Do they simply become less effective? Do they break down? Do they change into poisonous substances?
– Inspired by a packet of Neo-Citran that didn’t do bugger-all for my stuffed-up nose… then I noticed that it expired eight months ago.
I imagine that it’s different for different drugs and runs the gamut.
Drug companies conduct stability testing on new products, as well as on-going stability of existing products, in order to ensure that they are stable from day of manufacturing to the end of their shelf life. A typical stability study will be over the course of three years, although shelf-life expiry dates may be set at a shorter time frame than that “to be safe”. A drug is deemed stable if it’s dosage (amount of active) and impurity product profiles stay below a certain limit throughout that time frame (for tablets and capsules, dissolution profiles are also important). Other things, such as colour and pH also come into play for different products, although it isn’t always important (if you look at Listerine, it will say on the label that the solution might become cloudy over time, but there is no effect on it’s effectiveness as a mouth wash).
That said, there is no ticking time bomb that goes off the day after a drug expires, thereby making it less effective or more degraded. What and expiry date means is that there exists no data beyond this point to validate it’s effectiveness. I recall a study a while ago of 20+ year old aspirin from a military survival kit, that passed all the typical criteria for release as if it were a new lot… some molecules are very stable and stick around a long time. Others do degrade fairly rapidly though - this is especially true of products with special storage instructions, such as “dark place, in a fridge” etc.
8 months expired really isn’t all that long, and there is a very good chance the company that makes Neo-Citran has data for that amount of time (you might have a 3 year stability study, but assign a shelf life of 2 years, just to be safe). Were someone to analyse it, there is a good chance everything would fall into it’s specifications.
That said, it generally isn’t a good idea to take expired medications, because you might just come across that one product that is degraded, and if something goes wrong, you have no legal recourse against the manufacturer. Occasionally the degradation products of a drug are other drugs themselves, and if those become significant enough to have an effect on you, you could be in for some trouble, or at least unexpected side effects.
-mnemosyne- Analytical Chemist, Pharmaceuticals
I defer to mnemosyne’s credentials and add that I’ve put this question to my sister who is an MD. She reports that for most meds, especially OTC, the only risk is gradual decrease in efficacy.
Thanks, mnemosyne… only here on the Dope could I get an answer like that in less than a day without paying for it. 
I presume that drug formulations that did break down into actual hazardous substances, as opposed to inert ones, after a certain amount of time, would be less likely to be used?
I seem to remember that one common antibiotic–I want to say tetracycline–becomes poisonous. Most drugs mainly lose efficacy as they “degrade.” I imagine that a good few, a year or two past expiry, would be more likely to make you sick than to serve their intended purpose, for the same reason that that very old sesame butter in my cupboard grew quite unpleasant.
Sorry to bring up this zombie thread, but I missed this other question last time I checked up on it…
Pretty much, yes, they are less likely to be used, or would have a very much shorter shelf life.
When a drug molecule is discovered, part of the testing it must undergo for approval is forced degradation. That means a chemist will take that raw drug product and subject it to different “extreme” conditions; freeze-thaw cycles, exposure to UV light, exposure to strong acids, strong bases, etc. They will basically hammer away at it (chemically speaking) until it breaks down into other things, and that will identify it’s degradation products. Those will be classified as harmless or toxic or anything in between. The new drug product will also go through accelerated stability programs, where they will be stored in (for example) 40 C/ 75% relative humidity (RH) conditions and studied at 1, 2, 3 and 6 months (sometimes longer) to see if the drug degrades that way.
All of this will help establish the minimum impurity levels, so for a degradation product that’s ridiculously toxic, you might have a “no more than 0.1%” limit on it, but for something harmless, that limit might be as high as 2% (I don’t know if there is an upper bound on non-toxic things).
The drug product will also go through regular, “realistic” stability programs, such as long-term storage at 5C/Ambient RH, 25C/60% RH, 30C/60% RH etc. A typical study will test at 1, 3, 6, 9, 12, 18, 24, 36 months, and the appearance of the degradation products will be tracked. If they never change, and never go above the limits, thats a good thing. If they gradually increase and pass that limit at, say, 18 months, then they might either be given a very short shelf life, or the formulation (recipe) will be changed, or it might pass at 5 degrees and not 25, so the product might need to be refrigerated, etc.
Just to specify, degradation products are tracked, as well as impurities and related substances… impurities being a trace amount of something in the mixture for the drug that they can’t (or is too costly) to remove, and related substances being things like synthetic precursors, things that might have been “left behind” in the manufacture of the drug. Stability studies track all of these, and often consider them to be the same, at least in terms of the analytical tests needed to find them!
Once the drug is on the market, stability studies continue. I forget the frequency, but every couple of lots made, or a couple lots a year or something, must go into a basic stability study, stored at similar conditions to the “optimal” found in the early studies (often 25C/60% RH). The same rules apply, or are sometimes even tighter. Where I work we have an internal limit that is often narrower than what the FDA approves, so that problems can be identified sooner rather than later. These studies are behind certain recalls, where a drug that was placed on the market is called back a year later, even if it’s not expired, because a certain lot’s impurity profile might have gone a little wonky.
As I said before, just because a drug is past its expiry date doesn’t mean it has gone bad… I just tested a 48 month stability on a product, labeled to expire in 2004, and it passed everything but it’s colour test (it was no longer “slightly yellow” it qualified as “yellow”… very subjective test!) Pretty much, it was fine. But that isn’t always the case, so it really is best to follow the manufacturers directions!
Um… that’s all I can think of right now!