Why you shouldn't take Nexium

The sciencebloggers are abuzz after a WSJ editorial mentioned Nexium, a heartburn medication, repeatedly by name, implying that it is some kind of wonder drug. Nexium was developed by AstraZeneca because its flagship anti-heartburn med, omeprazole (sold under brand names like Prilosec or Losec) was going off-patent. I take omeprazole for reflux, and it works just fine. I've never tried Nexium, and now I'm glad I steered clear of it, as it is an absolute ripoff in every sense of the word: a compound that never should have been granted a new patent, whose "improvement" over omeprazole was demonstrated by cooking the research.

In clinical trials the only difference between Nexium and its off-patent parent drug are modest improvements in some symptoms at distant time points; however, it is standard in these trials to compare 20mg of Nexium to 20mg of Omeprazole. In other words, the trials that have justified the use of this drug compared to the generic only show that when two times the amount of the active compound is used (1 nexium = 2 omeprazole), a slight improvement in some symptoms (87% vs 90% for cure of gastroesophageal reflux disease at 8 weeks) is achieved.[1-2] This is a result that is certainly not worth 4-8 times the cost.

Based on patent law AstraZeneca should never have been able to patent esoomeprazole as a new drug since they had already patented the same active ingredient when they patented prilosec. They effectively patented the same drug twice, thus doubling the time their drug can avoid generic competition. However, in order for the scam to work they had to pull one over on the regulators (coincidentally they spent millions in lobbying congress the year before Nexium was approved), then advertise the hell out of Nexium to make it appear it was somehow superior to it's chemically identical sibling drug Prilosec.

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

(Image: Nexium, a Creative Commons Attribution (2.0) image from tomsaint's photostream)

• [CLamb]

  I have used both Prilosec and Nexium and find that Prilosec works better for me.

  • [Can Koçak]

    Try stopping wheat consumption…

    • [Adam Pearce]

      Try stopping giving random dietary advice.

      • [awjt]

        Exactly.  What works for one person may or may not work for another person.  I took Nexium (a $250 prescription!) and it worked exactly the same as the Omeprazole that I take now ($30!!!).  No difference.  The key, for me, is to take it EVERY night.  Yes, I also try to eschew things that cause my acid to gurgle up, like acidic foods, coffee, alcohol, too much food too late at night, etc.  And to get more exercise and de-stress… but that’s MY bag, and CLamb’s situation is CLamb’s business.

      • [HenryPootel]

        Wow, that’s a lot of animosity (and likes) for someone making a suggestion of something to try.

        As a hurty gerdy kind of person myself, I find that red wine and coffee really set it off. But I’ll keep that advice to myself.

      • [wrybread]

        > try stopping giving random dietary advice.

        Why? A little self experimentation is easy enough, and the advice is also easy enough to ignore. But sharing a tip that you’ve found useful strikes me as a very nice and harmless thing to do.

        It reminds me of a recent BoingBoing article about how migraine sufferers were using the internet to pool their experiences to identify some non obvious triggers. Some people were able to identify some simple cures (avoid using a specific cleaning product, for example) without having to take harmful and expensive drugs. It didn’t work in every case, and wasn’t being proposed as a substitute for traditional medical help, but it certainly helped lots of people.

        As a corollary, how do you feel about lay people posting their experiences with taking a specific drug? Are they also supposed to keep quiet about their experiences?

      • [Ronald Pottol]

        Yeah, because long term use of a drug that leads to getting sick more often (and who knows what else)  is a great idea. Yes, by reducing your acidity, you are not killing everything you should be, so you get sick more often, and probably have worse absorption of nutrients.

        Short term, sure, long term, diet changes work for many people. Have a look at http://chriskresser.com/heartburn for some thoughts on diet and such.

    • [CLamb]

      So if I avoid wheat products Nexium will work better than Prilosec?

• [Stefan Jones]

  When you think about it, popping a Nexium is like taking the Red Pill and the Blue Pill TOGETHER.

  Man, would that be confusing!

  • [dmatos]

    Ob xkcd:

    http://xkcd.com/566/

• [Jonathan Peterson]

  Interesting.  It might not deserve a separate patent, it probably has some different side effects because of buffering agents, impurites, etc.  

  my kid has wicked reflux.  prilosec for 30 days actually made it worse.  the nexium works well.  At some point we might try doubled dosage of prilosec to see if it works.  the savings would be considerable.

  • [Trent Hawkins]

    It’s rare but Prilosec does have Paradoxical effects in some people, so taking more of it will just make things even worse.

• [gratefulvideo]

  I used to get Nexium for free and took it every other day and it worked fine.  Prilosec seems to increase my heartburn the day after I take it, a rebound effect I suppose.   I quit smoking all together and stopped soft drinks in the evening and I now rarely get heartburn.

• [phead]

  It did nothing for me, but my specialist says it does work over omeprozale in some cases, and he has no axe to grind.

• [Steve Bedi]

  I’m taking Nexium and find that it works for longer periods of time than other OTC stuff. Not to mention it’s FREE through my insurance. So, I’ll stick with it, and save my money.

• [kjh]

  I take various versions of the prazoles, omeprazole, pantoprazole, rabeprazole but when I take nexium I can’t sleep for three days.   I keep well clear of nexium.

• [TooGoodToCheck]

  Interesting.  Not the first time that the active isomer of a drug has been isolated and sold as a new thing.  I remember reading about escitalopram, which an isomer of citalopram.

  I’m actually surprised that they’d want to compare 20mg of nexium to 20mg of prilosec if 10 mg of nexium is the equivalent dose.  I would have expected that, instead of trying to sell people on taking twice as much active ingredient, they’d be pushing the story that by not consuming a bunch of the unwanted isomer, you should be able to reduce the frequency of adverse events.

  Also, comparing 20mg of nexium in their model will murder them on an incremental cost-benefit analysis.

• [GeekMan]

  Also taking PPIs. Recently switched from omeprazole to pantoprazole. Works slightly better but I get more headaches. Still trying to figure out if the tradeoff was worth it.

• [BonzoDog1]

  After a friend had his heart blown out by Vioxx (quadruple bypass — he survived) I told my doctor I’ll only take time-proven generics. They’re cheaper, usually nearly as effective (at least for my maladies) and time-tested.
  I also despise Big Pharma’s control of our lawmakers.
  By the way “free” meds from insurance are not free.

• [aek]

  All of the PPIs have psychotropic adverse reactions, and they also cause B12 deficiencies.  How to get off them and eliminate heartburn/GERD?  Eliminate all added sugar foods/beverages and eat unlimited fruit/vegetables instead.  Over 90% of the time, that’ll do it.

  • [kim holburn]

    Almost all modern drugs antagonise particular nutrients.  There was someone here in Canberra who did a PhD on this and compiled a compendium of drugs and their nutrient antagonisms.  Unfortunately I have no idea how to find it.  This should be basic information for anyone who takes medical drugs.

• [Guido]

  Drugs seem to be a lot like software these days. If you get the latest version you might be affected by some nasty bugs and you will be paying a lot for “upgrades” that often are not that impressive.

• [CSMcDonald]

  I’ve been on Nexium for a couple of months now – Prilosec did nothing for me,  changing my diet completely didn’t help.   I’ve actually been able to eat normally since being on Nexium with the extra benefit of not throwing up on a regular basis because of bad acid reflux.   With all things, YMMV.   It’s a $35 copay with my insurance and worth it for me.

• [Melinda9]

  I suffered with vicious stomach acid for years. Prilosec and the others gave me no relief. In October I had an endoscopy; the biopsy found helicobacter pylori. I was given a prescription for antibiotics and Nexium. That day was the first day in years that I didn’t have acid gushing in my stomach. Now I’m weaning myself off Nexium and it’s going well. But I’m glad I took it initially. Maybe, just maybe, you don’t know everything.
  (That headline scared the crap out of me – I thought it was about some hideous new side effect.)

• [arcfinn]

   Had to stop taking this entire class of drugs (PPI’s) because they were causing symptoms like a gallbladder attack, I’ll take a Zantac and skip the pain these caused me.

• [ephcee]

  I panicked a little reading the title since I’ve been relying on Nexium for the past several months. I started taking nexium after the daily zantac stopped working. They switched me to the generic for a while and the symptoms came back. Not sure if it’s because it was less effective or there is some other underlying issue, but now I’m just doing the name brand Nexium and so far the intense pain and barfing hasn’t returned.

  Plus with my coverage either med is $5, so I ain’t care.

• [awjt]

  Reading all these great blurbs on this thread.  It’s always amazing to me how different people’s experiences can be.  We have all these trials and rigorous appreciations of these compounds, and people still have such wildly different experiences.  Amazing.

• [Shannon Larratt]

  Unfortunately playing games when a drug goes off patent is a common story. Another (worse, because it’s not a “harmless scam” like this appears to be) example is Lyrica (pregabalin), brought out as a patent-controlled drug to take the place of gabapentin. It’s in theory “more potent”, which for a great many people does not mean “better”. It often just means “more unpleasant side-effects”. As someone with a rare genetic disorder that’s had doctors try out a plethora of drugs on me, it seems like each new patented drug becomes less effective and adds more side effects. It’s hard not to be cynical and believe it’s not just a game of making sure they’re selling a drug they can squeeze the most profit out of.

• [hadlockk]

  Oh good, unsolicited medical advice from someone without a medical degree. Thanks Cory! Next up, what chemo regimen would you recommend for my thyroid cancer? I’m not happy with what my current doctor prescribed.

  • [Andrew Squitiro]

    Should all medical news be off-limits?

• [Will Smiff]

  It’s nice that the media is finally mentioning something those of us in the medical field have been harping on for over a decade, but it would have been nicer if they hadn’t conveniently waited till Nexium was 11 years old, logging about 5 to 6 billion in sales per year at an enormous markup, helping spiral health insurance costs higher and higher for everyone.

  Now, WSJ, please cover the fact that Lexapro is an unethical rebranding of Celexa, Pristiq is an unethical rebranding of Effexor, Lyrica is an unethical rebranding of Neurontin, Xyzal is an unethical rebranding of Zyrtec.

  And that’s just the active isomers I can remember off the top of my head.  I haven’t even touched on the other unethical things they’re doing — with FDA approval and/or RICO law nonenforcement — that spiral our healthcare costs up without providing anything of added value for patients.  I (and many, many others) have been ranting about this scandalous drug company behavior online and in public for years and nobody in the MSM seems to care, probably because their commercial breaks are filled with drug ads that aren’t even legal to air in other first world countries.

• [Mantissa128]

  AstraZeneca did exactly what they were programmed to do in the capitalist-regulatory system we’ve created. They used questionable judgement, but it was in pursuit of their fiduciary duty: to return value to their stockholders by whatever means possible.

  If we want this system to behave differently, we have to program it differently. We need to make it so that the natural goals of the system are ones we want it to achieve. What is AstraZeneca’s purpose in society? What purpose do we want it to have?

• [Wayne Dyer]

  I’ve had bad stabby GERD pain on and off since I was in high school.  I’m 48 now.   Skipping the deep personal history, I ended up on Nexium after developing stage 2 esophagitis.  Insurance wanted me to take lansoprazole when I was prescribed Nexium, but it gave me massively rumbly tummy to put it gently, so I got a waiver and the purple pill.

  It worked, I healed, all was well, but I’d occasionally have problems so the MD suggested I stay on it, but i did switch to omeprazole as getting the Rx filled was a pain.  Also I read the studies.  They compared 20mg omeprazole to 40mg esomeprazole if I recall correctly.  Justification that I read was that cutting out the inactive enantiomer enabled them to use a higher, and more effective dosage with the same side effect profile.  (Would have to find a cite — check the Nexium prescribing info) I had no problem with the standard OTC dose of omeprazole, and it worked, so I stuck to that.

  I have weaned myself off of omeprazole onto famotidine though for several reasons that I won’t bore people with here, but I’m happy with that.

• [hab]

  I only prescribe Nexium if the patient absolutely positively insists on it having tried at least 2 other PPIs. I am not impressed by the data presented by the drug reps, which compared “starting doses” of esomeprazole (Nexium) 40mg versus omeprazole 20mg. The direct-to-consumer advertising did infuse a placebo advantage to the branded medication. That said, I believe that most (not all) GERD and associated problems in the U.S. are because we consume things that our organism has not evolved to process very well.

  Don’t stay on a PPI for too long if you can avoid it.

• [Florian Klinglmueller]

  I have several issues with this post:
  1.) As to the patent, as it seems to me this is a different (if only slightly) compound. so why should it not get a seperate patent?
  2.) As to FDA approval, it has been shown that the compound is non-inferior to the current best standard treatment. Even more two pivotal trials show it superior in a (possible secondary and not so much) disease relevant endpoint.

  It is a problem with US regulatory bodies that they have to take cost-effectiveness into consideration and may not concentrate on their purpose ie. FDA control safety and efficacy Patents ensure novelty. In Europe public health insurance then takes the role of checking cost efficiency and if the new compound does nothing that warrants a 5 times higher price they may simply not subsidize its use. Because at its worst nexium is just an overpriced equivalent compound to a drug for which a genericum exists.

• [Handletag]

  From the cited blog:
  

  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. 

  • [Florian Klinglmueller]

    Comments 15-17 on the original blog post pretty much clarify my opinion. I think much of the outrage is due to the double responsibility of US regulators to also ensure cost effectivity.
    As to patentability you may be right or not. But I don’t see any practical problems with the patent because nobody is hindered to market generica of the old compound, neither are patients forced to spend their money on the new compound.

• [Camp Freddie]

  It’s not merely a purification, it’s optical isomer separation.  That is patentable  and that’s a good thing too.
  Optical isolation is a big focus of most regulators because of safety concerns.  If only one isomer is active, then you don’t want to be sticking the other useless (and potentially harmful) half in people’s bodies. All drugs have side effects, and all hazards should be eliminated where possible, even if the risk from that hazard is low.

  The mode of action of many side-effects are unknown for many drugs. Maybe they’re caused by the active isomer, maybe by the inactive one, maybe they’re isomer-independent. For safety reasons, most regulators will want you to isolate the active isomer if possible.  If you remove the 50% inactive isomer and reduce the dose by 50%, you WILL have a safer drug. In the world of statistical uncertainty, this is about as solid a fact as you’ll ever find. 

  I work in a related field in the EU and many regulators are hostile towards registration of racemic mixtures, unless you can show that both isomers are active.  The thalidomide scandal really put a rocket up the arse of regulators, so they really hate any optical ambiguity (though thalidomide isn’t quite the same since it racemises on its own, optical isolation in manufacturing won’t prevent the nasty isomer from forming) .

  I suspect we’re not getting the full story since you couldn’t register a drug unless you’ve done trials at the actual dose level. It’d be a very simple matter to compare studies of 10mg optcal vs placebo against 20mg racemic vs placebo. Presumably they’re the same effectiveness.

  I doubt the 20 mg vs 20 mg trial was the deciding factor and saying that it only boosted response by 3% is misleading.  For most drugs, you get little or no benefit from exceeding the standard therapeutic dose.

  Of course, it’s possible that metabolism is zero order and optically non-selective, which could mean that the racemic mixture has advantages in persistence. Unlikely, but possible.

  Dammit, posts 15-17 on the original blog have beaten me to most of this.

  It should be patented and approved by regulators because it’s a novel process that reduces the required dose.
  It probably shouldn’t be used by clinical providers as their preferred drug because it is much more expensive but doesn’t provide a noticeably better effect or safety profile.
  This is one reason why I’m glad the UK has the NICE authority, which makes cost-benefit decisions for the NHS. Unfortunately, stories about supposed “wonder-drugs” like this being “banned” by NICE mean that they are a very undervalued regulator (I don’t work for or have any dealings with NICE!)

  • [Alan Wexelblat]

    Do you have the actual USPTO number for the patent in question? I tend to agree with you that if it’s a novel formulation or purification process that’s a reasonable patent topic, even if the FDA approval test was hinky.  The two are separate issues.

    I spent some time searching in the patent database but couldn’t find the patent(s) in question, either using “optical isomer separation” as a key phrase or looking for AstraZenica as the assignee.

• [Trish Fitzsimmons]

  US 6,369,085 claims the magnesium salt of esomeprazole, US 6875872 claims enantiomerically pure esomeprazole, and US 7411070 claims the trihydrate form of the Mg salt.

  The Orange Book is a good source of patent information for approved drug products. http://www.accessdata.fda.gov/scripts/cder/ob/default.cfm Search by generic or trade name, and then you can click through to get patent info, including expiration date.