It seems to me that most everyone hates high drug prices (me too) so everyone heads toward generic the moment it is available. But we are facing problems with that. We all know that many of the generic drugs are manufactured in places without US standards and though the FDA and pharmaceuticals swear that they are safe and equivalent, there have been exceptions to that and lawsuits followed.
However, here I want to evaluate if doctors and the FDA understand chemical structure and if they are looking at that to see if the generic is a true equivalent to a brand name in active ingredients.
This blog is about the danger of your doctors not understanding the chemical structure of the medicines they prescribe, so cannot catch if there is a difference between a generic or a brand name. They do not (cannot) compare if the chemicals will be able to do the same in the generic as in the brand name in your body. Surely we know that we can fool our bodies and eat rubber thinking it is sugar. If it is sweet and looks like sugar, we will think we eat sugar but we may still die at the end of the day from eating a chemically different food from what we thought we ate.
This is definitely true in the case of food–just look at the history of several artificial sweeteners. So what about generic drugs? Do they have the same chemical structure as the brand name? And most importantly should they? What is a generic versus a brand name? That is what I want to discuss and want to guide you through one particular drug that I bumped into and nearly got killed by.
The brand name of the drug in question here is Singulair and unless you fall into the 1% of asthmatics for whom this is a life saver, you probably have never heard of it. Think of it as an environmental protection against asthma. I have asthma and I happen to be in this 1% so the chemical structure is important to me and it should be important to my doctor. It is important to note that many more asthmatics take Singulair than they need to. To test if you need it, stop taking it for a couple of days. If your asthma does not change (provided your environment does not change) you are in the 99% who do not need this medicine.
The generic name of a drug represents the name of the key ingredient(s) in the drug–by law. So for example, Advil is Ibuprofen since that is the key ingredient in both. There are generics for many drugs but of course brand name drugs have patent block for 20 years so until then, companies who manufacture generics do what is called “backward engineering.” Backward engineering takes the drug, looks at the patent information that contains just enough information to know what the end product looks like. They then chemically untangle and try to rebuild to have similar behavior in the generic drug to the brand name with the same active ingredients–also by law.
NTI (narrow therapeutic index) drugs can be tricky because the blood concentrations you need to achieve a therapeutic dose and the concentrations that will cause harm are very close together. Small changes in concentrations can lead to ineffective or toxic responses. Medications for seizures, heart arrhythmias, thyroid hormone, warfarin (blood thinner), and lithium are all NTIs. (source)
Not being equal to a brand name is fine as long as the name of the generic reflects the difference. Most do. Take Singulair. The main ingredient in the brand name is Montelukast Sodium. Generic medications providing the same are all called Montelukast Sodium and they come dime a dozen. But someone up or down in the food chain of drugs decided that oh.. sodium is not important… and dropped it and came out with a generic called Montelukast.
Montelukast is not Montelukast Sodium, as the name depicts. In fact, the generic manufacturers honestly state that by showing even the chemical differences–mind you this is already against the law. The law clearly states that the active ingredients in a generic must match that of the brand name 100% and only the inactive ingredients can be different (source).
Here is the chemical name and the look of the chemical chain of Montelukast Sodium, i.e. Singulair:
As you can see on the top right it has Na+ at the end–Na+ is sodium ion that will ensure it will attach to the proper receptors in the body. It is positively charged so it seeks out a negatively charged ion, in this case you see COO– there. This combination is important in the metabolism of the brand name drug–or generic drugs with the same chemical signature.
Now let us look at Montelukast, which is pretending to be generic for Singulair:
It is not listed but the molecular weight is 582 so way less than Montelukast Sodium that is 608.18.
Note how cleverly, wherever you see this chemical chain, it is always up-side-down – relative to how the Montelucast Sodium chemical chain is drawn. Why may that be? Could it be to deliberately take the eye off of the importance that instead of COO–Na+ we now have HO and O ? Plus many other changes!
To bring the point home easier, I transposed Montelukast’s chemical chain drawing into the same direction as Montelukast Sodium so you can see some of the differences better. It is not only the missing sodium. Here is what the two look like when they are side by side. Molenkulast Sodium (Singular) on top and Molenkulast on the bottom:
Oopsy! We have a big problem here! Not only is the sodium missing but also the chemical chain is broken in a different place in a different way and Molenkulast Sodium has H2C whereas Molenkulast has CH3 instead and an HO appears in that triangle in a different place. These have important indications in the human body! Perhaps the best way to put this is imitation crab versus the real crab: it may look like it and may even taste like it but the chemistry of the imitation crab is nothing like the chemistry of the real thing.
AMENDMENT on 8-26-2016: Since 2 doctors have commented below stating that the two molecules are identical (doctors Steve and Angela Grant), I would like to clarify in the article itself that the two molecules are completely different–my responses are written in the comments but to make it clearer, I add them here as well.
Dr. Steve suggested that the two molecules are the same because 1) the human body is always full of sodium so if the molecule needs a sodium it will pick it up and 2) as the molecule rotates in real life, taken in another view or angle the two are the same. So let me address his concerns since he is wrong on both accounts.
- Yes indeed, the body is always full of sodium. And as Dr. Steve correctly points out, in the body everything breaks down into ionic form and so he suggests–based on the molecule being able to pick up sodium from the body–that the sodium we have in the body is not already tied down by something else. That is chemically impossible since sodium (Na+) is an ion and as such, it will do everything possible to become a complete molecule and grab anything that has a negative ionic charge since sodium ion is positive (missing an electron). Exception to this are the ionic channels (all of our cells have many) in which case the function of the ions is to remain ionic and generate electricity taking advantage of the ionic charge differences. Sodium is unstable as ion and most certainly cannot await the arrival of a medicine. All sodium ions are already tied down in the body doing some tasks–or are to remain ions to conduct electricity. Most sodium is used as part of our electrolyte and as such it is used by our body to maintain hydration and to clear toxins out of the body.
- Furthermore, what Dr. Steve suggests assumes that a molecule–such as Montelukast–can pick up ions. A molecule is a stable form and it resists any changes to its structure. Thus as it disintegrates in the body into ionic components, it will perhaps pick up whatever else it can but at that point it is no longer Montalukast but its different ions, none of which necessarily will attract a sodium ion. In medicine, assumptions made are often dangerous guesses.
- Montelukast’s chemical formula is C35H36ClNO3S with molecular weight of 586.184 whereas Montelukast Sodium’s chemical formula is C35H35CINNaO3S with molecular weight of 608.18. As chemical equations, the rotation of the molecule no longer matters since it is a mathematical equation in which the left side of the equation must be the same as the right side. So let’s put them side by side and you decide: C35H36ClNO3S ?=? C35H35CINNaO3S Are they the same molecules? Not even close.
Dr. Angela Grant first suggested that since the body has “a lot Salt in the form of NaCl [sodium chloride]. I imagine Montelukast will pick up the Na+ regardless because of [its] strong affinity and our organs bathe in a pool rich with NaCl and other ionic compounds”.
- I provided answers to this in my response to Steve in point 1 above but this comment also assumes that NaCl remains NaCl in the body, in molecular form that is. NaCl is pure salt molecule that is stable and does not have the propensity to break up into ions unless it is forced to do so. The assumption that NaCl remains NaCl in our body ignores the metabolic chemical changes of anything that enters our body–though apparently this doctor was a chemistry major and is also a medical doctor. I wonder if NaCl stays as is, how on earth do we generate voltage that requires positive and negative ions on the two sides of all cellular membranes? Without NaCl breaking up into Na+ and Cl– to generate action potential, we have no cellular voltage at all. Action potential is when Na+ moves into the cell as Cl– remains on the outside of the membrane. Resting potential is when the positively charged potassium ions K+ flow into the cells as Na+ leave. Without ionic movement there is no life. Thus making the assumption that molecules don’t break up into ions is not understanding biochemistry and human physiology.
- Dr. Angela Grant also took the ingredient list of Singulair and Montelukast: “Each 10-mg film-coated SINGULAIR tablet contains 10.4 mg montelukast sodium, which is equivalent to 10 mg of montelukast...” lol… not sure on what planet is 10.4 mg of something equivalent to 10 mg of something but not on planet earth, as far as I can tell, that is an F- in math.
- However, she also states that we all are different and respond to medications differently and thus what may seriously affect my health may not affect yours. Totally true. However, when it comes to a medicine that is a standardized formula, there is no such allowance that a generic drug having a different active ingredient from the brand name is permissible because some people are different.
End of Amendment
Now you would think that a head doctor at a very famous and prestigious medical institution would check for such chemical differences before prescribing Montelukast instead of Montelukast Sodium to an asthmatic, whose ability to breathe may, in fact, be compromised by the generic drug!
Do you think they did? No. Why did they not check? Because of 3 reasons that I can think of:
- If you visit the Wikipedia and look for Singulair, you will get Montelukast and though I had a big fight with them, they refuse to see its significance since they say that on the FDA website the two, meaning Montelukast and Montelukast Sodium are the same–but that is actually not true.
- It is cheaper to produce Montelukast than Montelukast Sodium and thus medical facilities will pay less.
- I noted earlier that only 1% of the asthmatics benefit from the drug. Many get it who do not benefit. So for them it makes no difference if it is Montelukast or Montelukast Sodium since neither would work anyway. Thus there is no way to check, except in those rare cases, like mine, where it matters, if the generic as Montelukast works equivalently to the brand name that is Montelukast Sodium. This muddies the importance of getting the correct chemical formula!
Thus the answer is clear; those of us for whom the real stuff would work end up getting the fake stuff that will get us sick. This is not unique; it happens all the time to others as well. What makes it unique is that this time I was able to identify the difference and rest assured they will not get away with it without either changing to the real stuff or making the news as the bad guys. One of the two will happen! Their choice!
This is also a warning for you all out there who read this post! Our medical system has deteriorated to the point where we as patients must be better knowledgeable about our illnesses than our doctors are! It is time for us (you too!) to start taking a giant magnifying glass to all medications we take and compare ingredients and look at chemical charts. You don’t need to know what the chemical stuff means; you just need to see if they look alike!
I would love to hear your thoughts!
Amendment – July 22, 2014:
I would like to add to this article some important information. Today I called Merk, the pharmaceutical company that manufactures Singulair. They confirmed that indeed, Montelukast is not equivalent to Montelukast Sodium and the active ingredient in Singulair is indeed Montelukast Sodium.
I recommended they check the postings on Wikipedia on Montelukast and also on the NIH website (I linked here only one article but there are many more) because these articles are incorrect and wrongly represent Merk’s great product Singulair, which is Montelukast Sodium. It also gets people like me sick, since Montelukast does not have the necessary ingredient of Montelukast Sodium–in other words, Montelukast Sodium is one molecule. It is not equivalent for me to take Montelukast and a pinch of salt. Nope.
I thought I update you since now the assault on all fronts of the wrong information is on and my medical company better provide me with the correct drug!
I was also given the brand name medicine by my medical provider, resolving my problem.
End of amendment.