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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 36. This is the beginning of the thread.
Posted by linkadge on January 6, 2007, at 15:09:15
So, generics are allowed to be as much off as +/- 20%?
That means that for a 20mg prozac you could get as little as 16mg or as much as 24mg.
That means you could have 8mg difference between two days.
If you were taking 375mg of effexor, you could have as much as much as 150mg difference between two doses.
Isn't there something wrong here? If I dropped 150mg of effexor in one day, I'd be in hell.
Now effexor isn't generic yet, but what if it was your anticonvulsant? You could have a seizure if you dropped this much.
Linkadge
Posted by laima on January 6, 2007, at 15:35:19
In reply to +/- 20% really sucks, posted by linkadge on January 6, 2007, at 15:09:15
Really?? That's a lot! They shouldn't be considered interchangeable with brand name then.
Posted by ed_uk on January 6, 2007, at 16:45:45
In reply to +/- 20% really sucks, posted by linkadge on January 6, 2007, at 15:09:15
Hi Link,
>So, generics are allowed to be as much off as +/- 20%?
>If you were taking 375mg of effexor, you could have as much as much as 150mg difference between two doses.
No, the amount of drug in a generic tablet/cap will be almost identical to the amount of drug in a branded tablet/cap. When comparing a new generic product to the orginal branded product, bioequivalence studies are performed. In the UK, the following criteria are assessed:
Product A = the test product ie. the new generic
Product B = the reference product ie. the original brandA group of volunteers are given the medication. Pharmacokinetic parameters (AUC, Cmax and Tmax) are determined for each product (A and B). The ratio of A/B for AUC and Cmax and 90% geometric confidence intervals for AUC and Cmax respectively are determined. These values must fall within the accepted regulatory range of 80-125% (0.80-1.25 range) to indicate that A is bioequivalent to B.
Ed
Posted by SLS on January 6, 2007, at 18:14:59
In reply to Generics » linkadge, posted by ed_uk on January 6, 2007, at 16:45:45
> Product A = the test product ie. the new generic
> Product B = the reference product ie. the original brand
>
> A group of volunteers are given the medication. Pharmacokinetic parameters (AUC, Cmax and Tmax) are determined for each product (A and B). The ratio of A/B for AUC and Cmax and 90% geometric confidence intervals for AUC and Cmax respectively are determined. These values must fall within the accepted regulatory range of 80-125% (0.80-1.25 range) to indicate that A is bioequivalent to B.
Go get your Ph.D. and be done with it.
- Scott
Posted by linkadge on January 6, 2007, at 18:32:10
In reply to Re: Generics » ed_uk, posted by SLS on January 6, 2007, at 18:14:59
Yeah, you lost me!
Linkadge
Posted by LlurpsieBlossom on January 6, 2007, at 19:00:50
In reply to Generics » linkadge, posted by ed_uk on January 6, 2007, at 16:45:45
> Hi Link,
>
> >So, generics are allowed to be as much off as +/- 20%?
>
> >If you were taking 375mg of effexor, you could have as much as much as 150mg difference between two doses.
>
> No, the amount of drug in a generic tablet/cap will be almost identical to the amount of drug in a branded tablet/cap. When comparing a new generic product to the orginal branded product, bioequivalence studies are performed. In the UK, the following criteria are assessed:
>
> Product A = the test product ie. the new generic
> Product B = the reference product ie. the original brand
>
> A group of volunteers are given the medication. Pharmacokinetic parameters (AUC, Cmax and Tmax) are determined for each product (A and B). The ratio of A/B for AUC and Cmax and 90% geometric confidence intervals for AUC and Cmax respectively are determined. These values must fall within the accepted regulatory range of 80-125% (0.80-1.25 range) to indicate that A is bioequivalent to B.
>
> EdOh goody! statistics!
how come the confidence interval is so large? I thought that the alpha for most peer-reviewed studies examining significant differences was .05?In my field we use a 95% confidence interval when we report such things.
Hmm false positives occur more often as alpha increases. Thus, a significant difference between brand A and brand B would be more likely to be detected when alpha is larger. I guess having a larger alpha is in the best interests of detecting differences between brand A and brand B.
Now the crucial statistic here is a FAILURE to find a difference, when one actually exists. In order to minimize this danger, one would want to have a large sample size, thus having enough ´´power´´ to detect a difference.
see, if me and eduk and linkadge and phillipa are the only volunteers to test a set of drugs, we may all have very different patterns of response to brand A.
me .1
eduk 1
linkadge 10
phillipa 100and our average is 111.1/4 or about 27, but our standard deviation is HUGE!!!
but, if we test a whole BuncH!! of people the outliers are much less likely to affect the statistics.
then, when we find out that the average for drug A is 25 with a standard deviation of plus or minus 3 and another drug B has average of 43 with a standard deviation of .01, then we know that theres something kooky. someone spiked the punch, you know ?
okay, I have statistics withdrawal. oh, how I miss my silver computer with all the SPSS and SAS and all that good stuff. heck, Id just settle for having an American keyboard. I can{t get apostrophes and these ñññfunny letters keep popping up all over the place!
`CIAO MY LOVELIES,
LLUIR´STJHPIE
Posted by halcyondaze on January 6, 2007, at 19:37:54
In reply to +/- 20% really sucks, posted by linkadge on January 6, 2007, at 15:09:15
> So, generics are allowed to be as much off as +/- 20%?
>
> That means that for a 20mg prozac you could get as little as 16mg or as much as 24mg.
>
> That means you could have 8mg difference between two days.
>
> If you were taking 375mg of effexor, you could have as much as much as 150mg difference between two doses.
>
> Isn't there something wrong here? If I dropped 150mg of effexor in one day, I'd be in hell.
>
> Now effexor isn't generic yet, but what if it was your anticonvulsant? You could have a seizure if you dropped this much.
>
>
> Linkadge
>
>This is why I pay for brand-name Parnate instead of going with the generic. Thankfully, on my insurance, brand is $30 (as opposed to $10 for the generic) but I remember my mother paying $200 for her Prozac, which just wasn't the same as generic fluoxetine.
Plus, many times pharmacies are connected to several retailers, meaning that you can get -20% one month and +20% the next month from the very same pharmacy.
Posted by linkadge on January 6, 2007, at 20:14:20
In reply to Re: +/- 20% really sucks, posted by halcyondaze on January 6, 2007, at 19:37:54
So are you saying that a prescription could be +/- 20% of brand name, but less than that between pills in a given single prescription?
Linkadge
Posted by blueberry1 on January 6, 2007, at 20:41:12
In reply to +/- 20% really sucks, posted by linkadge on January 6, 2007, at 15:09:15
I have never trusted generics. Don't know why. My gut instincts I guess.
As I think back on it, prozac kept me fairly well for many years. When did I start having problems with it? About a month after switching to generic. Hmmm. Dunno.
All that statistical bioequivalence stuff? I don't trust it. There is something the scientists have overlooked, not recognized, or don't know about. As I see it anyway.
There have been plenty of reports here over the years where people have found major efficacy differences between generic xanax and brand, or generic antidepressants and brand, or whatever. Some prefer generic, some prefer brand, some can't tell a difference. Clearly though, there IS a difference. But it is not the kind of a difference we can see or measure. But at a molecular level, the genes can tell.
There is no room for error. Not even 2%. Not to mention 5% or 20% or whatever.
Just my thoughts on that. I do not trust generics. And I don't have a real good reason why.
Posted by notfred on January 6, 2007, at 20:50:43
In reply to Re: +/- 20% really sucks, posted by blueberry1 on January 6, 2007, at 20:41:12
How much is the brand allowed to deviate from the official (monograph or PI ?) values ?
Posted by Phillipa on January 6, 2007, at 22:52:54
In reply to Re: Generics » ed_uk, posted by LlurpsieBlossom on January 6, 2007, at 19:00:50
Lurpsie I hate math with a passion!!!!!But it's true generics can differ by up to 20% higher or lower. Love Phillipa ps thanks for putting me in your study. But I'm l00?
Posted by yxibow on January 6, 2007, at 23:20:34
In reply to Generics » linkadge, posted by ed_uk on January 6, 2007, at 16:45:45
> Hi Link,
>
> >So, generics are allowed to be as much off as +/- 20%?
>
> >If you were taking 375mg of effexor, you could have as much as much as 150mg difference between two doses.
>
> No, the amount of drug in a generic tablet/cap will be almost identical to the amount of drug in a branded tablet/cap. When comparing a new generic product to the orginal branded product, bioequivalence studies are performed. In the UK, the following criteria are assessed:
>
> Product A = the test product ie. the new generic
> Product B = the reference product ie. the original brand
>
> A group of volunteers are given the medication. Pharmacokinetic parameters (AUC, Cmax and Tmax) are determined for each product (A and B). The ratio of A/B for AUC and Cmax and 90% geometric confidence intervals for AUC and Cmax respectively are determined. These values must fall within the accepted regulatory range of 80-125% (0.80-1.25 range) to indicate that A is bioequivalent to B.
>
> EdYou can go to Drugs@FDA and search around for the generic table, I dont remember offhand but I think I posted something about it in the past -- we do the same AB for generics. Most generics are labeled as AB.
The important thing is not the hue and cry over generics being different than the expensive "original" -- which I understand -- its that if your insurance is much cheaper for the generics, insist that your pharmacy start you on a particular brand of generic -- typically like for the benzodiazepines there can be half a dozen -- and keep you on it and inform you if there are changes. Also remember, and this may sound mean spirited, but there is a placebo effect knowing that you are getting a different generic or are being switched off to a generic. That very knowledge can cause subtle changes especially in affective/anxiety disorders to fool the mind into thinking that their medication is no longer working. I'm not saying it can't be the case -- as Ed was explaining about the AUC curve, but for medications like long half life benzodiazepines, its really should not be an issue to take a generic -- Klonopin is at least 16 hours and Valium is more than 24 hours.
Now there are a few medications, biologicals, a few rare antibiotics, insulin, synthroid, etc, that are not AB rated. Those are I think by decree to be have to have a closer tolerance, original or not. Don't quote me on that but I believe it is the case.
-- Jay
Posted by Quintal on January 6, 2007, at 23:50:15
In reply to Re: Generics » ed_uk, posted by yxibow on January 6, 2007, at 23:20:34
My old psychiatric nurse once asked a psychopharmacologist (the much maligned Prof. Heather Ashton no less) for her opinion on the old generic vs. brand debate. It was her personal opinion that there was a difference and it was probably due to the different binders and colorants used by the companies as well as variable amount of active ingredient. She stressed that this was just her personal opinion and there was no empircal evidence to support it though. That said, my psychiatric nurse saw a lady who only responded to one particular make and it wasn't the brand name Prozac, it was the generic 'Dr. Reddy's' fluoxetine. If a person responds well to a generic they should make sure they stick to that particular brand and not accept any other generic if possible. My guess is that generic drugs produced by the same company will be fairly reliable at giving a consistent dose of active ingredient but switching between brands could be a problem.
I've rarely used brand name drugs at all, and if I have it's simply because there isn't a generic available, not that I have much choice in any case.
Q
Posted by laima on January 6, 2007, at 23:54:44
In reply to Re: Generics » yxibow, posted by Quintal on January 6, 2007, at 23:50:15
Perhaps then the various generic companies dinker with the recipees a bit- that's still unfair, but it's not like each pill in the bottle is different. On the other hand, I vaguely remember hearing somewhere that the companies who make the brand name drugs are under greater FDA scrutiny, and that the generic companies are more often left alone. But it doesn't make sense, so I don't know if it's true.
Posted by blueberry1 on January 7, 2007, at 2:35:25
In reply to Re: Generics » LlurpsieBlossom, posted by Phillipa on January 6, 2007, at 22:52:54
To make peanut brittle sugar needs to be heated to just the right temperature for just the right amount of time. Slight minor variations will still produce the brittle, but the brittle will be different...maybe a little softer, a little harder, a little darker, a little lighter, different stomach absorption times, and the taste is different...even though it is still just the same original sugar molecules.
Are the generic vs brand recipes exactly the same? I mean, times, temperatures, fillers, everything? If they aren't, then it makes me wonder how they could be identical end products. Very close for sure. But identical? I think there is enough difference that people can tell. Maybe some are placebo but my hunch is most are real.
Posted by LlurpsieBlossom on January 7, 2007, at 5:18:44
In reply to Re: Generics, posted by blueberry1 on January 7, 2007, at 2:35:25
What about if the active ingredient must have a particular configuration, for instance an enantiomer? I guess lexapro and celexa are the same molecules, but lexapro is only one enantiomer, whereas celexa is a blend of both.
from the earlier posts though, I thought that the key factor is how the human body reacts to drug A vs drug B, not about how a chemical analysis finds that they are similar or different?
anyways...
Phillipa youre 100 because youre special. like an A+ :)
Ll
Posted by ed_uk on January 7, 2007, at 7:27:28
In reply to Re: Generics, posted by blueberry1 on January 7, 2007, at 2:35:25
Hi Blueberry
>Are the generic vs brand recipes exactly the same?
Sometimes yes, sometimes no. In some cases, the 'generic' is simply the branded product repackaged into a different box. For example, in the UK, generic fexofenadine (a popular antihistamine) has just been introduced. Although this 'generic' is much cheaper than the Telfast brand, opening the box will soon reveal that this 'generic' is simply Telfast in a cheaper looking box. The companies which make the 'name brand' often supply the generic companies with product. This is especially true when 'name brand' companies have a branch of the companies which supplies generics eg. Sanofi Aventis has a generic arm called Winthrop Pharma.
Some more examples......
TEVAs 'generic' rampril tablets are actually Tritace tablets!
Winthrop's 'generic' alfuzosin 10mg tablets are actually Xatral XL.
Generics UK's lofepramine 70mg tablets are actually Gamanil.
A cheap UK brand of co-codamol 30/500 tabs (I forgot the company) is actually
Winthrop's zolpidem tablets are actually Stilnoct (Ambien).
It's funny how much cheaper these 'generics' are, despite them being identical to the brand :)
Ed
Posted by ed_uk on January 7, 2007, at 7:42:41
In reply to Re: Generics » yxibow, posted by Quintal on January 6, 2007, at 23:50:15
Hi Q
>If a person responds well to a generic they should make sure they stick to that particular brand and not accept any other generic if possible.
......if they pharmacy will allow. In the UK, the system of payment to pharmacies relies on the fact that the pharmacy can choose which generic they use. The £6.65 prescription charge goes to the government, not the pharmacy, and does not cover the cost of the medication. The pharmacy is paid a fixed price by the government for a particular medication eg. fluoxetine 20mg caps, regardless of which generic they dispense. Because different generics vary in price, they pharmacy may refuse to dispense a particular generic if it is too expensive because they would loose a lot of money. Of course, if the patient receives a private prescription and are paying for the medication out of pocket, they can receieve any brand which they want.
GPs are not allowed to demand specific generics (eg. TEVA, Alpharma, Generics UK) on NHS prescriptions. It is up to the pharmacy which generic they give. GPs are, however, allowed to prescribe branded products on the NHS eg. they could prescribe Prozac 20mg caps. In this case, they pharmacy will dispense the brand, often as a European Import. European Imports are used widely in UK community pharmacy because the government pays pharmacies based on the assumption that European Imports will be used. Because of this, the pharmacy will loose money if they dispense the 'English' brand.
Although GPs *can* prescribe drugs by brand eg. Prozac instead of fluoxetine, this practice is strongly discouraged because it wastes vast amounts of NHS money, something which the cash-strapped NHS can ill afford. In short, if people want brands on the NHS, taxes will have to go up!.........a lot!!
Regards
Ed
Posted by ed_uk on January 7, 2007, at 7:45:23
In reply to chiral molecules?, posted by LlurpsieBlossom on January 7, 2007, at 5:18:44
Hi L
>What about if the active ingredient must have a particular configuration, for instance an enantiomer? I guess lexapro and celexa are the same molecules, but lexapro is only one enantiomer, whereas celexa is a blend of both.
The generic will be produced to match the brand. Like Celexa, generic citalopram is a racemate. When generic escitalopram is eventually introduced, it will be a single enantiomer, like Lexapro.
Regards
Ed
Posted by LlurpsieBlossom on January 7, 2007, at 9:40:51
In reply to Re: chiral molecules? » LlurpsieBlossom, posted by ed_uk on January 7, 2007, at 7:45:23
I was just curious about this for molecules for which the effects of different enantiomers has NOT been studied.
like, maybe seroquel is a mix of one active and one inactive enantiomer. The company producing seroquel has a precise way that they do the reactions, which they dont share with their generic competitors. The generic chemists come up with a set of reactions that produces the same molecule, but the racemic mixture contains different ratios of the active vs. inactive enantiomer.
maybe some people respond to one species and others respond to another.
anyways... Am I correct that it is tricky to analyse the composition of enantiomers in a racemic mixture? Maybe its a piece of cake for the professionals. I just remember that this was a notoriously tricky thing back in my days as a chemistry student...
ciao
Ll
Posted by ed_uk on January 7, 2007, at 10:03:41
In reply to Re: chiral molecules? » ed_uk, posted by LlurpsieBlossom on January 7, 2007, at 9:40:51
Hi L
I don't think the generics companies always manufacture the drug substance, they often just make the tablets etc. AFAIK, the source of the drug itself is sometimes the same for both the brand and the generic.
Manuafacturing racemic drugs (eg. citalopram) which consist of 50% R-enantiomer and 50% S-enantionmer is probably relatively basic. The manufacture of single-isomer products such as escitalopram is technically more challenging.
Regards
Ed
Posted by naughtypuppy on January 7, 2007, at 10:58:18
In reply to Re: chiral molecules? » LlurpsieBlossom, posted by ed_uk on January 7, 2007, at 10:03:41
Perhaps the coating/fillers have something to do with the point in the digestive system that the active ingredient is most readily absorbed. Something like Depakote which is absorbed in the small intestine since stomach acids break it down. Or like time released capsules.
Posted by notfred on January 7, 2007, at 12:23:01
In reply to Re: chiral molecules?, posted by naughtypuppy on January 7, 2007, at 10:58:18
> Perhaps the coating/fillers have something to do with the point in the digestive system that the active ingredient is most readily absorbed. Something like Depakote which is absorbed in the small intestine since stomach acids break it down. Or like time released capsules.
>
That is the major difference between brand and generic. The actives remain the same, and often made by the brand manufacure. In any case lorazepam is lorazepam is lorazepam no matter who made it.coatings/fillers/binders effect how much drug is taken up by the system. You cannot just take the raw active compound and expect to absorb it properly. There is a lot of science in delivering and absorbing the drug into the body. This is where the differences between generic and brand play out, if any.
Posted by ed_uk on January 7, 2007, at 13:20:14
In reply to Re: chiral molecules?, posted by notfred on January 7, 2007, at 12:23:01
>There is a lot of science in delivering and absorbing the drug into the body.
Definitely. Some generics have an identical formula to the original brand, whereas others have different excipients.
Ed
Posted by ed_uk on January 7, 2007, at 13:29:05
In reply to Re: chiral molecules?, posted by naughtypuppy on January 7, 2007, at 10:58:18
Hi
As an example, here is a graph which was produced when determining whether Dr. Reddy's lamotrigine generic was bioequivalent to the original brand: Lamictal..........
http://www.mhra.gov.uk/home/idcplg?IdcService=GET_FILE&dID=25158&noSaveAs=0&Rendition=WEB
Open the link and scroll down to page 14.
The x-axis shows time. The y-axis shows the drug level in the blood.
As you can see, the two formulations are very close. Dr. Reddy's generic appears to produce very slightly higher blood levels than Lamictal, but this may just be due to chance.
Ed
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