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The FDA Announces Two More Antacid Recalls Due to Cancer Risk (wired.com)
91 points by elliekelly 8 days ago | hide | past | web | favorite | 52 comments

This whole thing seems overblown. The conditions required to induce NDMA accumulation are so far outside the normal bounds as to be farcical. Every drug I’ve ever seen advises you to keep it in a controlled temperature environment.

I can see people keeping some Zantac in their car and that gets quite hot (140+) in the summer.

I don’t think the penalty for not storing your medicine quite right should be ingesting a carcinogen.

It was 130C / 260F that is considerably higher than the inside of a car.

Still, this suggests that ranitidine may not be stable and its breakdown products may be risky. If mixing it with nitrite produces NDMA under condition found in the stomach that is another risk case. I wonder if there is any breakdown over time just sitting on the shelf?

Oh I didn’t notice that. Then I agree this is silly. No you should not heat your Zantac to 266 F haha.

I assume that's 140 Fahrenheit. The testing in question was conducted at 140 Celsius (which is quite a bit warmer...).

I also think it's unlikely that those people who are keeping their meds in their car are also keeping their meds dissolved in a solution with high levels of nitrite.

If the temperature in your car is 140 Celsius, you have bigger problems than carcinogenic medicine.

Or rather, you should stop driving your oven.

The article is highly misleading. in the heating test, they heated the drug to 130 C, far beyond the temperature you'll find in a car. The gastric simulation with nitrites seems legit though.

Failing to follow manufacturers directions should not result in a Recall, it is not their fault people are stupid

From what I’ve read (the FDA website is fantastic), it’s an issue, but not a huge one.

Valisure said “these levels are too high”, the FDA came back with “you’re testing it wrong”, so the FDA retested and determined a few of the drugs has higher than allowed NDMA, but we’re talking 10-50% too high (of a very small limit), not the 20,000% too high that Valisure claimed.

My guess is the FDA will institute new guidelines on testing, manufacturers will change their processes and ranitidine will come back in a year or so.

nitrosamines are nasty stuff in general. I would not be surprised this ends up in revision of safe levels.

> Every drug I’ve ever seen advises you to keep it in a controlled temperature environment

And yet even pharmacies have no problem shipping via consumer services in the dead of summer, and show zero care for whether "overnight" actually means "over weekend".

I used to work in QA for a major drug company where we'd store the drugs for years at different temperatures and humidity, and every 3/6/12/18/24/48/60 months we'd test them in spectrometers, as well as testing for clumping in powders, colour changes, etc. One of our jobs was to make sure they didn't turn into anything nasty, but it was mainly making sure they stayed stable.

For all day-to-day drugs it's really a precaution rather than anything else. Usually they just become a little less effective by becoming less concentrated, but most of the ones I worked with even the 50/80(?) ones were still fine years later (stored at 50 degrees celsius, 80% humidity (I think? Was 20 years ago)). We had a special warm room where all the samples were kept.

Heh. Funny sorry:

One time I was on a drug that had to be shipped to me from an out of town pharmacy in a refrigerated vehicle. The delivery guy demanded that my apartment leasing office refrigerate it, which led to them almost losing it.

Next time I had it shipped to a local pharmacy instead for pickup. That pharmacy didn’t refrigerate it at all and insisted that was kosher. (They also almost lost it.)

I called the original pharmacy and they assured me it doesn’t actually need to be refrigerated, as long as it doesn’t reach its melting pint of like 100 F.

The package said it needed to be refrigerated.

Sometimes the official recommendations they file with the FDA and what they know from their internal testing vary.

If you call the company, they can basically answer any question you ask, even for un-approved indications.

But for them to bring it up without you asking is a big Nono.

Drug contamination is very real and overseas generic drug manufacturers have a long history of contaminating the drugs they sell to the US.


It’s not just Zantac. It’s blood pressure medication and now diabetes 2 medication to lower blood glucose. If you read the Bloomberg article linked in the post, it’s even more scary. Basically they don’t test the drugs which is why They are being discovered one by one.

If you’re on any sort of generic medication, it’s probably manufactured in India/China and it’s probably contaminated. And if it’s not contaminated it might not even fit to specifications, ie too much of the drug or too little per pill. It’s happening all the time and the FDA is reactive not proactive. There’s a quote in the Bloomberg article about a judge not wanting to peel the onion because it could be too bad.

US companies aren't immune from these problems either.

This is not necessarily correct, and I suspect specifically not correct in this particular case.

The first step in the synthesis of ranitidine is a Mannich reaction on a furan compound (furfuryl alcohol) to produce essentially one half of the molecule. The key reagent in that step is dimethylamine hydrochloride.

The final steps of the synthesis involve conditions that will form nitrosamines from amines.

Thus, if any dimethylamine hydrochloride is left over after the first step, conditions exist to turn it into NDMA.

Dimethylamine is a bugger to get out of a reaction mixture, and it would not surprise me to find that a poorly-designed or badly executed reaction scheme may fail to remove some trace amounts, therefore opening the door to producing NDMA. In other words, as an impurity existing from the first step of the synthesis.

So it's not just a case of "NDMA accumulation".

I have had experience witnessing syntheses of pharmaceutical APIs at Indian manufacturing plants, and have seen some horror stories.

The NYT reports that Sanofi's recall "applied only to the United States and Canada, and that its products sold outside the two countries were sourced from different suppliers", which is fairly common practice. So it may be that only some API makers have the problem, which is likely a manufacturing and QC problem.

This is not correct. Studies have clearly shown that if you give someone a moderate dose of ranitidine, the NDMA levels in their urine skyrocket. upwards of 400 times higher if I remember correctly. This is higher than in people who have bladder cancer due to schistosomiasis, a disease causing increased levels of NDMA in the body.

There are somatic processes, likely starting in the stomach and concluding in the liver, which are efficiently converting ranitidine to NDMA. Here's just one study. https://academic.oup.com/carcin/article/37/6/625/1744630

If you add nitrite to ranitidine and heat it to 140 the levels of NDMA produced become carcinogenic. The person who made the discovery has a business built around consumer fear about contaminated pharmaceuticals.

Yes, it looks pretty obvious that V@lisure is running a scare campaign to boost traffic towards their services. I wonder if there's another play at hand here, though.

Did they get in a spat with suppliers? Are they trying to dump the price of ranitidine and nizatidine to buy up at markedly reduced value? Perhaps drive down demand from drugs with less margins towards higher ones?

For those downvoting: this is business as usual in entrenched markets like pharmaceuticals -- especially since the FDA has no capacity to enforce anything.

And on more thorough review, it looks like the hysteria has spread to many other countries as well -- how quaint.

For those that really aren't aware of what good hysteria marketing looks like, please take a look at: https://www.valisure.com/blog/uncategorized/detection-of-ndm...

Anyone that works in the world of marketing/PR can see it plainly.

I don't feel like digging into what strings they had to pull in order to get this viral, but anyone possessed by curiosity should take a look at their team: https://www.valisure.com/about-us/ After reading their profiles, two members should instantly pop out at you.

Which two members' profiles? I didn't immediately see something.

Cunningham and Gortler top out at MVPs -- if you base off their bios alone.

Jirstrand is runner-up from all the impressive PR work she's done.

Berkal: very weak maybe.

> Valisure also conducted tests with simulated gastric fluid (at body temperature, 37 degrees Celsius) and added sodium nitrite, simulating a diet with high levels of the common preservative found in processed meats, and found high levels of NDMA

See page 7: https://www.valisure.com/wp-content/uploads/Valisure-Ranitid...

They did NOT simulate a normal diet with common levels of sodium nitrate. At 10 mM there is no NDMA found. Sodium nitrate concentrations for meat are much lower than 10 mM. The FDA puts a strict upper limit of sodium nitrate concentrations in meat at 100mg/kg, so around a concentration of .015mM (!)

I don't need to do any further math to tell you no one is eating that much cured meat in a single sitting (it's simply not possible).

Not very helpful with knowing how much sodium nitrite they added. Are they simulating the diet of someone who eats a bologna sandwich for lunch every day, or the diet of someone who eats nothing but twenty pounds of straight bologna every day?

Edit: sibling comment provides some evidence that the concentrations of nitrites where they observed NDMA are much higher than what might be expected in a normal diet.

There is a huge amount of ignorance in this thread right now. More people need to read the papers that have been out for 10 years on the issue of conversion of ranitidine to NDMA inside the body. The real issue is not tainted drugs or exposure to heat, it's processes in the body which are converting ranitidine to NDMA, which result in NDMA levels in the body increasing over 400 fold. Here's one https://academic.oup.com/carcin/article/37/6/625/1744630

Traveling in South Korea and went to pharmacy to get rantidine but it was told it was no longer available bc, thought I heard "it is now used for cancer" which seemed weird but guess it was language issue and it was "it can cause cancer".

IANAD, but antacids are the wrong approach to solving digestive dysfunction. IME, pancreatin and ox bile have eliminated the vast majority of my digestive issues.

It’s debatable how effective antacids are anyway; for example, if you have an H. Pylori infection, antibiotics would be way more effective.

I think physicians already understand the difference between H. Pylori-induced reflux and general GERD and have some experience on which treatments to recommend.

Yes of course if you have an h. pylori infection you want to deal with that. If you have bile duct obstruction or gallbladder stones then supplementing with the stuff you don't get due to the obstruction will be effective. If you have GERD, then you need a different treatment. Welcome to medicine 101 "How to treat basic digestion issues". There's no profound discovery to be made and no conspiracy theory behind any of the drugs involved. The different therapies are tailored to the different causes of digestion issues.

> IME, pancreatin and ox bile have eliminated the vast majority of my digestive issues.

That suggests that you have a gallbladder dysfunction. You might want to get an ultrasound for gallstones.

Wired has started doing something strange.

This URL doesn't load in my version of Firefox (old and heavily tweaked, I admit). And it crashes Midori.

But this works fine:

$ w3m -dump https://www.wired.com/story/the-fda-announces-two-more-antac...

Edit: OK, it works in my Firefox if I hit escape as soon as the page has loaded. So maybe there's some non-content module that loads more slowly, and triggers the problem. It could be a "turn off ad blocker" popup. Given that I block popups.

I’m constantly amazed by comments like this one posted by highly technical people who manage to become unable to view a simple website by making the endeavor vastly over-complicated.

Meanwhile, Grandma can read the article just fine when she double clicks on the blue e.

I'd like to find out more about what kind of setup Grandma has, in that case. I'm sitting here on an unmodified Safari installation, and the top of the window is obscured by a giant floating banner ad, while the bottom is obscured by a "subscribe" banner, which is _itself_ obscured by an oversized cookie notice. All of which leaves less than 80px of height to read the actual article content. Given the nice large font size, that means I can see three lines of text at any given moment. I didn't have the same issue that GP did, but it's definitely true that Wired has been adopting some awful web development practices for a while now.

(Side note: My kids' grandma is a retired software developer. So I guess maybe it's just that the average grandma is more sophisticated than we are?)

Huh. So maybe my problem is some mix of blocking ads and popups.

I’ve noticed certain sites, like government websites (my local healthcare.gov site), banking sites, insurance sites, only work if you disable tracking protection entirely in safari/firefox, and one of them (I think the healthcare site) only worked in chrome with no ad blocker.

Folks, this is not a good sign.

Yeah, it's an arms race.

Don't tell us, make the call - and don't disable.

It's more like blocking exploits, I'd say. Which your prototypically clueless Grandma is vulnerable to. So her machine is likely sending spam, or worse.

Let's not confuse invasive ads and tracking cookies with "exploits." We can dislike both, but they are definitively not the same thing and one is clearly a bigger real threat than the other.

how many times do ad services have to inadvertently push malware until we can just lump them into the 'malicious' category?

I consider tracking to be an exploit.

I mean, there are laws against stalking, right?

A simple website is HTML and CSS. They work everywhere.


I have no problems with maybe 90% of sites. So I'm pretty confident that the rest are doing something odd, and likely not in my best interest.

Some cool sites do require WebGL, which I block. But I can't imagine that's needed to display text and images. And I can even handle NYT's trippy images layout.

I really have no clue what some sites are doing, however. It could be ad blocking, or the fact that I'm using a German VPN exit. Or maybe one or both of those plus blocking popups. Maybe referrer and/or fingerprint obfuscation.

But it's easier to find workarounds for that ~10% than figure out just exactly how they're breaking basic HTML and CSS.

Most of the comments are to let others/the page owner know about bad or unexpected behavior - like not working with JS disabled, or not loading under edge conditions.

Those same technical people get to help grandma when that simple webpage has eaten the blue e. PEBBAS - Problem Exists Between Browser And Site/Server/Storage.

If it were a simple website it wouldn’t be broken. The over-complication here isn’t in the browser, it’s in the website.

Loads perfectly for me with js disabled via ublock origin, just a clean article.

What browser?

Are you in the EU?

You are blocking ads, I presume?

Do you see any popups?

Android Firefox with uMatrix in the EU. All js disabled. No popups. Site works fine.

This is my setup, yeah. Except ublock origin rather than umatrix.

Blocking ads, blocking js, EU. Firefox on Android.

Additionally, my traffic and dns go through a (also EU hosted) DO droplet which is running pihole and dnscrypt.

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