,first reason is you can’t afford it,2nd being that if you need surgery or whatnot it is much much harder to get out of the body and out of your system,it has shown up in urine tests as long as a year or more after discontinuing the sublocade,so that stuff stays in the body for a long long time

      Reply

  18. Posted by Daniel Hopkins on July 17, 2020 at 4:52 pm

    I am 55 years old and I’ve been taking a massive amount of oxycodone like 200 mg a day I stopped for 24 hours and then went directly to 24 mg of Suboxone within two days I felt like me again perfectly fineAnd I don’t give a shit what the ph armacist thinks it’s how I feel and that’s that it works great for me

    Reply

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