Table of Contents (hide)
- 1. Introduction
- 2. What’s the difference?
- 3. A Dose by Any Other Name
- 4. Four Out of Five Doctors and Pharmacists Agree
- 5. How Much More Proof do You Need?
- 6. What Does the FDA Have to Say About it?
- 7. I Can Make it Really Simple for You Paper-Pushing Morons at the FDA
- 8. Sometimes It’s So Fucking Obvious. Except When It’s Not.
- 9. And it all Comes Down to…What?
One of the most debated issues in health care today concerns the difference between brand name (also called branded, innovator, and pioneered) drugs and their generic versions (usually called “equivalents”). While most everyone can agree generic drugs are less expensive than the branded versions,1 whether or not generics are always the same as brand is another question. “Different” doesn’t always mean “not as good.” In some cases a generic drug can be better than the branded version in more ways than just being significantly less expensive.
This page is about prescription, dosage-critical medications, mostly antiepileptic drugs (AEDs). When it comes to something you can buy at a bodega/corner store/convenience store like Aleve (naproxen sodium) or Advil (ibuprofen), you’d be an idiot not to get the generic2. Unless you’ve had a bad experience with the store brand of whatever store you find yourself in.
The party line answer from the FDA, the AMA,3 big pharma, and most pamphlets, books, TV commercials, and any other source of information is: generic drugs are exactly the same as brand name medications.
Reality is more complicated than that, especially in the world of crazy meds. Like so many things it depends on the drug, the condition being treated, and the person taking the medication. The odds are it won’t make much of a difference as far as you’re concerned. But if you do notice a change in how well your meds worked, side effects, or anything else after you were switched from a branded/brand-name medication to a generic, or from one generic to another (the pills look different, and/or the numbers changed), it’s not all in your head. Literally. In spite of these drugs usually targeting your brain, your brain has little, if anything, to do with any difference in effect when taking meds made by different manufacturers.
We’ve got a lot of terminology to cover.
We pretty much all know that “Generic” is the generic term for any drug made with an active ingredient that is no longer on patent and is no longer protected by FDA exclusivity4. Only a few crazy meds are almost always referred to by their generic names, like lithium and phenobarbital. “Generic” is both a noun and an adjective.
“Brand name” is complicated. “Brand name,” or “trade name,” are fairly straightforward. Unfortunately they are not universal. The term “branded” is also used, as is “brand.” You may even see terms like “pioneered drug,” “innovator’s product,” or “originator tablet,” but those aren’t used very often these days. Except for “innovator” drug/medicine/some other term, which is still used in research papers. “Brand” alone is confusing because many people use “brand” to refer to generics made by different manufacturers (e.g. “I never had any problems with Teva’s brand of lamotrigine…”), while “branded” is problematic because of the term “branded generic.”
“Branded generic” has three meanings:
- A generic drug produced by a generics manufacturer that is a wholly-owned subsidiary of the company that makes the branded version. E.g. Greenstone Pharmaceuticals makes gabapentin, and they are owned by Pfizer, who also own Parke-Davis, who bought Warner-Lambert, who pioneered Neurontin.
- A branded generic is also a generic drug given a ‘brand’ name by the manufacturer (e.g. Teva’s Budeprion), but otherwise has the same active ingredient as the original branded version (Wellbutrin).
- A branded generic is also a generic drug given a ‘brand’ name by the manufacturer and uses a salt of the active ingredient that is different from the original branded version and other generics. E.g. Sanofi-Aventis’ Aplenzin, which is bupropion hydrobromide, while Wellbutrin, Budeprion and most of the others are bupropion hydrochloride. The FDA says they’re the same thing, and, as usual, the data are contradictory.
In English: A generic drug is as safe, effective, and acts the same way as the brand name drug at the same dosage. I.e. it lives up to the promises that everyone makes about generic drugs.
Drug products are considered to be therapeutic equivalents only if they are pharmaceutical equivalents and if they can be expected to have the same clinical effect and safety profile when administered to patients under the conditions specified in the labeling.
FDA classifies as therapeutically equivalent those products that meet the following general criteria: (1) they are approved as safe and effective; (2) they are pharmaceutical equivalents in that they (a) contain identical amounts of the same active drug ingredient in the same dosage form and route of administration, and (b) meet compendial or other applicable standards of strength, quality, purity, and identity; (3) they are bioequivalent in that (a) they do not present a known or potential bioequivalence problem, and they meet an acceptable in vitro standard, or (b) if they do present such a known or potential problem, they are shown to meet an appropriate bioequivalence standard; (4) they are adequately labeled; (5) they are manufactured in compliance with Current Good Manufacturing Practice regulations. --the Orange Book 5
Most of the therapeutic equivalence standards are essentially paperwork. The only things that requires any testing are bioequivalence (BE) and bioavailability (BA). These are the numbers with the allowed 80–125% variance everyone talks about. Like most people without any training6, I wrote that had to do with how well the active ingredient got absorbed and distributed, which would be its BA. At least I wasn’t as wrong as everyone who that that was how much of difference in the actual active ingredient a generic med could have in it. The 80–125% range actually refers to the confidence interval (CI) of different pharmacokinetic parameters (see below for those). In English: if you remember what you learned in statistics class I probably don’t need to explain it to you, which is a good thing, because years of poorly treated epilepsy and bipolar have fried the part of my brain that remembered and understood math more complicated than adding and subtracting anything larger than 3-digit numbers. As for the rest of us it means their math looks good when they show there’s not too much of a variance.
So BE essentially means the pharmacokinetics (PK) are fairly close, and with a CI of 80–125% the actual difference in BA shouldn’t be more than 5%. Sometimes that’s enough, and sometimes it’s way more than that in spite of passing the BE tests. Why?
First of all, whenever generics manufacturers run BE/PK testing on humans, they do one test on 24–36
professional guinea pigs “healthy volunteers” who are mostly white males between the ages of 18 and 55. The tests are always the same, one dose, often the lowest anyone would ever take, first thing in the morning on an empty stomach. It doesn’t matter if it’s a sleeping pill that works better (even to deal with side effects) when taken with a meal, it’s the same routine every time.
If they want to be really thorough - but not go so far as to have on group of patients taking the brand name med and another group taking their
placebo generic version - a generics manufacturer will do a crossover test. That’s where they’ll get two groups of professional guinea pigs healthy volunteers. One group will take a single dose of the generic and one group will take a dose of the brand, and the only PK values that seem to matter are measured. Then two or three weeks later each group gets the other med. In that way anyone who is a poor or rapid metabolizer of a drug won’t skew the numbers. The crossover test makes a lot of sense, with a single-dose test it’s meaningful only for medications with active metabolites like Trileptal and Risperdal, where the pill you take isn’t what works on your brain, your liver needs to transform it first.
The rest has to do with the complexities of PK…
Pharmacokinetics (PK) is what your body does to a drug. It’s a geek’s paradise of hardcore technical data, full of data regarding how well a drug is absorbed and distributed, how long it takes to clear from your system, what potential drug-drug interactions there can be, and so forth. As far as BE goes, the FDA cares about two things: the maximum blood plasma concentration (C-max), and the plasma concentration time curve (AUC). If you look at Paxil’s PK, including most of the popular BA / BE parameters,7 there are a hell of a lot more data that can be used to nail down the theoretical difference in BA / BE, or to explain why an actual difference exists. Somehow the FDA thought those two were enough.
So with only those two parameters used, and only after a single, often sub-therapeutic, dose, it’s way too easy for a drug to appear equivalent when it’s not.
These all mean the same thing, which is two different things.
- First is what we’re discussing here - how the slightest change in a med’s dosage (how much you take), or dosing (when and how often you take it), is the difference between a med that works and a med that doesn’t work or has side effects that suddenly suck worse than the condition being treated. Lots of people who take Topamax or Lamictal know what a huge difference there can be between 375mg a day and 400mg a day of either. Lots of people who take Effexor or Keppra know that taking your pill a few hours late can sometimes lead to a world of hurt.
- Then there’s the original meaning - that there’s not much of a difference between an effective dosage and a toxic dosage.
I use dosage critical for the former and narrow therapeutic index (NTI) or margin for the latter. There aren’t very many crazy meds with an NTI. Lithium is one. For bipolar disorder a blood plasma test usually determines, or at least strongly influences your dosage. The therapeutic range is 0.6–1.2, but lithium toxicity can start at a level of 0.9.
This page, and the concept itself, has nothing to do with drugs that are not dosage-critical. I have no idea if the therapeutic margin is so narrow there can be a difference efficacy between brand Viagra and generic sildenafil, but I find it highly unlikely there will be much of a difference in efficacy between brand Propecia and generic finasteride. Differences in side effects due to inactive ingredients are always a possibility regardless of the drug.
Actually it’s more like half of doctors and pharmacists surveyed say when dosage-critical drugs are involved, there can be a significant difference between brand-name and generic drugs, as well as between meds from different generics manufacturers. With doctors it tends to depend on their specialty. But more and more doctors from more and more specialties are getting behind the new party line:
- If their patient began treatment with a brand-name, dosage-critical drug, or drug with a narrow therapeutic index, then they should stay on the branded med.
- If their patient began treatment with a generic dosage-critical drug, or drug with a narrow therapeutic index, then generics are fine. And, if at all possible, they shouldn’t be switched from one manufacturer’s med to another’s without a good reason. E.g. an allergy to an inactive ingredient.
- Many individual prescribers and pharmacists are with us in that they know some manufacturers are churning out sub-standard products that no one should take, unless they should be taking a placebo. As far as I know no organized group has come out to call specific drug manufacturers on that, or to recommend the FDA do something about it, etc.
How do I know doctors & pharmacists are starting to come around?
- Roughly half of all neurologists have had a patient lose seizure control or some other new adverse reaction after switching from brand to generic.
- The 50% statistic also comes up in this paper.
- In this survey One hundred and ninety-six (67.8%) neurologists reported breakthrough seizures after a switch from a brand name to generic AED; 93 (32.2%) did not.
- the Italian League against Epilepsy agrees with the policy of not switching between brand and generic, or between different generics manufacturers. They go one step further and don’t want to switch between immediate and extended release without a damn good reason.
- Pharmacists questioning use of generic AEDs?
- Patient and physician reactions to generic antiepileptic substitution in the treatment of epilepsy - no hard numbers in the abstract, just a lot of people think it’s a bad idea.
- American Academy of Neurology (AAN) is trying to ban automatic generic substitution of AEDs
- New York Times article on brand vs. generic meds
- L.A. Times article on the FDA’s standards for bioequivalence
- Denmark has tightened its standards. 80–125% CI isn’t good enough for some meds, and there can be no generic substitutions for others.
Nothing is ever cut & dry in pharmaceuticals.
- The price we pay for physician gullibility on generics. With a title like that…oh, it’s an HMO-sponsored publication. Still, the author raises the obvious point: there’s a hell of a lot more money to be made by Bigger Pharma (i.e. drug pioneers/innovators) pushing brand name drugs than Not-Quite-So-Big Pharma (companies that make nothing but generics) with big box stores selling $4 generics.
- A lot of people making noise about the problems with generic meds, like the Epilepsy Foundation, get a shitload of money from Bigger Pharma.
Once again, don’t just take my word for it.
- Switching from brand AEDs to generic is just not a good idea.
- Switching to generic = trip to the ER. This study found that epileptics who were taking A-rated (AKA the good stuff) meds and had to go to the ER were 81% more likely to have been switched to a generic.
- Here’s one survey of people forced to switch to generic where 13% of those taking lamotrigine had to switch back to Lamictal.
- And here’s another where 27.5% switched back to brand Lamictal, 20.8% to 44.1% switched back for various other AEDs.
- No surprise: switching from brand Dilantin resulted in more seizures. The steady state blood plasma concentrations were significantly different. You know, what you’d have after taking your medicine for a week or so, and not just one day.
- Here’s another Dilantin vs. generic phenytoin. This is exactly the sort of double-blind, brand vs. generic test I think should be done. Oh, wait, people could lose seizure control and prove a generic drug is bullshit before it hits the market. We can’t have that.
- Switch from brand Topamax to generic once and it’s not too bad, but switch to yet another generic (and another, and another) and it can really mess you up.
- Even something ancient like phenobarbital can’t always be trusted. You should be thankful you don’t live somewhere … Oh, wait, this is the Internet. You just might live in Mauritania, or somewhere else where phenobarbital is a first-line treatment for epilepsy.
- Money is the one argument the generics usually win. Not this time. Here are two studies that looked at the total costs switching people from brand to generic AEDs. While Economic burden associated with the use of generic antiepileptic drugs in the United States could easily be filed under “how to lie with statistics,” Generic antiepileptic drugs and associated medical resource utilization in the United States has hard, actuarial numbers that make a lot more sense. “Such as 20% increased risk of injury” during the period in which they were taking the generics.
- As for psychiatric applications…
- It’s not cheaper for the hospitals to switch your crazy meds. As with AEDs it can cost hospitals more money to deal with symptom relapses.
- Symptom relapse after switch from Celexa to generic citalopram
- I haven’t found anything regarding bupropion HCl vs. bupropion HBr, but paroxetine…
- Paroxetine mesylate: comparable to paroxetine hydrochloride?
- Adverse effects after switching to a different generic form of paroxetine: paroxetine mesylate instead of paroxetine HCl hemihydrate.
- While it’s not just crazy med per se, amlodipine is a calcium channel antagonist, and down the list of off-label treatments for bipolar disorder. This study looked for accounts of differences between amlodipine besylate and amlodipine maleate.
- The difficulty with reports of problems with meds of different salts is how much was due to the active ingredient and how much was due to excipients.
- Here’s a report on seven people inadvertently switched from Clozaril to generic clozapine. They were in a long-term, residential facility and had their schizophrenia symptoms under control. After the switch they “experienced a rapid and profound deterioration.”
- As if you didn’t have enough to deal with when taking lithium, controlled-release products aren’t necessarily all that controlled. If you can’t get brand Eskalith or Lithobid, try to get Roxanne’s generic.
- Lack of BE between brand and generic amoxicillin
- This Danish study found no significant difference in the blood plasma levels of people taking brand Lamictal and those taking generic lamotrigine.
- Comparing Depakote with valproic acid usually pisses me the hell off, but in this blatantly pro-generics study, they admit the two are different drugs. The results: although they ended up taking more valproic acid, and the GI side effects sucked more, there was no difference in how many people stopped taking either med. Although the people taking Depakote were on it a hell of a lot longer than those taking valproic acid.8
- There are probably more, but searching for this sort of thing is like looking up side effects on teh InterGoogles, complaints will always outnumber reports of everything being just fine, because hardly anyone reports “I didn’t have any side effects.” A bit further down I’ve got a bunch of clinical trials where the generics tested as well as the branded versions…
In case you were wondering how all the accidental and “inadvertent” switches happened, this study, 30% of doctors and pharmacists randomly selected from a teaching hospital were unable to identify any of the three meds placed in front of them.
The case that brought the differences between branded and generic medications into the public and media spotlight (but not, unfortunately, congress) was Teva’s Budeprion XL. Teva manufacturers a hell of a lot of generics, and they rarely have any problems. Like many of my fellow nutjobs I request Teva’s topiramate and lamotrigine from my pharmacist, as I’ve yet to have a form of topiramate from anyone else that’s acceptable and I prefer their generic lamotrigine to GSK’s brand-name Lamictal.9 So, what happened with Budeprion XL? Impax (the actual manufacturer) used a matrix system to delaying the release of bupropion HCl, while GSK had originally designed Wellbutrin XL to use a reservoir system. You’ll need to read the article, as I can’t explain it any better.
Teva’s once-a-day XL version was acting more like the twice-a-day SR version, some people even reported it working like the three-times-a-day immediate-release version. The nature of side effects and specific lack of efficacy all centered around one simple fact: it wasn’t a true once-a-day pill. So, how did the FDA respond to the complaints? Here are the key points:
First up, Budeprion XL passed the required tests, so there absolutely can not be a problem.
The basis for approval of Teva’s bupropion XL was that there was no significant difference in the rate and extent of absorption as measured by the plasma bupropion concentrations between 150 mg of the Teva XL product and 150 mg of Wellbutrin XL. Because of the potential risk of seizures at higher doses, the 300 mg strength was not studied. This practice is used when evaluating the pharmacokinetic profile of a drug in normal volunteers, especially when a drug’s adverse effects increase with dose. The pharmacokinetic profile is not expected to differ between 300 mg and 150 mg doses of bupropion.
The area under the drug plasma concentration over time curve (AUC) is a graphical and statistical representation of the total amount of drug absorbed. The average bupropion AUC from the volunteers receiving the Teva generic product under fasting conditions was 98% (90% CI, 91.9%−104.4%) of the average AUC from all of the same volunteers after receiving the Wellbutrin XL under fasting conditions. Under fed conditions the average bupropion AUC for the Teva product was 108% (90% CI 101.4% −115.4%) of that for the Wellbutrin XL product.
The average maximum bupropion plasma concentration (Cmax) produced by the Teva product was 89% (90% CI, 80.3% – 98.2%) of that produced in the same volunteers by Wellbutrin XL under fasting conditions and 110% (90% CI, 103.2% - 118.0%) under fed conditions.
The established bioequivalence limits provide that the entire 90% confidence interval (CI) for the generic/reference comparison of both AUC and Cmax be within 80% to 125%. Thus, the small differences observed in AUC and Cmax, with no consistent direction, are within the established limits for bioequivalence between brand name products and generic versions, and are not considered clinically relevant.
The major active metabolite, hydroxybupropion, which is responsible for much of bupropion’s effect, also met the AUC and Cmax bioequivalence limits. — Review of Therapeutic Equivalence Generic Bupropion XL 300 mg and Wellbutrin XL 300 mg 10
I highlighted the two areas in this section I have a problem with. It was a sub-therapeutic dosage11, and they didn’t provide any data for the active metabolite. Who is hiding what?
Next we see why Cmax and AUC by themselves are pointless
The time to maximum drug plasma concentration (Tmax) was examined but is not required to be within any specified limits. The bupropion Tmax was faster for Teva’s XL product (2–3 hours) than Wellbutrin XL (5–6 hours). The median Tmax values for hydroxybupropion (the active metabolite) with Teva’s product was 10 hours while Wellbutrin’s hydroxybupropion Tmax was 12 hours (in both fasting and fed subjects). These differences in Tmax for both bupropion and its active metabolite, however, were not considered clinically significant. The somewhat more rapid times to maximum concentration, with no differences in the plasma bupropion concentrations (including the lowest levels, known as trough levels) throughout the day, would not lead to decreased effectiveness. This is supported by the fact that the bupropion Tmax of Teva’s XL product was similar to that of the marketed Wellbutrin SR and was, in fact, slower than that of Wellbutrin IR, a dosage form shown in clinical trials to be effective. The pharmacokinetic profiles of the generic and branded products do not support a conclusion that the reported lack of antidepressant effect and new onset side effects are the result of differences between the two products. —ibid
This is a remarkable new level of willful ignorance. I’ve been writing that bureaucracy is the antithesis of logic for years, but this takes it to a new low. The FDA spell out the problem, that Budeprion XL is bioequivalent to Wellbutrin SR, not Wellbutrin XL, and choose to ignore it none the less. They even include it as a graph in the document they use to tell everyone that there is no problem!:
If there’s no difference in efficacy between the IR, SR, and XL forms, why should GSK bother making SR and XL forms in the first place? Why is only the XL form approved seasonal affective disorder? Why is Zyban (bupropion SR) the only form approved for smoking cessation?
Once again, don’t just take my word for it:
[N]umerous postmarketing reports have cited loss of antidepressant effect and/or emergence of side effects when patients were switched from a proprietary formulation of bupropion XL (using a reservoir system) to an approved generic formulation (using a matrix system). Evaluation of the bioequivalence data revealed small PK differences that were within the equivalence boundaries and an earlier Tmax that was similar to that of bupropion SR. — A Horse of a Different Color: How Formulation Influences Medication Effects Meghan M. Grady and Stephen M. Stahl
That’s right bitches, no less than Stephen freaking Stahl wrote the exact same thing I’ve had on this site for over a year, including using the FDA’s own graph to show how wrong they are about Budeprion XL being equivalent to Wellbutrin XL.
So, what caused the problem? According to the FDA: it’s all in your head - the so-called nocebo effect - or it was just a coincidence and you were going to have a relapse of symptoms anyway. From their response:
The recurrent nature of MDD offers a scientifically reasonable explanation for the reports of lack of efficacy following a switch to a generic product. The adverse effects (e.g., headache, GI disorder, fatigue and anxiety) reported following a switch were relatively few in number and typical of adverse drug events reported in drug and placebo groups in most clinical trials (i.e., including, but not specifically for, bupropion). Although many of these adverse effects are seen soon after drug therapy is initiated, adverse effects are known to occur throughout the course of a patient’s therapy, as well as among patients on a stable dose of medicine or in patients receiving placebo. — ibid
Are the people at the FDA in charge of this complete idiots, criminals, or both?
As of 3 October 2012 the FDA decided that they got it a little bit wrong by calling Teva’s 300mg Budeprion XL bioequivalent to 300mg Wellbutrin XL, and asked Teva to voluntarily pull it from the market. 150mg Budeprion XL is still rated as bioequivalent in spite of the fact that IT’S NOT! I go into great detail about the FDA’s announcement and why Budeprion XL is not bioequivalent to Wellbutrin XL in any dosage on the Expanded Wellbutrin Comments page.
Amazingly enough, prior to that bullshit admission of being sorta kinda not all that wrong about it, the FDA had decided to change things a little when drugs have complex PK like
Wellbutrin Ambien CR. These two documents explain it:
Minutes from the FDA meeting on new bioequivalence standards for drugs with complex PK
The slides from the presentation referenced in the minutes.
What does it all mean? In English: it explains, in dense PK terms, why the FDA totally fucked up approving Teva’s once-a-day Budeprion XL when it’s, at best, twice-a-day SR; and how the new method they will now use more-or-less works with something like Ambien CR, but there could still be problems.
Why will there still be problems? Because all they’re going to do is add a couple more useless PK parameters to their tests.
There is an incredibly easy solution to all of this that would have one standard of testing for all medications, regardless of their PK.
A double-blind trial with people who are already taking the brand-name drug to treat an approved condition. You give half of them the generic and half of them the brand for a month. If no one can tell the difference, it passes; if too many people have a relapse in symptoms, it fails. You collect all the PK data, but that would mainly be for any failed drugs. How fucking difficult is that? It must be extraordinarily hard to do, since no one has done it before. Oh, wait, it has been done before.
- Epitol vs. Tegretol. A double-blind, cross-over study that lasted for 90 days. 40 epileptics, half seizure-free, half no such luck on meds. The results: a tie.
- They can even do it in Thailand. Tegretol vs. 2 branded generics and one other generic carbamazepine. They gave 18 people who had been taking Tegretol one of the four meds, waiting until they were at steady state, and started taking blood samples. Two of the three passed the important test of “did it work?”. The abstract reports breakthrough seizures, but it doesn’t state if that was for the failed product or what. Good to know who has better standards, Thailand or the good ole U!S!A! U!S!A! U!S!A!
- Generic clozapine vs. Clozaril. 17 schizophrenics switched from brand to generic. This study is a bit fuzzy on details - the abstract is all about the white blood cell count and other side effects - and has been challenged by Novartis. But at least Zenith (now part of IVAX) had the balls to run trials using actual patients.12
So why don’t we do it that way here? No, really, I’d like to know the answer to that question. Why don’t we use that method to test generics? Are the generics companies too chickenshit to put their meds in head-to-head competition with the real thing?
So far article, along with most of the debate regarding the differences between brand/pioneered/innovator and generic drugs, has concentrated on the obscure and eye-glazing-over subject of PK, when a far more common cause of problems is a difference in one or more inactive/inert ingredients (known as excipients in pharmacologyese). If you’re highly allergic to some inert ingredient that is in one version of the drug but isn’t in another, you obviously need to take the allergen-free version. Simple, right?
- Assuming you know what you’re allergic/sensitive to.
- And you can get the list of inert ingredients, as not all generics have complete PI sheets available.
What this also means is, as mentioned at the beginning of this article, some generic drugs are better than the brand name med in addition to being better than other generics.
- This is the most jaw-dropping example. Although tested on rats, it seems a generic form of vancomycin - a drug to treat colitis that is potentially effective against one of the deadliest and most frustrating problems in hospitals today: multiple drug-resistant Methicillin-resistant Staphylococcus aureus (MDR MRSA) - is far less likely to destroy your kidneys than the brand-name version when taken at dosages high enough to be effective against MDR MRSA.
- Most generic crazy med tablets are white. I couldn’t find an example in the literature, but this study of topical corticosteroids found the generic versions had far fewer allergens than the branded products, thus far fewer adverse reactions.
- So if you have, or you suspect you have an allergy/sensitivity to something used as a binder/filler/dye, etc., that could be causing an adverse reaction (and not, technically, a side effect) unrelated to the med’s active ingredient. It doesn’t matter if you’re taking the brand version or a generic, if corn starch or D&C Red #2 causes you to break out in hives, and there’s a version of a med that doesn’t have either of those, ask your pharmacist to order that one. It’s possible that a drug may work for you after all, and it was an inactive ingredient that was screwing with you. Cornstarch is especially popular as an excipient and, despite what the FDA thinks, lots of people are allergic to corn13.
So what’s the takeaway from all this?
Significant problems caused by the differences between brand-name drugs and their generic ‘equivalents’ are infrequent but real.
What do I mean by “infrequent?” Based upon all of the examples I’ve used, and all the ones I didn’t include, and all of the anecdotal accounts I’ve come across, problems caused by switching from brand medications to generic drugs or one generic drug to another generic drug comprise, at the very most, 1–2% of the adverse reactions / negative experiences / “side effects”-that-aren’t-really-side-effects everyone has had with crazy meds from the 1990s until now. Maybe. Extrapolating adverse reactions caused by allergies and/or sensitivities to excipients in both branded and generic meds, including those mistaken for side effects of the actual active ingredient, increase that to, at the very most, 5%. That’s my best guess14. I honestly don’t think it’s much more than that.
However 2% is the approximate rate of schizophrenia, and 5% is approximately how many people have affective mood disorders serious enough to require medication. 2–5% is an unacceptable number of people. I’m an outlier in many ways, as are most of the people on Crazy Talk, and we’re well below 1% of the crazy population, which puts us way under 0.2% of the general population. 2–5% is too much.
I have no clue at all what the numbers are like for other dosage-critical and narrow therapeutic margin meds, like those used to treat cancer and immunosuppressants for organ transplants.
As it stands…
- With some people a slight change in a med’s PK can cause a change in side effects and/or relapse of symptoms.
- With other people, a different inactive/inert ingredient/excipient is all that’s needed to cause new side effects.
- The two are not mutually exclusive groups.
- The FDA doesn’t give a rat’s ass about it, otherwise they’d institute real tests and not more of the same bullshit PK testing.
- Which allows Bigger Pharma to keep forcing the generics manufacturers to spend more money on lawyers arguing about FDA-approval for the generic drugs instead spending it on real testing.
- And PK has absolutely nothing to do with allergies & sensitivities to inactive/inert ingredients/excipients. You’re on your own with that.
- Good luck getting the FDA, or Congress, to mandate highlighting any ingredients that cause people those sorts of problems. The most I’ve seen, as far as neurological and psychiatric medications are concerned, is mentioning if there’s lactose in a pill, and that’s buried in the PI sheet.
- So in the end, we’re fucked. The pioneering companies will get to keep FDA exclusivity for their meds longer, keeping the prices up; and we won’t really know which generic versions, if any, are truly equivalent until most of us are paying to take them for a year or more, instead of a couple hundred or so getting paid to take them for 30–90 days.
- Which means we have to always be on guard about which versions we get from our pharmacists. As if our lives weren’t difficult enough. At least we have some tools.
- There’s an entire forum on Crazy Talk dedicated to issues with switching to/between generic meds.
- I have a section on some of the drug pages listing and known differences between brand and generics, and if there are any preferred generics (e.g. Lamictal vs. various generic lamotrigine products).
- While I’ve been writing about the differences between brand and generic meds since 2004, the site that started the uproar about Budeprion XL is The People’s Pharmacy. They have an entire section to report all sorts of medical problems. As far as crazy meds go, that site is almost all antidepressants.
- In any event, there’s not a damned thing we can do about it. Congress won’t act, let alone overreact, unless you’ve got a bunch of weeping mothers telling them, and the two dozen people watching C-SPAN, the stories of the children who died of socially-acceptable conditions like cancer, or something requiring an organ transplant, because of substandard or allergen-packed generic medications.
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2 Want to know the difference between the non-narcotic (i.e. without the hydrocodone component) prescription versions of Aleve and Advil and the regular stuff you can just walk into any store and buy? The dosage is twice as much. That's it. As long as you don't have any other health conditions involved and aren't taking any meds that can interact with them, you can safely take twice as much naltroxen sodium and ibuprofen as listed on the bottle. But if you weren't taking a shitload of meds and/or had a clean bill of health you probably wouldn't be reading this site in the first place, would you?
3 You just assumed I meant American Medical Association, didn't you?
4 This gets super complicated. The short explanation is: The FDA will let drug companies keep exclusive rights to sell their brand name drugs for months, even years, after the patents expire for many different reasons. The main reason being they have really good lawyers.
5 What the FDA calls its big book about generic meds. It must have been orange at one point. I don't even know if they still print it out on paper.
6 And plenty who did.
7 I usually can't find other useful ones like volume of distribution (VOD).
8 I also wonder if anyone who was severely crazy enough to be hospitalized for a long time then allowed back outside is going to bitch about side effects that much in the first place. Wanting to spench every day sucks, but it sucks a lot less than hearing the people in your bathroom whispering their latest plans about how they're going to kill you.
9 Teva's lamotrigine tablets are, easier to split, don't dissolve so quickly, and aren't a weird shape, so they're a lot easier to take in addition to being less expensive. Anyone who has a problem with the differences between brand and generic meds shouldn't be splitting their pills in the first place, but I'm not as sensitive to the differences in Lamictal as I am with those in Topamax. Plus I don't need to split them at all now, and when I do a split pill would be just part of my daily dosage.
10 For some mysterious reason the FDA keeps moving this document all over their site, and sometimes it completely vanishes. Fortunately I made of copy of it. The links to parts of the FDA's site and other documents don't work, but all the salient data are on that page.
11 While I'm the world's biggest advocate of starting and staying at sub-therapeutic dosages that work, most people taking most meds will be doing so at the typical target/therapeutic dosages. In Wellbutrin's case that's 300mg a day.
12 While the schizophrenic are among the most vulnerable people in our society, with so many being seen at community clinics who will end up being switched to generic versions of what they take no matter what, the schizophrenia community will be best served by people with conditions in the psychosis spectrum volunteering to participate in brand vs. generic testing than letting the FDA rubberstamp an approval for nothing more than a PK test carried out on the usual suspects.
13 Next time you're looking at the ingredients list of packaged food, note how foods with common allergies & sensitivities are highlighted. Soy, milk, wheat, nuts and their derivatives. Take a look at anything with corn. Fortunately for me the amount of cornstarch in meds is too small to cause me any problems. Other people aren't so lucky.
14 I.e. Numbers I pretty much pulled out of my hemorrhoid-laden and frequently-constipated ass.
Page created by: Jerod Poore. Date created: 26 February 2011 Last edited by: JerodPoore
Page design and explanatory material by Jerod Poore, copyright © 2004 - 2014. All rights reserved.
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Almost all of the material on this site is by Jerod Poore and is copyright © 2004, 2005, 2006, 2007, 2008, 2009, 2010, 2011, 2012, 2013, and 2014 Jerod Poore. Except, of course, the PI sheets - those are the property of the drug companies who developed the drugs the sheets are about - and any documents that are written by other people which may be posted to this site will remain the property of the original authors. You cannot reproduce this page or any other material on this site outside of the boundaries of fair use copying without the express permission of the copyright holder. That’s usually me, so just ask first. That means if want to print out a few pages to take to your doctor, therapist, counselor, support group, non-understanding family members or something like that - then that’s OK to just do. Go for it! Please. As long as you include this copyright notice and the following disclaimer, I’m usually cool with it.
All rights reserved. No warranty is expressed or implied in this information. Consult one or more doctors and/or pharmacists before taking, or changing how you take any neurological and/or psychiatric medication. Your mileage may vary. What happened to us won’t necessarily happen to you. If you still have questions about a medication or condition that were not answered on any of the pages you read, please ask them on Crazy Talk: the Crazymeds Forum.
The information on Crazymeds pertains to and is intended for adults. While some information about children and adolescents is occasionally presented (e.g. US FDA approvals), pediatric-specific data such as dosages, side effects, off-label applications, etc. are rarely included in the articles on drugs or discussed on the forum. If you are looking for information regarding meds for children you’ll have to go somewhere else.
Know your sources!
Nobody on this site is a doctor, a therapist, or a pharmacist. We don’t portray them either here or on TV. Only doctors can diagnose and treat an illness. While it’s not as bad as it used to be, some doctors still get pissed off by patients who know too much about medications, so tread lightly when and where appropriate. Diagnosing yourself from a website is like defending yourself in court, you suddenly have a fool for a doctor. Don’t be a cyberchondriac, thinking you have every disease you see a website about, or that you’ll get every side effect from every medication1. Self-prescribing is as dangerous as buying meds from fraudulent online pharmacies that promise you medications without prescriptions.
All information on this site has been obtained through our personal experience and the experiences family, friends, what people have reported on various reputable sites all over teh intergoogles, the medications’ product information / summary of product characteristic (PI/SPC) sheets, and from sources that are referenced throughout the site. As such the information presented here is not intended as a substitute for real medical advice from your real doctor, just a compliment to it. You should never, ever, replace what a real doctor tells you with something from a website on the Internet. The farthest you should ever take it is getting a second opinion from another real doctor. Educate yourself - always read the PI/SPC sheet or patient information leaflet (PIL) that comes with your medications and never ever throw them away.
Crazymeds is not responsible for the content of sites we provide links to. We like them, or they’re paid advertisements, or they’re something else we think you should read to help you make an informed decision about a particular med. Sometimes they’re more than one of those things. But what’s on those sites is their business, not ours.
All brand names of the drugs listed in this site are the trademarks of the companies named on the PI/SPC sheet associated with the medication, sometimes on the pages about the drugs, even though those companies may have been acquired by other companies who may or may not be listed in this site by the time you read this. Or the rights to the drug were sold to another company. And any or all of the companies involved may have changed their names.
Crazymeds is optimized for the browser you’re not using on the platform you wish you had. Between you and me, it all looks a lot cleaner using Safari or Chrome, although more than half of the visitors to this site use either Safari or Internet Explorer, so I’m doing my best to make things look nice for IE as well. I’m using Firefox and running Windows 72. On a computer that sits on top of my desk. With a 23 inch monitor. Hey, at least you can make the text larger or smaller by clicking on the + or - buttons in the upper right hand corner. If you have Java enabled. Like 99% of the websites on the planet, Crazymeds is hosted on domain running an open source operating system with a variety of open source applications, including the software used to display what you’ve been reading. As such Crazymeds is not responsible for whatever weird shit your browser does or does not do when you read this site3.
No neurologists, psychiatrists, therapists or pharmacists were harmed in the production of this website. Use only as directed. Void where prohibited. Contains nuts. Certain restrictions may apply. All data are subject to availability. Not available on all mobile devices, in the 12 Galaxies Guiltied to a Zegnatronic Rocket Society, or in all dimensions of reality.
‘Everything is true, nothing is permitted.’ - Jerod Poore
1 While there are plenty of books to help you with hypochondria, for some reason there’s not much in the way of websites. Then again, staying off of the Internet is a large part of curing/managing the disorder.
2 Remember kids, Microsloth operating systems are like TOS Star Trek movies with in that every other one sucks way, way more. With TOS Star Trek movies you don’t want to bother watching the odd-numbered ones. With Microsloth OS you don’t want to buy and install the even-numbered ones. Anyone who remembers ME and Vista knows what I mean.
3 Have I mentioned how open source operating systems for commercial applications is one of the dumbest ideas in the history of dumb ideas?
[begin rant] I rent a dedicated server for Crazymeds. It’s sitting on a rack somewhere in Southern California along with a bunch of other servers that other people have rented. The hardware is identical, but no two machines have exactly the same operating systems. I don’t even need to see what is on any of the others to know this. If somebody got their server at the exact same time, with the exact same features as I did, I’m confident that there would be noticeable differences in some aspects of the operating systems. So what does this mean? For one thing it means that no two computers in the same office of a single company have the same operating system, and the techs can spend hours figuring out what the fuck the problem could be based on that alone. It also means that application software like IP board that runs the forum here has to have so many fucking user-configurable bells and whistles that even when I read the manual I can’t find every setting, or every location that every flag needs to be set in order for a feature to run the way I want it to run. And in the real world it means you can get an MBA not only with an emphasis on resource planning, but with an emphasis on using SAP - a piece of software so complex there are now college programs on how to use it. You might think, “But don’t people learn how to use Photoshop or Adobe Illustrator in college?” Sure, in order to create stuff. And in a way you’re creating stuff with SAP. But do you get a Bachelor of Fine Arts degree with an emphasis on Photoshop?
Back in the Big Iron Age the operating systems were proprietary, and every computer that took up an entire room with a raised floor and HVAC system, and had less storage and processing power than an iPhone, had the same operating system as every other one, give or take a release level. But when a company bought application software like SAP, they also got the source code, which was usually documented and written in a way to make it easy to modify the hell out of it. Why? Because accounting principles may be the same the world over, and tax laws the same across each country and state, but no two companies have the same format for their reports, invoices, purchase orders and so forth. Standards existed and were universally ignored. If something went wrong it went wrong the same way for everyone, and was easy to track down. People didn’t need to take a college course to learn how to use a piece of software.
I’m not against the open source concept entirely. Back then all the programmers read the same magazines, so we all had the same homebrew utilities. We even had a forerunner of QR Code to scan the longer source code. Software vendors and computer manufacturers sponsored conventions so we could, among other things, swap recipes for such add-ons and utilities. While those things would make our lives easier, they had nothing to do with critical functions of the operating system. Unless badly implemented they would rarely cause key application software to crash and burn. Whereas today, with open source everything, who the hell knows what could be responsible some part of a system failing. [/end rant]