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The Myth of Drug Expiration Dates

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Re: The Myth of Drug Expiration Dates

#251

Post by civilitty »

sevenfive wrote: post #230
civilitty wrote: post #156

Earlier quoted context omitted.

I do not believe that you have the requisite knowledge of pharmacology to talk intelligently on these topics so you should stop correcting people who do, especially when your other comments suggest that your knowledge is based entirely on recreational drug databases. Anyone who has spent time working in the pharmaceutical industry knows that "therapeutic index" and "therapeutic ratio" are used interchangeably and tha…

But what you said was still totally wrong, regardless of whether you're talking about toxicity or anything else. LSD is not so finicky that a 25% change in the dose makes a noticeable difference -- most people would be hard pressed to tell the difference between a 100 ug tab and a 125 ug one. It also does not follow that because a drug is active in small amounts, i.e. micrograms instead of milligrams, that a small pe…

LSD is an agonist for most classes of serotonin, dopamine, and adrenergic receptors - most of which have sensitive, nonlinear responses and all of which uptake the agonist at very different rates depending on individual biochemistry. We don't have the data to say for certain because of prohibition and the DEA's reluctance to allow researchers to study LSD but every other drug combination that operates on such a diverse set of receptors is extremely sensitive to dosage because all of those receptors have interdependent feedback loops - which makes them mostly useless for therapeutic uses. This is also why monoamine oxidase inhibitors (MAOIs) are so dangerous with such a wide array of drugs - the enzymes that break down monoamine neurotransmitters are regulated by serotonin+dopamine receptor interactions and even a tiny amount of MAO inhibitors can wreck havoc on that balance, causing some severe symptoms up to and including death. This happens because, even though MAOs are rather indiscriminate on which monoamines they target, their effect on each different neurotransmitter is variable and nonlinear.

In my personal experience (a decade of Burning man), when you do have a known concentration of liquid LSD (measured with an LCMS) that you carefully handle, store, and dilute for dosages, 100 mcg and 125 mcg can mean the difference between a good trip and a bad one in at least a tenth of my sample size and can drastically change the intensity of hallucinations (going from zero to fractal visuals to aliens) in a good quarter - not to mention the effect on the body high and introspection. If you're buying tabs, the chances that you are even close to the original concentration falls rapidly the further removed you are from the original source. Most people can't tell the difference between a 100mcg and 125mcg tab because those dosages are exaggerated and many people feel stereotypical effects at lower dosages. You can easily test this by eating a significant fraction of a blotter: you are extremely unlikely to experience the effects described by the literature of 50 ng/mL blood concentrations even if you're lucky enough to get to 5 ng/mL effects with a few tabs.

Re: The Myth of Drug Expiration Dates

#252

Post by civilitty »

chillwaves wrote: post #228
civilitty wrote: post #142

Earlier quoted context omitted.

You and the GP talking about entirely different things. You're talking about how investigators choose the initial dose for the clinical trials, he's talking about the dosage that is actually prescribed by doctors. Hence the 'The dose we take is not a "BEST GUESS"' (emphasis mine). Unless you're a lab animal or a person in a clinical trial, the does you take is the end result of lots of money spent on first figuring o…

> Antidepressants are a unique group of drugs because the dosage is highly dependent on each person's unique brain chemistry and a huge part of a good psychiatrist's job is working with their patients to find the right dosage and combination. How does one accomplish this absent trial and error? This fact undermines the entirety of your argument. "Best guess" is exactly what they do.

You do know what "unique" means in this context, right? Hint: it means that antidepressants are the exception to my argument because psychopharmacology is so much more dependent on genetic/environmental factors than the rest of the pharmacological field that we cannot draw conclusions on the effectiveness of dosages pre-treatment without spending 100-1000x more time and money on the clinical trials than we do now.

Please take your clearly ignorant bias and anti-pharma prejudice somewhere else - you have no idea what you're talking about.

Re: The Myth of Drug Expiration Dates

#253

Post by StavrosK »

johnnyhillbilly wrote: post #181
StavrosK wrote: post #114

Earlier quoted context omitted.

I don't understand your comment. You say they test at a controlled pressure, whereas conditions in the typical medicine cabinet vary wildly, and then say that that's why the drugs expire much earlier than they should. Do you mean that varying conditions make medicines last longer? You can't mean that medicines would last much longer if stored in perfect conditions, because that's not expiring "earlier than they shoul…

I'll chime in. Most chemical processes happen faster with a higher temperature. Some drugs decay into harmful substances (e.g. Aspirin). Other factors, such as humidity or UV, may play a part as well. Rather than testing every permutation of storage conditions over time, manufacturers put a safety margin. Individual consumers aren't in a position to remember exactly how they treated any given container of pills. Even…

Ah, I see, thanks.

Re: The Myth of Drug Expiration Dates

#254

Post by Broken_Hippo »

GordonS wrote: post #249
seehafer wrote: post #227

Earlier quoted context omitted.

Unfortunately, ALT is not a solution, because it's not accepted by FDA, except as a temporary measure. Any drug submission that supports shelf life via ALT data will be expected to also say "and we're doing real time testing to support this", and FDA will expect the follow up real-time data.

Then perhaps the solution is for the FDA to allow HALT testing. Having said that, I imagine there is little incentive for pharma companies to willingly extend the shelf life of their products - perhaps the real solution is for the FDA to actually require HALT testing.

I think the real thing here is, "Better safe than sorry". It's fine to use things like HALT testing initially to say, "this drug should be effective for 8 years" so that folks can get it to market before 8 years have passed.

But if, in reality, that drug only lasts for a strong 5 years, after which time it loses effectiveness, especially in high humidity or with high UV exposure. We could catch this with real-time tests and adjust accordingly - before it actually affects the general public's health.

Re: The Myth of Drug Expiration Dates

#255

Post by Broken_Hippo »

paublyrne wrote: post #247
perseusprime11 wrote: post #220

Earlier quoted context omitted.

I see medicines in foreign countries wrapped in some kind of aluminum foil. Will that prolong the life of the medicine given there is no oxygen to react? Given the amount of money spent on medicines, I really think there is a good moral business case to identify the correct expiration dates and save money for people. We just went through the Health care ordeal. Money saved anywhere is money saved for people who despe…

There may be other ways to approach this from a moral point of view. High prices for medicines are defended on the basis of high research costs, not high manufacture costs. A case could be made for legislation that obliges free replacement of out of date medication for the original purchaser, perhaps with a small surcharge.

A case could be made for smaller packages so people are less likely to take out of date medications as well.

Re: The Myth of Drug Expiration Dates

#256

Post by alikoneko »

sliverstorm wrote: post #192
BrandoElFollito wrote: post #147

Earlier quoted context omitted.

I live in France and cannot remember the last time I saw pills not in a blister pack. I remember vaguely having seen pills in bottles maybe 20 or 30 years ago. Again this is for France, I know that e.g. in the US one gets refills. Which by the way I find great because the waste of pills is tremendous. It would have been much better to get the specific number prescribed.

It is a waste of pills- but in many cases the marginal production cost of a pill is incredibly small. See generic asprin, many hundreds of pills for a few dollars at an ordinary grocery store. More than you need, but the packaging & marketing probably still costs more than the pills. Over here, benadryl is the main over-the-counter drug I see in blister packs. They say it's to slow down the meth cookers.

I think you mean Sudafed. Sudafed is pseudophedrin, which is a great decongestant and used to make meth. In most states, you have to go up to the counter and ask for it, as well as supply ID and sign a form promising not to do anything illegal with it. Benadryl is diphenhydramine, which is just an antihistamine, and you can totally get in bottles (in the states). I tend to always have both on hand in case of an allergy attack. Granted, I'm more likely to reach for the Sudafed than the Benadryl. Benadryl has the side effect of intense drowsiness (I guess you can't sneeze if you're in a coma). I also buy a year's supply of Zyrtec and benadryl at Costco. It might seem like a "waste" but when you suffer from bad allergies, it really isn't.

I'm a long time pollen allergy sufferer living in the hell that is South Florida. I know my allergy meds.

Re: The Myth of Drug Expiration Dates

#257

Post by maxerickson »

wolfgang42 wrote: post #196
maxerickson wrote: post #108

What's going on with our healthcare system that pharmaceutical grade baking soda is being rationed? W T F.

More discussion here: https://news.ycombinator.com/item?id=14798615 It seems the problem is that the suppliers' supplier had a problem supplying a component (not the bicarbonate itself, but the vial it comes in, I think) and this caused production to come to a halt while the issue was being sorted out. Presumably this particular component has been certified in some way and replacing it with an alternative requires re…

That's the proximate explanation.

I wonder more about whether such a fragile supply chain is inevitable in a mostly capitalistic society or whether we could do more to ensure stability.

Re: The Myth of Drug Expiration Dates

#258

Post by sevenfive »

civilitty wrote: post #251
sevenfive wrote: post #230

Earlier quoted context omitted.

But what you said was still totally wrong, regardless of whether you're talking about toxicity or anything else. LSD is not so finicky that a 25% change in the dose makes a noticeable difference -- most people would be hard pressed to tell the difference between a 100 ug tab and a 125 ug one. It also does not follow that because a drug is active in small amounts, i.e. micrograms instead of milligrams, that a small pe…

LSD is an agonist for most classes of serotonin, dopamine, and adrenergic receptors - most of which have sensitive, nonlinear responses and all of which uptake the agonist at very different rates depending on individual biochemistry. We don't have the data to say for certain because of prohibition and the DEA's reluctance to allow researchers to study LSD but every other drug combination that operates on such a diver…

IME bad trips are mostly determined by how neurotic the tripper is. If you can accurately say that a 25% increase causes a 10% increase in bad trips, you must have quite a lot of experience. I at least know that if some people take one tab and others take two at the same time, the ones who took two don't go flying off the walls.

Saying that a 25% change is more significant for more potent drugs is illogical on the face of it, because a % is a dimensionless quantity. If there is some subtle reason why this trend exists I'd love to hear it.

Re: The Myth of Drug Expiration Dates

#259

Post by qxamak »

mechnesium wrote: post #222
kbenson wrote: post #219

Earlier quoted context omitted.

The point is we don't necessarily know, or know to the degree of certainty the FDA requires, how many of these things degrade. Perhaps in certain conditions, they degrade at one rate, but in other conditions (such as a temperature difference), they degrade at a different rate. Testing how drugs perform years after production in multiple different scenarios is necessarily time consuming, because it takes at least that…

I'm a test engineer. Highly accelerated life testing (HALT) can probably be used to closely approximate the shelf life of medicine. You need to look at the parameters that cause degradation (humidity, temperature, light exposure, etc). HALT the samples at different temperature/humidity/lighting extremes and use mass spectrometry to check purity. Use the data to create an algorithm that approximates the product lifeti…

The largest barrier to accelerated life testing right now is that we really don't know all the mechanisms that cause degradation (or understand their impact on stability). There are many lab instruments that already provide HALT metrics on how stable a drug sample is expected to be under different conditions. And the Arrhenius and Eyring equations are useful for empirical modeling. These tools are great for quickly identifying when formulations are unstable. But it's very difficult to say with certainty (at least in the pharma world) that something will be stable for X years unless you actually test it for X years.

For the vast majority of manufactured products, HALT makes sense because any uncertainty that remains after testing is not likely to harm users. But with some of these drugs, any uncertainty, even after HALT, could cause major problems for users. And it seems that the FDA is unwilling to accept that risk. But as far as I know, the FDA is actively seeking methods for performing HALT that produce accurate and repeatable results.

Re: The Myth of Drug Expiration Dates

#260

Post by larelogio »

TheKarateKid wrote: post #234
Kalium wrote: post #161

Earlier quoted context omitted.

There's also the not-irrelevant issue that testing is slow and potentially other than free. How do you find out when a drug expires? You have a bunch of it sit around and test it periodically, right? I assume that would be done after bringing a drug to market, otherwise drugs could easily be delayed 10+ years if they're shelf-stable.

If scientists are able to calculate the longevity of chemicals, food, and other products without having to wait the actual time period, I don't see how or why pharmaceutical drugs would be any different. It's very likely it is not favorable to companies to look into this, just as it was revealed that the EpiPen expiration date was not really true.

Are they?

"able to calculate the longevity of chemicals, food, and other products without having to wait the actual time period"

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