University Promotes Off-Label Use of Topamax
39 CommentsBy Ed Silverman // October 9th, 2007 // 4:28 pm
For those of you not familiar with Topamax, the drug is used to treat epileptic seizures and migraines. But a study in this week’s issue of the Journal of the American Medical Association suggests the med, which is sold by a Johnson & Johnson unit, was effective in combating alcoholism. Heavy drinkers given Topamax had “fewer heavy drinking days, fewer drinks per day and more days of continuous abstinence than those who received placebo.”
Topamax “has emerged as a promising treatment for people with alcohol dependence,†says the lead author, Bankole Johnson of University of Virginia Department of Psychiatry and Neurobehavioral Sciences, in a statement about the company-funded study. “Our finding in this national study was that (Topamax) is a safe and highly efficacious medicine…”
Johnson may have toasted his success a little too quickly. The university is being accused of promoting Topamax for off-label use by Public Citizen, because a Q&A included in a press kit appears to encourage patients to ask their doc for Topamax - even though the drug isn’t approved for treating alcohol dependency. Still worse, the prescribing info says Topamax shouldn’t be taken if one drinks (see page 8), because it can increase sleepiness and dizziness.
The Q&A can also be found on the UVA web site. Here’s the controversial part:
Q: Can my doctor prescribe me topiramate for alcohol dependence?
A: Since (Topamax) is currently FDA approved for seizures and migraines, it is available for your doctor to prescribe it to you off-label. Off-label means that it is not being prescribed for its FDA approved purpose, and therefore, many insurance companies will not cover topiramate for substance dependence.
“It’s very brazen. This clearly violates off-label promotion regulations,” Public Citizen’s Sid Wolfe. In a letter to the FDA today, he notes that the study showed “a statistically significantly increased incidence of dizziness (doubled), injury (almost tripled), and difficulty with concentration/ attention (quadrupled) in patients” given Topamax. [UPDATE: In our conversation, Wolfe added that there were company "fingerprints," because the J&J unit funded the study and six of the study authors are Ortho employees, and FDA regs may have been violated for these reasons. ANOTHER UPDATE: We'd like to add that Johnson is an Ortho consultant, which is noted at the bottom of the JAMA study].
A UVa spokeswoman wrote us and insisted that “no off-label drug use is being proposed, advocated or promoted.” But a spokeswoman for Ortho-McNeil Janssen was upset: “We weren’t involved in the preparation of the Q&A material and weren’t aware of the material. We called the UVa and asked them to remove the reference,” she tells Pharmalot, adding that “we didn’t know it was on the web site.”
Lori
The WSJ is also reporting that “the lead author, Bankole Johnson of the University of Virginia, has financial ties to the company”.
Jack
People who don’t work for the company can say what they want about a drug. Company fingerprints? Why would J&J take a risk to promote a drug that just got the 2 minute warning time-out before patent expiration (apologies for the football analogy). Do they love Teva?
Lisa Van S
Ortho wasnt aware…ohh please!!
James
Based on recent interpretations of off-label promotion rules, the FDA could go after UVa, or at least the study’s investigator, if they found a questionable financial relationship.
The Peter Gleason case is likely a test case of this interpretation. Depending on how that works out, you could see the OIG going after cases like the UVa one listed above if some untoward financial arrangement exists.
jason
So you don’t like pharma giving information on off-label use of meds. You don’t like independent organizations giving their advice on medications. So we can now only prescribe as documented on internet blogs?
This has been in the literature for a long time if you were paying attention and actually treating patients. Just someone smart picked up on it and wanted to share their success with physicians who might not have heard about it. Please look at the numerous studies and the results obtained. One of the best options outside of injectable naltrexone.
Look around at any CME conference put on by an academic institution. It is all off-label. We already know on-label information. The only way to get docs to something is to provide new information. By and large that is off-label. I guess the gov’t should go ahead and file with every college of medicine and academic hospital. I can guarantee I have heard much more questionable and experimental than this.
Laurie
“So we can now only prescribe as documented on internet blogs?”
How about we prescribe what is FDA approved for use? If offlabel use is fine, then we don’t need the FDA. And IF this drug is so good for this use then get it approved.
Wayne van Saun
This is a bit strange, U Va is not a pharma company. Think of all the medical-scientific papers written with off-label information. This scientific discussion by itself is not promotion, even if the research is paid for by pharmcos. I find this statement about the off-label use to be informative, defining off-label for people, NOT PROMOTIONAL!The other issue to ponder here is what UVa gains by promoting a drug whose profits go to a pharmco??!!
Ed Silverman
Hi Wayne,
I believe the issue being raised is the extent to which, if any, the investigator is carrying water for the company. There is a consulting relationship and the study was funded by Ortho, which is why Ortho was so quick to disavow the university’s Q&A material. Whether the FDA would go after the investigator or the university or the company remains to be seen. But as another reader pointed out last night, it’s not impossible.
As to your question about what the university gains - well, its built a reputation for researching addiction issues. It may not gain profits, specifically, from additional scrips, but it gains visibility by having a researcher conduct studies that gain visibility. And again, this researcher has a relationship, which is clearly stated, with the manufacturer, which funded this study.
This isn’t to suggest the Q&A is entirely useless. But it may not have been the place for off-label discussion. I hope this helps. And thanks for stopping by.
ed at Pharmalot
jason
Laurie - over half of all scrips are written off label. It isn’t as if the FDA will hear about this and investigate in on their own. If Topamax is going generic soon, there is no way any company would fund multiple studies, spend hundreds of millions of dollars, take 2-4 years, to get a generic drug an additional indication.
Off label prescribing happens, everyday, actually every hour in my practice. If it isn’t approved that doesn’t make it wrong. If you do your homework, it isn’t dangerous, but necessary to treat patients.
If the relationship is clearly stated, I think that is all that is needed. YOu can take it with a grain of salt. But when you put it with all the countless data available on this, it all just substantiates the information already out there.
Laurie
Oh, believe me I know how many drugs are prescribed offlabel. What concerns me about this practice is the fact that GP’s will jump on this bandwagon without researching the potential downside of Topamax. Will they warn their patients about the cognitive impairment,sudden onset glaucoma, metabolic alkalosis, that are so common with this drug? Will the warn against rapid discontinuation creating an increased seizure risk?
This is my problem with offlabel. This practice so often results in indiscriminate prescribing based on “talk”, not on adequate research of risk vs benefit.
The “Topamax “has emerged as a promising treatment for people with alcohol dependence” makes this sound like a cure all for alcoholism, when in reality it may slow the drinking, but doesn’t address the behaviors associated with alcoholism. AND it adds it’s own group of side effects.
They don’t call this drug “dopeymax” for no reason.
Chris
Laurie, I don’t think you are giving much credit to physicians who you assume will prescribe drugs on the basis of ‘talk’ and with no research into the background of the drug. As Jason mentioned before there are plenty of drugs that block dopamine receptors and these are already in use for treatment of substance abuse, so nothing new here.
As far as Topamax (or any other drug) failing to address the behaviors of alcoholism - I don’t know, I’m not an expert. I did work on a team with some excellent researchers in New York though who specialize in substance abuse; a team of ‘first responders’ who provide support, counselling and medication (where appropriate) for alcoholics; and also an ex alcoholic and cocaine addict (a physician) who spoke eloquently about the need for alternative support in trying to break addictive behaviors. The conclusion seemed pretty consistent among these experts that medication can help significantly and as such, it should be offered where possible. If that helps caregivers and addicts address their behaviors, good for them.
Chris
MD
All,
This discussion is split down the middle. I’d like to know who works for Big pharma in their PR department - jack, Jason, Wayne or all three.
Jason - FYI - Big Pharma is not to direct or conrol content of any CME program, but the commercial groups just can’t help themselves. The company may not be willing to invest in a new program for a new indication, so they decided to use the quick PR hit by an unknowing investigator at a prestigiuos institution as a driver for increased off-label use.
Jack - FYI - “People” cannot say what they want about a drug in an open public forum such as a press release if their research is being funded directly by the company. Instead of waiting for a medical meeting for the presentation of new data, the company no doubt pushed for sensationalistic media release to drive their sales by off-label prescribing. Maximum awareness in advance makes a lot more $$$$$.
Wayne - FYI - UVA and the puppet investigator will no doubt get additional research funding due to their willingness to cooperate with the company’s desires. In fact, the new deal may have already been cut in advance of this announcement.
I’m sure that this tactic will be repeated now that one company thinks it has figured out a new way to beat the system. I’ve been inside a few Big Pharma companies and been very disgusted by their actions. As a physician, I couldn’t condone it because there were serious safety issues for patients and physicians only get the part of the information that the company wants to share. Given the recent news, most or all of these Big Pharma companies have the stench of corruption and we need to rember that the fish starts rotting from the head.
The sad truth is that most of them will never be caught and never have to pay for these dirty deeds. They’ll just laugh all the way to the bank and view the patient morbidity and mortality that they contribute to as simply the cost of doing business in their quest to rise to the top of the garbage heap.
MD
Chris
>
Well, fair balance here then.
BD
Chris,
It’s fine that docs make their own prescribing decisions, but they are not allowed to be driven by off-label publicity that pharma has a hand in.
Fair balance in pharma means present the whole picture of efficacy and safety - potential benefits and potential risks. This is not in the UVA release.
jason
MD,
If you are a physician, and went thru any training at an academic institution, how can you reasonably believe that this is some unknowing investigator that is so easily duped by pharma.
Where I trained, another public institution, there is no way a pharma company could find there way in and direct that. How could a doc make it thru med school, do research, be surrounded by veteran researchers, and still somehow do the drug company’s bidding?
Why would a University go along with an industry playbook? I am not denying the fact that the industry has influence. But in my opinion, there is no way that this could be some large pharma company’s directive. Too much at risk for everyone: researcher, University, as well as the company.
If a University makes this kind of deal with the devil, don’t they ultimately lose credibility in the long run. If they are no longer a bastion for solid research, they stop getting money from other places. So ultimately it would cost them research dollars, not earn them $$$.
Now if this was carried out by Joe Horn, DO at the University of Akron poly tech institute of medicine, dentistry, podiatry, pharmacy and nurse practitioners - well then your scenario is plausible. But a big name institution has more to lose than there is to gain. Risk/reward ratio at work.
Do you really take anything either from a pharma or in the press at face value? There is no way I would read a release, and immediately adopt it for my practice. Haven’t we all been burned enough over the last 10 years to have learned our lesson?
jason
Laurie,
Come on now - first give PCP’s more credit for ability to actually do some research on their own.
Second - don’t you think there is a downside to alcoholism? Risk/reward is the key.
Chris
BD - thanks. I do understand the regs but thanks for clarifying. My ‘fair balance’ post was (admittedly sarcastic) in response to MD’s somewhat bilious characterisation of an entire industry.
As far as I know the UVA release isn’t subject to the same restrictions as pharma.
Tks
Joe Horn, DO, University of Akron poly tech institute of medicine, dentistry, podiatry, pharmacy and nurse practitioners
Jason,
I resent that comment ;-)
Someone
Jason,
You have got to be kidding us all! Of course it is exactly as MD said, if not more.
It happens all the time. Just a year ago I saw, first hand I might and, some Key Opinion Leader doc scare the daylights out of patients by telling them the only drug that would keep them alive was the drug from the Pharma company he was being sponsored by. Such a moron actually, literally prostituting himself in front of patients who saw right through him and told him so afterwards. He didn’t care, the grant money, free travel, and prestige were so much more important. We all have our price don’t we?
It is all so unnecessary and yet these people keep doing it. Influence selling is just what the doctor (or wannabe doctor) ordered! Who needs a medical degree? The marketing people will invent the disease (carefully selected to fit the pill), and laugh all the way to the bank…The FDA is just one little obstacle, easily bought off by the lobbyists…
If you didn’t feel sick before, you should now…
Lisa Van S
Jason,
Didnt your mother ever warn you about stepping on People’s Toes..
Laurie
Jason, I will give PCP’s more credit when I see the evidence that they ARE doing the research. Some may be very good at looking beyond the marketing, but alot are content to take the information in the shiny brochure and write away. I see it every single day, and while you would never admit it, you see it too!
Yes, alcoholism, with it’s devastating effect on the body, is a horrible thing to deal with. But to imply that Topamax is “safe and efficacious” is denying the KNOWN warnings about Topamax. One of the biggest warnings on topamax is about it’s use in those with liver impairment…that would be the alcoholic.
jason
Laurie,
Just FYI - we can actually do what is called a Liver Function Test - we call it LFT’s. That tells us exactly what damage, if any has been done to the liver. No one estimates liver function by asking how many drinks you have had in the last week. Not all alcoholics have liver issues and some who have abstained do have hepatic dysfunction. There is a reason Topamax is not the first line agent for seizures, and that is ADR/SE’s. These are not foreign to PCP/GP’s - on the contrary, we all know about the downside to Topamax. That’s why we use other agents first for seizures, again, give me more credit than that. Occasionally we do write for a rep, marketing, etc - BUT not in serious medical conditions. For instance if you come to me for seasonal allergies, it does not matter which antihistamine I give you. I will list the options, if the patient doesn’t care, I guess it is up to me to pick one. If you have HIV, I am looking at hard data, not slick brochures.
If your doc isn’t doing the research, well you are seeing the wrong guy. I do diligent research for the benefit of my patients. If there are those out there not doing it, don’t trust your health to them.
Again, every activity and medication has KNOWN side effects. How many runners have dropped dead from MI’s? How many hundreds of thousand people has aspirin killed from NSAID ulcer/GI bleeds. I will say it again and again, it is benefit/risk tradeoff for everything. If you have advanced cancer you will take chemo and radiation. If you have a migraine, even if it would work, you would opt to live with the headache. If you are an alcoholic and losing everything and killing yourself, I am guessing you would be willing to put up with a little drowsiness. But that’s where professional judgement and actual discussion with patients comes into play. Did the UVa state that Topamax was “safe and effective”?
What I read states it is being studied for alcoholism. It mentions discuss with your physician. It also lists side effects/ADR’s. How much more do you want on full disclosure. If you are going to cite this, you have to look at the entire document, not just what Ed has highlighted. Actually the most words and amount of space is spent on ADR/SE’s. It certainly does not claim to work every time with absolutely no risk, quite the opposite in my opinion.
Someone,
I am not sure why anyone is “marketing” to patients. Anyone who uses the term “Key Opinion Leader” is in the industry. Keep in mind, just because you have limited knowledge on a small area of medicine does not mean you know more the the esteemed physician speaking. I would love to hear about what the doc was telling these patients, as you might be very wrong and the doc was onto something. But either way he should have definitely placed it as an option to discuss with their personal physicians. No one is going to step on the relationship the doc has with their patients.
Lisa,
I have learned you have to be honest and direct - if you sugarcoat important information, your patients will absolutely not concern themselves with it. But not real sure whose toes I was stepping on. But either way I can live with it.
jason
Also,
Joe Horn, I sincerely apologize and thank you for a laugh! Someone out there is doing smart comedy and it was great.
Laurie
” we call it LFT’s”
Please don’t insult my intelligence, I know what an LFT is. AND while you appear to be the perfect presribing physician, there are many who are not. These are the ones that I worry about. You know as well as I do, that they are out there. Handing an alcoholic a prescription without providing support and behavior modification changes nothing. Once again the “magic pill” mentality comes into play.
Lisa Van S
Jason,
“I have learned to be honest and direct”
Really!!..Now thats funny!..
Laurie
“And while you appear to be the the perfect prescribing physician,”
In all your years of nursing,have you ever known a Physician who rambles on as much as Dr.Jason does…
Bob
Lisa-Spouting her mouth off once again.
Don’t you have a lawsuit to conjure up?
jason
Lisa,
Have you ever known a physician you didn’t smear on the internet or bring suit against?
Now I know from reading the press clippings you e-mailed me a while back that you are very impressed with your effort and truly believe you are changing the world. I am here to actually provide an educated contrarian opinion. Because in my opinion - it is this mentality that is hindering my ability to practice medicine and when you have people deathly afraid of medications you are doing more harm than good. I know you won’t be able to believe that, but it is the truth.
Of course I don’t have quite as much time to post as others, but the ER I am covering is slow for a moment. I am out there in the trenches 6-7 days/week. I know I am not changing the world like you, but doing my best 1 patient at a time.
Sorry to ramble on, I guess in NJ they don’t do things like they do here in the beautiful midwest. Docs here talk to their patients, have them decide on treatment, create an actual doctor/patient relationship. I will honestly be amazed if anyone files a lawsuit against me, because even if I screw up it is an honest mistake not caused by negligence or not caring. They know they can call me at anytime and I am there for them. I even make housecalls to those that can’t get out of their homes. So, if I ramble, it is because I care too much about people.
So keep up your crusade if it makes you feel better, but do us all a favor. Try to get into med school and get educated on all aspects of medicine and what goes into treating patients. If you feel exactly the same after that experience I would gladly lay off and let you say whatever it is you want. But I am willing to bet you would have a new appreciation for medicine the way good physicians practice it.
jason
FYI,
I would gladly put in a good recommendation for my alma mater:
University of Akron poly tech institute of medicine, dentistry, podiatry, pharmacy and nurse practitioners.
Weird things is that it is in Cleaveland. But great place to learn
Sincerely,
Jason Joe Horn, DO, DC, DPM, R.Ph., PharmD, NP, OD, PA, Esquire, Jr. the IIIrd
MD
Jason,
Money talks and lots of Big Pharma money ($19 billion last year) went to touting their products, paying lobbyists, and greasing the palms of many physicians. Many of the so-called academic researchers, KOls and KTLs are simply the most expensive prostitutes around ($500-1000 per hour, $2000-3000 per talk, $5000-7500 per day). Some of these guys rake in hundreds of thousands of dollars per year as they help to peddle drugs. You scatch my back and I’ll scratch yours.
No institution is clean. No individual physician is exempt. In many cases, the worst behavior eminates from the nation’s most prestigous medical universities and their most prominent professors. It’s capitalism at its’ worst in the business of people’s health. Money talks and lots of Big Pharma money talks loudly, often and everywhere. It won’t stop talking until our government gets serious and develops the guts to put a stop to it and protect the citizens of the US from some very real “drug abuse.”
MD
Lisa Van S
Jason,
“It is this mentality that is hindering my ability to practice medicine”
Unlike you..I have never pretended to be something Im not.
jason
jam packed day today so this will be my only comment - sorry to not give you a target today Lisa.
Luckily in my community they trust and believe in me, even if some random internet lady does not.
I have never pretended to be anything. All I want to be is the best I can at my profession and a great father and caring husband. I can assure you I have never pretended to be a great parent as ever extra minute is spent with the family I love. I have succeeded in everything important in my life. So you can keep trying to take down everyone who might disagree with you, but you aren’t going to take me down with you.
Keep making all the papers you can. Me, I am going to take a different, quieter route in my pretend life. Actually in my pretend life I am much taller as well, and I am president of the US. If you are going to pretend, I set my sights a little higher than a job that takes up too much of my time and too little time to enjoy it. So really a doc, really a great dad.
MD - hey, we all know these guys, and if you haven’t figured out who to trust and believe and who is on the dole I am not sure what is wrong with you. Look around junior, there are bad people ALL over the place, not just medicine. As long as this is a business people are not to be entirely trusted. I can point you to many specialists who specialize in cranking out unneeded procedures. Do I send my patients to them? - of course not. Unfortunately it is much easier to figure out who is supporting the pharma companies than to figure out if you really need an invasive procedure or if the specialist knows that is the best move for him financially. So I will certainly agree the world is not perfect, but this is still the best system I know of.
Lisa Van S
Jason,
I have seen a photo of you,and yes, you do appear to be quite tall.
But,then again, I am only 4′10″ everyone appears tall…
jason
Lisa,
Which pic did you see? If it is the article with the foster kids, I have lost about 20 pounds since then. If it is from the hospital website, that is probably the most current. Let me know, should I go ahead and shave my head or start on Propecia. Tough decision, but starting to recede more than I want.
I value your opinion, so please let me know what you think.
Another great day in the Midwest. Just about done with my coverage of the urgent care. Calling it a day and taking a 3 day weekend. Hopefully warm enough to do some biking with the kids. Have a great weekend everyone!
Lisa Van S
Jason,
None of the above..It was a College photo.
You are muscular,..and quite dashing,..one can see that you take physical health and appearance very seriously.
Lisa Van S
Bob,
I will repeat myself…Your’e an “ASS”
Lisa Van S
Jason,
Took a second look at your post,”Start on Propecia”.
Please tell me your not serious!!..
Ive stated you appear dashing..I am sure you dont want me to add “Being Stupid”…Do You?…
jason
Wow, thanks Lisa. Although I will recommend you to a good opthamologist. As you can tell I am ALWAYS the smartest guy in the room - at least I think so. But I have never been called dashing. I finally got past pudgy, but again, muscular has never been used to describe me. But I will go ahead and tell my wife that someone else was fooled. She was pretty sure she was the only one who thought I cute. Of course, she is blind, luckily love is as well!
Lisa Van S
Jason,
Already have a great opthamologist..NJ’s Best.
Thanks for the offer anyway!…
Donna
Here’s something everyone can agree on “There’s Humor in Everything”….have a great weekend all.