WHAT! YOU'RE TAKING EXPIRED DRUGS!

It often elicits a hue and cry from guardians of civil society steadfast and obsessed in the notion that expired drugs are harmful or ineffective.

The "expiration date" labeling of drugs started with the 1979 FDA edict requiring expiration dates for prescription drugs, over-the-counter medicines, and dietary/herbal supplements, as an assurance that the products are potent and safe to use and will work as intended until that date.

Thus started the trashing and dumping of "expired drugs" from hospital supplies (over $800 million annually), nursing home leftovers from deaths or discharges, tons of drugs routinely tossed out from pharmacies, along with  immeasurable amounts dumped from millions of household medicine cabinets (billions of dollars each year) - tantamount to a pharmaceutical landfill of "expired" drug estimated at more than $750 billion a year, equaling a quarter of the U.S. health care spending.

But the edict on drug expiration has long been contested and challenged as too arbitrary, low on science, and horribly wasteful. Questions abound: What does the expiration date really signify? Do medicines really lose potency on expiration dates? Are expired medicines harmful? How long could potency remain after "expiration dates?

What does the expiration date signify?
The "expiry date" or "expiration date" does not indicate a point when a medication loses potency and is no longer effective or becomes harmful. There are two variants of "expiration dates": Manufacturer's and Pharmacist's.

The manufacturer's expiration date is the final day it guarantees full potency and safe3ty. It is an estimated date based on stability testing standards determined by the FDA - a date "required by law" generally set at 12 to 60 months after the '"manufacture date" of new medicines, usually stamped on the original packaging. Once the medication container is opened, manufacturers cannot guarantee drug stability and the expiration date is no longer guaranteed.

The pharmacist's expiration date for filled prescriptions is usually dated a year after being dispensed from the original container. The "do not use after. . . " or "discard after. . . " dates are required by the Board of Pharmacy in 17 states. The manufacturer will not guarantee drug stability after the original bottle is opened and the drug is repackaged into another container. Therefore, the United States Pharmacopoeia (USP), the body that sets the standard for pharmaceutical quality, recommends using the "beyond use" date. The beyond use date would never be later than the manufacturer's expiration date on the bottle. (3)

There are no stringent guidelines. Drug companies admit there are no real data and that since some drugs expire earlier or faster than others, most manufacturers make arbitrary or calculated guesses at shelf life, then cut that in half to avoid legal consequences. 

Potency studies
The question often raised is how long and how much potency persist after the expiration date. Studies done to test the stability of drugs beyond the expiration date have shown that stored under reasonable conditions many drugs retain 90% of their potency for at least five years after the label's expiration date; sometimes, much longer.

An FDA study of more than 100 drugs showed that 90 percent of both prescription and over-the-counter medicines were perfectly good to use even 15 years (!) after the expiration date. The exceptions were insulin, liquid antibiotics and nitroglycerin.

The Shelf Life Extension Program (SLEP) undertaken by the FDA determined the actual shelf life of stockpiled military medications of over 3000 lots, representing 122 different drug products. Based on stability data, expiration dates on 88% of the lots were extended beyond the original expiration date for an average of 66 months.  About 12% of the lots remained stable for at least 4 years after expiration date. Of the 2652 lots, 18% were terminated due to failure. Some of the common drugs tested with no failures included amoxicillin, ciprofloxacin, diphenhydramine, and morphine sulfate injection. The extension on expiration dates on these products ranged from 12 to 184 months (over 15 years). Potassium iodide, stockpiled for radiation emergency, showed no significant degradation (3)  In June 2020, the FDA allowed extension of certain stockpiled influenza antivirals stored under labeled conditions and for emergency use in some states: Tamiflu (oseltamivir) for 10 years and Relenza (zanamivir) for 10 years. The caveat in the SLEP study is that the military stockpile of medicines is kept in a climate-controlled regulated area, rather than the humid environs of bathroom cabinets and shower areas. (4)

A study by Cantrell and Gerona to evaluate for potency beyond expiration date was done on decades-old drugs containing 14 different compounds, including antihistamines, pain relievers and stimulants, all in their original sealed 100% containers, most 30 to 40 years past expiration dates. Results showed 12 of the 14 compounds were as potent as when  manufactured, some with almost 100% of labeled concentrations.

Factors Affecting Degradation
While most drugs retain potency beyond expiration dates, eventually they lose potency in varying degrees. Various factors influence degradation of drugs: formulation, presence of preservatives, temperature and humidity fluctuations, storage conditions, hydrolysis, oxidation and photo-degradation by light.

- Formulation: Tablets, capsules, and unreconstituted syrups and injections have a shelf-life at room temperature of at least two years. However, once reconstituted, the syrups have a shelf-life of 14 days at room temperature, and injections should be used immediately. Some excipients or drug vehicles do not tolerate the heat and humidity of tropical climates.
- Packaging / Bottles vs Bisters: Both packaging have undergone stability testing to ensure adequate barrier of protection of the medicine from moisture, oxygen, of chemical migration -- which can all affect medication efficacy. Blister packaging providing indvidual pill cavity protects the dose inside until needed for use. For bottle medications, once the cap is removed the barrier protection is compromised, and each time it is opened ambient air and humidity is introduced to the remaining products, which may compromise stability, efficacy, and potency. (13)
- Oxidation and photo-degradation: Protection from light may reduce the rate of oxidation of injectable solutions. Packaging may also protect against photo-degradation, i.e., use of amber glass or color film for blister-packing.
- Temperature: The rate of chemical reactions doubles for every 10°C rise in temperature. Reconstituted penicillin syrup is stable at room temperature (25°C) for 14 days, longer if refrigerated.
- Storage: Vaccines and insulin are usually stored in the refrigerator. Refrigeration or storage of the medications in a cool place will help extend its potency for many years. However, most impoverished Third World countries do not have the luxury of refrigeration or cool storage places, and stability studies need to be done for drugs in the environ of prolonged heat and humidity. Read the labels for storage instructions, and avoid storing medications in bath and shower areas.

Of course, discard pills that have cracked or split or changed in color, turned powdery, or smell strong; capsules that have discolored or hardened; liquids that have turned cloudy or filmy; or tubes of creams that have hardened or turned liquid. I have seen such changes in some medications a year away from expiry date.

Loss of potency and harmfulness
Loss of potency does not translate to harmfulness. Other than a contested report associated with use of degraded tetracycline causing Fanconi's syndrome, there are virtually no reports of toxicity from outdated drugs.

A testing reported in The Medical Letter showed many medications were still potent decades beyond expiration dates and noted there are no published reports of human toxicity due to ingestion, injection, or topical  application of a current drug formulation after its expiration date. (3)

Is the expiry date a mere marketing ploy? A commercial ploy that tags obsolesence to still potent drugs?  Is there a lobby to continue the dumping based on expiration dates?  The  economic cost of trashed "expired" drugs is staggering.  While manufacturers justify expiration dates as essential for "product integrity", consumers decry it as a wasteful profit-making ploy. There is no incentive for drug makers to study the potency of drugs beyond the FDA mandated expiration date. The dumping has been a cash cow opportunity to the delight of big and small pharma.

Alternative guidelines on expiration dates
For many grappling with old myths and concerns regarding "expired drugs" studies have suggested guidelines on how to maneuver through the issues related to expiration dates.

- Studies have shown that most drugs do not expire on expiration dates and many retain potency long after depending on storage and various degradation factors.
- Store medicines in a cool, dry place. Avoid exposure to extreme or fluctuating temperatures. Discard medicines that are discolored or showing signs of degradation even if not yet expired.
- Many commonly used drugs like amoxicillin, ciprofloxacin, diphenhydramine, among many others, retain potency beyond expiration dates.
- Medications in blister packaging most likely retain efficacy and potency longer than bottle-sourced medications, protecting the medications from moisture, oxygen, or chemical migration. Blister packaging with each individual pill cavity protects the dose inside until the pill is removed from the package for use.
- In general, drugs in liquid forms (solutions and suspensions) are not as stable as those in solid forms (tablets and capsules).   Solid dosage forms such as tablets and capsules remain potent and most stable past expiry date. Reconstituted drugs in suspension form (such as amoxicillin suspension), which require refrigeration, may not have the required potency after expiration date. (8)
- Some drugs need refrigeration for storage. Avoid exposure to high temperatures. To ensure proper shelf life, store medicines in cool, dry places. In the kitchen, store medicines away from hot appliances and the sink because of changing temperatures and humidity.
- Drugs in solution, including injectables, should be discarded if it has visible precipitate, discoloration, or cloudiness. This includes liquid drugs (topical solutions, eye and ear solutions, oral liquids), which may have undergone solvent evaporation.
- Expired medications containing preservatives (eye drops) may be unsafe after expiration dates. Outdated preservatives may be a medium for bacterial growth.
- Some suggest discarding liquid medications past expiration dates as they may provide a medium for bacteria and fungus to grow.
- Many physicians feel comfortable doubling the time of use from manufacture to expiration date. Some simply add two years to the expiry date.
- Studies have suggested that some drugs should not be used beyond expiration date: nitroglycerin, insulin, and EpiPen.
- Birth control pills should not be taken past expiration date as the slightest variation in hormone levels may allow ovulation to occur. (9)
- Thyroid medications are also sensitive to expiration dates, and expired drugs may not be able to effectively stabilize the thyroid stimulation hormone (TSH). (9)
- EpiPen auto-injectors: While manufacturers suggest that they should not be used after expiration date because of concern that epinephrine potency may have been lost. In a study of over 30 pens that expired 7.5 years earlier, the decrease in epinephrine content was proportional to number of months past expiration date. Another study of 46 autoinjector devices showed 80% (37 devices) retained 90% epinephrine content after two years expiration; devices 6 months past expiry date showed 100% epinephrine content. In another study of 100 autoinjectors up to 11 years after expiration date and kept in EMS vehicles, only 13% to 31% of labeled dose remained. (3) In cases of life-threatening anaphylaxis using expired epinephrine, if it is the only choice, is better than just waiting for emergency services arrive.
- Diabetic Test Strips: Glucometer test strips also survive beyond the expiration dates. I have compared unexpired test strips to 6 months, 1 and 2 years expired strips and found no significant difference. Some claim similar results for test strips more than 5 years expired. Before you throw your expired test strips, compare results with unexpired ones.

So for many of the common day-to-day maladies, familiar and recurrent complaints like headaches, toothaches, aches and pains, diarrhea, among many others, it is quite reasonable to use "expired" drugs without visible signs of degradation. For acute and potentially life-threatening conditions like epilepsy, asthma,  pneumonia, symptoms suggestive of cardiac cause and diseases requiring blood thinners, one should use unexpired drugs. But in emergency conditions without immediate access to treatment, as often occurs in many indigent boondock communities, the availability of "expired" medicines can be godsend.

The pharmaceutical landfill of expired drugs can be a potential gold mine of recycled medicines that can benefit many segment populations. In Third World countries where the prescription medicines cost more than daily wages, a recycling or reuse of "expired" but still potent drugs can provide a pharmaceutical lifeline to indigent populations who cannot afford the cost of medications. Cost is the most common cause of non-compliance—patients taking medicines once daily instead of three times daily, or twice or thrice a week instead of daily. It will require a re-education of "what! expired!" mindsets, access to "expired" drugs, monitoring programs, repackaging, and potency and stability screening facilities, and setting up of storage and refrigeration. Rather than incineration, redistribution of these discarded and left-over medicines for recycling and reuse in Third World countries will be godsend and life-saving to the healthcare of countless indigent communities.