Today on SuboxForum people were writing about their experiences with different buprenorphine formulations.  Doctors occasionally have patients who prefer brand medications over generics, but buprenorphine patients push brand-loyalty to a different level.  The current thread includes references to povidone and crospovidone, compounds included in most medications to improve bioavailability.  Some forum members suggested their Suboxone doesn’t work because of the presence of crospovidone or povidone.  Others shared their experiences with different formulations of buprenorphine and questioned whether buprenorphine products are interchangeable, and  whether buprenorphine was always just buprenorphine, or whether some people respond better to one product or another.

My comments, including my observations about patient tolerance of specific buprenorphine products, are posted below.

Suboxone tabs
Suboxone tabs

Just to get some things straight about povidone and crospovidone (which is just another synthetic formulation of povidone),  both compounds are NEVER absorbed, by anyone.   They are part of a group of compounds called ‘excipients’, and are included in many medications to help with their absorption.  They act as ‘disintegrants’– meaning they allow the medication to ‘unclump’ and dissolve in liquids, such as saliva or intestinal secretions.

Molecules tend to clump together, sometimes into crystals, sometimes into other shapes.  A pile of powdered molecules molded, packed, and dried into pill form wouldn’t dissolve in the GI tract if not for povidone or other disintegrants.  I remember reading somewhere about cheap vitamins that could be found in the stool, looking much the same as they did when they were swallowed.  Not sure who admitted to doing the research for that article…

Buprenorphine IS buprenorphine.  Period.  The absorption isn’t affected much by excipients, because nobody ever complains that their Suboxone or buprenorphine won’t dissolve.  Povidone or crospovidone are also added to increase the volume, because an 8 mg tab of buprenorphine would be the size of 100 or so grains of salt.  Excipients like povidone and crospovidone also help some drugs dissolve, especially drugs that are fatty and don’t usually dissolve well in water-based solutions.   This last purpose does NOT apply to buprenorphine, since buprenorphine is very water-soluble.  Zubsolv is supposedly absorbed more efficiently in part because it dissolves very quickly, and maybe that is due to excipients.

I realize that when I write ‘bupe is bupe’ it sounds like I don’t believe those who complain about their medication.  But honest, I work with people over this issue every day…  I have an equal mix of people who insist Suboxone doesn’t work for them and people who insist ONLY Suboxone works for them.    Today I was reading TIP 43–  a guide about medication-assisted treatment put out by SAMHSA and the Feds that is over 300 pages long, very well-cited– in a section that cited studies about the psychological triggers for withdrawal symptoms.  TIP 43 and other TIPs can be downloaded for free… just Google them.  TIP 43 is primarily about methadone, but some of the information applies to methadone and buprenorphine.  The pertinent section was around page 100, if I remember correctly.

The TIP information mirrored what I see in my practice.  For years, I’ve noticed that patients will complain about withdrawal symptoms even at times when their buprenorphine levels are at their highest.  Patients also report that their withdrawal symptoms go away ‘right away’ after dosing, when in fact buprenorphine levels won’t increase significantly for 45-60 minutes.  People who have been addicted to opioids may remember how even severe withdrawal mysteriously disappeared as soon as oxycodone tabs were sitting on the table in front of them.   The bottom lline– withdrawal experiences are remembered, and those memories are ‘replayed’ in response to triggers or other memories.

In my experience as a prescriber, I’ve come to believe that patients with an open mind will learn to tolerate any type of buprenorphine (the exception being the 1 patient I’ve met who developed hives from meds with naloxone– hives that appeared consistently on three distinct occasions).  But withdrawal symptoms seem to be triggered, in many people, by the expectation of withdrawal symptoms.  So someone convinced he will never tolerate Zubsolv, Bunavail, or Suboxone Film will probably never tolerate those medications.

As for buprenorphine, it IS just buprenorphine.  Molecules with a certain name and structure are always identical to each other.  They are not ‘crafted’ products like bookcases or tables;  some buprenorphine molecules aren’t made with a quality inferior to other buprenorphine molecules.  And once a molecule is in solution, I don’t see much role for excipients.  Of course a tablet or strip could contain too much or too little active drug, but that is an FDA issue, not an excipient issue.


12 Comments

Bford · March 14, 2017 at 2:05 am

I have never commented on any blog but because of my recent attempt to quit 16 Mil a day suboxone cold turkey which was horrible, I feel compelled to warn anyone thinking of trying this to please take my advice and taper off slowly. It was the worst hell I’ve ever been through and I’ve quit a lot of things cold turkey. I made it 7 days before begging my doctor to get me back in and each day was still getting worse than the one before. This drug fooled me into thinking I could easily quit because I could go several days without a dose and not have withdrawl symtoms but after around 5 days it became unbearable and I’m a pretty tough guy. Please don’t start this medication unless there’s no other alternative. It saved my life in many ways but I’m not sure if I’ll ever be free from it now and it’s extreme affecting my health negatively.

    Jeffrey Junig MD PhD · March 14, 2017 at 6:46 am

    A couple things to clarify. There is NO doubt that withdrawal from Suboxone (buprenorphine) is LESS severe than the withdrawal from other opioids.
    Opioid withdrawal is caused by tolerance, manifest primarily by changes to mu opioid receptors. When outside opioids are removed, those receptors are no-longer activated by the person’s endorphins and the pathways shut down, causing withdrawal symptoms. The symptoms slowly improve as the receptors return to normal– a process that occurs in the same fashion regardless of whatever opioid created the tolerance in the first place. The intensity of symptoms mainly depends on the degree of tolerance, and to a lesser extent on the rate that the opioid is removed- i.e. suddenly or over a period of time.
    There are two reasons that buprenorphine withdrawal is less severe than the withdrawal from agonists. First, the degree of tolerance is limited with buprenorphine. Buprenorphine cannot activate opioid receptors beyond a certain level– beyond the activation created by about 40 mg of methadone, or about 60 mg of oxycodone. People addicted to heroin typically have much higher tolerances than people on buprenorphine (which is why they experience precipitated withdrawal from buprenorphine, which pulls their tolerance lower). Second, buprenorphine leaves the body over several days, different from the immediate clearance of heroin.
    People often make the mistake of thinking that withdrawal ends when the drug is gone. That is not true; withdrawal resolves when receptors return to normal. That process takes about 8 weeks, regardless of the opioid that created the tolerance.
    People on buprenorphine medications forget the misery of withdrawal. The comments by Bford are common. The consequence of that forgetfulness are frustrating, knowing that there are people risking their lives from heroin who could almost immediately be freed from the obsession to use opioids through treatment with buprenorphine. Why do people forget? I’m not sure, because I surely haven’t forgotten my own experiences 15 years ago. When I left fentanyl behind I was sick for over 2 months. I lost 30 pounds (I am 6′ tall and I weighed 135 pounds at my lowest during those days). I could barely walk; I was extremely fatigued and winded after 50 feet, and that fatigue lasted for weeks. My sleep and appetite took 2 months to normalize.
    People in Bford’s position also always forget the main difference between buprenorphine and opioid agonists as far as detox goes: A person CAN taper off buprenorphine, or even stop it suddenly. But it is much rarer for a person to do the same with opioid agonists. If Bford is like most patients, the very reason he started buprenorphine is because he could not stop agonists.
    Beyond the frustration that those types of comments will turn people away from help, the comment and others like it are annoying because of how they serve as a way to avoid responsibility for our actions. We get addicted to opioids through our own actions, and we have a chance to live again because of a medication– but then we blame the medication for our opioid tolerance. That tolerance was caused by use of opioid agonists; the detox was prevented by buprenorphine, and postponed until our lives are in order…. but the correction of tolerance still must occur. But that tolerance is on you, Bford– not on buprenorphine. Buprenorphine lowered your tolerance significantly, and allowed you to have an opportunity to stop opioids. It is just too convenient to now say buprenorphine is the problem!
    I have seen a number of patients forced to stop buprenorphine by parents, partners, or parole officers. I’ve read the obituaries of 6 patients who were stable on buprenorphine before being pushed to stop the medication. Many others are now incarcerated; others are in the streets. If you are addicted to opioids, there is a way to turn off your addiction if you truly want to do so. Visit my forum if you need more information, at http://www.suboxforum.com .

      Bford · March 14, 2017 at 11:58 pm

      I completely agree with everything you wrote. I was feeling very frustrated yesterday because I after a year on suboxone am ready to be free from dependency but in many aspects it has saved my life. I am responsible for the reason I began the suboxone in the first place and I have finally gotten to live a normal, productive life since I started the medication. I am now very focused on slowly tapering off and my intention is to not prevent anyone from trying this approach to freedom but to make it clear to others thinking of trying it that’s it’s only a tool and to be informed of just how powerful of a drug it is because I was told by doctors before starting the program it would be extremely easy to stop suboxone and would feel only mild symtoms even stopping cold turkey and that is simply untrue. I will keep everyone informed on how the taper goes but quitting cold turkey is, for me anyway, impossible to do and maintain a job and take care of my family. I believe clinics make money from prescribing any medication so there forth minimize the truth of the struggle still to come. Although I was frustrated yesterday I will still promote this program because although I sometimes forget, it has saved my life in so many ways. Thank you for reminding me

        Jeffrey Junig MD PhD · March 15, 2017 at 6:57 am

        Thank you for your response. I reacted harshly to your post, with anger that comes from many, many other comments– so it was harsher than you deserved. I don’t doubt what you are saying; I realize there are doctors out there who do not fully inform people about where everything will lead– just as there are doctors who started this whole mess by starting pain pills, escalated the dose, and then cut their patients off, pushing them to find drugs on the street.
        Yes- buprenorphine is very powerful(!), and even a tiny piece of a tablet or strip contains a potent dose of narcotic.
        A couple thoughts about your situation. Please use my forum– http://www.suboxforum.com — during the taper. It is very helpful to have support at 3 AM, when you can’t sleep– and people there are happy to provide that support. Many people there are working on tapering as well.
        I’ve learned from methadone work that it is possible to taper without misery– but it has to be very slow, on the order of less than 5% reductions every 1-2 weeks. That is possible with methadone, but very hard with a pill like buprenorphine. The film can be cut, and that helps… but with the pill form it can be hard, and require creativity. People have used dissolved pills and eyedroppers, for example, dosing a certain number of drops per day for a week, then reducing by one drop, etc. There are other alternatives for people taking buprenorphine for pain, using Butrans patches… the largest patch releases 0.5 mg per day, which is about the same dose as 2 mg of sublingual buprenorphine (because only 25% of a sublingual dose gets absorbed).
        Your taper will be easier if you have a doctor willing to help with ‘comfort meds’. Their use is controversial, but really shouldn’t be, as there are ways to use them safely in stable patients.
        Thanks for stopping by, and I hope you consider using the forum!

          Bford · March 16, 2017 at 12:03 am

          Yes I will definitely use the forum. Now that I’m back on the medicine and thinking rationally I realize that blaming others has never gotten me anywhere. I have Graves’ disease and it was in remission of sorts until I started the suboxone and can’t seem to get it under control now. I’m also worried about my prostate which has been irritated since starting it. I read a lot of information talking about possible liver damage and hepatitis due to prolonged suboxone use and if nothing else the attempt to quit cold turkey scared me and for the first time in my life at age 40 I’m beginning to question what I’m putting in my body. I was addicted to meth at one point years ago and I’m sure that’s done plenty if damage. Suboxone has brought me to a place where I believe I can be drug free and live happily with extensive counciling so I understand your harsh response when people forget what led them to buprenorphine, in my case years of opiate abuse, just know that I was expressing how I felt at that moment where 7 days clean from 16 mg strips a day and wanted to crawl out of my own skin. I put my body in shock and am still 3 days later feeling the affects. I would just like to advise others to only try tapering off if they want to quit. Thanks again for everything! I’ll see you on the forum hopefully doc.

          Jstrong · May 14, 2017 at 6:31 pm

          What are the comfort meds you are talking about I’ve been on 2 films a day for 2 years now and am ready to stop but the withdrawal scares the hell out of me because I do remember what it was like so would you let me no what you are talking about.

          Jeffrey Junig MD PhD · May 14, 2017 at 8:14 pm

          By ‘comfort meds’ I’m referring to medications that are provided by some detox programs that target individual symptoms caused by withdrawal. People go through the misery of lowering opioid tolerance in a range of settings, and under a variety of conditions. Traditionally, people addicted to opioids went through the experience with assistance based ONLY on the ‘balance of risks’. Since people don’t usually die from opioid withdrawal, the general practice was to avoid any medications, and ignore the misery that the person experienced. That’s actually what things were like when I went through the experience 16 years ago, in a room at the end of a hall where I wouldn’t be disturbed, and where I wouldn’t disturb anyone. The experience was horrible in a way that only other people addicted to opioids can understand…. a unique combination of physical discomfort, depression and shamne, autonomic activation and insomnia, intense loneliness, and distortion of time, so that the passage of 5 minutes seemed to take an hour or more.
          More recently there are a few physicians out there who make an effort to understand, and treat, the intense dysphoria caused by withdrawal. I think most doctors still believe that a bit of suffering is ‘no big deal’ for people addicted to opioids, but I think things are moving in a humane direction, albeit in baby steps. One end of the spectrum would be the medications provided during rapid or ultra-rapid detox. Those programs use benzodiazepines in doses that provide amnesia, or sometimes propofol, to induce amnesia, and in some cases general anesthesia. And of course the other end of the spectrum would be the hospitals, jails, or ‘treatment’ programs that provide nothing at all.
          In between are the detox units that provide clondine to reduce autonomic hyperactivity, Imodium to reduce GI motility and diarrhea, and benzodiazepines to reduce anxiety and provide sedation, or at least treat insomnia.
          When I write about ‘comfort meds’, those are the medications I have in mind. The use of benzodiazepines will always be controversial, though, because 1. most overdoses involve benzodiazepines combined with opioids, and 2. many people addicted to opioids have problems controlling use of benzodiazepines too. When I prescribe benzodiazepines during the detoxification from opioids, I provide limited amounts, under tight monitoring– i.e. providing a maximum of a week supply, keeping in regular contact sometimes with daily (or greater) frequency. They are most-helpful during the worst part of withdrawal, when opioids have been discontinued completely, for a max of one or two weeks.
          These medications should NOT be used for ‘self-detox’, outside of the direction of a physician. We all once thought we were smart enough to act as our own doctor… and people should remember how that turned out!

        Nicky Marino Nicholas · July 17, 2017 at 4:48 pm

        I’m wondering if just takeing suboxone for 3 weeks is my receptors opiate ones finally not feel depressed 8mg 3 times per day

TootÑTheBoot · July 17, 2017 at 3:48 am

Withdrawal’n From Everything Suckz & Everyone Should Already Know This But Yet We All Still End Up Do’n These Things To Ourselves & For Y Just To Put Ourselves Through Pure Ass Hell Time After Time…
Sum Of Us Addicts Finally Grow Up To Were We Just Wanna Move On With Our Life’s & Grow Outta That Stag In Life & Move On With Our Life’s & Learn From Our Past & Say Yea… I Been There Done That & Got That Shirt & Now It’s Time To Move On With Our Life’s…☛☜☞☚☛☜☞☚☛☜☞☚☛☜☞☚
So Really No Matter What Drug U Decide To Get On Ur Go’n To Go Through Sum Kind Of Withdrawal Regardless So Get Ready For It…

Lee · July 23, 2017 at 12:21 am

I have chronic pain due to three major surgeries to the same area. I was eventually sent to a pain management clinic that eventually put me on Suboxone. It hasn’t worked sufficiently since the first subscription. There is nothing I can do to get off of it aside from just stop going to pain management. I’ve heard the horror stories from quitting it cold. The pain is bad enough without the withdrawals. It grinds my gears that my Doc would do that, but there’s no recourse for me. Also, I have 2 more major surgeries coming. Doc says there’s something that can be done but won’t disclose what that is. It seems I’m stuck in a prison that I committed no crime to get into besides having a lot of unmanageable pain. Kinda sux.

Bford · July 29, 2017 at 7:12 pm

It’s amazing to me that someone who’s supposedly battled addiction can say ” hey everyone grow the hell up and move on with your life”. thank you for the complete lack of respect for the people struggling to live and work two full time jobs and raise kids and and have made a complete life change! Thank god for people like dr Jung because most of the world thinks like tootntheboot

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