Those Pesky Inactive Ingredients in Generic Drugs! Cipro vs. Ciprofloxacin.

I thought I wrote enough about generic versus brand name already but then the antibiotic dug class quinolone hit my radar screen and here we go again. In talking to friends and sufferers on Facebook and elsewhere who have access to attorneys specializing in cases like this, the subject of inactive ingredients came into question as a result of two cases that went in front of court where people tried to sue a generic manufacturer but were unsuccessful. Both cases ended up at the US Supreme Court, which is odd since their job is to decide on Constitutional matters and generic drugs would not seem to be appropriate for that.

The first case referred to was handled by the US Supreme Court in 2010: Pliva, Inc., et al v. Mensing and the second case in 2012: Mutual Pharmaceuticals Co., Inc. v. Bartlett. In both cases, however, the supreme court decided on the side of the pharmaceuticals, noting that “Once a drug is approved, a manufacturer [including generic drug manufacturer] is prohibited from making any major changes to the “qualitative or quantitative formulation of the drug product, including active ingredients, or in the specifications provided in the approved application…. [including] labeling,” which also consists of all adverse side effects listed on the brand name drug’s list of adverse side effects. (emphasis added)

Thus what the Supreme Court suggested is that the generic manufacturer’s active ingredient in the generic drug must be the same as the active ingredient in the brand name and since the active ingredients in the brand name and the generic drug are the same, and the FDA approved it “as is” already, there can be no changes made. The FDA approved the brand name drug based on the safety of the active ingredients in the brand name drug. Since the brand name drug and the generic drug active ingredients are the same, this relieves the generic manufacturer from any responsibility. Whether it caused adverse side effects not listed on the box label is irrelevant since there can be no changes made once the drug was FDA approved.

Note that there is no mention anywhere in the US Supreme Court case about the inactive ingredients!

Hold it right there! If I am a generic manufacturer and my inactive ingredients modify the absorption of the active ingredient and thereby convert the good drug under the brand name into a toxic generic drug then… well what then?!

As it happens, this is the case more often than not. In the case of Cipro in particular, the active ingredient is Ciprofloxacin. One of the most important inactive ingredients is a film coating (meaning it probably absorbs in a place other than the stomach) but the generic equivalents need not contain that film coating because it is considered to be an inactive ingredient.

So if the pill absorbs elsewhere in the body in the generic than in the brand name, does it not modify the generic drug to be a different drug from the brand name? Should the generic that works so differently not require a new drug application (NDA) and an FDA approval the same way as any new drug would have to? One of the reasons why brand name drugs are so expensive is precisely because of all the work it takes to pass the NDA process and all the clinical trials that come with that.

Thus this is the main problem: inactive ingredients matter in how the drug is absorbed but they are not considered to be necessary and are not active ingredients.

Here is the example for you with Cipro brand name and one of the generic manufacturer’s Ciprofloxacin, generic for Cipro:

Cipro brand name:
Active ingredient: ciprofloxacin

Inactive ingredients:

cornstarch, microcrystalline cellulose, silicon dioxide, crospovidone, magnesium stearate, hypromellose, titanium dioxide, and polyethylene glycol

Cimprofloxacin generic:
Active Ingredient: Ciprofloxacin

Inactive Ingredients:
Hypromellose 2208 (15000 MPA.S), lactose monohydrate, magnesium stearate, modified corn starch (1-Octenyl succinic anhydride), sodium starch glycolate type a potato, titanium dioxide, triacetin, (cornstarch, microcrystalline cellulose, silicon dioxide, crospovidone, hypromellose, titanium dioxide, and polyethylene glycol)

Inactive ingredients that are in the generic drug but not in the brand name drug:

  • Hypromellose 2208 (15000 MPA.S), 
  • lactose monohydrate, 
  • modified corn starch (1-Octenyl succinic anhydride),
  • sodium starch glycolate type a potato,

Inactive ingredients that are in the brand name drug that are not in the generic drug:

  • cornstarch, microcrystalline cellulose,
  • silicon dioxide,
  • crospovidone,
  • hypromellose,
  • polyethylene glycol

Inactive ingredients in both the brand name and the generic drug:

  • magnesium stearate
  • triacetin, 
  • titanium dioxide

The differences between the inactive ingredients of the brand name and the generic drugs may explain why of the 1800 complains against this drug, in the quarter ending June 2014 in the FDA database, 1600 complaints were about generic and only 200 about the brand name drug!

The two lawsuits against the generic manufacturers were set up on the wrong legal base. Given that adverse side effects grow every day and are added to the FDA database but not to the drug’s warning–remember, once the drug is FDA approved, modifications are not possible, the list cannot be amended except in special circumstances. I now understand that fighting on the grounds of the adverse side effects not being listed cannot be done without a constitutional argument; hence these cases ended up at the US Supreme Court! A case fought on losing grounds cannot win. The attorneys should have known better!

Why did the attorneys not fight on the basis of the inactive ingredients instead? Apparently I am told some attorneys believe that the inactive ingredients must also be the same as the active ingredients (lawyers should not be believing anything until they researched the facts)! But if one reads the cases carefully, it is clear that only active ingredients matter in the eye of the law. There is room for a discussion (and a fight) on the inactive ingredients since they modify the active ingredient’s absorption, thereby creating a new drug that was not FDA approved

Do we have a case to fight generic drug makers whose inactive ingredients modify the drug to be different form the brand name? You bet! A generic drug that behaves in the body differently from its equivalent brand name drug is a different drug and needs FDA approval! It is an illegal drug that is sold without being approved by the FDA. It is that simple!

Are you an attorney? Please contact me!

Comments are welcomed!

Angela

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About Angela A Stanton, Ph.D.

Angela A Stanton, PhD, is a Neuroeconomist focusing on chronic pain, electrolyte homeostasis, and genetics. She lives in Southern California. Her current research is focused on migraine cause, prevention and treatment without the use of medicines. As a forever migraineur from childhood, her discovery was helped by experimenting on herself. She found the cause of migraine to be at the ionic level, associated with disruption of the electrolyte homeostasis, resulting from genetic variations of all voltage gated channels that modulate electrolytes and voltage in the brain, insulin and glucose transporters, and several other related variants, such as the MTHFR variants of the B vitamin methylation process and many others. Migraineurs are glucose sensitive and should avoid eating carbs as much as possible. As a result of the success of the first edition of her book and new research and findings after treating over 4000 migraineurs world wide, all ages and both genders, she is now finishing the 2nd edition. The 2nd edition is the “holy grail” of migraines, incorporating all there is to know and also hypotheses. It includes an academic research section with suggestions for further research. The book is full of citations to authenticate the statements she makes to be followed up by those interested and to spark further research interest. It is a "Complete Guide". Due out in the summer of 2017. Dr. Stanton received her BSc at UCLA in Mathematics, MBA at UCR, MS in Management Science and Engineering at Stanford University, PhD in NeuroEconomics at Claremont Graduate University, and fMRI certification at Harvard University Medical School at the Martinos Center for Neuroimaging for experimenting with neurotransmitters on human volunteers. For relaxation Dr. Stanton paints and photographs. Follow her on Twitter at: @MigraineBook
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2 Responses to Those Pesky Inactive Ingredients in Generic Drugs! Cipro vs. Ciprofloxacin.

  1. Leroy Kollock says:

    Hi Angela my name is Leroy and I too have been having trouble keeping attorneys to fight for my rights since this drug ruined my life. I do agree with what you said because the inactive ingredients are different and thus makes it another drug that was not approved by the FDA. There have to be something that can be done to fight this decision because my life is totally ruined. Is there something that I can do to help the situation and also fight since I lost a 75,000 a year plus job.

    Liked by 1 person

    • Be Healthy says:

      Wow, very sorry to hear about your struggles Leroy! I hope that I may be helpful here.

      Not knowing your exact injuries–since there are more than one kinds–and also not knowing your age (youth helps), I am guessing here but hear me out and see if I make any sense. You may already have tried my recommendation. I was lucky and only have (so far) felt the effects of being floxed in partially torn Achilles tendons, which I was able to recover from though it took me some time. I am just now starting up new symptoms that I call “vibrating” which I think is better defined as an “internal tremor” (similar to essential tremor only not visible and is the lower half of the body). I am not sure it is connected to being floxed, but in any case, these are my damages so far as I can feel that have no other explanation. I don’t know what yours are but I assume you are facing more disabling nerve damage.

      I am in the field of neuroscience and so have done a lot of literature search and also self experimenting. I found (and read a lot about) that the ketogenic diet has some very interesting benefits. It is not the diet per se that is helpful for cell regeneration and the trashing of the damaged ones but fasting. Since quinolones damage mitochondria DNA, and since mitochondria replicates in-cell as an “untouchable” and because it is the one providing all the ATP, changes are only possible by removing the damaged mitochondria and replacing it with new one. The magnitude: each cell in the body has over 100,000 mitochondria and brain cells over a million. The cell is not able to tell the mitochondria to commit apoptosis (programmed suicide) since all mitochondria in the cell would have to be killed and that causes cell death. Rather, generating stem cells (your own stem cells) with undamaged mitochondria is the way to go.

      In fasting process the body becomes more aware of cells that are not functional and it removes them and replaces them with new ones it creates from stem cells. It also increases the number of healthy mitochondria in order to get more energy from the little each cell has access to as a result of the fasting (starvation) and so there is a better chance for cell replacement and mitochondria replacement. This is the only way mitochondria can be “repaired” by replacement since unlike the human DNA that contains a ton of unused DNA fragments that can be used as fixing, the mitochondria DNA is “exact” meaning no empty or unused DNA. Repair is not possible. So forcing new cell generation is clearly the way to go but…

      Unless one in on the ketogenic diet, fasting can be harmful and very uncomfortable so if you haven’t yet tried it, I recommend you do. There is much ketogenic information out there that is either incorrect or is incomplete. If you are interested to learn the real kind, I have 2 groups for this purpose on facebook. One is called “keto mild for migraines” which, as the name implies, is geared toward migraine prevention but is a good intermediate step to get into keto the proper way.

      The other group is called Floxed and is very specific to those who have been floxed only it is very small since I just started it and have little time to focus on it now (finishing the 2nd ed of my migraine book).

      The keto mild group has much more information for now on the how to and what to do and those who join with things other than migraines receive different help. I suggest you join so we can chat (these are closed groups) more openly and discuss what works and why.

      In terms of the law: that is unfortunately a bigger issue than we can fight. It would need to be a lawsuit against the FDA for its regulation of treating generic drug manufacturers to a lesser requirement than brand name manufacturers. Next, assuming that we won and the FDA changes its rules to hold generic manufacturers to higher standards, we also have to win a near constitutional magnitude lawsuit to allow individuals to sue generic drug manufacturers. Both of these would be financial nightmares since something like these would not be possible pro bono. The legal expenses of expert witnesses alone could end up in the millions and who will pay for that? Furthermore, the expert witnesses themselves would be of lesser quality (unless they were floxed themselves) since the FDA would pick up the most experienced expert witnesses and with deeper pockets will outcompete. A lawsuit like this may last longer than we live as well.

      Next, we need to observe that none of our cases can have any applicability to these new laws (assuming we won) since no law can be retroactive to hold a company up to the new standards that did not exist at the time we took those medicines. In some cases though, like in car manufacturing issues, this is different. I am not familiar enough with the law to know how that works and why there they can act retroactively but elsewhere they cannot.

      I hope you find this helpful–albeit I am aware I did not provide a solution.

      Hugs,
      Angela

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