A New Version Of Dilantin Is Giving Pfizer Fits
73 CommentsBy Ed Silverman // May 21st, 2008 // 11:59 am
One way that brand-name drugmakers fend off generic competition is to charge that a copycat version lacks bioequivalency, another way of saying the generic is absorbed differently in the body. Even though the FDA may have approved a generic as sufficiently similar to the brand-name med, slight differences can still cause some patients to experience problems if they switch drugs.
In an unusual twist, Pfizer seems to have created a switching problem for itself. Last fall, the drugmaker began marketing a new version of its age-old Dilantin med for treating epilepsy. Citing a need to upgrade manufacturing, Pfizer stopped selling Dilantin Kapseals and began selling Dilantin capsules. But some epileptics are complaining that the new product is causing seizures.
On one forum, for instance, Mike from Springfield, Illinois, writes: “Recently I was switched to the new dilantin. Not long after the switch I experienced a grand mal seizure. It is kind of wierd because my blood level was therapeutic. I had been stable and seizure free on dilantin kapseals for years. What is going on here? Any other folks experiencing problems?”
In effect, the world’s largest brand-name drugmaker is accused of causing some patients the kind of problems associated with a switch to a generic. Ironically, this occurs at the same time that the Epilepsy Foundation, which is supported by Pfizer and other drugmakers, has urged legislators in 18 states to introduce bills that would ban generic substitution for epilepsy drugs.
In fact, a foundation spokeswoman tells us any switching, in general, can be problematic. “Our anecdotal evidence shows there can be a difference and it could be fatal.” Although the new Dilantin isn’t considered a generic, the Abbreviated New Drug Application for the new version was approved by the FDA’s Office of Generic Drugs, not the neurology products division, an FDA spokeswoman tells us.
The new version “is not exactly the same, and that’s where the problem lies,” says Ilo Leppik, a physician, University of Minnesota pharmacology professor and director of research at Mincep, a Minneapolis clinic for epileptics that has issued a warning about the new Dilantin. “When it comes to switching drugs, epileptics are a special case. Even small changes can make a fairly large difference in blood levels.”
For its part, a Pfizer spokesman denies the drugmaker claimed there was no difference between the two versions. To know the extent, you must read the fine print in a letter sent to healthcare professionals last fall, where Pfizer disclosed that bioequivalence studies were conducted. But the new capsule failed to meet acceptance criteria for something called AUC, which is an index of drug absorption among patients who ate before taking the med. (There were also studies on patients who fasted before taking the capsule).
However, the criteria Pfizer used was not requested by the FDA to show bioequivalence and was different from the FDA criteria, according to an FDA spokeswoman. She adds that the FDA was unable to review the study protocols before Pfizer proceeded and the agency doesn’t know why Pfizer chose different acceptance criteria. Nonetheless, the agency did approve the new Dilantin.
To some experts, the FDA approval is sympomatic of a wider problem involving the approval of generics and bioequivalency. Leppik, for instance, says “their standards are too loose. It may be okay for approving painkillers, but with epilepsy, it’s a fine line.”
To Joe Graedon, a pharmacologist, author and talk-show host who runs The People’s Pharmacy web site devoted to issues with meds, the Dilantin episode is reminiscent of the recent flap over generic Wellbutrin, which caused patient side-effect complaints but was cleared by an FDA probe. “We could have a somewhat similar situation,” he says.
Michael Privitera, a University of Cincinnati neurology professor, who also is also a speaker for Pfizer and other drugmakers, says that, “You have to ask whether the new and old versions are truly bioequivalent…In general, we’ve seen that there’s a subgroup of patients that clearly have some kind of problem with generics.”
Of course, Pfizer isn’t marketing its new Dilantin as a generic which, as Privitera notes, makes the situation both a “little unusual and, yes, ironic.”
Renae Kelley
Thank you for reporting on our plight.
palm beach tone
THANK YOU FOR LISTENING ,MR. SILVERMAN.
Justice in Michigan
Warner-Lambert’s Dilantin has a sordid history. The drug was one of the first prosecuted fraud cases for covering up manufacturing defects, which continued to happen. The problems continued to happen, despite a variety of warning, remedial programs, etc. etc.
Justice in Michigan
Back during the earlier Dilantin fraud cased, there was also a lot of noise from the company about the dangers of generics.
The irony was not lost on many.
jerry1967
thank you -finally someone is listening.
Paloma
Thank you, Mr. Silverman
Susan
Thanks so much, Ed,
The sickest part of this is that we were not informed in advance so that we could change medications safely. Some people are still enduring dangerous med changes. No one would sign up for that voluntarily, it’s a horrible and terrifying experience.
Equally sick is that our doctors wrote No Substitutions on our prescriptions… which caused us to get this new formula of Dilantin, because Pfizer saw fit to keep the same name for it’s altered formula.
We have been told over and over that it is the same medication. And it is still phenytoin, but the NMP and the difference in excipients caused the dissolution to be different. Which is indeed the argument against generics. Dilantin is now nothing better than a generic with a brand name.
Many of us had seizures and many became toxic after years of good control on the decades old formula.
This has been reported to Pfizer and to MedWatch, to government officials on the state and federal level. No one would speak to it until now. Thanks so much to you and to the sources you found who were willing to cooperate.
As far as the approval of abbreviated drug applications go, this one was a serious mistake that has endangered the lives of Pfizer’s Dilantin consumers.
Melody
I believe Pfizer followed Lilly’s playbook, used so successfully with rDNA human insulin, and successive insulin analogs. If the product can be introduced into the consumer/patient stream, tons of money can be made while the disease and the patient(s) shoulder the ‘blame’, suffering ridicule, being ignored by regulators, researchers and doctors. Interestingly, I found a link that indicates there is, indeed, a ‘formula’ for dealing with negative outcomes. (This was used by Novo Nordisk re: their rDNA insulin.) http://web.archive.org/web/20000914070827/http:/www.keycommunications.co.uk/solutions/novonordisk.htm
While I have long railed against the (mis)treatment of diabetic patients, I never believed that they were an isolated population, singled out for exploitation. Your Dilantin revelation merely supports my belief.
Susan
This Pfizer spokesperson who denies saying that the drug is the same…
Pfizer kept the same name knowing full well that our Doctors write No Substitutions on our prescriptions. I discussed that on the phone with a person from Pfizer’s offices. She WAS aware that our prescriptions were often written that way.
Every pharmacist that I went to in a quest for the old Kapseals (after the NMP product made me horribly ill)… the pharmacists that were even aware they had a new drug on the shelf at all… the ones that were not in utter shock when they opened those bottles… all told me the same thing. That it is EXACTLY the same except for the appearance.
I will gladly hand this article to everyone of them.
My same experience was reported over and over on forums discussing experiences with this new product. People devistated because someone with a financial interest was able to convince their doctors and pharmacists that they (as patients) were the problem rather than the medication. I have to believe they were ALL getting that same story from somewhere.
Whatever Pfizer said… they sure didn’t broadcast that it was different. Which, of course, would have been the responsible thing to do for the safety of their consumers.
I know there are Pfizer reps that report on this site. Anonymously please, what were you telling our doctors when they questioned you, after we (the patients) were left to inform them of the change? Because my doc sure didn’t know and told me he would ask the Pfizer rep about it.
It was the first time in 13 years that my doc wrote me a prescription that did not say No Substitutions. So that I could get Kapseals if I could find them, or get a generic to try, knowing that the new Dilantin was not an option for me.
Barbara
Thank-you so much for listing Mr Silverman, something really needs to be done for the quality of our lives. I’m very grateful someone is on our side and finally believes what we are telling them. I was never so sick in my life til I went on the new dilantin, found some old to hold me over until I have to go through a change…hopefully we will get our old dilantin back. This is a very serious drug for a very serious reason
cindy
thank you for hearing us. If only Pfizer had thought long and hard prior to the death of several epileptics, including children, and countless problems for others, this could have been avoided. Needless suffering and loss has been piled onto a group of people who need this like a hole in the head. Sorry to say, this is not like any other group of medications. Thank you Mr. Silverman, for bringing this to the table, and thanks a lot Pfizer for making our lives total complete hell.
keiner
Interesting… the same kind of discussions we had in Europe 10 years ago, when generics became popular. Nowadays generics are no longer under discussion… The acceptance criteria for bioequivalence studies (the scientific basis to obtain marketing authorisation for a generic) are about the same world-wide.
As you wrote patient’s blood levels were therapeutic when he experienced a seizure under the new formulation of Dilantin, were they lower than before?
According to Pfitzer’s letter cited above, FDA criteria for bioequivalence were met when the capsule was applied in (overnight) fasted (resembling drug intake in the morning before breakfast) as well as in fed state (resembling intake after breakfast). Unfortunately, at the FDA-homepage there is no information available on the more strict acceptance criteria proposed in the study protocol, which were NOT met in the study in fed state. The SPC of the old product does not recommend intake in a specific state (fasted/fed):
http://www.pfizer.com/files/products/uspi_dilantin_kapseals.pdf
From a scientific point of view it will be impossible to show that the reports on seizures are in any way related to the change in the drug formulation, unless a significant change in blood levels of the drug in patients has been documented…
By the way: I have nothing to do with Pfitzer or so, I never worked for them in the past…
keiner
PS: Bioequivalence is a mature scientific concept used over decades now. And what makes the discussion a little bit bigoted: The large pharmaceutical companies (and not only the generic manufacturers) use this concept frequently, when large-scale, pivotal clinical trials during drug development are conducted not with the “final” drug formulation, which is marketed later. To show equivalence of the formulation used in the trial and the formulation to be marketed, typically a bioequivalence trial is performed…
Just A Thought
Keiner,
Looking back at the information provided when this man first posted on another forum. Five days after he started the new formula he seized and awoke in the ER. His level WAS in the therapeutic range, which is why he asked the question that he did. He had not lost consciousness in a couple of decades of good control on the old formula.
Without getting further into his personal information or credentials (I do not feel it is my place), here is one of the things he mentioned:
“most of the dilantin you take hooks onto the protein in your blood, particularly albumin. Only a small portion of the dilantin you take is free to get to your brain and work. Only what can get to your brain can prevent seizures. Labs have the ability to measure free protein, but usually they don’t.”
The absorbancy of this medication may explain his situation. He also goes on to discuss kinetics and many other things that I do not fully comprehend.
A good many of people did move into elevated or subtherapeutic ranges after changing to the new formula. Ed chose him from one of many people posting on the site (one forum) that he linked to in his article.
People who had been well controlled for decades on Pfizer’s old formula started having everything from eruptions on their skin to grand mal seizures. The list is long in both adverse reactions and the people having them.
I would like to add here that there were people from all walks of life, including the medical field, who were affected by this switch.
keiner
Hmmm,… protein binding of a drug is not altered by changing the formulation. Except if the new formulation does not contain the same amount of the same active ingredient at the same level of pharmaceutical quality. But that’s a quality issue and has nothing to do with bioequivalence/generics, its just poor quality then. But such faults are easily detected when analyzing the medicinal product.
My point is: there is NO rational to assume that adverse events such as those reported by you (skin reactions) might occur simply by changing the formulation. Skin reactions are listed in the SPC of the drug and might occur at ANY time during drug intake, no matter which formulation … “Post hoc ergo propter hoc” is not valid (remember West Wing…). That is exactly the point we had in Europe: after switching a drug, every adverse event is suddenly related to the ALTERED FORMULATION and not to the drug, which simply is not true.
ON THE OTHER HAND lack of efficacy might occur, if the drug release in the gastrointestinal tract from the new formulation is totally different from the old one. But this is excluded by the concept of bioequivalence. The FDA decided that the bioequivalence study was performed and evaluated properly (hopefully not only in a single-dose, but also in a multiple-dose trial, as the drug is an extended-release formulation afaik). Then no such thing as lack of efficacy should occur…
And: NO, I get no money for writing this, it’s simply that I’m interested in this issue..
keiner
PS: … my question was NOT “were the concentrations in the therapeutic range”, the question was (is):
Were they lower than before?
Just A Thought
I believe he was down 2 points. I’ll have to look that up, and what others reported, and get back to you. It’s a lot of information to sift through. I know people reported troubles with their levels, I just don’t know them off the top of my head.
It may not seem rational but it happened. It doesn’t seem rational for a company to change a necessary medication and foist it on their consumers unaware either, especially knowing the dangers.
It’s not like these consumers can just avoid their medication if a new one is ineffective. To do so could place them into Status Epilepticus (a continuous state of seizure) possibly causing brain damage and/or death.
If you are sick because you can no longer get your medication you are placed in the very precarious situation of trying to find something that works. Sometimes trying several different drugs while you seize or become toxic until you hit on a winner. Not every epilepsy drug works for every person or every type of epilepsy. Some have black box warnings for allergic reactions. Some require weeks of slow introduction. To be safe, people often gradually increase one drug while decreasing another. And if one drug fails during the switching process, you get to start over with something else.
Pfizer did not allow for that transition.
One person described this situation as being like having their air taken away. People were living perfectly normal lives until this happened. After the switch everything from driver’s licenses, to jobs, to their ability to care for their families were placed in the balance.
Maybe rational is one of those gray words like say… ethical.
keiner
I guess there are two things we should strictly separate:
1. Is it a psychological issue to change medication in severe chronically ill patients? No question, I guess: Yes (I have worked a couple of years directly with patients and know that for sure).
2. Is there a lack of quality in this very special case?
- Pharmaceutical quality (e.g. quality of the phenytoin used): This might influence the adverse event profile. Is the rate of adverse events higher than for the “old” formulation? Impossible to estimate from spontaneous reporting, as this is strongly biased… However, lack of pharmaceutical quality is quite easy to assess.
- Biopharmaceutical quality (has the bioequivalence been tested accurately): This might influence the efficacy of the product, including the occurrence of the underlying disease (fits). I proposed some things to be reviewed regarding this issue in my postings above. This might help elucidate, if there is a real problem with the availability of phenytoin to the body of the patient from the new formulation. Unfortunately, the respective data is not available at the FDA homepage (and not at FOI online).
Interestingly, the FDA guidance document on phenytoin extended release formulation demands on SINGLE-DOSE studies to be performed. In Europe ANY extended release formulation of ANY given drug has to be tested following MULTIPLE-DOSE administration. To me it’s unclear, why a multiple-dose study should not be necessary for phenytoin, as such a study much better reflects the situation in patients.
http://www.fda.gov/CDER/GUIDANCE/bioequivalence/recommendations/Phenytoin_ERcap_84349_RC5-07.pdf
http://www.fda.gov/CDER/GUIDANCE/bioequivalence/recommendations/Phenytoin_Sodium_Ecap_40298_RC5-07.pdf
You should focus on point 2, I guess. Otherwise you mix up science with emotion and this might do harm to your request.
Just A Thought
1) Is there a psychological issue to change medication in severe chronically ill patients?
Is it a psychologigal thing to be seizure free for decades and then have the rug ripped out from under you? You’re kidding, right? One day you’ll be aghast at your own statement, as all bodies deteriorate and some bonehead will surely confuse a physical occurance in your body with a psychological problem. What an easy mark you think we are.
2) Your little links for bioequivalence are guidelines for generics. Dilantin is not a generic, is it? Because if it is, there has to be some legality concerning using a brand name for a generic and for not informing medical professionals that the next prescription they write may as well be for Mylan’s phenytoin.
If it isn’t a generic, then Pfizer changed the standard by which this medication is evaluated, based on the new AUC, because the brand name medication sets that standard for the approval for generics. Feel free to correct me if I’m wrong.
If this is allowed to go unpunished, a precedent is being set for any branded drug to become a generic. To strive to become bioequivalent to the generics that were approved by the FDAs looser standards. I wouldn’t be bragging that this drug is the next best thing to a generic. AEDs are one of very few drugs that have the ability to keep brand name drugs a viable option, to keep the big pharmaceutical companies above water.
And we fought for the right to this brand name drug when out insurance companies were trying to keep us from getting them. Pfizer should be throwing us a party instead of screwing us out of our well being.
Yeah, that made me emotional.
keiner
Is my English that bad? You didn’t get a word from what I was trying to say… Best regards! Over and out.
keiner
PS: Just one thing: Dilantin NEW is not a generic, but Pfitzer (as usual in such a case) used the same approach as used for generics to show equivalence of the new formulation to the old formulation. That’s why I cited the bioequivalence rules of the FDA.
pg
Keiner, your English is good - but perhaps the ‘way’ you explain is not so easy to understand for some of us and some sentences are easy to misinterpret due to that, and I might well be doing the same here :)
I also can understand how Just a Thought feels emotional. It is very difficult for people to put emotion to one side when they experience unpleasant and sometimes life-threatening effects from a drug and yet are continually told from various sources that this cannot be so, which in itself infers that those experiences are not real but ‘psychological’.
I think you are right where you said in your first comment:
“From a scientific point of view it will be impossible to show that the reports on seizures are in any way related to the change in the drug formulation, unless a significant change in blood levels of the drug in patients has been documented…”
I believe that reports are being documented. Here is one place that appears to be recording blood level changes. http://www.mincep.com/dilantin.htm
Hopefully for the sake of all who take the new Dilantin and are having problems with it, even if, as is often the case, it is only seen in a relative minority of patients (though a minority in large populations is a significant number), the majority of physicians will take note and send in ADRs so that further investigations take place, improvements in the treatment follow, and the situation is improved for those people.
pg
Perhaps I need to reword this sentence a little:
“…life-threatening effects from a drug and yet are continually told from various sources that this cannot be so, which in itself infers that those experiences are not real but ‘psychological’…”
to “…life threatening effects from a drug, or from some as yet unknown change in its formulation…”
Thats as technical as I can get as I’m no pharmacist, but hopefully that is enough to explain :)
Melody
From the outside looking in, it appears the onus for proving that the “new” Dilantin is different than the ‘old’ formulation is placed squarely on the patients’ shoulders (laboratory tests, non-psychological parameters, etc.) . . . patients who do NOT have bottomless pockets. The FDA supposedly looks out for patients (NOT!), so the situation should be reversed . . . where pharma has to PROVE that the product IS identical instead of the patient having to PROVE that it isn’t. Sadly, FDA currently sets the bar so low for pharma, that the patient is generally placed in a lose-lose situation.
pg
Very true Melody and the onus being on the patient to prove issues about negatives seems to be the case with so many drugs. Hopefully though things are beginning to change and perhaps enough physicians and organisations will be able to put enough pressure on the FDA (and other regulatory bodies) to get them to actually DO the work they are designed to do - ie, to protect patients rather than the industry.
Thats all we can hope for at this stage I suppose and they DO get around to protecting patients then we just have to keep ‘doing it ourselves’, whichever way we can.
pg
“UNTIL they do get around to protecting patients.” As yet they DON’T. Sorry for the error!
Just A Thought
Apologies for the spelling, punctuation, and wording crisis of my last post. *blush*
Keiner, I would not be wasting my time if I did not have the very troubles that you appeared to be defending as not possible or plausible. It rubbed me the wrong way. As if these troubles could have just as easily been the result of the rotation of the sun. I see now that you are curious and possibly playing devil’s advocate. It has lead me in another direction (actually two) which is not a bad thing at all. So thank you. I am sorry if I made you feel bad. And thanks to pg and Melody too for their complete understanding.
This is going to be my last comment on this topic. I am not going to prove my case here.
I do have a little bit of a dilemma.
The epilepsy foundation (largely funded by big pharma) is urging all of these state legislators to introduce bills to ban generic substitutions for epilepsy drugs. I would have been behind this legislation completely several months ago.
Let’s just assume that it can be proven that Dilantin is now a generic with a brand name.
Pfizer changing their brand name drug has put a troublesome little spin on this legislation and I almost feel obligated to do something to prevent it. Pfizer stands to benefit from this legislation by being the maker of a brand name AED (no matter what the drug is now). Sadly, for Glaxo’s Lamictal and whoever else may stand to benefit from this attempt, I think that it is necessary to bring to the argument that at least one brand name maker of an AED has changed their drug in such a way that some of their consumers were switched to generics. Switched because the new formula was ineffective and dangerous for them.
Even if it could not be proven that Dilantin is now a generic. To pass this legislation there must be some statement involved about consistency. Because if the branded drugs are not consistent then how can these legislators argue that people are more safe taking branded AEDs over generics?
anonymous
This is an interesting posting. Pfizer reps have not been advised about this issue, probably because the company doesn’t market Dilantin anymore. The reps aren’t educated about Dilantin, other than the basics, so they aren’t legally allowed to address it. I will email my boss and ask if there is a specific person to whom patients and physicians may address questions, or something like that.
In the past, with other older drugs, we have been given phone numbers to give to physicians. I will follow up on this.
MD
I have been confused from the beginning about how Dilantin Capsules could be anything more than an generic version of Dilantin Kapseals. The information distributed to professionals indicated in the foot note the capsules could only meet bioequivalence requirements for generics under some situations. The capsules could not meet the “in house” biioequivalence standards that would differentiate them from the generics.
Also, and most importantly, we are not looking for blood levels. We are looking for clinical response. Blood levels are just a predictor of what may or may not be happening clinically. Did some patients get a different clinical response when they were switched to the capsules? Did it happen to more than one patient? Is there a pattern? Is there something we haven’t thought through yet as clinicials? If there were patients who got a different clinical response why? I know this is very difficult information to short through clinically, but there is a responsibility to the patients for it to be pursued.
Ed Silverman
Hi MD,
I can only site anecdotal reports, predominantly from the Epilepsy Foundation forum and the other forum to which there is a link provided in the quote in the story. Also, a few people wrote me privately.
Unfortunately, I don’t have numbers to provide, only indications that a few individuals did experience different clinical responses. Perhaps this is something the FDA should review.
Thanks for writing in,
ed
keiner
Just a thought:
“The epilepsy foundation (largely funded by big pharma) is urging all of these state legislators to introduce bills to ban generic substitutions for epilepsy drugs. I would have been behind this legislation completely several months ago.
Let’s just assume that it can be proven that Dilantin is now a generic with a brand name.”
That’s the irony: they made “you” (and other patients) fight against generics, and now you come back to them with the SAME arguments and fight them for changing the formulation of Dilantin. THAT’s (one of) my point(s)! I didn’t mean to offend you, but generics are not bad as hell in general! If adequate testing is performed…
@MD
“Also, and most importantly, we are not looking for blood levels. We are looking for clinical response.”
If concentrations of a drug in the central compartment are no predictor for (central nervous) effects than we can through away the concept of pharmacokinetics. If two formulations result (under all circumstances! REPEATED DOSE in FED and FASTED state) in identical blood levels than there is no scientific rational to assume that the effect might be different.
(sorry, I said I would not come back, but I could not resist…)
Melody
MD, you said: we are not looking for blood levels. We are looking for clinical response. Blood levels are just a predictor of what may or may not be happening clinically. Did some patients get a different clinical response when they were switched to the capsules? Did it happen to more than one patient? Is there a pattern? Is there something we haven’t thought through yet as clinicials? If there were patients who got a different clinical response why? I know this is very difficult information to short through clinically, but there is a responsibility to the patients for it to be pursued.
This is an argument used by diabetics who were forced to switch from natural (animal) insulin to rDNA insulin when all natural products were removed from the U.S. market. BUT MOST DOCTORS would not listen. Most doctors dismissed patient ‘anecdotal’ reports, in favor of pharma propaganda. Using only blood-glucose-lowering effect (average bG’s or HbA1c’s), manufacturers could advance specious claims of identical-ity; the ‘regulatory’ bar was set VERY low; and the ‘evidence’ disappears. Insulin manufacturers NEVER had to prove bioequivalency . . . and to my knowledge, analytical technology does not exist today that would allow them to prove this. Additionally, since batch-testing requirements were removed from insulin production, some diabetics feel that each new ‘batch’ of rDNA genetically-engineered insulin is a GENERIC . . . and no one listens, no one investigates.
keiner–your argument rests on identical ‘blood levels’ to validate scientific rationale. Do you suppose there are yet-to-be-discovered blood tests that would support clinical claims? Is anyone looking outside the box to find tests that would/could support ‘anecdotal’ clinical claims? I doubt it.
Just A Thought
The Epilepsy Foundation doesn’t even have the “New Dilantin” listed on it’s drug list, but rather, the Dilantin Kapseals which were discontinued last September.
http://www.epilepsyfoundation.org/answerplace/Medical/treatment/medications/typesmedicine/dilantin.cfm
keiner
@Melody
I don’t think you need to find new tests. You have to test (as I wrote ) under RELEVANT conditions. However: As usual, all data in medicine is based on statistics, while any patient is an individual….
I guess (!) that the cases of lack of efficacy with Dilantin can be explained by altered blood levels (due to a food effect, probably), but unfortunately no detailed data (from FDA on drug approval and on the altered blood levels in such patients) is available to be analyzed.
Just A Thought
I know I wasn’t going to post here anymore, but damn.
http://www.epilepsyontario.org/client/EO/EOWeb.nsf/web/Dilantin+Extended+Release+100mg+Tablets
“Even though there is a change in U.S.P. dissolution specifications, dosing recommendations for DILANTIN 100 mg extended release capsules remain the same. It is important that you continue to take your DILANTIN as prescribed by your health care professional.”
Just A Thought
Seriously, read that article. Maybe my pills were from test one or test five. God only knows. There was not sticker saying they were a test product. Maybe you have to be a Canadian to be pre-informed.
Just A Thought
Nevermind, I didn’t notice the date of that article. I can’t find the dissolution rate of the new product at the USP site though.
keiner
The article is dated “November 8, 2002, Pfizer Canada Inc. “. I guess that has nothing to do with anything going on nowadays…
keiner
Results from in vitro dissolution testing are difficult to interpret/assess regarding their in vivo relevance, you need a lot of (frequently inside-FDA/pharma-only) data. The in vivo data (bioequivalence trial data) would be more interesting to know.
Melody
keiner–
I wrote a long message, only to have it disappear as my computer disconnected. Suffice it to say: AGREED. The problem has now become finding someone to collect and analyze the information . . . and none of the current players have interests in doing this. The patient-advocacy groups–which would appear to be the ideal interface for the collection of data (adverse events, detailed medical histories, etc)–have become quasi-corporations, heavily underwritten by industry. Likewise, our educational/research institutions no longer strive for scientific integrity, but instead rely on industry dollars, and thus are industry-influenced. Individual doctors–much like individual patients–have neither the time nor deep pockets to advance research. Goverment regulators are mired in politics. WHO WILL (CAN) COLLECT AND ANALYZE DATA? Who will ask the RIGHT questions?
keiner
Melody-good question… The FDA will have to investigate the case, if there is a health concern. So I think, this is the place to bring all the data available (and they are the only ones with the relevant data from the company. In my opinion the patients should get their doctors to report all details…
http://www.fda.gov/medwatch/how.htm
From “here” (old Europe) I have no overall view of this “case”, how many cases have been reported so far? Isn’t there something like an independent institution run by pharmacists or so, who might take a look at that?
You may contact AAPS (they have focus groups e.g. on bioequivalence), maybe they have someone to contact in academia, who knows how to get FDA involved….
keiner
Hmmm… food-effect with phenytoin is not really new:
http://www.ncbi.nlm.nih.gov/pubmed/11524464?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=1&log=relatedarticles&logdbfrom=pubmed
Susan
Dilantin Kapseals had such a small variable fed or fasted that there was no requirement to take it either way for it to be effective. And I took it both ways with no difference in effect. Now before you dispute this, you may want to keep in mind that I was on this drug for many many years.
I’d like to point you to that information, but when Pfizer discontinued their 100mg Kapseals they also removed the information for it from their site.
What they didn’t remove was the page for their 30mg Kapseals because they evidently have some obligation to make that dose for pediatric purposes.
They just changed the information on the page for the 30mg Dilantin to make it match the information on their New 100mg Dilantin page.
One bit of information that they changed on that page was the storage temperature. I believe it now reads that the 30mg Dilantin is to be stored between 68 and 77 degrees (which matches their new 100mg product). But I have 2 bottles of 30mg Dilantin, the white bottles, labled by the manufacturer, that clearly states it is to be stored under 86 degrees F.
That does not prove anything of absorbency, only that they have altered information.
You’re going to have a hard time proving this is not a bastard child of it’s previous formula. But I can prove it, I am just not willing to do it here for their eyes to see.
Susan
This article states that there are fasted bioavailabilty problems with generics. Hmmm, sounds like the new Dilantin.
http://www.medscape.com/viewarticle/414647
“One of the studies published in the August 28, 2001 issue of Neurology showed that bioavailability (defined as area under serum concentration-time curve from 0 to infinity [AUC0-]) of Dilantin Kapseals was the same when it was taken after fasting or with high-fat meals (see Figure 1). This study included 24 healthy volunteers who took single 100 mg doses of Dilantin Kapseals either after an 8-hour fast or a breakfast of two eggs scrambled in butter, two pieces of white toast spread with 2 teaspoonfuls of butter, 2 ounces of hash browns, two pieces of bacon, and 4 ounces of whole milk. While some intraindividual differences were noted among the 10 men and 14 women, overall pharmacokinetic parameters were almost identical between the fed and fasting states: Maximum concentrations averaged 6% higher after the high-fat meal, and AUC0- was 2% higher after fasting.”
Susan
If you cannot access the article from the above link, try this one.
http://images.google.com/imgres?imgurl=http://www.medscape.com/content/2001/00/41/46/414647/art-pt0710.03.fig2.gif&imgrefurl=http://www.medscape.com/viewarticle/414647&h=517&w=390&sz=65&hl=en&start=10&tbnid=Rw3DrM5q80C4iM:&tbnh=131&tbnw=99&prev=/images%3Fq%3DDilantin%2BAUC%26gbv%3D2%26hl%3Den
Click on the http://www.medscape.com/viewarticle/414647 link under the Google frame.
Justice in Michigan
Below is Public Citizen’s (Health Research Group) summary of the criminal felony convictions re: Dilantin Kapseals in the mid-90s. As Sid Wolfe points out, the problems did not go away even after WL pleaded guilty to the criminal charges.
Even Wolfe seemed amazed at the depth and systematic nature of the problem.
******************************************************
Statement by Sidney M. Wolfe, MD, Concerning Warner-Lambert Criminal Conviction and Poor Manufacturing Practices… Includes Dilantin Recalls (HRG Publication #1380)
Statement by Sidney M. Wolfe M.D.
Public Citizen’s Health Research Group
Concerning Warner-Lambert Criminal Conviction
and Poor Manufacturing Practices
Although the company has pleaded guilty to criminal charges for withholding important information about sloppy manufacturing practices from the FDA and FDA has indicated that the problem seems to have been solved, an alarming number of recalls of their prescription drugs continues to occur. In the first 11 months of 1995 alone, there were 20 recalls of Warner-Lambert products including 8 recalls for Dilantin and 3 recalls of Nitrostat.
Since 1990, there have been a total of 64 recalls of Warner-Lambert products as listed in FDA recall reports. In 1990 there were 3 recalls; 1 in 1991, 3 in 1992, 24 in 1993, 13 in 1994, and 20 thus far this year. For Dilantin alone–a drug used primarily for treating seizure disorders and one where the amount of the drug in the blood is critical–there have been 12 recalls since 1990. Most of these - 9, involved problems with the drug dissolving, which can result in an insufficient amount of the drug being absorbed by the body. Over 975,000 bottles (some of which contain 1000 capsules) and over 30,000 injectable doses of Dilantin have been affected by these recalls.
Given that these recalls continue at a record-setting pace, FDA must investigate the systemic and ongoing problems at Warner-Lambert and prosecute those in charge of company policy and ethics-the highest levels of coporate management. Almost three months ago, in the face of the continuing flood of recalls, we requested copies of all FDA inspection reports of Warner-Lambert since 1990. As of now, we have received only one inspection report, from a South Carolina plant.
In all of the years of following drug recalls, I am not aware of any company which has had so many recalls involving such a large number of bottles of pills pulled back from the channels of distribution. It is time for more vigorous enforcement by FDA and a strong message to consumers that brand name companies such as Warner-Lambert–many of whom have bent over backwards to denigrate the poor quality of generic drugs–should look in the mirror at themselves.
11/29/95
1994 & 1995 DILANTIN RECALLS
4/7/1994 FDA ENFORCEMENT REPORT CLASS II
Product: Dilantin (Extended Phenytoin Sodium Capsules, USP) Kapseals, 100 mg, in bottles of 1000, for control of seizures. Recall #D-191-3.
Code: Lot numbers: 01021 FA, 03691 FA, 03891 FA.
Manufacturer: Warner Lambert, Inc., Fajardo, Puerto Rico
Recalled by: Parke Davis, Division of Warner Lambert Company, Morris Plains, New Jersey, by letter 2/12/93. Firm-initiated recall ongoing.
Distribution: Nationwide
Quantity: 12,105 bottles
Reason: Product does not met dissolution specifications.
4/19/95 FDA ENFORCEMENT REPORT CLASS II
Product: Dilantin Kapseals 100 mg bottles of 100. Recall #:D-112-5
Code: Lot numbers: 05634FA
Manufacturer: Warner-Lambert Company, PR
Recalled by: Parke-Davis, Morris Plains, New Jersey by letter. Firm initiated recall ongoing.
Distribution: Nationwide
Quantity: 40,242 bottles
Reason: Doesn’t meet dissolution specifications through expiration date.
5/17/95 FDA ENFORCEMENT REPORT CLASS II
Product: Dilantin Kapseals 30 mg bottles of 100. Recall #: D-168-5
Code: Lot numbers: 52264L
Manufacturer: Warner-Lambert Company, Lititz, PA
Recalled by: Parke-Davis, Morris Plains, New Jersey by letter. Firm initiated recall ongoing.
Distribution: Nationwide
Quantity: 30,964 bottles
Reason: Doesn’t meet dissolution specifications through expiration date.
5/24/95 FDA ENFORCEMENT REPORT CLASS II
Product: Dilantin Kapseals, 100 mg bottles of 100 & 1000. Recall #: D-174-5
Code: Lot numbers: 05254FA, 08354FA, 05354FA, 02364FA
Manufacturer: Warner-Lambert Company, PR
Recalled by: Parke-Davis, Morris Plains, New Jersey by letter. Firm initiated recall ongoing. Distribution: Nationwide
Quantity: 83,886 bottles
Reason: Doesn’t meet dissolution specifications through expiration date.
7/19/95 FDA ENFORCEMENT REPORT CLASS II
Product: Dilantin Kapseals, 100 mg. bottles of 100. Recall #: D-210-5
Code: Lot numbers: 064N4FA
Manufacturer: Warner-Lambert Company, PR
Recalled by: Parke-Davis, Morris Plains, New Jersey by letter. Firm initiated recall ongoing.
Distribution: Nationwide
Quantity: 39,510 bottles
Reason: Doesn’t meet dissolution specifications through expiration date.
8/9/95 FDA ENFORCEMENT REPORT CLASS II
Product: Dilantin Kapseals. Recall #: D-229-5
Code: Lot numbers: 27224L
Manufacturer: Warner-Lambert Company, Lititz, PA
Recalled by: Parke-Davis, Morris Plains, New Jersey by letter. Firm initiated recall ongoing. Distribution: Nationwide
Quantity: undetermined
Reason: Doesn’t meet dissolution specifications through expiration date.
8/16/95 FDA ENFORCEMENT REPORT CLASS III
Product: Dilantin injection. Recall #: D-232-5
Code: Lot numbers: 00515
Manufacturer: Warner-Lambert Company, Rochester, NY
Recalled by: Parke-Davis, Morris Plains, New Jersey by letter. Firm initiated recall ongoing. Distribution: Nationwide
Quantity: 15,157 packages
Reason: Discoloration resulting from use of incorrect stopper.
10/18/95 FDA ENFORCEMENT REPORT CLASS III
Product: Dilantin brand Phenytoin Sodium Injection, 100 mg, in 2 ml vials.
Recall #D-005-6.
Code: Lot #00815P, N0071-4488-47, EXP 11/96.
Manufacturer: Warner Lambert Company, Parke-Davis Sterile Products Division, Rochester, MI. Recalled by: The Parke-Davis Division of Warner Lambert Company, Morris Plains, New Jersey, by letter 8/11/95. Firm-initiated recall complete.
Distribution: Nationwide and Virgin Islands, Trinidad, Jamaica.
Quantity: 15,416 packages
Reason: Product discoloration resulting from use of incorrect stopper.
11/29/95 FDA ENFORCEMENT REPORT CLASS II
Product: Dilantin (extended Phenytoin Sodium Capsules, USP), Kapseals, 30 mg, antiepileptic drug. Recall #D-021-6.
Code: Lot #27324L EXP 4/96.
Manufacturer: Warner Lambert Company, Lititz, Pennsylvania.
Recalled by: Manufacturer, by letter dated 10/3/95, followed by telephone. Firm-initiated recall complete.
Distribution: Nationwide
Quantity: Firm estimates none remains on the market.
Reason: Product does not meet dissolution specifications.
Susan
Wrong: This article states that there are fasted bioavailabilty problems with generics.
Correction:
This article states that there are ~~~FED~~~ bioavailabilty problems with generics.
I misspeak that every single time :-/
MD
To whoever commented earlier that if levels in the central compertment are not a predictor of clinical effect then we need to throw out pharmactokintecs. I would argue that pharmacokinetics is an evolving field as are all scientific fields. We will know alot more about kinetics twenty years from now than we do today. Any time we fail to investigate situations we block scientific advances. There was no reason to predict that vytorin would not prevent heart attacks. We know now that it doesn’t. I’m seeing all kinds of theories develop now about why it doesn’t, but five years ago everyone was assuring me that it must prevent heart attacks. The “science” was on their side. Not here are all kinds of theories about why vytorin doesn’t prevent heart attacks. Those theories will be investigated and science will be advanced. The same thing will happen in kinetics. It could be that the same thing will happen as people investigate further the clinical consequences of the kapseal capsule switch. If we just blow it off we have done the patient and science both a disfavor!
keiner
@MD: Nice idea, but that’s simply not compatible with the principles of thermodynamics. Pharmacokinetics have a sound mathematical/theoretical basis (it’s natural science, while medicine is NOT). Think about it in a quite moment….
keiner
“There was no reason to predict that vytorin would not prevent heart attacks.”
Yes, there were a lot of good arguments against that, but nobody wanted to listen. It’s always the same with insufficiently validated clinical surrogate parameters….
MD
Keiner, it sounds like you are taking the position that blood levels are always a valid clinical surrogate parameter
of efficacy. It would be great if the world were that simple. Pharmacokinetics does indeed have sound mathematical/theoretical basis. I am saying two things. First, the theory has limitations. Seccondly, I still hold that we will know more twenty years from know that we do today. If we are indeed seeing what seems to be clinical responses which the theory would not predict it is a disservice to patients to say I am sorry you just have to live with those repsonses because they don’t fit in the mathemateical model. If some bright grad student somewhere looks into this situation he or she may find a whole new nuace to the model we haven’t even imagined yet. It is what science is all about, constantly moving forward. And yea, sometimes we do chase ghosts, but that is part of the game. I still go back to the fact again and again that what we are looking for in clinical response.
keiner
“…we are looking for in clinical response.”
Year! That’s why we know nearly nothing about the mechanisms, how modern drugs work, but we have a whole bunch of colorful clinical study results, nobody can interpret…
It’s not that any patient is “outside a mathematical model”. It’s simply that people don’t use their brains. I tell you a story (fiction, you see):
A company doesn’t want any generics in a certain therapeutic area. So they make patients fight for their medication. With good and less good arguments. They say, the concept of bioequivalence is not valid in this therapeutic area.
Unfortunately, the same manufacturer wants to switch the formulation of a drug in this area. Hmmm… they taught their patients: bioequivalence is not valid! To show clinical equivalence, they would have to perform large-scale clinical trial (non-inferiority is hard to proof). Expensive and by the way: ethically nearly not justifiable.
So what to do? BIOEQUIVALENCE trial! They set up tighter margins to accept bioequivalence of the new and the old formulation (to save their face and because they have data showing that…), perform the study and…miss the tighter margins in on of the studies (let’s assume it’s the study drug applied together with food).
BAD LUCK! Now you can go back to the lab, do a re-formulation of the new drug… or have a second glance on your data: The “usual” acceptance criteria for bioequivalence trials are met! Perfect! Move on the agency, get an approval… (STOP! A look in the literatur reveals that meeting only the “usual” acceptance criteria might put some patients at risk… Hmm… Every other solution is expensive and will result in a considerable loss of time… Just go to the agency and see what they will do…)
The agency has a guideline and decides: The bioequivalence studies (although not meeting the specified targets) are in line with that guideline. APPROVAL GRANTED!
… The rest of the story I leave to your fantasy. JUST FICTION!
And you want to blame this to the concept of bioequivalence? No really?
MD
If there are any citations in the literature before the ENHANCE study that combining two drugs which both lower choleterol, one of which was known to reduce cardiac events(HPS Study) would perhaps raise cardiac events in some patients I would like to see them. I hear alot of theories now about what is perhaps going on here (I think in 2011 we will have a fuller picture), but I didn’t hear them until after the ENHANCE study.
Even if we want to take the position that pharmacokinetic kinetic theory will never advacne beyond where it is at the persent time we still have to deal with a question. Why did a pharmaceutical manufacturer say in their own literature that it is important for a a drug(Dilantin) to exceed the 85/125 guideline and then when it couldn’t meet the more strigent self-imposed guidelines market the drug anyway? Many of the physicians who prescribed the drug and many of the patients who took it were looking for something beyond the 85/125 guidleines set for generics. If Dilantin Capsules could not meet those criterea everyone needed to know-and a foot note at the end in small print does not in my mind meet the criterea of notification.
By the way, Keiner it has been fun. I too have a real job so hopefully I won’t be back. It would be fun to sip a scotch some day and talk about our different world views.
keiner
Just one final point:
Do you know why you end up with such a lot of “surprising” clinical trial results? You typically correlate shoe size with income in your trials and find a perfect correlation. People with larger feet have higher income, is the outcome. But what you realy have is that men have larger feet than women and men have frequently a higher income. But this side of the story is unknown in most clinical trials!
Cheers!
Renae Kelley
I have been on a clinical trial most of my life!
If there has been a change to the Dilantin, the manufacturer should have told the consumer. Epileptics need to titrate off and onto new medicines.
Immediately my thought process changed. I told my brother that I have never felt so bad in my whole life. Sick. anxiety, in a fog all day, hard to concentrate at work or remember things. Dizzy spells on and off. You just live with these things at times having epilepsy. I have always tried to push myself through them. I could go on about how my body has been reacting to the medicine and me trying to avoid full seizure. After 6 months of suffering, and symptoms progressively getting worse. I new I had better see my doctor and then it all connected New Dilantin.
Seizure free on Dilantin for a combined 30 years . I had problems in 1990 when there was manufacturing problems with Dilantin…no one spoke to me then. Spent 3 years on other medicines. Again, problems when my doctor tried to put me on a generic.
I can not believe that I was so ignorant to the fact that in reality I started a new medicine! Even though the pharmacist told me it was just a packaging change.
Just A Thought
The generic I am now on (and which I just refilled a few days ago) is kicking my butt.
The first fill was bad and I cried every morning that I had to swallow it.
The second fill had me feeling pretty damn good and I thought I had adjusted to it and might just remain on it forever.
The 3rd fill makes me wonder if I’ll make it at all.
It’s all the same drug but most likely different lots. It still doesn’t make me as sick as the New Dilantin did or I wouldn’t be on this generic.
This is my life since Pfizer changed Dilantin. Maybe I should be thanking them (or PD or WL) for so many years of no suffering instead of damning them for causing this problem for me now.
I seriously don’t know what to do. Try something else? My house looks like a pharmacy. The last drug I tried landed me in the ER. I guess I’ll have to try to work up the nerve to swallow something else.
If Keiner implies that I didn’t eat the same way from lot to lot….
OneEyed Man
No physician should ever have qualms about substituting a generic for a Pfizer product again, since this episode reflects an unswerving belief by Pfizer in the adequacy of the bioequivalence requirements of the FDA.
OneEyed Man
One angle that needs to be investigated is Pfizer’s motivation for making this formulation change. Why go through the extra costs of doing the work for an ANDA, manufacturing changes, etc. just to substitute your own product? Were these changes the result of manufacturing consolidations due to merger consolidation and downsizing? Have other aspects changed, such as the source of the active ingredient?
As with many older products, the testing specifications, certainly the USP, may not cover all of the subtleties of differences that may occur with manufacturing changes. (This is one reason why I tend to favor the original product or branded generic, since the originator should know much more about a product than is ever reflected in what is required. But Big Pharma is loosing knowledge daily with all of the current turmoil.)
Just A Thought
Yes, OneEyed Man, USP is something that has been discussed.
The old product being:
ORIGINAL (discontinued)
DILANTIN® Kapseal®
(extended phenytoin sodium capsule, USP)
100 mg
The new product being:
NEW LOOK
DILANTIN® (phenytoin sodium) 100 mg
Extended Oral Capsule
Is the new product USP certified, overall?
About the Abbreviated New Drug Application…
What the heck is a sANDA and how does it differ from an ANDA?
From the VA (Google VA Dilantin sANDA)…
“The FDA recently approved a supplemental abbreviated new drug application (sANDA) for Dilantin® Extended Oral Capsules 100mg.”
Melody
These stories are incredibly in-sync with genetically-engineered insulin. I guess the captive diabetic population have embraced Just A Thought’s sentiment: Maybe I should be thanking them (or PD or WL) for so many years of no suffering instead of damning them for causing this problem for me now.
Insulin-using diabetics seem willing to embrace the “latest, greatest” technology, and willingly serve as guinea pigs every 10-12 years or so (as patents expire and new synthetic insulin-like analogs are promoted). Perhaps they are so busy ‘thanking’ industry for technological improvements (monitors, strips, test-and-test-often exhortations) that they forget that neither quality of life, expense, nor morbidity/mortality metrics have improved. Perhaps a thank-you note is in order:
Dear Lilly and Novo,
Thank you for providing me safe, efficacious insulin for years. To express my appreciation, I will, for the remainder of my life, serve as unpaid guinea pig for each new, unproven, expensive antiglycemic formulation you produce. I bow to your greatness, and consider it an honor to pay for the inferior, dangerous products you currently offer. ‘Til death do us part . . .
Just A Thought
So sorry to hear about that, Melody. Is it just that someone got so freaked by mad cow disease that they changed insulin? Vegetarians complained? Animal rights activists? Seems to me that a choice could be offered and that those willing to risk mad cow disease should be allowed to do so, even if they have to sign a waiver. Vegetarians can have their rDNA.
After all, if human stem cells can be a treatment option, why not animal based products? I admit to knowing very little on either subject. My heart goes out to you.
Just A Thought
P.S.
Pure sarcasm:
Maybe I should be thanking them (or PD or WL) for so many years of no suffering instead of damning them for causing this problem for me now.
Melody
Just a Thought: Thanks for asking. The Mad Cow scare was just that–a scare. You didn’t see gelatin capsules and other bovine-derived products removed from the market, did you? [HPLC filtration actually provides greater purity for animal-derived insulin than the current rDNA production method affords the genetically-engineered products.] When rDNA insulin was created the hue and cry went up for ‘first of its kind’, latest and greatest. The only need for the product was for a small segment of the insulin-using population that was allergic to porcine or bovine insulin. But with skillful manipulation, data was put forth that there would soon be a shortage of pancreases. NOT! (The mea culpa for miscalculation using kilograms vs. pounds did NOT make headlines.) It was also promoted as “just like the human body makes.” NOT! Twenty-five years later the industry still cannot validate THAT claim.
When the rDNA product did not ‘move’ well–many patients and doctors did not embrace arbitrarily switching from a known to an ‘unknown’–Lilly began removing natural products from the market–they were ‘unpopular’, don’t you know? As each product was removed, guess what ‘grew’ in popularity–rDNA insulin. When it was the ONLY product available(until new foreign hormones like Humalog, Lantus, etc. were created), it was indeed quite popular. As patent expiration approached, however, and newly created/patented hormones were waiting in the wings, the shortcomings of the ‘first of its kind’ were quietly revealed to advance the newest, latest greatest product for insulin-consuming patients. There is also a generic vs. branded controversy brewing in the insulin market.
As one commenter posted above–he/she got a scrip written without the ‘no substitution’ and then chased from one pharmacy to another trying to obtain the ‘old’ product. Many insulin users did the same thing . . . until there was no ‘old’ stock remaining. Expect Dilantin ‘complainers’ received the same assistance from FDA/ legislators/ advocacy support . . . no one could ‘make’ a company continue producing a needed product. “Get over it” seems to be the proffered advice. When one’s life hangs in the balance, and quality of life is severely degraded by the absence of a needed drug . . . it’s not really easy to “get over it.”
Just A Thought
This article was released by the FDA two months before Pfizer put out the new Dilantin.
“Characterization and Functionality of Magnesium Stearate Derived from Bovine and Vegetable Sources”
http://www.fda.gov/cder/offices/otr/DPQRresearch.htm
They sound fairly uncertain about it to me.
To say that manufacturers will have to use the vegetable based product makes no sense at all. There are surely other manufacturers (if not, there’s a niche for any struggling company to pursue). I want to know who is not using it. Call it magnesium stearateV and the question is gone. I think our doctors and pharmacists deserve to know when an excipient is changed to this extent, as they are as frustrated about our treatment dilemma as we are. I want the option to test if this product is damaging me. I want to know… is Pfizer using it?
Carla
My sympathy goes out to all those poor people who are suffering with epilepsy. I, too, took these ridiculous drugs for over 40 years to combat grand mal seizures. I’m happy to report that I researched my condition and succeeded in being seizure free for over 6 years now without the aid of these dangerous drugs. Vitamin D did it! My only hope is that someone will see this comment and contact me for more particulars, and we can spread the word, giving hope to all those victims who are at the mercy of the pharmaceutical industry who dispenses these medications with a myriad of horrnedous side effects.
Melody
Carla–
You might want to share your story at a fledgling blogsite designed for such purpose: trusera dot com. Will be checking there to ‘meet’ you.
Carla
Melody,
I visited the website and filled out registration. However, I need a password and am unable to find out how to get it. I’d love to connect with you, but obviously registration takes awhile. Is password forwarded to my email address, and do I have to wait for receipt. How do I find you?
Carla
Melody
Carla–
You might contact the site owner who posted the article: see
http://www.alliesvoice.com/
I’ve visited the site . . . but since anything I might wish to share would involve “volumes” I’m not sure it is appropriate for me . . . but plan to keep checking back regularly to see how it evolves.
Carla
Melody,
I succeeded in registering at the site - their email gave me instructions. Go to the site and look under epilepsy in the search area - I’m the one in New Jersey. Are you an epileptic? I’d love to converse with you - we don’t need to go into volumes.
Just A Thought
Here we go again. Valeant has changed Mysoline. So what does Valeant say about the “new” Mysoline?
“The two tablets do differ slightly in their inactive ingredients.”
http://www.valeant.com/mysoline/index.jspf
There are no slight changes in inactive ingredients where the treatment of epilpsy is concerned. Excipients contribute to dissolution and absorption. The things that are critical to maintaining the kinds of steady results needed to avoid seizures without toxicity.
I found this on the Epilepsy Foundation forum today. This is not a drug I’m familiar with but the story is eerily familiar.
You cannot mess with meds used to treat epileptics! It is deathly dangerous.
This is that little group of folks, if you recall, who are often mentioned in the attempt to keep insurers paying for branded drugs because the danger of switching to and between generics holds such a danger.
As with the rhetoric that only Dilantin’s appearance had changed, this person is reporting that Valeant is stating a color change and manufacturing issues. Where the hell is the FDA? This poor soul may have dodged the Dilantin bullet, as would about 70% of Dilantin consumers, but now has to see if he/she can dodge another?
In part…
“I have a call into the FDA I have another call into a member of the Board of Directors of Valeant. It would be nice to have a straight answer and know ahead of time when meds you have taken for years are all of a sudden no longer available. I only say this because generic is usless for me and if I’d had know this sooner I could have started researching other meds and possibly taken a last vacation as it took 7 years to figure out meds the first time.”
http://www.epilepsyfoundation.org/efforums/forum/messageview.cfm?catid=3&threadid=79395&enterthread=y
Evidently Dilantin users were ineffective enough that the same garbage could happen to someone else. I am so sorry.
Just A Thought
The most recent reaction to this change in medication, that I am aware of, leads to this comment by a guy who is suffering on the new Dilantin. Dated 07/08/2008. He writes:
“I finally recieved a letter from my congressman stating his office contacted Pfizer and was told even though the new dilantin is a little different we should not be having trouble with it. Pfizer told his office the problems could be in the inactive ingredients. Pfizer believes any problem is related to reactions to the inactive ingredients.”
So, is it that people should not be having a problem or that the inactive ingredients (which Pfizer put into their new formula) are the cause of the problem?
I assume they know the role excipients play in how drugs are delivered into the system. No?
jerry1967
I am the person that was contacted by my congressmans office and told the inactive ingredients could be the problem.
I was very disappointed his office didn’t investigate any futher.So I guess we have to live with this situation.
Freddd
I was on Dilantin for 13 years for controlling whole body muscle spasms and neuropathic pain but no longer need it due to nutritional changes. My daughter is still on Dilantin for neuropathic pain. She called me and asked if Dilantin had been changed since it was no longer working as it had been. I asked her if she was sure that a generic hadn’t been given her instead. Nope, but it was the new and disimproved formula. I am on methylcobalamin injections daily and can feel the difference within hours, as my feet numb up more from neuropathies if it has broken down to hydroxycoblamin because of exposure to light and break out in acne within days. As this is a compounding pharmacy product I suppose I am reasonably lucky to get good methylb12 most of the time and it was replaced when it wasn’t. Also, only certain brands of methylb12 sublingual are predictably active and some are not at all active. Anybody interested in a protocol that will reverse at least some neuropathies of some causes? Good luck all.
I am working on a solution for data collection and analysis that will hopefully help find answers in situations like this, and many others. It will be at least a couple of months, probably longer, until I have it ready to put up. I have parts of it prototyped but other parts remain to be done, and it isn’t first in line at this time.