Expired anti-biotics

[mistermack]

Does anybody have any info on whether antibiotics are safe, long after the use-by date? I'm talking about tablets or capsules that are stored at room temperature in comfortable dry conditions. 

Last night I had a horrendous toothache, I was nearly hopping round the room, I was downing Ibuprofen but it hardly touched the pain. In desperation, I dug out some old drugs that never got used, and I found a bottle of antibiotics that looked brand new, and I had written " for toothache" on the label. I would have used them, I was that desperate, but I looked at the date, and it was 2002 !!    Even so, I was in so much pain, I was hovering on the verge of taking them, but I resisted in the end.

Amazingly, I eventually passed out and got some sleep at about five O'Clock, and when the alarm went off at 8:30, pain gone !! And it hasn't returned. So I've been counting my blessings all day. But if I had taken the expired antibiotic, and woke up with no pain, I would of course have put it down to rapid action from the antibiotic. How could you not ??

So the moral of that story is that if you try a treatment, and get miraculously better, be very wary about concluding that the treatment worked.

But I'm left wondering about expired antibiotics. Does anyone have any info about whether it's safe? 

[CharonY]

The answer is for the most part, we do not know. Pharma companies have to provide expiration date based on specific testing regimen, that vary by region. But roughly, they are stored at specified conditions and then tested for quality and purity after time has expired. So if a company wants to claim e.g. a 3yr shelf life, they have to provide test data for samples that shows that the quality is maintained for at least 3 years.

There are also accelerated schemes (usually only allowed for claimed stability times of less than 3 years, I believe) where samples are stored at what is called accelerated temperature (to increase degradation rate).

Samples are analyzed at set intervals and based on that information manufacturer have to show what the maximum time is where they ensure no drop in quality. 

Unfortunately that data is generally not publicly available, AFAIK, so we cannot really project stability much. That being said, these estimates are conservative (as they have to show no difference between the beginning and whatever expiry date they want to submit). And degradation is rarely sudden. So even after expiry there is usually a fair amount of potency left, that drops over time. The one thing to look out for is if there are known degradation products that might be harmful, and there was some discussion about that surrounding tetracycline, for example (but as far as I recall it was no clearly linked to the drug).

[TheVat]

Another problem with decreased potency is that, if it's an antibiotic, say amoxicillin, you might actually help any offending bacteria develop an immunity to that compound by offering a weakened sample.  You really want the full potency.  For a toothache, you also want a dentist - the problem might not be bacterial at all.  

NSAIDs are probably okay for a few years after expiration, and I've used old acetaminophen (paracetamol to you Limeys) to good effect up to seven years iirc.  There are no hazardous decay products, they're just weaker.  

[geordief]

My partner got an attack of shingles ,naturally on a Sunday at the beginning of this year.  We were unable  to even see a doctor until the following day.

I knew how important it is to take the antiviral as soon as possible and I happened to have some left over medication from my own bout of shingles around 8 years previous to that.

 

I had kept them for such an eventuality(I have already had shingles twice)

I thought I should ring around the hospitals and the all night medical numbers for advice as to whether we should use these date expired medicines until such time as we could get  proper medicine from a doctor.

I was repeatedly  told not to do this (some circumlocutions) and as a result we started the treatment some 36 hours later than  we otherwise might have.

Should I have disregarded this advice and started the treatment anyway with the old medication? (acyclovir ,from memory).

As it turned out my partner has had to be prescribed the shingles antiviral 3 times since and ,some 10 months on from the initial infection  is just now ,hopefully putting it behind her.

I understand that the medication I had had doubtless lost efficacy but felt they might have been of some use in the circumstances .

But I didn't want  to go against the  medical advice I was given over the phone.

[StringJunky]

@geordief Are you aware there's a vaccine now for it and existing sufferers can take it to deal with future eruptions? Over 70 it's free in the UK.

[geordief]

6 hours ago, StringJunky said:

@geordief Are you aware there's a vaccine now for it and existing sufferers can take it to deal with future eruptions? Over 70 it's free in the UK.

Yes ,I know it is available

I have read that it is effective but less so than the Covid vaccine.

I have a penchant for putting things on the long finger  and especially so when it comes to visiting the doctor....

The reason ,incidentally that my second shingles infection also went untreated was that it also , naturally showed up on a Sunday -as well as my being convinced that you could not get shingles twice. (so that I ignored the signs until it was quite late and so had to go to hospital for a week)

[CharonY]

20 hours ago, TheVat said:

Another problem with decreased potency is that, if it's an antibiotic, say amoxicillin, you might actually help any offending bacteria develop an immunity to that compound by offering a weakened sample.

So, the conventional wisdom is that if you shorten the treatment you can promote the selection of resistant bacteria. Generally speaking there is a minimum inhibitory concentration (MIC) at which they inhibit bacterial growth which is dependent on the strain, but can also be influenced by their growth condition (in the lab standardized media are used to measure MIC, which might not be exactly the same in the body).

Now if the effective concentration of the compound drops below MIC, the effects are actually a little bit weird. If you look at defined cultures, e.g. mixing non-resistant with resistant bacteria, you still see a selective effect. But if you take a more complex sample, say fecal cultures or wastewater, the studies have been quite mixed whether there is a selective pressure (and/or there are other factors that would override it). It is fairly fascinating, actually.

[guidoLamoto]

Tetracycline oxidizes and becomes toxic with age, although it's rarely prescribed anymore. I'm not sure if the newer minocycline, doxycycline etc forms show the same thing. (Most drugs don't generally deteriorate significantly with age-- although ASA & NTG are notable exceptions, oxidizing and losing potency rapidly (weeks) once the bottle is opened.

The problem of antibiotic resistance and short courses of treatment is more theoretical than practical. Every time an antibiotic is used, the  pressure is for an increase in the gene frequency of resistant alleles in the population of surviving bugs.....Resistance is, after all, a phenomenon of neo-Darwinian evolution, not Lamarckian.

The population curve of a bug being treated shows an exponential decay over time, so, for a short course, a larger surviving population remains at the end of the course...but the survivors, no matter how few after even a longer course, have as much time as they need to re-populate... The med can't give 100% mortality-- It's purpose is to cut down the population of invaders enough that the natural immune response will finally polish them all off.--Resistance actually occurs out in the environment, not so much in the patient, when the free-living bugs are exposed to the "spillage" of the antiobiotic and the final "mop up operation" of the immune system is not available.

Edited December 3, 2023 by guidoLamoto

[LuckyR]

It's my understanding that the only product required to have data to back up expiration dates is infant formula. Everything else the manufacturer gets to put whatever date they want. And in my experience there is a financial incentive for the manufacturer to put a date that is much shorter than average. Mostly to have the consumer repurchase rather than reuse, and also (in the case of foodstuffs) to not run the risk that the consumer eats old product and associate suboptimal taste as being the actual quality of the product.

Long story short, with a few exceptions, medications still have efficacy long after the "expiration" date.

[CharonY]

45 minutes ago, LuckyR said:

It's my understanding that the only product required to have data to back up expiration dates is infant formula. Everything else the manufacturer gets to put whatever date they want. And in my experience there is a financial incentive for the manufacturer to put a date that is much shorter than average. Mostly to have the consumer repurchase rather than reuse, and also (in the case of foodstuffs) to not run the risk that the consumer eats old product and associate suboptimal taste as being the actual quality of the product.

Long story short, with a few exceptions, medications still have efficacy long after the "expiration" date.

I think you are confusing the regulations for food with those for medication. For the latter the manufacturer have to have potency testing done and the expiration date is the minimum guaranteed time where they retain potency. They could remain effective for longer. This has been discussed earlier in this thread, though. And roughly a year back.

[LuckyR]

On 9/13/2024 at 10:30 PM, CharonY said:

I think you are confusing the regulations for food with those for medication. For the latter the manufacturer have to have potency testing done and the expiration date is the minimum guaranteed time where they retain potency. They could remain effective for longer. This has been discussed earlier in this thread, though. And roughly a year back.

We're both right. Yes, the FDA "requires" the manufacturer to provide data to support their experation date, but those chosen dates are up to over 20 years too early, likely to boost profits by encouraging repurchasing over reusing. 

 

"The best evidence of acceptable potency of the medications beyond their expiration date is provided by the Shelf Life Extension Program (SLEP) undertaken by the FDA for the Department of Defense. The aim of the SLEP program was to reduce medication costs for the military. SLEP has found that 88% of 122 different drugs stored under ideal conditions should have their expiration dates extended more than 1 year, with an average extension of 66 months, and a maximum extension of 278 months.^3"

[CharonY]

1 hour ago, LuckyR said:

We're both right. Yes, the FDA "requires" the manufacturer to provide data to support their experation date, but those chosen dates are up to over 20 years too early, likely to boost profits by encouraging repurchasing over reusing. 

 

"The best evidence of acceptable potency of the medications beyond their expiration date is provided by the Shelf Life Extension Program (SLEP) undertaken by the FDA for the Department of Defense. The aim of the SLEP program was to reduce medication costs for the military. SLEP has found that 88% of 122 different drugs stored under ideal conditions should have their expiration dates extended more than 1 year, with an average extension of 66 months, and a maximum extension of 278 months.^3"

No, you are just misunderstanding how it works. Remember, manufacturer have to provide empirical data for the shelf life of their products and it doesn't make sense for them to figure out the max shelf life (which could be decades) before putting them to market. These are not randomly chosen, to bost sales. Though the market average is likely calculated to provide the optimum balance for profits.

Remember, if they determine a longer shelf life, they might be wnle to charge more from their customers. Also, you might have missed the fact earlier in this thread that there is acclelerated program to dtermine longer shelf lives, which would run counter to your assumption that manufacturers want to minimize shelf life.

[swansont]

1 hour ago, LuckyR said:

We're both right. Yes, the FDA "requires" the manufacturer to provide data to support their experation date, but those chosen dates are up to over 20 years too early, likely to boost profits by encouraging repurchasing over reusing. 

 

"The best evidence of acceptable potency of the medications beyond their expiration date is provided by the Shelf Life Extension Program (SLEP) undertaken by the FDA for the Department of Defense. The aim of the SLEP program was to reduce medication costs for the military. SLEP has found that 88% of 122 different drugs stored under ideal conditions should have their expiration dates extended more than 1 year, with an average extension of 66 months, and a maximum extension of 278 months.^3"

You should include a link when providing a quote.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040264/#R3

The SLEP program assumes ideal storage conditions, and the article points out that “The bathroom and medicine cabinet are not ideal places to store medications due to heat and humidity”

[LuckyR]

1 hour ago, CharonY said:

No, you are just misunderstanding how it works. Remember, manufacturer have to provide empirical data for the shelf life of their products and it doesn't make sense for them to figure out the max shelf life (which could be decades) before putting them to market. These are not randomly chosen, to bost sales. Though the market average is likely calculated to provide the optimum balance for profits.

Remember, if they determine a longer shelf life, they might be wnle to charge more from their customers. Also, you might have missed the fact earlier in this thread that there is acclelerated program to dtermine longer shelf lives, which would run counter to your assumption that manufacturers want to minimize shelf life.

That's one opinion. I and the Department of Defense disagree. 

 

The Pharma industry's interest in profit maximization, needs no citation, commonly performed through even shadier techniques. 

Edited September 16 by LuckyR

[CharonY]

56 minutes ago, swansont said:

You should include a link when providing a quote.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040264/#R3

The SLEP program assumes ideal storage conditions, and the article points out that “The bathroom and medicine cabinet are not ideal places to store medications due to heat and humidity”

Also the SLEP program is independent of the approval process- it was a cost saving measure and pharma companies have no incentives to start such studies by themselves (unless there was grant to do so- there might be).

 

15 minutes ago, LuckyR said:

That's one opinion. I and the Department of Defense disagree. 

Then kindly quote the passage where the DOD states that pharma companies willfully shorten the lifetime by greed rather than by a lack of legislation to provide incentives for long-term testing. Specifically, kindly show the passage that supports your claims of:

 

On 9/13/2024 at 10:45 PM, LuckyR said:

Everything else the manufacturer gets to put whatever date they want. And in my experience there is a financial incentive for the manufacturer to put a date that is much shorter than average.

And while at it, please indicate what you mean with "average" in this context. 

[swansont]

39 minutes ago, LuckyR said:

That's one opinion. I and the Department of Defense disagree. 

 

The Pharma industry's interest in profit maximization, needs no citation, commonly performed through even shadier techniques. 

We try to deal in facts, though. Your opinions are not worth much, by themselves 

[LuckyR]

5 hours ago, swansont said:

We try to deal in facts, though. Your opinions are not worth much, by themselves 

I completely agree, neither of our (CharonY's and mine) opinions are worth much. And since neither of us made the decisions at the executive level at large pharmaceutical corporations, there are no "facts" available here.

 

You're free to discard your meds on their expiration date and rebuy new, I'll keep being invested in the Healthcare sector. Let's see who ends up ahead.

Edited September 16 by LuckyR

[CharonY]

10 hours ago, LuckyR said:

I completely agree, neither of our (CharonY's and mine) opinions are worth much. And since neither of us made the decisions at the executive level at large pharmaceutical corporations, there are no "facts" available here.

 

You're free to discard your meds on their expiration date and rebuy new, I'll keep being invested in the Healthcare sector. Let's see who ends up ahead.

Except you made a series of factually wrong statements, without providing support. I mostly pointed out how the actual process works. I could point out to FDA guidelines, if requested, but the article with the quote you provided also has a paragraph highlighting the requirements (which, again, counters you original assertions).

[J.C.MacSwell]

On 11/9/2023 at 10:16 PM, CharonY said:

Samples are analyzed at set intervals and based on that information manufacturer have to show what the maximum time is where they ensure no drop in quality. 

Is this factually correct?

I'm going to go out on a limb and claim you can't provide a link that peak quality is required to be maintained to that point in time.

[CharonY]

4 hours ago, J.C.MacSwell said:

Is this factually correct?

I'm going to go out on a limb and claim you can't provide a link that peak quality is required to be maintained to that point in time.

Of course I can, at least for the US (I believe Health Canada is mostly following FDA guidelines, but am not sure). The requirements are outlined in the code of federal regulations specifically 21 CFR 211.166 outlines the general requirements for stability testing https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=211.166. Additional requirements are outlined in 211.165: 

Quote

(a) For each batch of drug product, there shall be appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release. Where sterility and/or pyrogen testing are conducted on specific batches of shortlived radiopharmaceuticals, such batches may be released prior to completion of sterility and/or pyrogen testing, provided such testing is completed as soon as possible.

(b) There shall be appropriate laboratory testing, as necessary, of each batch of drug product required to be free of objectionable microorganisms.

(c) Any sampling and testing plans shall be described in written procedures that shall include the method of sampling and the number of units per batch to be tested; such written procedure shall be followed.

(d) Acceptance criteria for the sampling and testing conducted by the quality control unit shall be adequate to assure that batches of drug products meet each appropriate specification and appropriate statistical quality control criteria as a condition for their approval and release. The statistical quality control criteria shall include appropriate acceptance levels and/or appropriate rejection levels.

(e) The accuracy, sensitivity, specificity, and reproducibility of test methods employed by the firm shall be established and documented. Such validation and documentation may be accomplished in accordance with § 211.194(a)(2).

(f) Drug products failing to meet established standards or specifications and any other relevant quality control criteria shall be rejected. Reprocessing may be performed. Prior to acceptance and use, reprocessed material must meet appropriate standards, specifications, and any other relevant criteria.

There are also other passages of relevance (such the the regulation requiring expiration dates 21 CFR 211.137 and other regulations that I am not familiar with might also apply. The FDA is using these regulations and has built a set of requirements for the industry. A guidance document outlining the specifics (as per the FDA) can be found here: https://www.fda.gov/media/71707/download

A significant change from the original formulation is considered if any of the following is observed during the stability study:

Quote

·A 5 percent change in assay from its initial value, or failure to meet the acceptance criteria for potency when using biological or immunological procedures · Any degradation product’s exceeding its acceptance criterion · Failure to meet the acceptance criteria for appearance, physical attributes, and functionality test (e.g., color, phase separation, resuspendibility, caking, hardness, dose delivery per actuation). However, some changes in physical attributes (e.g., softening of suppositories, melting of creams) may be expected under accelerated conditions. · Failure to meet the acceptance criterion for pH · Failure to meet the acceptance criteria for dissolution for 12 dosage units 

In addition there are additional criteria, depending on the packaging. Note that they minimum test time is 12 months (or 6 under accelerated schemes). However, the industry standard is usually 2-3 years. The reason is, that (contrary to some assumptions in this thread) having a very short shelf life might make it difficult to sell. The reason why testing is rarely done beyond that is that as indicated in the guidelines, the testing has to be representative of the production. So if the manufacturer change packaging (in a substantial way) or formulation, they have to redo the whole process (meaning in many cases adding years to the process). So keeping it at the 2 years keeps things a bit more flexible. Also keeping the same schedule will result in ideally almost identical degradation profiles, without the need of additional statistical evaluation and one can basically just point at the previous approval.

However, this is the reason why you might be able to find the same drug from the same manufacturer with different expiration dates. They may have tested one version for longer than another.

I should add that there are relaxed requirements if the mechanism of degradation and its kinetics for certain drugs is very well known. Though in many cases folks tend to prefer to do empirical testing for their formulations to avoid arguing, if possible. It may depend on the specific types of pharmaceuticals. The areas where I am more familiar with tend to have more complex formulation requirements.

 

[exchemist]

On 9/16/2024 at 12:56 AM, LuckyR said:

That's one opinion. I and the Department of Defense disagree. 

 

The Pharma industry's interest in profit maximization, needs no citation, commonly performed through even shadier techniques. 

They are motivated by profit, but what @CharonY says about shelf life, specifically, has the ring of truth. I worked in the lubricants industry, in which we had to quote shelf lives for packaged lubricants: engine and gear oils and so forth. When a new product is developed, you can’t wait for 5 - 10 years or more before putting it on the market, just so you can determine when it may start to go off. Also, so much depends on storage conditions: temperature, moisture exposure etc. So what a manufacturer - any manufacturer, I suspect - does is come up with a safe “use by” date from the data on life they already have. As it will be an estimate, they will have to err on the conservative side for obvious legal reasons.

No need to ascribe malign motives: it’s a purely practical matter, faced by any manufacturer.

Edited September 17 by exchemist

[CharonY]

Yupp, often for initial approval manufacturers can provide shelf life data from production batches, provided they are reresentative and following the same guidelines. That data can sometimes only cover 12 month, but they can amend it after they make longer tests. There is a bit of a push to provide manufacturers with incentives to make longer tests or work within SLEP or similar mechanisms to prolong dates. But for longer periods at home storing conditions could complicate things.

[J.C.MacSwell]

Thanks CharonY. If you read what you quoted you will realize it refers to allowable drop in quality, not no drop in quality.

[CharonY]

Not really. The indicated changes are considered not statistically significant and generally also applied to batch production. I.e. the product is still virtually indistinguishable from fresh products. In case you are not familiar with the concept, in most of biology and medicine significance is established at the 5% level. There might be exceptions for certain types of drugs, where threshold can be lower, but I believe that these are outside of the general guidelines. The main quality concession there is related to accelerated (i.e. high temperature) experiments, as long as potency is not affected. 

Or are you referring to something else, in which case please clarify as I am curious to see why you'd think that I am not reading (or understanding) what I post.

[J.C.MacSwell]

4 hours ago, CharonY said:

Not really. The indicated changes are considered not statistically significant and generally also applied to batch production. I.e. the product is still virtually indistinguishable from fresh products. In case you are not familiar with the concept, in most of biology and medicine significance is established at the 5% level. There might be exceptions for certain types of drugs, where threshold can be lower, but I believe that these are outside of the general guidelines. The main quality concession there is related to accelerated (i.e. high temperature) experiments, as long as potency is not affected. 

Or are you referring to something else, in which case please clarify as I am curious to see why you'd think that I am not reading (or understanding) what I post.

Not necessarily. It depends on the nature and test protocol for the particular drug.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040264/

"Medication's potency gradually decreases starting from the moment of its manufacture."

While I'm not sure this is true in all cases it is certainly true generally.

(For balance and/or more context) It continues:

"This process is not in any way spontaneous after the expiry date.

Expired drugs have not necessarily lost their potency and efficacy. The expiration date is only an assurance that the labeled potency will last at least until that date. Ongoing research shows that stored under optimal conditions, many drugs retain 90% of their potency for at least five years after the labeled expiration date, and sometimes longer. Even 10 years after the expiration date many pharmaceuticals retain a significant amount of their original potency.²

Solid dosage forms, such as tablets and capsules, are most stable past their expiration date. Drugs that exist in solution or as a reconstituted suspension may not have the required potency if used when outdated."

Edited September 17 by J.C.MacSwell