Are Drug Expiration Dates a Myth?

What does the expiration date on medications mean? Since 1979, the US Food and Drug Administration (FDA) has required that manufacturers include an expiration date on both prescription and over-the-counter products. This is the date at which full potency and safety of the drug is still guaranteed. Typically, that date is between 12 and 60 months from the time the product was manufactured. In the case of medications dispensed by a pharmacist from a stock bottle, a "discard by" date of 1 year, required in 17 states, is often included.

Note that the FDA requirement is a date at which potency is still guaranteed. In most cases, the drug in question has not been tested for efficacy or toxicity past that date. There is also no incentive in the regulations for a pharmaceutical manufacturer to look for ways to lengthen that date of expiration.

The US military, which maintains large stockpiles of medications for both military and civilian populations for use during an emergency, became very interested in this issue following the 2001 anthrax scare. The cost implications were obvious. Throwing out large numbers of expensive drugs solely because they were past their expiration date was an expense that could potentially be avoided if it was determined that the drugs were effective beyond that date.

To provide this information, the FDA analyzed the potency of 122 common drugs representing a broad range of drug products and forms. The Shelf-Life Extension Program (SLEP), which is administered by the FDA for the US Department of Defense, checks the long-term stability of federal drug stockpiles. After vigorous testing of more than 3000 different lots of these drugs, almost 9 out of 10 lots were determined to have more than 90% potency at 1 year past the expiration date. The average extension of this degree of potency was 5 years. Some notable examples can be found in the Table.

Table. Examples of Products With Shelf Life Extensions

Extension Time (mo)
Drug Product Dosage Form Mean Range
Ciprofloxacin tablets 55 12-142
Naloxone solution 77 60-95
Amoxicillin tablets 23 22-23
Potassium iodide granules 254 225-278
Morphine solution 79 21-115
Ringer lactate solution 52 23-125
The authors emphasize that these products were stored under optimal conditions and caution that the additional stability period is highly variable.

A more recent, fascinating study examined the stability of active ingredients in drugs that were already expired. Eight medications containing 15 different compounds, all between 28 and 40 years past their expiration dates, were discovered in a retail pharmacy in their original, unopened containers. The compounded drugs included products such as Fiorinal, which combines four active ingredients (butalbital, aspirin, caffeine, and codeine phosphate).

The drugs were subjected to rigorous chemical analysis. The majority (86%) was found to be at least 90% potent; 12 of 14 of the medications retained full potency for at least 336 months, and 8 of these retained full potency for at least 480 months. Two notable exceptions were acetaminophen (38% of the labeled amount of active drug was found in the pills tested) and aspirin (between 4% and 10% of the active ingredient was found).

Another interesting study conducted by the British Antarctic Survey Medical Unit looked at drugs transported to that remote part of the world via a ship's hold that was not temperature controlled. The ship crossed through the tropics (air temperature of 25°C-30°C for approximately 3 weeks), and the drugs were then transported from the ship to the base, often in temperatures substantially below freezing. The researchers analyzed five drugs (atropine, nifedipine, flucloxacillin, naproxen, and bendroflumethiazide) that had been subjected to these conditions and were now expired. All were found to be stable.

There is limited research examining the stability of eye solutions which are past their labeled expiration date. The expiration date for travoprost 0.004% ophthalmic solution is 6 weeks after the laminated packaging has been opened. However, a study conducted in 2004 found that solutions of this product that had been opened up to 12 weeks previously resulted in patient outcomes that matched those found in patients using a product that had just been opened.

This result is of interest, but a single study is not sufficient to alleviate the concern that liquid in eye solutions could evaporate and change the concentration of the active ingredient or that there could be breakdown of the ingredient.

The cost implications of these studies are staggering. An analysis of the SLEP program concluded that each dollar spent to demonstrate longer than labeled drug stability could translate to $94 saved on repurchasing these products.

What About Epinephrine?
Recently much concern has been raised about the rising costs for epinephrine—and the expense incurred by families in replacing an expired EAI. Even more important is the concern about potentially administering a less potent drug in a patient experiencing a life-threatening event.

A number of studies have examined both safety and potency of expired epinephrine products. A chemical and microbial analysis of six EAIs 30 months beyond their expiration date that had been stored in a hospital pharmacy determined they were still sterile and detectably pure.

What about potency? Another analysis of 40 expired EAIs stored by an allergy practice in Florida concluded that all contained more than 80% of their label concentration at less than 25 months past their expiration date.

A systematic review of EAIs published in 2019 concluded that, although evidence was limited particularly for syringes with the 1 mg/mL concentration most commonly used in anaphylaxis, EAIs appear to be stable and sterile for a period of at least 90 days after the expiration date.

It should be noted that the SLEP analysis was conducted with drugs stored in optimal circumstances. The drugs found in a retail pharmacy that were the subject of the one of the studies discussed above may not have been stored in perfect conditions, but they were in their original containers and in a dry environment. A 2013 study of drugs stored in an ambulance and thus subjected to wide fluctuations in temperature concluded that some drugs became unstable. However, the investigators did find that epinephrine remained stable for several months even under these conditions.

What Is the Bottom Line?
Are patient fears justified that an expired medication, like spoiled milk, could be dangerous? The only expired medication that has ever been reported to cause toxicity was an older tetracycline formulation that is now off the market. In that situation, reported in the 1960s, four patients developed reversible renal tubular damage. A degradation product of the tetracycline was probably the etiologic factor. With this single exception, there are no published reports of human toxicity due to use of a current drug formulation after its expiration date.

I clearly remember a patient who did not administer an expired EAI because of his fear about using an expired product, and he subsequently became quite ill. In the case of a drug such as epinephrine used to treat a potentially fatal reaction, I'd rather my patient used an expired drug than no drug at all. So while I certainly refill expired EAIs, I suggest that my patients hang on to their older pen as a backup.

For pill and capsule formulations of drugs—especially for patients for whom cost is an issue—I am comfortable reassuring them that the expired drugs can be used. Solutions and suspensions may be less stable, and pitching them, particularly if they are cloudy, discolored, or have visibly precipitated, seems reasonable.

Douglas S. Paauw is the Rathmann Family Foundation Endowed Chair in Patient-Centered Clinical Education and a professor of general internal medicine at the University of Washington. He was elected to Mastership in the American College of Physicians (ACP) in 2009. He is a frequent lecturer at the ACP annual meeting, presenting yearly standing-room-only lectures on drug interactions and medical myths.

LINK: https://www.medscape.com/viewarticle/924683_2

Very informative; thank you.

"Expiration Date" on everything that we use/take/eat is a myth.

This confirms my prior understanding from asking this Q of a PA and from my mother a lifelong nurse. They don’t go bad/get dangerous, simply may lose some potency...so feel free to stock up on emergency/SHTF meds.

The cost savings from a patient standpoint and a pharmacy standpoint is huge if they were to ever extend those expiration dates.

I was visiting my mother around 2004 and needed a cough syrup. My hoarder mom pulled a prescription, for myself, from the back of her fridge dated 1972. It seemed to still work ok. 32 year old medicine. I guess since it was a script for my 4 year old self, I was GTG with the law.

I’ve always thought I could push those dates. Good to know about Tylenol and aspirin. I’ll have to rotate that more often.

quote:

Originally posted by 12131:
"Expiration Date" on everything that we use/take/eat is a myth.

I have one one word for that myth - "milk"

Always assumed 2 to 3 years was good

quote:

Originally posted by LS1 GTO:

quote:

Originally posted by 12131:
"Expiration Date" on everything that we use/take/eat is a myth.

I have one one word for that myth - "milk"

Nope, sorry, still myth. Milk expires today. I can still drink it a few days later without getting sick.

How about cheese left in the truck?

This problem has many facets, and the breadth of the many issues is not fully explored in the above commentaries. Decades I ago I worked for one of the larger ethical drug companies, aka big pharma in support of its very large pharmaceutical R&D division, and did so fairly often on these very matters. It might be helpful to initially list as many of the parties involved as have a hand in the process of establishing the limits under question. The matter begins with preparation of the total package of the FDA's required information package called the NDA(the acronym for a New Drug Application). While the drug is 'new' many well informed scientists at the company are reasonably sure that they know a bit about its stability and in particular those chemists who had a hand in its synthesis, however the FDA wants to see in the NDA as sound scientific evidence as can be had of the assertions that must be made in that regard. The FDA, from the start of any NDA, is in a somewhat legitimate 'a conservative Show Me' mode as they fear loosing another "thalidomide" like tragedy into wide usage, as happened in Europe, and which was only accidentally avoided here via lethargy in the approval cycle.

The shelf life or stability of a drug can and usually does depend on a number of factors, such as: ambient light though the packaging, moisture transmission rates of the packaging materials, residual gas(es) that are present from its possible sterilization, the degradation of the packaging itself from the above and other factors, the Arrhenius equation's guaranteed changes in all of the chemistries(the drug, the packaging, the sterilants, preservatives, etc) involved. The Arrhenius changes are the nonlinear temperature based accelerations and deceleration of the many possible chemical changes as functions of time and storage temperature fluctuations which affect the potency and safety of the delivered product at within the labelled expiration date.

This is a big, high dollar cost issue for the manufacturer and the consumer and the risk averse FDA is given the job of overseeing as correctly done. Each party is working within published guidance to achieve a desired endpoint while minimizing risk/cost for his contribution. Many new drugs have exceeded hundreds of millions of dollars in costs before the NDA is ever even submitted. I worked on one where the patents(17 years at the time) all expired before it was approved and that was for the approval of the exact same drug as initially conceived and developed. It was approved at 20 years and then subsequently fell into disuse due to a later encountered interaction with another popular new drug. A very sad near total loss event.

So how did my former employer(and most others do this)? Our first shot at stability testing was the usage of days, months, to ultimately years of controlled high temperature storage to avail ourselves of some statistical certainty regarding those predicted quantities of remaining shelf life. In parallel along the way, samples were regularly taken to assure the the accelerated testing model was remaining valid. Lots of quantitative chemistry was utilized along this path. In our suite of products an initial 5 year shelf life was a common goal. Revisions to that goal could and often were made further down the road in time following approval, and sometimes downward rather than upward. A famous(or infamous) one was the result of a far-down-the-road found interaction between the drug and the colorants used to distinguish between the different dosages of the very potent, susceptible, life supporting drug.

The real leverage of the FDA in this matter is the "Labeling" and that is the heavy hand of the LAW. If the product is ever in violation of its labeling then the manufacturer is at great legal risk, both tort and criminal.
The words on every FDA approved pharmaceutical label are very judiciously selected with much thought and labor going into those words thereon(and therein on the 'insert' within some packaging). For the reasons stated physicians, attorneys, and top management all have a lot to say about every word there.

There are many many more factors to be weighed, these paragraphs barely scratch the surface. But let's pose this very rational and very basic business management question: Who should pay for the studies needed and the liabilities of extending the shelf life labeling of a perhaps small fraction of the remaining inventory of a drug if they substantively increase its costs? From the manufacturer's point of view it is highly plausible that an 'old' product can be very easily replaced at far lower cost by discarding the old and replacing it with new product(always assuming users abide by the expiration date label). And that's not having to consider the cost of retrieving, destroying, and certifying that 'out of date' drugs are safely beyond access ever. It might even be most cost effective to simply periodically run out of the drug using a tight supply chain. FIFO or LIFO, FILO or LILO? Labeling is a real administrative 'can of worms'! And each product can be very different from its neighbor. Been there, done that, and the questions never seem to end....

Expiration dates were bought and paid for by lobbyists for big pharma and the big food processing industry for great profit when 'expired' product is replaced by new. Note some of the lower level big box stores sell food close to or at expiry dates...

quote:

Cassandra

No matter how you came to have your screen name, it is, mythologically speaking, spot on!

quote:

Originally posted by 12131:

quote:

Originally posted by LS1 GTO:

quote:

Originally posted by 12131:
"Expiration Date" on everything that we use/take/eat is a myth.

I have one one word for that myth - "milk"

Nope, sorry, still myth. Milk expires today. I can still drink it a few days later without getting sick.

Having chugged a mouth full of curds, I believe your definition of "sick" may be technically correct, however my definition of "projectile vomiting" is close enough for me to vote with LS1 GTO.

Worked as a pharmacy tech for a few years and pharmacists all concurred that stuff doesn't go bad, just might lose potency. So take a heavier dose if it is expired!

If I remember right, while almost every drug tested was still good but maybe a bit less potent, there was one single med that actually becomes dangerous. Doxycycline maybe? I thought it was one of the antibiotics.

There are many, many biologically derived therapeutic drugs that millions of lives depend upon, used every hour of every day worldwide, which have absolutely mandatory and patient safety derived expiration limits. One with which everyone is surely familiar is whole blood. The preservative added, refrigerated life of this class of products is either 3 weeks(21 days) or 5 weeks (35 days) depending on the preservative. It is prominently so "Labeled". Beyond those dates the product no longer meets the needed therapeutic value for which it is administered. The prevalence of ignorance hereabouts is staggering as is the triviality and the cynicism of many comments.

Food products are another issue entirely separate from ethical drugs and their 'sell by' dates seldom are there due to any great hazards(thanks to the industry and the FDA; when was the last time you heard about a case of clostridium botulinum poisoning) and more aligned with degraded or altered 'taste' issues about which few may agree. Chasing possibly food-born diseases such as the nCorona virus can make chasing murderers look trivially easy and safe.

If asserting that all of the drug scientists, physicians, and their corresponding government regulators serve in a morally corrupt industry we might as well conclude and admit that the entire community of law enforcement conducts themselves likewise based upon the output of our pitiful excuse for a news media and some bad apples. Such assertions are preposterous. As for pharmacists' knowledge of exotic chemistries, they aren't called 'pill rollers' without reason even though I have had many as friends. (sarc/off)

quote:

Originally posted by LS1 GTO:

quote:

Originally posted by 12131:
"Expiration Date" on everything that we use/take/eat is a myth.

I have one one word for that myth - "milk"

Not to derail the drug question, but I buy only Lactaid milk. The expiration date is usually 2 months from purchase. It’s usually good for 10-15 days past the expiration date.

That’s why I buy Lactaid milk instead of regular milk, I never have to throw it out.

And now back to regularly scheduled programming.

quote:

Originally posted by OKCGene:

quote:

Originally posted by LS1 GTO:

quote:

Originally posted by 12131:
"Expiration Date" on everything that we use/take/eat is a myth.

I have one one word for that myth - "milk"

Not to derail the drug question, but I buy only Lactaid milk. The expiration date is usually 2 months from purchase. It’s usually good for 10-15 days past the expiration date.

That’s why I buy Lactaid milk instead of regular milk, I never have to throw it out.

And now back to regularly scheduled programming.

If its anything like the almond milk the wife buy this is not entirely accurate. The use by date is a month or two. However once opened the carton says to use within 5-7 days.

quote:

Originally posted by 12131:

quote:

Originally posted by LS1 GTO:

quote:

Originally posted by 12131:
"Expiration Date" on everything that we use/take/eat is a myth.

I have one one word for that myth - "milk"

Nope, sorry, still myth. Milk expires today. I can still drink it a few days later without getting sick.

The FDA cracked down on use of the word expiration, b/c food doesn't suddenly expire. Thus the industry standard is "Best by ___."

In practical terms, "Best by," means the supplier forces the retailer to rotate out stock by the printed "Best by" date. The food is still good, it just isn't at its arbitray best. In other words, "Best by" for the consumer is truthfully a suggestion.

As far as dairy products, if unopened and refrigerated properly, they will last long past their "Best by" dates, especially if stored in opaque containers. I know this will turn some stomachs, but I have on many occassions put dairy to the the smell, taste, and stomach tests. I have many times drank newly opened milk 4 weeks past its "Best by" date. It tasted fine, and I suffered no ill effects.

A couple months ago I came across a cup of unopened yogurt that had sat idly in the back of a refrigerator for 4.5 years.
Out of curiousity, I opened and ate a few spoonfuls. It tasted fine to me. It didn't show any signs of spoiling. It wasn't worth the risk of food poisoning, so I didn't eat it all, but a few spoonfuls did nothing wrong to me.