Why no one should take Nexium and it should never have been approved

I get the impression that this is a common scam. The same thing was reportedly done with loratidine (Claritin/Clarinex).

Maybe you should have titled your post - Why no one should take protein pump inhibitors at all - unless you want to increase your risk of pneumonia, c difficile, fractures, heart rhythm problems and more.....How about a Tums?

What surprises me is that it is difficult to find omeprazole in less than 20 mg. Fortunately, it seems to have a long half-life. I find that once every three days does the trick for me. But if I stretch it to four days, I get a little reflux. Yeah, I know: break the pills. But it's just as easy to take it every third day.

Herb -- I used to practically *eat* Tums. Omeprazole changed my life. You may think nobody has heartburn that bad, but actually some people do, to the point where the increased risks are well worth it. After all, erosive esophagitis is not only excruciating, it's also a major risk factor for esophageal cancer, which is frequently fatal. I was already finding it difficult to swallow properly due to a buildup of scar tissue. Omeprazole is wonderful. It is not for everyone; if you need one Tums a week, you do not need a proton pump inhibitor. Tums is fine for that. If you can eliminate heartburn by changing your diet or getting in shape, that's preferable, and will likely be good for you in other ways as well. But when you've exhausted all of that and still cannot sleep without sitting completely vertical, and are risking much worse pneumonia (yes, heartburn can be so bad you aspirate stomach contents), then PPIs can be your salvation.

Russell -- I so wish I could take such a low dose! Maybe you'd be better off with one of the H2 inhibitors like ranitidine or cimetidine. Have you tried those? I take 40mg of omeprazole daily, and if I miss a dose, I start to get heartburn. (BTW, just so you know, omeprazole does not actually prevent reflux. You still have reflux. It just isn't burning your esophagus so much.) If I miss two, I get horrendous heartburn -- one of the downsides to taking a PPI is that you get "rebound heartburn" when you discontinue it, because your body has attempted to adapt to the low acid production. It sorts itself out over time, but it's not fun in the short term.

For me, my only alternative to Prilosec would be surgery, and the studies I've seen have shown roughly similar long-term safety profiles for both. However, the short-term risks of surgery exceed the short-term risks of the drug, so as long as I can control it with 40mg omeprazole, I'm sticking with that. I do have a good friend who opted for the surgery, though in her case there was a secondary reason (obesity; depending on which surgery is selected, it can double as bariatric surgery). Also, her reflux was worse than mine. It turned out very well for her.

Now, as to omeprazole versus Nexium.... I've taken both. Both worked for me. I am happy taking omeprazole, as it's much cheaper and it definitely does the job for me. But there is actually a legitimate reason to pursue approval for both Prilosec and Nexium. From a regulatory standpoint, the main one is that they *are* different drugs. Yes, there is Nexium in Prilosec (so to speak), but the FDA deals in specifics, and the delivery mechanism counts. This is not a unique situation by any stretch of the imagination, so I'm not sure there would be a legal basis for refusing either the patent or the new drug application. I think you would need to change the law before you could preclude situations like this.

Herb, you comment is totally off base

PPIs are very good drugs. Yes those are all potential side effects, but also quite rare. Most the problems you describe are issues with inpatient use of the drugs and involve slight increases in things like nosocomial c. diff or pneumonia infection risk. The fractures are a slight increase in risk with very prolonged use of the drug.

There still these drugs are incredibly useful, allowing us to clear H. Pylori infections, help stop GI bleeding, help ulcers heal, and prevent the formation of stress ulcers.

For the typical outpatient use of the drug, a 2 week course, these drugs have excellent success rates compared to H2 blockers and tums. Many times the patients only need to take a course to resolve their symptoms for months or years.

For folks like Calli Arcale, who need these drugs to maintain quality of life with severe heartburn suffering, the one side effect of concern is fractures, and they might require monitoring of bone density or additional calcium/vitD supplementation. But that versus life with constant heartburn? Tums doesn't touch these people.

Finall Calli, I disagree with your last paragraph. Under current patent law this drug should not have been licensed. Nexium is not a different delivery mechanism. It is merely a purification of the same drug. AstraZeneca effectively patented a 50% pure drug, then 10 years later patented a 100% pure drug. That is illegal. It should never have been allowed. Further, if you look at the cited articles, the differences between the two are so small as to be laughable, and are easily explained by the fact they were effectively delivering twice the omeprazole dose with the nexium group. This was a highly unethical maneuver.

Thanks so much for this post. I was prescribed Nexium to take on a regular basis and it has helped me immensely. I have my vitamin and calcium levels checked regularly because of the caveats Mark mentions, but I think that's good to do anyway.

I'll give Prilosec a try, it's certainly a heck of a lot cheaper!

MarkH -- even if you restrict it to purifications of chiralities, it's not the only time that's ever happened. Focalin was patented despite it being just dexmethylphenidate (essentially, right-handed Ritalin). I'm not an expert in patent law, but whether or not it deserved FDA approval, I think that does actually make it different enough to earn patent protection. Hell, if XR formulations can get patent protection, why not? I am not the biggest fan of the drug patent system, mind you. I'm just unconvinced this violated it. After all, you can patent methods, and the patentable thing in this case would be the method of separating out the desired chirality. (I didn't finish my chem major, having fallen in love with computer science, but I did get far enough to learn that purifying by chirality is often challenging.)

More concerning is that you seem to be saying 20mg Nexium is as effective as 20mg Prilosec. That would suggest that in fact both chiralities are equally effective. Nexium might therefore be pointless (unless it reduces side effects, which I think would justify it, though I don't know if it does), but being pointless is not the same as being illegal. If I'm wrong, I would appreciate being educated on it; this is not at all my specialty, and I'm just an interested outsider.

Incidentally, I had similar results from my six-week course of Nexium following my first endoscopy as I did from beginning OTC Prilosec years later. Thinking back, I remember a couple of episodes of heartburn while on 20mg Nexium, but have had almost none while on 40mg Prilosec. (Those that I've had have been in association with either missed doses -- nasty -- or the flu, which, well, frankly that's pretty much a missed dose as well. You take it, but it comes back before it can do any good and there's no point throwing another dose down after it.)

James P -- my mother switched from Nexium to double-dose of OTC Prilosec when she lost her health insurance coverage. She's been doing okay as far as I know, though she's also the sort to say she's fine when she isn't, so I can't be totally sure. But it's worked well for me.

I'm actually not saying that nexium and prilosec are equal dose for dose. In fact Nexium worked a tiny bit better than an equal dose of prilosec in these trials, and I attributed that to the fact it was effectively twice the dose of prilosec.

So a not to James P, if you switch, you may need to take a bigger dose of omeprazole to acheive the same effect.

Finally, a method for purification of an enantiomer might be patented, or if the drug had a different side-effect profile from elimination of the other enantiomer. But how can you say that a mere purification deserves a patent? If I were to patent a drug that's 50% simvastatin at most and ten years later they gain the ability to purify it to 99% is that a new and novel drug?

Patents exist to encourage and protect novel discoveries. Enantiomers and their purification are not novel, the first such purification, of tartaric acid, was over 100 years ago. I did it in organic chem class in the 90s. Worse, many drugs are racemic with efficacy from just one chiral molecule, does that mean every drug maker with a patent on a racemic drug can double the patentable life of their compound just by making it more pure?

I'm not an expert on patent law but my understanding is that purifications don't represent novelty and can't justify a new patent. I feel like they pulled one over on the patent examiners with this one. If there's a patent lawyer out there reading, please chime in.

So it was slightly better? If it's really a case like Focalin, I'd expect a *significant* improvement over omeprazole with what amounts to a double dose. I suspect that both of the enantiomers are actually helpful, and that Nexium is just a lot of work on the manufacturing side for not a lot of gain.

I realize enantiomers are not novel, but since this has happened more than once, I'm inclined to suspect it is indeed something that is considered patentable. And if not, well, the *fact* that it has happened twice may constitute precedent.

Finally, a method for purification of an enantiomer might be patented, or if the drug had a different side-effect profile from elimination of the other enantiomer. But how can you say that a mere purification deserves a patent?

That's pretty much why I'm wondering whether it has a different side-effect profile. That *is* the case with Focalin, which I'm aware of because my daughter takes it. She tolerates it better than Ritalin, and it is effective at half the dose of Ritalin (exactly what you'd expect if, indeed, all the benefit is coming from one chirality, which from what you've said may not be the case with Nexium).

Calli, the only difference between the two, which AZ used to claim superiority so it could sell in US, was Nexium had a 90% cure rate at 3 months versus omeprazole at 87%. What it reflects is that once you've saturated the proton pump with drug (which it irreversibly binds to and inactivates) higher doses don't make much of a difference. The D-enantiomer of omeprazole has no biologic effect.

Now that it's been done, of course, this scam is becoming more popular. Lexapro (escitalopram) is the S isomer of Celexa (citalopram). Pretty much any generic name with "es-
" tacked on the front will likely be following this scam, in order to extend a patent (legally?).

I've never willingly prescribed Nexium for this very reason, but at the beginning to 2011 I got a lot of letters from insurance companies refusing to cover omeprazole and demanding that my patients be switched to Nexium. It seems AZ made a deal with a lot of insurance companies to get a good rate or something and keep the drug in circulation. Many of those now seem to be switching back, so I get letters refusing coverage again and now demanding that patients switch back to omeprazole. I'm sick of the paperwork but I'm sure my patients are much more sick of switching meds all the time.

Remember thalidomide? It was teratogenic? Turns out that thalidomide was racemic, and the inactive enantiomer caused birth defects. I believe that with ibuprophen, the inactive enantiomer actual inhibits the action of the biologically active enantiomer, but it's a moot point, as there is an enzyme that interconverts the two. With naproxen, only the biologically active enantiomer is sold.

Look at it this way: why take twice as much of a chemical compound than you need to take? With Nexium, this isn't the case, but it is with most single enantiomer drugs.

A single enantiomer is chemically different from the racemic mixture, that's why you can patent an enantiomer of a drug as different from the racemate.

I've taken both for chronic GERD and the omeprazole (generic) stopped working after not too long and when I went back to Nexium, it fixed the problem. So, they aren't identical in how every person responds. Also, just because the one enantiomer isn't biologically active as a PPI doesn't mean it doesn't interact with some other cellular or subcellular component we don't know about and I'd rather not find out down the road that THAT interaction was bad news. This is the same reason I stay far away from acetaminophen.

The same thing was done with Celexa (Citalopram) and Lexapro (escitalopram).

There are some claims that Lexapro works better for some people, but Citalopram costs about $8 a month and Lexapro is still under patent protection and costs a lot more.

I have used Lexapro and Celexa interchangeably when I was on vacation and my sister had Lexapro instead of Celexa. I didn't notice any difference.

Is anybody able to contrast omeprazole with pantoprazole?

I think there's a misunderstanding of patent law here. Companies may patent novel formulations of old drugs and have completely new intellectual property... when the old patent expires, anybody can sell the old formulation of the molecule, but if they have a new extended release formulation that gives improved pharmacokinetics and a resulting improved side-effect profile, then they have a novel product worthy of patent protection. Same thing with enantiomer separation. In fact, ANYBODY who could figure out how to separate the two enantiomers before Astra-Zeneca figured it out could have patented the single isomer. This would have effectively prevented them from marketing the single enantiomer.

I'm not saying that AZ wasn't shady here, but it's all within patent law. If AZ didn't have a valid patent, they probably would have had it invalidated in court by generic drug manufacturers right after they obtained marketing approval.

It's also worth noting that FDA did not approve Nexium based on any supposed superiority over Prilosec. As you can read for yourself here, FDA clearly states that AZ did NOT show that Nexium was superior.

As far as I know, there is no requirement that a "new" drug must be better than an old one to gain FDA approval. And personally, I don't think there should be.

I agree that it's probably silly and wasteful for patients (and insurance companies) to pay extra for Nexium. But I think it's incorrect and inappropriate to claim that AZ's patents on Nexium are illegal, or that they obtained FDA approval unethically. The problem is not in the patent or approval systems. The problem is the systems that lead MDs to prescribe, and insurers to pay for, a more expensive medicine that offers no clinical benefit.

Exactly so qetzal. One must separate patent law from FDA new drug approval. They are really separate beasts. FDA is tasked with assessing whether a new drug is effective and safe. Efficacy does not need to be better than currently prescribed drugs - witness the use of newer blood pressure meds that are not more effective than the older meds but are simply newer and more heavily marketed by big Pharma.

It is patent law that protects the manufacturers and that which needs to be addressed. In that, I disagree with your last statement qetzal. That is only half of the problem. The other half is the broken patent system.

Mary, patent law could surely use reform, but I fail to see how it's an issue in this situation. If we agree that Nexium offers no clinical benefit over Prilosec, who cares if AZ has a patent on Nexium? That doesn't prevent MDs from prescribing generic Prilosec, nor does it force anyone to take (or cover) Nexium. It prevents anyone else from making and selling a generic Nexium, but again - so what?

I would add to the uses for omeprazole that it's essential as preventive treatment for some people who must take large doses of NSAIDs such as ibuprofen, naproxen, or the various prescription NSAIDs. I developed some form of unidentified (non-rheumatoid) arthritis in my early 30s, and had to take a hefty dose of NSAID painkillers daily, along with mild opioid painkillers, to keep the pain in my hands under control enough that I could work and do basic everyday things. After a few years of this, I ended up in the hospital with so much bleeding from a duodenal ulcer that it nearly killed me. To make a longer story short, research has shown the combination of omeprazole and an H2 inhibitor are the gold standard of treatment for people taking large NSAID doses, and once I healed I was able to continue taking my medication together with omeprazole and ranitidine et al. without further serious ulcers.

(The severe arthritis pain has nearly vanished in recent years, as mysteriously as it appeared, so now I take none of those daily - but I've been exceptionally lucky.)

The real culprit in the Nexium story, in my opinion, is the marketing of new medicines without significant improvement over existing ones, and the willingness of doctors to be persuaded to prescribe specific medicines by questionable research.

Nexium is a mild case - look at the Celebrex and Vioxx story for a case where the new wonder NSAID not only proved eventually to have no benefit in ulcer reduction, compared to the older alternative, but had far worse side effects. Or look at the history of Serevent (salmeterol), which proved to be actively harmful in long-term use by the asthma and COPD patients it was prescribed to, actually doubling their chances of death due to asthma according to some studies. Even after the research was out, some doctors pooh-poohed it and continued to prescribe it until it was banned, and many are still prescribing Advair, which is salmeterol compounded with fluticasone and has not been shown to be any safer.

At my job, we have an expression for doing something that could make a kazillion dollars but ironically has no value to society. We call it "changing the side chain on Lipitor." Same deal as re-patenting this s-enantiomer.

I also like that they just added the 's' sound to the beginning of the drug name... ugh, did this have to pass a panel for approval, and if so, how did it pass?

Qetzal, Oh Qetzal!
Don't you understand this is all about the dollars? If AZ has an exclusive patent all they have to do is convince prescribing physicians -(ie marketing)-that their drug is "New and improved" and they can rake in the cash that comes from having a monopoly. This issue with AZ actually came to court in Arkansa in 2009 and the court ruled that AZ was well within its rights to play this sort of game to enhance profits....It's the American way!

ledoc,

Exactly. "All" AZ had to do was convince MDs and patients and insurers that Nexium was better than Prilosec, even though the clinical data showed no meaningful difference. THAT'S where the problem lies.

How did they do that? If they used misleading statements or bribes or kickbacks, then those are the problems that needed to be addressed here. However, if MDs agreed to prescribe Nexium over Prilosec even when they knew there was no clinical benefit, that's a different problem.

The fact that AZ had a patent is ancillary. The point is that they shouldn't have been able to convince people to use Nexium.

MarkH: "What it reflects is that once you've saturated the proton pump with drug (which it irreversibly binds to and inactivates) higher doses don't make much of a difference. The D-enantiomer of omeprazole has no biologic effect."

Really? That surprises me, because I definitely get measurably better control with 40mg omeprazole than with 20mg. Do you have a reference on that? I'm interested to read it. 87-90% seems like so small a difference I have to wonder if it's clinically relevant, yet I and several people I know have had a measurable improvement by either switching to Nexium or doubling their dose of omeprazole. (I'm talking about relatives here; GERD runs strongly in my family.)

ledoc: Of course it's all about the dollars to AZ; that doesn't change his point that what was done is not actually illegal. And I have to agree that I don't see why the FDA should not have approved Nexium. As qetzal said, there's no rule that says a new drug has to be superior to an old one. It just has to be safe and effective for the approved indication. Anything more is beyond FDA's jurisdiction. They're not in the "telling people what meds to take" business, as much as the alties want us to think.

The marketing problem is a separate problem, and I think needs to be addressed from a different angle. Restrict advertising, perhaps, but better to enlist doctors themselves.

KrisS: "I've never willingly prescribed Nexium for this very reason, but at the beginning to 2011 I got a lot of letters from insurance companies refusing to cover omeprazole and demanding that my patients be switched to Nexium."

Seriously??? Everybody I know (including myself) had the opposite experience: their insurance companies refused to routinely cover Nexium, or other drugs such as Protonix, when generic omeprazole was available. Your experience seems to run counter to an insurer's best interests.

Now, I *could* see an insurer refusing to cover omeprazole on the basis that it is available without a prescription and permitting Nexium (at a higher copay, most likely, due to being brand-name) because it's not. I had to switch off of Allegra years ago because my insurer wouldn't cover it -- this was the year that Claritin went OTC, and they needed some sort of doctor justification for not using Claritin (which they would not be obliged to pay for). Now, of course, Allegra is not only available OTC but is available in generic form. I stuck with Claritin, though; Allegra's gigantic.

You state that the elimination of this redundancy could save the healthcare system $5 billion annually. How many other opportunities are there to save ourselves money by bringing greater clarity to drug formulation? Conversely, how many jobs would be eliminated if the newly-less-desired product is made in the USA. Then, how many jobs would be created on K Street, where lobbyists would go back to congress and start all over.

Count me as an asthma sufferer who is willing to risk the mysterious possible long-term bump in mortality rate for the actually being able to function effect serevent gives me. *Maybe* the reason epidemiology shows serevent users more likely to die of asthma in the long term is that *the doctors wouldn't be giving us this extra medicine if we weren't already suffering worse than other asthma patients*.

Is there a difference between this case and Escitalopram/Citalopram by Lundbeck ?

Samantha -- former Advair user here. I stopped not because of the salmeterol thing but because I didn't need it anymore. (My asthma has fluctuated in severity over the years.) They actually controlled for severity of the asthma; they were looking particularly at mild-to-moderate asthma. As I understand it, the main speculation was that because salmeterol was so danged good at suppressing symptoms, it became easier for some patients to believe they weren't really that sick and stop taking their condition seriously and maybe even stop taking their controller medications. (Steroids and whatnot.) Advair got a bit of a pass because it includes a controller medicine right there; you can't forget to take your controller medicine with Advair, because it's part of the package. This speculation is unproven, but fairly compelling, especially since the difference in mortality was mainly seen among minorities, who tend to be lower income and thus might be more inclined to hoard or even discontinue a medication if they don't feel they absolutely need it right at this second.

Personally, I think it's mostly a reminder of the need to a) take your asthma medications exactly as directed, b) discuss with your doctor if you feel it needs to change, and c) get regular checkups to monitor your condition, especially if your asthma is severe.

Salmeterol may be associated with increased risk of death compared to albuterol; but no one who has taken both can deny that salmeterol is a lot more comfortable. It lasts longer and it doesn't give you the shakes. I have a collection of albuterol inhalers squirreled away in various locations around the home and office; the stuff does work, and I *love* it for that. But the side effects are definitely unpleasant, and that can sometimes justify the increased long-term risks. The main thing to remember with any bronchodialator is that it does not treat asthma. It only relieves the symptoms. For a very mild attack, that can be sufficient; for moderate to severe asthma, you need steroids to get the inflammation down, or you'll be gasping for breath again as soon as the bronchodialator wears off.

Consider the following scenario. A patient is given omeprazole. Symptoms subside somewhat but not completely. The physician considers doubling the dose or giving Nexium. I think a good case could be made for giving Nexium as the prefered choice (see #12 above).

This seems at least a good enough reason to put the product in the hands of physicians. If it is over-prescribed, it is a failure of the physicians not of the FDA or PTO.

so in other words, you get less strength for the same drug. Well, as it stands I'm taking $75 worth of OTC Prilosec a month and it's not completely effective. Now if I take Nexium, it cost half as much with my insurance and twice as effective....sounds like a solution for me.

The problem with calling it, "shouldn't have been patented", is that you also get cases where the mirror image formulations of a drug actually have *different* effects, not just one inert one. This can lead to either side effects that the purer form doesn't, or even counteract the ones you do want.

So, yeah, removing inert/counterproductive parts *can* be a legitimate reason to patent a new form of it, since since the patent isn't just the product, but the process to get to it. However... Whether this is the case in all circumstances, such as this one, where the mirror does nothing at all, is another issue.

Charlotte -- depending on your insurance plan, you might want to consider prescription-strength omeprazole. I'm on that. Under my insurance plan, which has a much larger co-pay for non-formulary brand-name medications such as Nexium, this is much cheaper. You might want to explore that option as well, but check the details of your insurance plan first.

it s rather unfortunate...it s a collusion of d power that be ...d lawmakers soldout!

Interesting reading all the flatulent arguments against the only drug that gives me any effective relief...

All I know is 40mg Nexium costs $96 a month in Canada for 34 pills, I don't know why a months supply is 34, but it is. Anyway,I got OTC 20mg Omezprazole in the US at Costco for $5.66 a box of 14,with the enclosed advice to use only one 14 day course of therapy evey 4 months.I wasn't aware of such a restriction for Losec ! So a years supply is $17, versus $1152 for Nexium. My doctor happily prescribes a full course of Nexium each month. The Nexium does have a nice box though. Hmmm.

Mike,

OTC omeprazole has that warning to make sure that you see a doctor at some point instead of just self-treating. After all, heartburn bad enough to require a PPI could be a sign of a very serious underlying condition, such as esophageal cancer, and puts you at risk of several other serious conditions that you should probably be checked for. There are also potential long-term risks, so it's good to be under a doctor's care when using it long term.

If your doctor is okay with you taking OTC omeprazole, it's probably safe to ignore the "don't use it more than x courses of treatment per y months" and just take it all the time. I'd ask your doctor.

I have occasional reflux, with the occasional burn from it. I would never take it if I hadnt been presribed it before. I've also had PARIET...rabeprazole, which says its the same as NEXIUM..an H+,K+-ATPase inhibitor...so whats the difference there then, except Pariet is 10mg?. All these ""eprazole" drugs become very confusing as they all appear to do the same thing at vastly different prices. Rab..Om..Esom ? At least people in the US have OTC stuff, we finally got 150mg ranitidine (and 81mg aspirin) here in Canada and my doc didnt even know about it! Who's ripping who off? It seems to me its all about money