Wednesday, June 3, 2009

Generic drugs: I'm on to your tricks now

I've been thinking about writing this post for a long time, but was finally kicked into gear by LookyDaddy's recent post referring to the dangers of generic epilepsy drugs.

My first experience with this was about a year ago with Toprol XL. I'd been taking it for months with no problems. Then one refill the pills were clearly different. It turned out that Walgreens was now sourcing generic Toprol XL from a different manufacturer: Ethex instead of Sandoz. They didn't think this was worth mentioning. I only noticed because the size and shape changed.

Right away I started having trouble. During the course of the day I'd go through periods of incredibly low energy and blood pressure -- like, unable to move low -- and periods of jumpy heart racing.

Randy hypothesized that the release rate of the Ethex generic wasn't flat enough. During the low periods it was releasing the drug too fast: beta receptors too blocked, heart going too slow and weak. During the jumpy periods it was releasing too slow: receptors not blocked enough, heart going too fast and hard.

These problems went away within a few hours of getting the name brand. After that, we poked around on the web and found that lots of other people had the same problem with the Ethex generic.

More recently, I started experimenting with bupropion to try to deal with dopamine deficiency. Again they gave me a generic: Teva Budeprion XL. Again there was instability: high dopamine in the morning, sudden crash in the afternoon, ok in the evening after a nap. I thought at first that this was just startup edge effect, but it went on for weeks.

Again, these problems went away right after changing to the name brand. Again, lots of others had similar problems. We learned that two other people we know and care about were also getting screwed up by Teva Budeprion XL and got better when they stopped taking it. Ok, we thought, better put out a warning...

Now, I know this is all anecdotal and there's plenty of people on the net to complain about anything. However, consider this: the time release mechanisms in drugs are considered *inactive ingredients* and are therefore not regulated. They differ between brand name and generic, and even between generics from different manufacturers. The ones that are sophistocated enough to give reasonably flat release profiles are pricey. Generics have low profit margins. Seems like a good target for cost cutting.

Another problem with inactive ingredient substitutions is that they can be a problem for people with sensitivities. The one I have to watch out is potato starch (discussion of use in generics here). Pharmacists don't seem to have access to inactive ingredient information but will supply the phone number of the manufacturer.

I'm sure not all generics are bad, but after getting messed up by the last two in a row I no longer swallow the claim that they're "equivalent." If you're taking a generic, it may perhaps be a good idea to do an experiment:
  • Get one refill, or a partial refill, of the name brand
  • Watch yourself carefully for a few days while still on the generic, then compare how you do with the name brand
  • If you can't notice a difference, go back to the generic with restored peace of mind
  • If you notice a difference for the better, think about how much that quality of life improvement is worth to you compared to the cost differential
I know that for me it's well worth the $15 extra per month to be free of what the Ethex and Teva generics were doing to me.


  1. Interesting post. Before moving to neuroscience, I started my PhD in Pharmacology, and I totally agree that generics can be sketchy. In addition to inactive ingredients, another thing that isn't regulated is the manufacturing environment. For example, a factory making a generic drug could have a higher humidity level in the environment, which in turn can definitely affect the potency of the active ingredients.

    That being said, for some drugs, generics are A-ok. Like you put it, you just have to test it for yourself, and be careful about the perceived efficacy effect caused by branding campaigns.

  2. Update: according to this NYT article, generic Toprol XL, aka metoprolol succinate and "an extended-release generic version of Wellbutrin" have been recalled. Hooray for the good guys!