Thursday, July 17, 2008
TD buprenorphine for everything and everyone
European Journal of Pain has a review of transdermal 
buprenorphine for pain. It's an interesting article and makes some dizzyingly impressive claims on behalf of the drug, which I note below.
Buprenorphine is a partial mu-opioid agonist and a kappa-opioid receptor antagonist. The article states that despite being a partial agonist no ceiling effect of analgesia has been observed in humans, and that it acts like a full mu agonist when used at 'analgesic doses.' On the other hand they present data that there is a ceiling effect to buprenorphine's respiratory depression effects (meaning that it's theoretically safer than other opioids regarding that toxicity; they note that dangerous respiratory depression is nearly unheard of with buprenorphine unless other CNS depressing drugs are being used). The article notes that buprenorphine not only does not induce mu-opioid receptor internalization (one of the mechanisms for opioid tolerance seen in other opioids) but that it actually increased cell surface density of mu-receptors, which may be an explanation for the impression that less analgesic tolerance is seen with buprenorphine than other opioids. It has an anti-hyperalgesic effect (as opposed to the hyperalgesic effects seen with other opioids). It has been demonstrated to have fewer side effects in head to head studies with morphine. It can be taken safely with other opioids with additive analgesic effects. In placebo controlled trials rates of nausea, dizziness, and tiredness were no worse with TD buprenorphine than with placebo. It's less constipating than morphine or fentanyl. At least one patch formulation can be cut to decrease the dose. It's had decent studies in both cancer and non-cancer pain. Theoretically people are less likely to have problems with psychologic dependence on it.
Whew. Reading this article leaves one with the feeling that TD buprenorphine is (in the parlance of my former residency program) liquid Jesus (i.e. good for just about pretty much anything - we would use it to describe drugs like aztreonam, etc.). Let's see: better analgesic with less side effects/tolerance/hyperalgesia which is nearly impossible to OD on? It seems almost too good to be true (there is no mention of who sponsored the article) and I sat here reading this saying to myself if all of this is true then why hasn't this revolutionized opioid pain management and why hasn't TD buprenorphine become the opioid of choice for chronic pain? It raises the skeptic bug in me, but perhaps this is simply because we're behind the times here in the US.
Transdermal buprenorphine is not available in the US (or Canada?), but sublingual buprenorphine is (it's approved for opioid maintence therapy in opioid dependent patients). I'm told that one can prescribe it for pain without a special license however I'm not entirely sure if that's true (this seems to contradict what I was told).
My questions are: 1) is anyone using this or seen sublingual buprenorphine used for pain in the US, 2) does anyone know if transdermal or sublingual buprenorphine are being evaluated for approval (for pain treatment) in the US?, and 3) are any of our European readers using this and if so is it good as this article tells us?
10 Responses to “TD buprenorphine for everything and everyone”
July 19, 2008
Hello,
I have used the nasal spray before. As far as I know, (that was '97), that was the only form of Buprenorphine available at that time. It was brought home from my doctor-husband, who had been sampled it, and used it for my migraines. It was marketed as a pain-reliever. I have Chronic Pain, and was being treated at that time by another doc, but I never used it for my back pain. It was extremely tiring, to me at least.
To hear of a Transdermal Patch and an SL form now, it is also of great interest to me why it has not taken over the pain industry yet! I do think that a doc with a DEA license to write (here's my age showing), triplicates, now security prescriptions, needs to prescribe this. Will there be a further look at this subject?
Thank you, great blog!
July 20, 2008
Back in the 90's I had occasionally used sublingual buprenorphine (marketed in Singapore as Temgesic) for cancer pain patients who couldn't swallow. But it seemed to cause q fair bit of nausea and dizziness.
But buprenorphine is now persona non grata in Singapore because of what happened after it was used as substitution therapy in opioid addicts. Instead it became another drug of addiction and people were also injecting it - with all the attendant problems of infections, psudoaneuryms and thrombosis - so now you can't get it at all. And highly unlikely that the patch form will become available.
NC
July 21, 2008
"My questions are: 1) is anyone using this or seen sublingual buprenorphine used for pain in the US?"
Sure - I'm in the US and have been on buprenorphine (Subutex as opposed to Suboxone) for pain for about a year now (8-12 mg SL daily divided TID - I take it as both my long-acting and breakthrough pain med).
Yes it can be prescribed for pain by any physician with a DEA license - no special asterisk or addiction credentials necessary. (My own pharmacist swore to me my physician could not prescribe it for me - and actually TORE UP the first script I presented for it. I told them to call the DEA while I waited --- they came back and apologized two minutes later.) IF ANYONE DOUBTS THAT ANY DEA-LICENCED MD CAN PRESCRIBE BUPRENORPHINE FOR PAIN, YOU NEED MERELY CALL YOUR FRIENDLY NEIGHBORHOOD DEA OFFICE. And, if you prescribe it, I strongly suggest you tell your patients to ask their pharmacists to please call the DEA if they are uncertain.
Bup is an old analgesic medication only recently reborn as an "addiction" medicine - which is why, I think, physicians and pharmacists nationwide have been struck dumb, so to speak, about its usefulness. Europeans, less brutalized by a drug war waged on physicians and patients, have not been so affected and therefore think more clearly about a medication which, again, is decades old and quite well understood (until recently, anyway).
Consider Buprenorphine for Combined Pain and Heroin Dependence, which I offer not as scientific evidence of any sort, but rather as an example of one GP's rational thinking circa 2001.
"2) does anyone know if transdermal or sublingual buprenorphine are being evaluated for approval (for pain treatment) in the US?"
No. Why not? Not sure - my guess would be that once a medication gets dubbed an "addiction" med, regular docs and researchers just want to run the other way. So, my guess is the distortion of medicine by drug war imperatives. Anyone else have an explanation or guess?
"3) are any of our European readers using this and if so is it good as this article tells us?"
I'd be interested in hearing from our Euro-doc colleagues about their experience with bup as an analgesic. My experience, as both doc and patient, is that it is an excellent, probably superior in several respects, therapeutic opioid.
In the same vein, I would guess that a lot of American "wisdom" about buprenorphine, based on theory-sans-experience, is likely wrong - for example that adding buprenorphine to a full agonist regimen will surely cause withdrawal - which we commonly hear in supposedly learned commentary on bup in the states, but which is NOT the published European experience.
Thanks Pallimed, as always, for this excellent medical blog.
..alex...
Alexander DeLuca, M.D., MPH
Senior Consultant, Pain Relief Network
July 22, 2008
Thanks for all the comments and insight. This medication has not really been seen much in the palliative care community and I agree with Alex about hearing a lot of fear about the mixed agonist/antagonist issues.
July 22, 2008
Re: buprenorphine not being much used recently or historically in the pallative community...
I had one other thought, Drew, and that is that even as recently as 2003 buprenorphine was Schedule V, I think; that is, it was scheduled and perceived as a "weak" opioid.
If it was any good, it would have been scheduled as DEA II, right? And you palliative guys ought correctly not have much interest in anything other than the real "juice," right?
So that might also be part of the discrepancy between the European lit and our own general dearth-of-lit (which I was also shocked by when I read the References you originally posted to this thread, Drew), and Palliative Medicine's particular lack of experience with this medication.
Just musing... thanks again.
..alex...
July 22, 2008
Shauna: I kind of love the fact that your husband was given it as a SAMPLE. To quote my 2 year old boy, 'Holy cow!' Especially given NC's experience in Singapore that it is 'abusable' it demonstrates the disconnect between science-policy-regulation-good practice.
Alex: I don't doubt you but what do you make of the FAQ I linked to in my post which suggests otherwise (perhaps this is the difference between the FDA and DEA - FDA cannot discuss the drug's use on their site other than approved??). I think you're right that once a drug is pegged as an 'addiction' agent it creates barriers to use otherwise; that said there are now years of experience with td buprenorphine as an analgesic in europe, and drug companies continue to show a lot of interest in analgesic development, td bup would be under patent and if it really is relatively safe and effective it might be a 'successful' drug for a pharmaceutical company.
Regarding its schedule: I think most of us consider DEA scheduling to be more regulatory/cultural/political than 'scientific.' Case in point heroin (diamorphine) is schedule I here (implying it has no therapeutic role); in the UK it has historically been the injectable opioid analgesic of choice....
July 24, 2008
Hi Drew (and apologies for randomly confusing your name and Christians) -
OK, well I did spend some time this morning with the FDA site you linked to. And then, annoyed, I re-registered for PDR-online and went through the inserts for Buprenex, Suboxone and Subutex.
You are absolutely correct - the info presented is incomplete, and therefore very confusing.
Sir, you are absolutely correct -- this is very definitely confusing.
Buprenex (amps with 0.3mg per cc) is indicated for "opioid analgesia."
Subutex (the exact same molecule in sublingual form) is indicated for "opioid dependence."
[This sort of madness is an example of what I call the Distortion of Medicine by drug war imperatives].
Nonetheless, Drew and physician readers of this blog, I AM CORRECT that nationwide buprenorphine, in whatever formulations are available or will become available, CAN BE PRESCRIBED BY ANY DEA-LICENSED DOC FOR PAIN. It is Schedule III - so YES YOU CAN PUT REFILLS ON THE SCRIPT.
Drew, the FDA info and PDR info on Subutex and Suboxone refer ONLY to bup use in opioid-dependence. Nowhere does it say it cannot be prescribed for pain; rather, I think, they just left out the fine print that it can be so prescribed.
When in doubt call, or have your pharmacist call, the DEA - I assure you that they will assure you that the opioid buprenorphine is a Schedule III controlled substance that may be prescribed for pain without any special addiction credentials.
The FDA link is accurate as far as it goes; but it only considers the addiciton usefullness of the medication, and says nothing about bup's traditional use as an analgesic. And very surely such a lazy ommission does indeed create confusion.
This is a sort of regulatory-confusion barrier that will unfortunately limit appropriate use of this good opioid for pain management.
..alex...
September 22, 2008
Just a note regarding a related article about transdermal buprenorphine:
"High Dose Transdermal Buprenorphine for Moderate to Severe Pain in Spanish Pain Centres - A Retrospective Multicenter Safety and Efficacy Study; Barutell, Gonzalez-Escalada, and Rodriguez; Pain Practice; 8(5): 355-361; 2008." (Source)
Here is a link to the: Abstract and brief comments, which refer to this Pallimed thread.
Enjoy!
September 22, 2008
Thanks Alex.
January 01, 2010
I have chronic pain due to an injury to my lumbosacral plexus. Because I also was an opiate addict in recovery no one would allow me to have any opiate. For 15 years I was treated as an addict and no one even treated my pain. Initially I was treated with SL buprenorphine. we tried both forms personally felt no difference. My dose quickly went to 8mg qid. The I was allow to take more as needed for pain. I have used as many as 10 pills in a 24 hour period with very little effect on my pain.
I later found out that buprenorphine has a high afinity for the recetor but poor eficacy. That was my experience. It holds onto the receptors but does not do much once it is on the receptor. I do not know if transdermal has better efficacy but SL was poor.
I have found help with an intrathecal pump supplimented with methadone. No problems with addiction have occured and my pain is comfortably controlled.
Great site,
Gary
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