Douglas S. Paauw, MD

Disclosures

February 05, 2020

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.

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