[higginsc]

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.

[JohnJamesRambo]

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.

[Tagbert]

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?

[JohnJamesRambo]

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

[JshWright]

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.

[sansnomme]

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

[waste_monk]

Or rather, you should stop driving your oven.

[deschutes]

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.

[syshum]

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

[refurb]

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.

[internet_user]

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

[mindslight]

> 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".

[mattmanser]

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.

[lowTthrowaway54]

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.

[Scoundreller]

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.

[remote_phone]

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

https://www.nakedcapitalism.com/2020/01/big-pharma-wont-let-...

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.

[linuxftw]

US companies aren't immune from these problems either.

[fnordprefect]

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.

[aiphex]

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