![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 13 to 37 of 62. Go back in thread:
Posted by laima on February 25, 2007, at 23:14:08
In reply to Drug manufacturing and quality control, posted by Squiggles on February 25, 2007, at 17:21:34
Yes, a little- my doctor consults on some drug trials and had much to say about how the fda holds generics to much lower level of scrutiny than brand name. Generics also are officially allowed to take certain measures to reduce their costs: ie, use different quality or amount of raw ingredients, and are not subjected to loads of tests and inspections. He didn't blink an eye or utter any disagreement at all when I suggested brand and generic adderall are not the same. Rather- "There could be many reasons contributing to that...many patients feel the same..." I wrote about it in one of my adderall threads. Apparently, fda is stretched thin, and more concerned with establishing safety or efficacy of new drugs, and slacks off considerably with generics. Sounds like as long as they are in the ballpark and the factory is sanitary- they are good to go. A couple months ago there was a thread here on babble about how generics are allowed by law a 20% give or take in difference from brand name. Pharmacists love to deny this, but personal experience begs to differ, and I'm thrilled that my doctor not only didn't deny it, but offered explanaitions.Think- fda can't even keep track of spinach or peanut butter quality!
> Does anyone know about the possible variability of quality control in drugs?
>
> Maybe this is the reason 300mg imipramine is required and is still weak (not my case).
>
> thanks for any tips you may have;
>
> Squiggles
Posted by notfred on February 26, 2007, at 1:19:56
In reply to Drug manufacturing and quality control, posted by Squiggles on February 25, 2007, at 17:21:34
>
> Does anyone know about the possible variability of quality control in drugs?
>
My understanding is that the variation is in bioavailability as generics must prove that they are bioequivalent to the brand. Bioavailability
is about how well the body takes up the med. This is where the inactive ingredients come into play and manufacturing process can also matter.
Posted by Squiggles on February 26, 2007, at 6:15:04
In reply to Re: Drug manufacturing and quality control » Squiggles, posted by laima on February 25, 2007, at 23:14:08
Thank you laima and notfred. I am suggesting
to my friend that she switch to Tofranol, and
not the generics; the problem may be that it
is not made *anymore*, and all that there is, is
generics-- these old drugs like lithium and imipramine may also not get the white glove treatment. But, I think that given the switch to a generic at around the same time that depression arose and other unexplained symptoms, it's worth checking with the pharamacist.I don't mind generics in electronics and shoes (or knock-offs as they are called in the new market), but when it comes to health products, we are in trouble.
Thanks again for your input.
Squiggles
Posted by ralphrost on February 26, 2007, at 6:52:56
In reply to Robert Whitaker and Zyprexa (trigger), posted by Squiggles on February 23, 2007, at 7:06:09
Freaking true and sad...
> Some posts ago, someone said i should take a look at what Robert Whitaker has to say about the antipsychotic drug, Zyprexa. Well, i looked and found a couple of articles under:
>
> http://www.thestreetspirit.org/August2005/interview.htm
>
> http://zmagsite.zmag.org/May2004/levine0504.html
>
> I'd like to add that Robert Whitaker is a member of Mindfreedom and takes a radical perspective on the mistreatment of patients by pharmaceutical companies. He is a prize-winning journalist (author of "Mad in America"). Personally, I don't have enough evidence or knowledge to believe that drug companies are more likely to mistreat the mentally ill through drugs, than hospitals or physicians or psychiatrists. In all cases, the rule of law is the best watchdog. Somebody said "if they won't do the right thing, make them".
>
> Squiggles
>
>
Posted by laima on February 26, 2007, at 8:56:53
In reply to Re: Drug manufacturing and quality control, posted by notfred on February 26, 2007, at 1:19:56
Yes- I am certain manufacturing processes and other such factors must play a role. But I feel I heard the part about how they "might" in some cases use lower quality or "less pure" raw ingredients from a pretty credible source. My doctor specializes in pharmacology, and has been involved as an independent consultant for some drug studies, so knows some stuff about fda regulations and industry rumours, etc. I should be clear- he never said anything like, "generics use poor quality ingredients"- but believes it's a definate indirect possibility. (He also has no grudge against generics, and prescribes them regularly--but acknowledges that some people do detect a difference of action in some cases, and in those cases, he specifically prescribes for them the version that works better for them.) Generics get to cut costs- fda gives them permission to take measures to do this---quality of ingredients are a way of cutting costs. I mean, isn't 99cent generic supermarket butter bio-equivalent to 6$ organic guormet Danish butter? But they don't taste the same. Isn't Maxwell House coffee technically bioequivalent to Starbucks, of same varietal? But they don't taste the same, and in processing, the darker the roast, the less caffeine. Well, I don't know if these are very good analogies, but I'm not thinking of a better ones off the top of my head. I also personally note that if the fda is failing at monitoring spinach and peanut butter quality- why should I think they are closely watching what the generics are doing, unless someone complains? I picture some inspector showing up time to time to see if the place is clean and the pills are still fit for human consumption. Generics are not advertising anything- so there isn't any need to bust them for false advertising. The brand versions already supposedly proved safety...and jumped through hoops to groom their product to perfection in order to sell well and gain a following--and their products are more visible and available for scrutiny by govt and public alike. I'm sure monitoring claims in their advertisements keep the fda pretty busy...I am also sure that each generic manufacturer is different as to their ethics, their choices of how to cut costs, perhaps they use different suppliers for their raw materials, and I bet it varies from med to med. Bottom line: they have permission to cut costs, and are not under the same level of fda scrutiny as are brand name versions.The single solitary med I ever noticed a quality/action difference for between brand and generic is in the case of Barr adderall-and it was NOT a matter of potency. If Shire brand consistently felt smooth, calm, and bright-with no noticible kick-in or crash, but had modest appetite suppression effect--and Barr generic sent me through a jittery, heart-poundy phase as it suddenly "kicked in", (particularly if I hadn't eaten), had zero appetite effect, was distinctly noticeable when it wore off- and even made me feel emotionally vulnerable at that phase- and eventually just made me plain depressed no matter what the time of day---how can they be bioequivalent? One brightened my mood significantly and didn't ever feel like being on anything, the other was choppy and made me very depressed after two weeks. Like two different drugs. Adderall was designed by Shire to be smooth--and in my case it lived up to the promise quite impressively--so if the generic version loses that key quality thanks to their manufacturing techniques or "inactive fillers"--it's not the same!
And what of that thread from a while ago, where it was reported that generics can be 20% less effective than brand, legally?
> My understanding is that the variation is in bioavailability as generics must prove that they are bioequivalent to the brand. Bioavailability
> is about how well the body takes up the med. This is where the inactive ingredients come into play and manufacturing process can also matter.
>
>
Posted by laima on February 26, 2007, at 9:27:03
In reply to Re: Drug manufacturing and quality control, posted by Squiggles on February 26, 2007, at 6:15:04
Hi Squiggles,I think it varies med to med, and from manufacturer to manufacturer. What cost cutting measures are they employing, who are their suppliers, are they using different "inactive ingredients", are the "inactive ingredients" REALLY inactive, and do they affect absorption? Maybe even it matters how complicated or simple the medication is. I've been perfectly happy with every single generic I've ever had, with that glaring exception of Barr adderall. However, the original's a very designed drug- so maybe it gives more opportunities for something to go "off", if production ingredients and methods are not followed EXACTLY? (Just my theory.)
And truely- yes, my psychiatrist does consult with some drug trials for brand name drugs, but he regularly checks "may substitute" on scripts and has nothing at all against generics. Just acknowledges readily, when asked, that they CAN be different in some cases, for some patients. And can offer concrete reasons as to why they can be different, while also noting that while the differences may be a big deal to some, others can't detect. I think that's a pretty balanced and reasonable position.
I guess my pet peeve is pharmacists and insurance companies who insist that there are NO differences between brand and generics, EVER- when clearly that hasn't been my experience with this med. I appreciate getting this validation about experiencing a difference, and gaining some insight as to "why"-and it's not "all in my head". I'll be amazed and impressed if your friend's pharmacist acknowledges that the switch to generic could be a reason for your friend's worsened depression. Well, when I asked if generics and brand are pretty much the same, an assistant at my pharmacy rolled her eyes and sarcastically said, "Supposedly! Funny how so many patients want brand when it comes to adderall, and so we are always out." She was on her 10th call to other pharmacies in search of brand adderall-and then the pharmacist walked in, boomed, "THEY'RE EXACTLY THE SAME YOU WANT IT OR NOT?" I regretted giving in, and she got in trouble, I guess for not going along with the Walgreens company mantra.
Another idea for your friend- if her med is no longer available anywhere in the version she's done well on- and the generic she tried didn't work out- maybe it's still worth trying some different brands of generic? There could be a difference- certainly they are not all manufacturing in the same way. I saw an interesting chart on an ADD/ADHD site, where the posters voted for their favorite version of adderall IR. There was the Shire brand, and something like 8 generics, and there was a very wide difference of popularity between the various generics. (Shire got 26% of the vote, and the least popular generics looked to be Barr and Ranboxy. One of the generics listed was almost as popular as Shire. Gosh, hope I bookmarked that page...) Very interesting.
Good luck to you guys!
> Thank you laima and notfred. I am suggesting
> to my friend that she switch to Tofranol, and
> not the generics; the problem may be that it
> is not made *anymore*, and all that there is, is
> generics-- these old drugs like lithium and imipramine may also not get the white glove treatment. But, I think that given the switch to a generic at around the same time that depression arose and other unexplained symptoms, it's worth checking with the pharamacist.
>
> I don't mind generics in electronics and shoes (or knock-offs as they are called in the new market), but when it comes to health products, we are in trouble.
>
> Thanks again for your input.
>
> Squiggles
Posted by Squiggles on February 26, 2007, at 9:43:10
In reply to Re: Drug manufacturing and quality control » Squiggles, posted by laima on February 26, 2007, at 9:27:03
Thanks laima,
I don't want to open up a *HUUUUGE* debate on the status of generics and WHO and the FDA, and the patent protection issues.
Like you, i have not had too much trouble with generics (with the exception of lithium which almost killed me); i did notice that clonazepam in generic form was weaker-- but that's it over a couple of decades.
I agree with you that i could be many factors -- it could that the drug is old, or the lab did not use the same ratio of filler and active ingredients, etc.
So, definitely it is a good idea to switch to another generic just in case. Unfortunately, this issue divides on political grounds and ideology. Well, i think it's a good idea anyway.
Chacun a son gout.
ThanksSquiggles
Posted by laima on February 26, 2007, at 10:11:41
In reply to Re: Drug manufacturing and quality control, posted by Squiggles on February 26, 2007, at 9:43:10
Yes, I guess you are right.I confess I've been a bit obsessed with the topic this weekend because of my own personal freak out over discovering that the manufacturer of my least helpful generic, a generic which actually ended up harming my mood, just took over the brand version of a med which worked out very, very well for me, and I'm quite scared right now that they will change it and my mood will go back into the toilet as a result. I haven't had an easy time finding a med combo that actually works for me. Feeling very aprehensive about all this, and feeling upset that the numerous pharmacies I went to in search of my preferred product have been scoffing, even sarcastically, at my concerns, and even at the notion that a difference could exist. It's quite a feeling to have people insist one's experience is imaginary. I guess time will tell how it all works out now with the change.
Posted by notfred on February 26, 2007, at 11:27:39
In reply to Re: Drug manufacturing and quality control » notfred, posted by laima on February 26, 2007, at 8:56:53
Note there is no mention of bioavailability of the brand vs. generic.
http://en.wikipedia.org/wiki/Generic_drug
A generic drug (pl. generic drugs, short: generics) is a drug which is bioequivalent to a brand name drug with respect to pharmacokinetic and pharmacodynamic properties. These drugs are usually sold at a lower price than the brand name drug. Generic medicines must contain the same active ingredient at the same strength as the "innovator" brand, be bioequivalent, and are required to meet the same pharmacopoeial requirements for the preparation. By extension, therefore, generics are assumed to be identical in dose, strength, route of administration, safety, efficacy, and intended use.
Reasons for cheaper price
The principal reason for the reduced price of generic medicines is that these companies incur less costs in creating the generic drug and are therefore able to offer a lower price and still maintain profitability.
Manufacturers of generic drugs are mainly able to avoid the following three costs that brand name pharmaceutical companies incur: (1) costs associated with the research and development of the drug; (2) costs associated obtaining regulatory approval (i.e. proving safety and efficacy of a drug); and (3) marketing costs.
First, Generic manufacturers do not incur the cost of drug discovery and instead reverse-engineer existing brand name drugs to allow them to manufacture bioequivalent versions.
Second, generic manufacturers do not bear the burden of proving the safety and efficacy of the drugs through clinical trials - rather, generic manufacturers must prove the bioequivalance to the existing drug.
Third, these companies receive the large benefit of the marketing that goes into pushing the innovator drug. The drugs that generic manufacturers are selling have been on the market for usually a decade or more and do not need additional advertising. For the same reason, generic manufacturers also do not give away sample doses to promote their products. The significant research and development and marketing costs incurred by the large pharmaceutical companies in bringing a new drug to the market is often cited as the reason for the high cost of new agents - they wish to recover these costs before the patent expires. Generic manufacturers do not incur these costs, with bioequivalence testing and the actual manufacturing process costing relatively little, and are able to charge significantly less than the "innovator" brand
Ensuring bioequivalence
In the USA the Food and Drug Administration (FDA) is responsible for making sure that generic drugs are "safe and effective." The approval process for generic drugs began in the late 1960s. Generic drug manufacturers were required to prove that their formulation exhibits bioequivalence to the innovator product. Over the past several years there have been studies that have shown the effectiveness and safety of some generic drugs. Generic drugs are always less expensive and can save patients and insurance companies thousands of dollars supposedly without compromising the quality of care. The FDA must approve generic drugs just as innovator drugs must be approved. Bioequivalence, however, does not mean that generic drugs are exactly the same as their innovator product counterparts, as chemical differences do exist. Some doctors and patients emphatically believe that certain generic drugs are not as effective as the products they are meant to replace (ie. Prozac, Oxycontin), and consumers would undoubtedly benefit from more clinical studies done on drug by drug basis. Generic drugs start out at first being fairly expensive, however the price of the generic product decreases as the rate of production increases.
As an interesting case study in the use of generic equivalents of name-brand agents, warfarin has been only available under the trade name Coumadin in North America until recently. Warfarin (either under the trade name or the generic equivalent) has a narrow therapeutic window and requires frequent blood tests to make sure patients do not have a subtherapeutic or a toxic level. A study performed in the Canadian province of Ontario showed that replacing Coumadin with generic warfarin was considered safe.[2] In spite of the study, many physicians are not comfortable in allowing their patients to take the branded generic equivalent agents.[3]
Posted by Squiggles on February 26, 2007, at 12:21:30
In reply to Re: Drug manufacturing and quality control, posted by notfred on February 26, 2007, at 11:27:39
Thank you. This issue is really beyond my head.
And as I said, I did not want to pit generic drugs as being truly bioequivalent or not. Many other factors could corrupt a drug at any time, in any dose, from any source.I *did* take a look at "Sheldon Preskorn" and
"generics" key words/phrases, and got many hits; among them:http://crazymeds.org/sites.html
This issue is very complex and it looks like all the statisticians and mathematicians who can make heads or tails of drug development, are involved. Ironically, they are involved in a question which has already been answered in the initial development of generics. I guess there are sceptics everywhere.
Squiggles
Posted by Squiggles on February 26, 2007, at 18:00:31
In reply to Re: Drug manufacturing and quality control, posted by notfred on February 26, 2007, at 11:27:39
Whenever I come across seminars of this type,
I feel as if I am spying.:-) It's pretty "inner-circle stuff", but it certainly gives you an idea of how and what decisions are made by the Government in the development, evaluation and decision-making process of how to treat the mentally ill population.This is a pdf file:
"UNITED STATES DEPARTMENT OF HEALTH AND HUMAN SERVICES, NATIONAL INSTITUTES OF HEALTH, NAT'L. INSTITUTE OF MENTAL HEALTH:
In the matter of:
FDA NIMH MATRICS Workshop on Clinical Trial Designs for Neurocognitive Drugs for Schizophrenia.
Neuroscience Center, Conf. Rm. C, 6001 Executive Blvd., Rockville, MD, Fri., April 23, 2004.
---------------------
What I find fascinating about this workshop, is the long-term search for appropriate antipsychotics targeted specifically at cognitive disabilities in schizophrenia. It seems to me that it is already assumed that cognitive disabilities in mental illness are neurologically specific. What I mean by that, it does not seem to be an option in the research, that affective maladies, as in manic-depression, can very well distort cognitive ability. Moreover, the search for drugs to stabilize neurocognitive states is imperative in the FDA. It sounds like the government wants the mentally ill to *appear* OK, with the new drugs, even though they do not feel OK.
Squiggles
Posted by laima on February 26, 2007, at 18:11:36
In reply to Re: Drug manufacturing and quality control, posted by Squiggles on February 26, 2007, at 12:21:30
Well- for me the Barr generic and the Shire brand adderall behave like two entirely different meds: radically different effects, not a matter of potency. So I am not quite "getting" this bioequivalency thing, though I comprehend that's the theory and intention for generics. I'm just not so sure it's always the reality. If the difference in this case was a matter of potency, I could simply take more. Biggest concern: one makes me depressed and feels like speed at times-especially when it suddenly kicks in, then later it ends in a "dump"; the other boosts my mood gently but significantly, and feels like not being on a drug at all-no perceptable anything as it wears off-takes effect so gradually I can't even tell how long after I take it that that is. My doctor is the sole person who is not surprised by any of this, and I'm sorry that I end up feeling defensive about it not just at the numerous pharmacies I visited while hunting for it, but here. It's not my imagination, and I'm not a pharmaceutical industry spokesperson on an anti-generic crusade, nor a mental case perceiving imaginary differences. Sorry there haven't been any answers or clues regarding my big question about who is now specifically calling the shots in the manufacture of the brand version, I guess no one really knows at this point, and really, sorry I mentioned anything at all. Insisting that what I'm experiencing with these meds isn't imaginary only makes me feel worse.
Posted by laima on February 26, 2007, at 18:13:54
In reply to Re: Drug manufacturing and quality control, posted by Squiggles on February 26, 2007, at 12:21:30
Thanks for the link, Squiggles. I really appreciate, and I'll do some research there later.
Posted by psychobot5000 on February 26, 2007, at 21:35:05
In reply to Re: Drug manufacturing and quality control » Squiggles, posted by laima on February 26, 2007, at 10:11:41
>
> Yes, I guess you are right.
>
> I confess I've been a bit obsessed with the topic this weekend because of my own personal freak out over discovering that the manufacturer of my least helpful generic, a generic which actually ended up harming my mood, just took over the brand version of a med which worked out very, very well for me,
>
I thought it might be useful to mention that, last time I heard about this issue, there seemed to be some people saying that Mallinckrodt Pharmaceuticals' generic dexamphetamine was as good as brand-name dexedrine. I have taken Mallinckrodt's version and found it effective. Perhaps the Mallinckrodt adderall (it exists) would be good quality as well.
Posted by laima on February 26, 2007, at 22:48:08
In reply to Re: off-brand manufacturer » laima, posted by psychobot5000 on February 26, 2007, at 21:35:05
Thank you, I really appreciate this information. it may come in handy.
>
> I thought it might be useful to mention that, last time I heard about this issue, there seemed to be some people saying that Mallinckrodt Pharmaceuticals' generic dexamphetamine was as good as brand-name dexedrine. I have taken Mallinckrodt's version and found it effective. Perhaps the Mallinckrodt adderall (it exists) would be good quality as well.
Posted by notfred on February 27, 2007, at 10:36:09
In reply to Re: Drug manufacturing and quality control, posted by laima on February 26, 2007, at 18:11:36
"So I am not quite "getting" this bioequivalency thing,"
Take a look at what Cam W or Ed UK have had to say about this, that might make it more clear.
Posted by laima on February 27, 2007, at 11:23:38
In reply to Re: Drug manufacturing and quality control, posted by notfred on February 27, 2007, at 10:36:09
You know what- you all can prove whatever you like about "bioequivalency", but the issue in this particular case is, Shire brand adderall and Barr generic adderall behaved LIKE TWO ENTIRELY DIFFERENT MEDS. That's the practical reality. Theories can't help me with that. So I don't care if they technically are considered bio-equivalent by anyone, for they produce SEVERLY distinct effects for me. THAT's what the problem is. After looking at some ADD blogs last night- lo and behold- loads of people had the same sorts of distinct reactions to Barr generic vs Shire regular as me. I'm grateful that at least I have a doctor who acknowledges that indeed, there can be differences of action with some generics vs some brand versions of the "same" meds.And if Barr bought Shire's adderall- will there be subtle changes enacted, ones deemed insignificant "biologically"? Ie, different suppliers of raw materials, shortcuts in cooking, whatever- that render it ineffective or unhelpful for me?
And do you really think the fda is carefully monitoring quality of generic drugs, when they've barely got any grip on brand name situations, ie zyprexa, and new drug trials? Not to mention looking into the fake drugs which are being reported as showing up in US pharmacies? Illegal importations? Monitoring online pharmacies? They are kind of behind on inspecting meat plants, spinache processing centers, peanut butter- do you really think they are scrutinizing every single generic medication carefully and regularly for quality conrol, and that every single manufacturer, out of the goodness of their hearts, is doing a top notch job of not skimping somewhere??
And if they are supposedly the same, why is Barr now working with a generic AND a brand version of same "bioequivalent" medication? And spent a fortune to buy it-especially since they already had their own "bioequivalent" version? They didn't kill it- they could have killed it and raised their own prices. Pharmacies push generics, so I doubt they were losing tons of sales to the much more expensive brand version offered by Shire. Walgreens seems to eclusively offer Barr generic for generic adderall- sounds like a profitable deal? But what about choices for consumers?
I've already noticed a new effect which I can't attribute to being psychsomatic. My appetite has VANISHED. When I am upset, I eat more, not less. I'm starving. I love food- but it now seems appealing in theory only. Sure, stims can do that- but somehow I haven't experienced this before anywhere near to this extent. Not even close. Even when my stomache was so messed up that I required an endoscopy- I ate. So what's up? And the new "brand" of Adderal, courtesy Barr, is the only new variable that I've got going.
I know you are a wikipedia fan- I did notice that they were a bit, how shall we say, "nuanced" in their "generic drugs" article.
> "So I am not quite "getting" this bioequivalency thing,"
>
>
> Take a look at what Cam W or Ed UK have had to say about this, that might make it more clear.
Posted by notfred on February 27, 2007, at 12:41:26
In reply to Re: Drug manufacturing and quality control » notfred, posted by laima on February 27, 2007, at 11:23:38
>
> You know what- you all can prove whatever you like about "bioequivalency", but the issue in this particular case is, Shire brand adderall and Barr generic adderall behaved LIKE TWO ENTIRELY DIFFERENT MEDS.
Right, that is the difference between bioequivalency and bioavailability. amphetamine is either amphetamine or it is not, there is no grey area as it is a very specific molecule, as all drugs are. Just because it is the same molecule does not mean both are of equal bioavailability
and would cause one med to be very different from the other.
Posted by laima on February 27, 2007, at 13:06:53
In reply to Re: Drug manufacturing and quality control, posted by notfred on February 27, 2007, at 12:41:26
Ok then, I appreciate your clarification of the definitions.>
> Right, that is the difference between bioequivalency and bioavailability. amphetamine is either amphetamine or it is not, there is no grey area as it is a very specific molecule, as all drugs are. Just because it is the same molecule does not mean both are of equal bioavailability
> and would cause one med to be very different from the other.
Posted by laima on February 27, 2007, at 13:18:37
In reply to Re: Drug manufacturing and quality control, posted by notfred on February 27, 2007, at 12:41:26
Yes, seriously, thank you for the clarification. I've had so many pharmacists, and a few others, insist that my perceptions of the differences are imaginary, that the drugs are "exactly the same", that it's a touchy and upsetting topic for me. Some of the pharmacists actually rolled their eyes and sighed dramatically at me even when I politely tried to explain, please, I want the version that was prescribed, they feel very different to me. Yes, very upsetting. So I'm out of the discussion- I'm just too touchy right now- though still gratefully welcome any helpful tips or constructive suggestions anyone might have.And thanks again for your definitions- yes, of course, I can understand that an amphetamine is an amphetamine. Can't disagree. It's those "other factors" which seem to be the difficulty.
> Right, that is the difference between bioequivalency and bioavailability. amphetamine is either amphetamine or it is not, there is no grey area as it is a very specific molecule, as all drugs are. Just because it is the same molecule does not mean both are of equal bioavailability
> and would cause one med to be very different from the other.
Posted by notfred on February 27, 2007, at 13:45:28
In reply to Re: Drug manufacturing and quality control » notfred, posted by laima on February 27, 2007, at 13:18:37
Ah ! Sorry I did not pick up on this & that it was not clear I was agreeing with you.
For many drugs you cannot just take the raw drug and expect it to be well/evenly absorbed. Often times raw drugs cannot be made into pills as the raw drug will not bind to itself, so binders and fillers are needed to form a pill that will hold its shape. Other additives make sure the med is released at the right place in your GI and/or is released smoothly. With the wrong additives it is possible to pass a pill through your GI without it ever breaking up.
Brands have to prove bioavalibility, generics do not prove that their bioavalibility is equal to the brand. Standards like USP make sure generic prozac is the same chemical as brand prozac but it is a totally different issue as to how well the generic prozac is taken up by your body vs. the brand.
Posted by laima on February 27, 2007, at 14:29:07
In reply to Re: Drug manufacturing and quality control, posted by notfred on February 27, 2007, at 13:45:28
Well, gosh, I can personally say it hasn't helped that I've been feeling so defensive and invalidated by umpteen pharmacists and pharmacy techs-that one being so bold as to say she was going to give me generic and over-ride the doctor's instructions even- so maybe if I read your post more carefully and without emotional investment the nature of the content would have been more obvious to me. Sorry about a misunderstanding. Thanks for all of your info.
> Ah ! Sorry I did not pick up on this & that it was not clear I was agreeing with you.
>
> For many drugs you cannot just take the raw drug and expect it to be well/evenly absorbed. Often times raw drugs cannot be made into pills as the raw drug will not bind to itself, so binders and fillers are needed to form a pill that will hold its shape. Other additives make sure the med is released at the right place in your GI and/or is released smoothly. With the wrong additives it is possible to pass a pill through your GI without it ever breaking up.
>
> Brands have to prove bioavalibility, generics do not prove that their bioavalibility is equal to the brand. Standards like USP make sure generic prozac is the same chemical as brand prozac but it is a totally different issue as to how well the generic prozac is taken up by your body vs. the brand.
Posted by laima on February 27, 2007, at 15:25:20
In reply to Re: Drug manufacturing and quality control » notfred, posted by laima on February 27, 2007, at 14:29:07
Before this unfortunate misunderstanding and generic vs brand debate, I actually did have a question. So- despite being hassled and scoffed at at pharmacies, I have stuck to my vow to insist on getting the Shire version of adderall, because it is the version that I've tried which worked out really, really well for me. Too bad it's the expensive version, but oh well. Then suddenly viola! I discovered that just this January, Barr aquired Shire's "brand version". So, having had such an uneven and ultimately bad experience with Barr's generic, my fear has been- what if they do something which ends up changing how "brand" works for me? What is it about their generic that doesn't make it work well for me, and will any of those factors now be introduced into the "brand" version? Will they use different suppliers than Shire for raw materials, or adjust the manufacturing process, or any other seemingly insignificant factors, which could add up to it acting differently? Obviously, it's scary to think that a sucessfully helpful med might vanish immediately after one discovers it. So one, I was trying to figure out who is actually in charge now, and what specifically this aquisition means. Did they just take over the profits, allowing it to still be made by the same people in the same place, etc--or did they take control over the entire manufacture? I haven't yet had any luck at all in trying to dig up this information. Mostly found a load of news stories about a currently active lawsuit by Barr vs Shire, Barr trying to get Shire to give up their patent for AdderallXR several years early- ironically arguing that Shire currently has a monopoly on AdderallXR-something like that. Ok.Naturally, I've tried to detect if there is any difference with this new version, but understand that maybe I'm not being objective enough to do so accurately right now, due largely to my fear and suspicion. I guess time will tell, after I chill out and stop scrutinizing. I do feel like I am feeling it differently- but it's only day 4, and I am well aware that my perceptions can be influenced by my concerns. I hate to use the term "psychosomatic"- but I can't think of a better one now. Here's my perceptions: I feel more depressed in the evening than before- not a full blown crash, but not an absence of crash, as before. I speculate this could indeed be psychological. Ok. Another thing I noticed is that 3 normal size glasses of wine over 3-4 hours, and with lots of water in between, made me very drunk last Friday (day 1)- and that is NOT what has ever happened before. Ok- there could be numerous reasons, including a light dinner. My perception of time seems to be different- it is suddenly feeling to zoom by at incredible speed. I don't get this part- when I'm upset- time usually slows down. I have insomnia, thoughh I haven't changed my dose schedule- no adderall past 1pm. Insomnia hasn't been a problem until just now. Ok- either the new med is hanging around longer, or this is psychological. But the factor that I am really least able to attribute to psychology is the very sudden and dramatic vanishment of my appetite. (Well I guess those last few zyprexa pounds won't be a problem anymore soon!) Again, when upset or fretting- I crave carbohydrates and tend to over-eat. The other stims I've used have had some modest appetite supression effects for me, but nothing major. Quite negligable. I've had no problem on them eating proper meals or even snacks. I'm always normallly very interested in food! It's this last factor, appetite, which has me concerned that the medication might be different now. Well, of course, regardless of what's going on, I guess I don't really know what I can do other than wait and see how the month goes, and if it doesn't go well, start looking into alternatives. Also talk to doctor at next appointment to see if he's got any info or opinions as to whether this stuff is psychological or not. Barr's only taken over less than 2 months ago-could they have even made any changes yet, if they even intend to? The tablets look exactly the same as before, if that matters.
So yes- I guess my question really was meant to be- has anyone else suddenly switched from Shire IR Adderall to this new Barr IR Adderall- any observations? And, anyone know the scoop on what specifically is going on with this particular Barr aquisition? Do these changes I perceive sound psychological, or drug-attributal?
And what on earth is up with the pharmacies all pushing generics so heavily? I would have thought they'd want to push brand, that brand versions would be more profitable for pharmacies. (Or is this just Walgreens, to whom, alas, my drug coverage insurance is tied to?) ?
Thank you.
ps- If anyone is using Barr and is happy with it- lucky you! I wish I could say the same- just doesn't work well for me.
I don't mean to offend.
Posted by Larry Hoover on February 27, 2007, at 15:34:48
In reply to Re: Drug manufacturing and quality control, posted by notfred on February 27, 2007, at 13:45:28
> Brands have to prove bioavalibility, generics do not prove that their bioavalibility is equal to the brand. Standards like USP make sure generic prozac is the same chemical as brand prozac but it is a totally different issue as to how well the generic prozac is taken up by your body vs. the brand.
I just checked the FDA site, and I'm going to have to say you've got it wrong, Fred. Generics must pass bioavailability studies, as part of demonstrating bioequivalence.
Here's the offical FDA definition of 'bioavailable':
"the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action...."Here's the official FDA definition of 'bioequivalent':
"the absence of a significant difference in the rate and extent to which the active ingredient or active moiety in pharmaceutical equivalents or pharmaceutical alternatives becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study."In the case of a generic drug, an application for an ANDA (abbreviated new drug application) must contain both BA and BE data, and the specific reported parameters (e.g. AUC, PPC) must fall within 80-125% of the values for the original (reference) drug. There are also special additional regulations for delayed release, XR, or CR generics. The take home message is that bioavailability is subsumed by the larger concept, bioequivalence. Two drugs with different bioavailability cannot be bioequivalent, and such a generic drug should not pass the FDA review.
Here's a nice slide show that sums up the concepts better than the text of the legislation itself: http://www.fda.gov/cder/ogd/02-10_BCBS_gjb/sld001.htm
If you want to read a more technical explanation, go to: http://www.fda.gov/cder/guidance/4964dft.htm
Of course, a generic company can submit whatever they choose, just as the original pharma companies are certainly guilty of doing. But there's another problem that I really think has been subjected to a cover-up; last year, a company that specialized in doing bioequivalence studies for generic drug manufacturers was accused of submitting completely false data. Some studies were never even done. I believe that 180 ANDAs were suspected to have been falsified? Something like that. After the initial press flurry, I never heard another word about it. Does anybody else remember hearing about this?
Lar
Posted by laima on February 27, 2007, at 15:52:17
In reply to Re: Drug manufacturing and quality control » notfred, posted by Larry Hoover on February 27, 2007, at 15:34:48
Wow- I never heard that! Horrifying!My doctor, a pharmacologist involved with some overseeing or monitoring of drug trials (something like that), has told me that generics are typically not as closely scrutinized by the fda as brand versions, though. The statement seemed neutral in judgement, part of a longer explanaition about possible reasons why some generics do not appear to be identical to the originals they are supposedly identical to.
Yet I had presumed part of the reason for that was that they were already considered safe and up to snuff?
Wow.
That's an intense story.
I did notice a brief "breaking news" blurb in the New York Times about two weeks ago- and then quite quickly it and the story vanished before I was able to go back to reread properly. Something about fbi or fda- someone pulled a surprise raid on Ranboxy Labs US office and shuffled through a load of papers, removing some documents, "no further info available", though a Ranboxy official confirmed it occured. Wonder what that was about?
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