Wednesday, January 19, 2011

A Difference Between Generic Meds And Why Your Customers May Not Always Be As Crazy As You Think.

"Bullshit Drugmonkey." You are saying. "My customers are fucking psycho. The only people who worry about which particular generic they are getting are crackheads who want the same color promethazine with codeine syrup that the rappers sing about."

I hear you. Trust me, I hear you loud and clear. And the one thing I can tell you without the least bit of uncertainty is what you and I have both heard a million times: generic meds are the same thing as the brand name. The same ingredient put into your body in the same amount. Period. Without a doubt.

Now that we have that settled though let's play a little game. I call it "find the mile-wide loophole in what I just said." Read that last paragraph again and think it over. If you need some help think about extended-release products and what I didn't say.

If you need another clue here you go:

Didn't say anything about rate did I? This chart is from the FDA's own data regarding the anti-depressant Wellbutrin XL and a generic distributed by TEVA Pharmaceuticals sold under the name Budeprion XL.  Look at the plasma concentration at two hours and five hours and tell me these meds are the same.  The FDA put this out in response to numerous consumer complaints that the 300 mg TEVA generic led to relapses of depression and increased side effects. That wasn't a typo. The complaints were about the 300mg version and the FDA responded by studying the150mg tablets. "Because of the potential risk of seizures at higher doses, the 300 mg strength was not studied" said the FDA, which makes perfect sense in a bizarro alternate universe where you wouldn't study the thing you want to learn about out of safety concerns after you had already declared the thing you want to learn about to be safe and effective.

Someone actually did study the 300mg tablets people were actually complaining about though, and if you were able to sneak past the paywall of and read their report this is part of what you'd see:

So... when someone actually took a look at the actual product people said affected them differently, and not a similar product used as a stand in by the FDA "for safety purposes," the differences were even greater than what the FDA found. Interesting. I won't say anyone was trying to hide anything, because I don't have any evidence for that. I will say that if you were trying to hide something though, what the FDA did might not be a bad way to go about it.

I also won't say that the differences the FDA and ConsumerLab found are clinically significant. It is entirely possible that what the FDA and ConsumerLab came up with, as striking as it may appear, would have no noticeable clinical effect.

I will say however, that when I dispense and you take a generic drug, we both expect it to be the same as its brand name equivalent, and that dumping 49% of a 24 hour dose over the course of four hours as opposed to 25% is not the same. It's almost twice as much. Which makes me wonder if maybe there's not a reason at least a few of my customers are so damn psycho.

It's also why I've started ordering Watson's version of Wellbutrin XL.


Dark Jay said...

Thanks for posting this, cher Drug Monkey. This issue was first illuminated in a couple of mental health message boards I frequent (Crazy Meds and Crazy Boards). I brought up the issue at a meeting with some public health docs and was gunned down as spreading inflammatory filth. I'm feeling a bit of vindication now. Makes me wanna go tilt at some more windmills!

Anonymous said...

What about the 53% dose between 4and 8 hours for the welbutrin? 25%>78%. To me that graph makes the teva look much more linear than the branded, which is what I would want from a modified release.

I agree with the difference in some brand/generics though. It is a particular problem with modified release drugs.

I think the crazier patients are the ones who apparently are eating the boxes from their medication. The parralel import haters, the drug is made by the same company, using the same recipe but was packaged in italy and over labelled in english. We have loads and loads of people that will argue until they are blue in the face that the stuff in the foreign boxes doesnt work or makes them sick, but never ever ever ever has someone told me that the english boxes are the inferior product.

Anonymous said...

I was actually taught this in school. Well, specifically that Budeprion is NOT bioequivalent to Wellbutrin.

Any data on the other generics for Wellbutrin XL?

Anonymous said...

I could swear there are no APIs in most Mylan products...

Anonymous said...

Did any of you read the article? Maybe the FDA's "established bioequivalence limits" of 90% confidence interval are too lax, but the Teva preparation meets them. I sure as hell don't know enough about pharmacology to question the 90% CI limit, but those limits seem to be the only thing about the article that is debatable. And if you're questioning the acceptable limits for this medication, you're questioning them for every generic time-release formulation that gets approved.

Anonymous said...

Well, call me crazy but does anyone remember the cooked test results on more than a few old time meds that served to preserve market share? "oh! you can't sub that! Look at the data?"...More recently, all types of "Brand" OTC meds pulled for who really knows why. Just today the FDA "punted" on a few changes. This week "statins used excessively". For any given person maybe 50:50 whether it's being used effectively or safely or both or is accurately portrayed in the literature. No matter how learned you only "know what you know" and apparently too often that ain't much

Rex Henricus

Anonymous said...

Well, this explains a whole lot. Thankfully my doc took me off Wellbutrin/generic independently of knowing this.

Anonymous said...

What is an orange book? Or a blue book or a little black book? Or a cookbook?

Anonymous said...

Yeah, the people on the front lines don't know jack. We are all crazy because we we don't have medical degrees and of course the the doctors/pharmacists/drug manufacturers know our bodies better than we do.
Inactive ingredients don't have to be the same in generics. And whose to say that won't affect the way "some" people process a drug?
And I'm not a crack addict or a pain medication user/abuser. I take an antidepressant and I think the generic works just fine. Just saying sometimes the person taking the drugs may actually know what they are talking about.

Anonymous said...

I already had "generic wellbutrin" in mind before I even got to the key part of this post. I don't usually pay attention to cries for specific generics, we have one woman who swears she feels "cleaner" with the brown simvastatin, but when wellbutrin went generic the complaints of our otherwise easygoing pts made me question all my other dismissals.

misbehavis said...

Is this why we're having such a hard time getting generic Wellbutrin XR 150 and 300 in stock? Our warehouse is out of stock and has been for weeks. Since when is the warehouse of a major chain pharmacy out of stock on such a common generic drug? We've been picking through various generics as they are available from our wholesaler, but availability is limited and we keep changing manufacturers on our patients.

Mike said...

I had a lady come in and tell me that the new Mylan metformin (the blackberry flavored one) doesn't work the same as the old shitty fish smelling Teva brand we've had for years. I think she's crazy. What say you, DrugMonkey?

Anonymous said...


So much for pharmacists being drug experts.

All y'all need to go back to your pharmacokinetics textbooks and brush up on steady-state.

tsk tsk Drug Monkey.

Anonymous said...

As far as generic wellbutrins go, a patient of mine swears up and down that the teva brand caused her hair to fall out, but that sandoz was perfectly fine.

Anonymous said...

It's why I started specifying non-Teva generic or brand almost immmediately when the "Budeprion" crap came out, after 4 (non-fussy) patients complained in a row.
None of the pharmacists here will stock the Teva stuff.

The Watson and Sandoz - no problem.

I have a few patients who have strong feelings about one of the generic lamotrigines (can't remember which one), but are fine with Dr. Reddy's. They're cash pay and were willing to pay full retail for Lamictal until that one came out. But no fussing about all their other generics.
95% of the time, things are great...

Heather said...

You can pick on me all you want, but I've known for years that certain generic crazy meds just don't work as well as their brand name counterparts. Depakote is another one that people struggle with. I personally had a severe reaction to the generic lamictal.

They may use the same active ingredients, but binders and such can make a big difference. I usually don't care about generic vs name brand. I'm all about saving money on meds. But when they start messing with me? No thanks.

I thought the "rule" for getting approval was that they needed to show the same concentrations +/- 10% bio-availability- which is actually a 20% range. Don't remember where I heard that, though.

Heather said...

Dark Jay-

I love crazy meds! It's a fabulous site. I've been going there for years.

Anonymous said...

Heather, the 'rule' has to be shown the drug meets USP specifications, for the FDA's Orange Book ratings.

There are several ratings for generics to be able to compare with the original 'innovator' brand-name drug. If generic drugs don't meet USP standard dissolution guidelines to be rated one way or another, then the generic company has to come up with a 'new drug application' which is a tad more work than the 'abbreviated new drug application' which is the minimal paperwork for generics.

Thirty years ago I was working on dissolution of sustained-release theophylline products e.g. Theo-Dur vs. Theo-24 etc. Some of the 'release' patterns of different generic drugs are significantly different to not be able to claim AB rating to the original proprietary product.

Depakote SR is significantly different from Depakote XL as well as Seroquel XR from plain Seroquel, Lopressor (which is metoprolol) and Toprol XL (which is an extended release formulation of metoprolol) and Wellbutrin SR from XL to have different dosing frequency recommendations.

Yes, tsk, tsk steady-state, but in humans (who are not simply dissolution test vats) there are other factors to consider, and not just limited to circadian rhythms, fat and protein content of meals, whether food is grilled, insulin secretion (Geodon HAS to be ingested on a full tummy), as well as my personal favorite, the placebo effect.


cjumper said...

I'm having trouble with the graph that shows 104% and 101% dissolution over time. Unless the figures are in relation to some reference point, but the axis labels don't say that. But then my statistics classes were so long ago that maybe I'm missing something obvious.

Anonymous said...

Question for you, DM.

Today I went to fill a script for Adderall XR. My insurance (BC/BS of IL) rejected the claim for generic and forced me to buy brand.

Any idea as to why they would do that? Have you ever seen it?

Anonymous said...

I have been taking acetaminophen with codeine 4, the generic version of tylenol 4, over the past roughly six years with no bad side effects. I do the monthly weening, the yearly detox, etc. My drug store recently switched me from one brand of tylenol 4 to another to the teva brand and now it's ineffective. It makes me high for twenty minutes then makes me nauseaus, and I constantly feel like I'm going to pass out within an hour after taking it. So my choices are pain or nausea. I'm going to talk to my doctor about this and find it hard to believe I'm not the only one who's experienced this with Teva products. thanks for posting this.