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As I discussed earlier this week and some time ago on Canvas, brand name and generic drugs simply aren’t the same, even with the same active ingredient. Switching to brand Wellbutrin XL and Adderall XR has made an enormous improvement in my ability to function. So the question I’m exploring today is, why?

Inactive Does Not Mean Irrelevant

I like my little orange friend on the right much better than its imitator on the left.

I like my little orange friend on the right much better than its imitator on the left.

Because the active ingredients that actually constitute the “medicine” are the same (by law, within 80%-120% of the original) today’s topic is the inactive ingredients. Therein lies the difference between brand name and generic medications. Don’t believe the lies perpetuated by the FDA and swallowed whole by everyone else under the sun: having the same concentration of the active ingredient does not an equivalent medication make, particularly for extended release medications.

I did a little research on the ingredients in Adderall XR and Wellbutrin XL to compare against the generics by manufacturer – notably, many manufacturers have multiple distributors for generics. I also looked up what some of the mysterious chemicals actually are, and then coded them by alarming qualities: allergens, carcinogens, animal products, restricted by some religions (beyond animal products), toxins and other health risks.  It’s all online but the source material is a mess.

Disclaimer

I am not an expert in pharmaceuticals, I was not exhaustive in my methods, and I do not guarantee that the data ore presentation thereof are error-free. I looked up the ingredients but not in depth, so other sources may list some ingredients as an irritant where I did not find such information. The data I assembled follows the discussion so that you can do your own research and draw your own conclusions.

Adderall XR

The only notable property, given my lack of success in searching out more manufacturers, is the inclusion of several common allergens in the Actavis generic, particularly food dyes. That is probably due more to the fact that the capsule is blue than anything else, because there are not many natural blue coloring agents besides indigo – a similar list of food dyes is probably present for the brand drug’s blue capsules too. However, food dye allergies are one of the causes of ADHD-like behavior in children who do not have ADHD, and presumably some who do. One of the dyes isn’t even approved for use in food (D&C as opposed to FD&C) which suggests it’s kinda nasty.

Actavis also appears to have substituted corn starch for talc, which seems odd given the rising rate of corn allergies, but talc is a carcinogen and it seems as though most substances that fulfill the same purposes (largely to do with the manufacturing process, as far as I can tell) are similarly problematic. But really, do these ingredients behave the same way in my gastrointestinal tract?

Wellbutrin XL

I dug deeper with Wellbutrin XL and its generics, in part because of the long-overdue FDA investigation into Impax and Teva for manufacturing a non-bioequivalent drug. Bioequivalence means that the drug should release at about the same rate and concentration, despite having different inactive ingredients that affect the release of the drug. With a long and profitable history, bupropion HCl generics are numerous, as are variations between the ingredient lists.

With few exceptions, the generics have longer ingredient lists than the brand drugs; in fact, I counted up to 11 ingredients that were not present in the original, and total ingredient lists that were twice as long. This is usually not a good sign in processed foods, where extra ingredients often make up for various deficiencies, real or perceived. But even the shortest generic recipe, which I’ve taken, is a far cry from the name brand in terms of efficacy – at least for me.

As is also apparent with the color-coding, the generics have more potentially objectionable ingredients as well, and a wider variety of them. For example, Wellbutrin XL contains only one ingredient I could find obvious problems with – povidones – which are needed for its sustained release, and are an allergen for only a very small number of people.

Granted, most of the potentially carcinogenic, toxic, and allergenic ingredients in all of these drugs are consumed in such small quantities that the FDA “Generally Regarded as Safe” label applies in spirit as well as letter, and most of us will probably come to no harm. That doesn’t mean people should be fed carcinogenic ingredients if there are alternatives, and usually there are.

We do not all metabolize these drugs the same way either, and as the Teva Budeprion debacle demonstrated, “extended release” may be more or less extended, which can have serious ramifications in terms of therapeutic response. As most adults in consumer cultures have learned, a “generic” label means that sometimes you get exactly the same thing, sometimes you get an equivalent but different thing, and sometimes you get an equivalent-looking but inferior thing. The intention of all the FDA rules is that you get an equivalent but different thing, because in pharmaceuticals, a generic can’t be the same as the brand due to intellectual property laws.

It seems, however, that we may often be getting an equivalent-looking but inferior thing. Perhaps the brand drugs use more expensive or trickier to manage ingredients, or higher quality versions of the same ingredients. We’ve all noticed that the soda pop that uses cane sugar costs more than the soda that uses high fructose corn syrup, right? In fact, it might be considered a defining characteristic of premium sodas: they use cane sugar, not corn syrup. Cane sugar is harder to work with and more expensive than corn syrup, I’m willing to bet, but it also tastes better.

Back in the world of prescription drugs, maybe glyceryl dibehenate costs more than methacrylic acid or is harder to handle – I really don’t know, but none of the generics use it. Or perhaps it’s substantially more expensive but causes fewer side effects, so that when the generic manufacturers choose alternative formulations, what they’re really doing is trading off cost against side effects. Certain side effects can be directly attributed to the active ingredients in these medications, but the so-called inactive ingredients can also wreak havoc on your innards.

The brand drugs can’t be raced to market quite as quickly as a generic version thereof, and if they’re preparing for first-round approvals, why let something avoidable like allergens in the filler spoil those very expensive trials? If you know that you’re going to be the only game in town when a drug goes to market, you’re more motivated to ensure that your product doesn’t include easily-avoided ingredients like lactose, gluten, and corn, which absolutely will make a lot of people sick. Given how much money they charge for a new miracle drug, it behooves them to avoid creating a quandary for vegans or those who observe strict religious diets, for example, making the brand drugs the last haven for the extremely allergic or seriously devout. Even in small quantities, allergens and ethics matter.

Conclusions

Read your prescription labels, figure out the manufacturer, and for goodness’ sake, look up what’s in that pill – especially if you have food and/or chemical allergies.

Remember the old adage, you get what you pay for? I’m afraid that despite the official party line claims that generics and brand drugs are “the same” (in some parallel universe, maybe) it seems the saying is just as true with prescription medications as anything else. And just like you don’t always need a brand name product to get the job done, sometimes there’s something about the original product that outshines its knock-offs.

In what world do we expect dollar-store generic goods to be every bit as high quality as a “household name” label? The only reason we believe generic medications will work the same is that we’ve been told that drug efficacy is limited to the active ingredient. The evidence suggests quite convincingly that it’s not.

Data

Coding scheme:

  • allergen
  • carcinogen
  • toxin, irritant, or other health risk
  • animal product
  • restricted by some religions
  • not in the brand drug

Also: I have organized the ingredient lists alphabetically to make them easier to read, and because I can’t tell if the order of ingredients is meaningful like it is on food labels. The likely function of some of the ingredients is described upon the first mention, but my explanations are best guesses based on limited web searching.

ADDERALL XR, 20 mg capsule, brand, manufactured by Shire or Barr:

  • ferric oxide red (capsule coloring)
  • ferric oxide yellow (capsule coloring)
  • gelatin (capsule)
  • hypromelloses (sustained release; other possible functions)
  • methacrylic acid – methylmethacrylate copolymer (1:1) (sustained release)
  • sucrose (sugar)
  • talc (for manufacturing process)
  • triethyl citrate (capsule/coatings)

DEXTROAMPHETAMINE-AMPHETAMINE SALTS, extended release, 20 mg, Global

  • same as brand, plus titanium dioxide (probably white pigment)

Same as above, Actavis – color-coded as light blue, instead of the orange that all other manufacturers use for 20 mg caps

  • corn starch
  • D&C yellow #10
  • FD&C blue #1
  • FD&C blue #2
  • FD&C red #40
  • ferrosoferric oxide (probably black pigment for markings on capsules)
  • gelatin
  • hydroxypropyl cellulose (disintegrant or binder)
  • methacrylic acid – methylmethacrylate copolymer (1:1)
  • methacrylic acid – methylmethacrylate copolymer (1:2) (sustained release)
  • propylene glycol (solvent)
  • shellac (excipient with several possible functions)
  • sucrose
  • titanium dioxide (usually a pigment)

WELLBUTRIN XL, 150 mg or 300 mg (pills are identical except for volume), brand, manufactured/distributed by Valeant, BTA, Physicians Total Care, Physicians Partners, or Stat Rx

  • ethyl cellulose (several possible functions, including preservative and bulking)
  • glyceryl dibehenate (several possible functions)
  • methacrylic acid – ethyl acrylate copolymer type a
  • polyethylene glycols (sustained release, binder; other possible functions)
  • polyvinyl alcohol (emulsifier, stabilizer)
  • povidone (binder, sustained release)
  • silicon dioxide (probably for manufacturing processes)
  • triethyl citrate

BUPROPION/BUDEPRION HCL XL extended release, manufactured by Actavis

  • copovidone (binder, sustained release)
  • hydrochloric acid (pH control)
  • hydroxypropyl cellulose (manufacturing process or possibly sustained release)
  • methacrylic acid (presumably sustained release)
  • polyethylene glycols
  • polyvinyl alcohol
  • silicon dioxide
  • sodium bicarbonate (odor absorption, antacid)
  • sodium lauryl sulfate (excipient)
  • talc
  • titanium dioxide
  • triethyl citrate
  • water (WTF?)

Same by Watson

  • colloidal silicon dioxide (numerous potential functions, including bulking)
  • ethyl cellulose
  • hydrochloric acid
  • hydroxypropyl cellulose
  • methacrylic acid – ethyl acrylate copolymer (1:1) type a
  • microcrystallized cellulose (excipient, other potential functions)
  • stearic acid (likely for manufacturing process; can be vegan but don’t count on it)
  • talc
  • titanium dioxide
  • triethyl citrate

Same by Edgemont, marketed as “Forfive XL” – 450 mg (max dose)

  • carboxymethylcellulose sodium (thickener; wheat-based)
  • copovidone K25-31
  • hydrochloric acid
  • hydroxypropyl cellulose type H
  • hypromelloses
  • magnesium stearate (for manufacturing processes; may affect release time; can be vegan but don’t bet on it)
  • methacrylic acid – ethyl acrylate copolymer (1:1) type a
  • polyethylene glycols
  • polyethylene glycol 8000
  • silicon dioxide
  • stearic acid
  • talc
  • triacetin (excipient; solvent, humectant, plasticizer)
  • titanium dioxide

Same by CMC CMO

  • hydrochloric acid
  • hydroxypropyl cellulose type H
  • magnesium stearate
  • methacrylic acid
  • PVP/PA copolymer (povidone/polyvinyl alcohol)
  • polyvinyl alcohol
  • polyethylene glycols
  • povidones
  • sodium bicarbonate
  • sodium lauryl sulfate
  • silicon dioxide
  • talc
  • titanium dioxide
  • triethyl citrate
  • water

Same by Mylan

  • ferrosoferric oxide
  • hydrochloric acid
  • hypromelloses
  • magnesium stearate
  • mannitol (sugar alcohol; can facilitate drug delivery to brain)
  • methacrylic acid – ethyl acrylate copolymer (1:1) type a
  • microcrystallized cellulose
  • polyethylene glycols
  • polysorbate 80 (emulsifier)
  • polyvinyl alcohol
  • povidones
  • silicon dioxide
  • stearic acid
  • talc
  • triethyl citrate

Same by Wockhardt

  • ammonium chloride (pH control)
  • ethyl celluloses
  • ferrosoferric oxide
  • glyceryl dibehenate
  • magnesium stearate
  • methacrylic acid
  • microcrystallized cellulose
  • polyethylene glycols
  • polyvinyl alcohol
  • propylene glycols
  • shellac
  • silicon dioxide
  • talc
  • titanium dioxide
  • triethyl citrate

Same by Anchen, distributed by American Health Packaging

  • alcohol
  • ethyl celluloses
  • hydrochloric acid
  • hydrogenated cottonseed oil
  • hydroxypropyl cellulose type H
  • isopropyl alcohol
  • methacrylic acid – ethyl acrylate copolymer (1:1) type a
  • povidones
  • silicon dioxide

Same by Anchen, distributed by Stat Rx

  • alcohol
  • ethyl celluloses
  • hydrochloric acid
  • hydroxypropyl cellulose
  • povidones
  • siicon dioxide
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