Drug expiry dates have been in the news following a ProPublica report on July 18. While Scott is taking a blogging break, here’s an update of his post on expiry dates from 2012.
Imagine that’s the contents of your medicine cabinet above. All of the products are expired. Would you still consider taking any of them? Why or why not?
Your answer is probably influenced by a number of factors, including perceptions of risk and benefit. Some feel the expiry date is purely a plot of Big Pharma to sell more drugs. Others believe that drugs start deteriorating long before the expiry date. Few understand how and why they’re calculated.
Expiry dates are the source of a lot of questions to pharmacists. Not only is the pharmacy legally responsible for ensuring your prescription is filled with “in-date” stock, we’re regularly confronted with dealing with expired drugs, both prescription and non-prescription. Because of expiry dates, an enormous quantity of drugs are manufactured and sold or dispensed, but never consumed. This creates a significant wastage issue: In April 2017, the U.S. Drug Enforcement Administration’s National Prescription Drug Take-Back Day collected 900,386 pounds (that’s 450 tons) of unwanted or expired drugs. Those are drugs that someone paid for, and are now being incinerated. If expiry dates are nonsense, extending them could have considerable economic and environmental benefits. So where does the expiry date come from? They’re based on the chemical characteristics of the product itself.
Calculating the expiry date
At some point after major clinical trials are concluded, but before FDA approval, a series of quality standards are established for each new drug. These are the manufacturing and testing specifications, which includes upper and lower limits for the amount of the Active Pharmaceutical Ingredient (API) in each dose unit (e.g., 500mg per tablet). The final dosage form may be a mix of the API as well as fillers, binders, and other ingredients to ensure the API is delivered to the body in a reliable and predictable manner. But what certainty do we have that this new dosage form will maintain all of these properties over time? What happens after it sits on a shelf for two or three years, or more? Few companies have the patience to wait, so drug products are put through accelerated degradation testing, or “stress” testing, to estimate how quickly a drug will deteriorate. Depending on the dosage form, stress testing may include short-term exposure to extremes of heat, light, oxidation, and humidity. After exposure over different time periods, the quantity of the API, and the other product characteristics, will be assayed again. Not only does this help us understand how stable a drug is, it illustrates the degradation pathways – what chemical reactions could be expected to occur over time. For liquid and injectable drugs, there will be additional tests for bacterial purity and chemical stability. All of these tests predict the overall stability of the dosage form – not just the amount of drug, but how that drug will be absorbed into the body. All of this is used to estimate what the expiry date should be: the date to which the manufacturer warrants the original product characteristics will be retained.
Expiry dates for drugs can vary dramatically. One of the shortest for a drug in common use is injectable epinephrine known as the “Epipen”, carried by those with severe allergies. Epinephrine for injection is unstable, and you’re lucky to find a product that expires more than 18 months after you get it. (The ProPublica article points out that this may, in fact, be overstated.) Other drug products are highly sensitive to moisture, requiring dispensing in specialized containers with dessicants to trap moisture and enhance stability. Many liquid antibiotics have very poor stability, so they must be prepared in the pharmacy at the time of dispensing. Refrigeration is necessary for other drugs, ranging from vaccines to eyedrops, which keeps the dosage form stable.
It is important to keep in mind that the expiry date of a drug is based on testing of previously unopened products, stored in its original container, and maintained under typical conditions. Once you open a bottle, or transfer it to another container (like a prescription vial), the manufacturer’s expiry date is no longer reliable. That doesn’t mean a drug will become ineffective rapidly, but the stability could be compromised once it has been introduced to light, heat, and humidity. Humidity’s effects are frequently noticeable with old bottles of Aspirin (acetylsalicylic acid) which breaks down via hydrolysis to salicylic acid and acetic acid giving old bottles a characteristic vinegar odour.
Are expired drugs still safe?
The first concern related to expired drugs is whether they are potentially harmful if consumed. Reassuringly, there is no published data to suggest harms from use of drug formulations after their expiry data. The example of degraded tetracycline causing kidney damage in cases dating back to the 1960’s, is drilled into every pharmacist’s brain. Reassuringly, this occurred with a version of the drug that is no longer available. While recognizing that case reports are an inaccurate and imprecise way of identifying harms, the lack of documented harms suggests that degradation of useful chemicals into toxic compounds is rare, if it occurs at all. Additionally, current requirements for stability testing of drugs should identify if expired products pose a safety risk – and there do not seem to be any other documented cases.
Are expired drugs still effective?
Again, the evidence is reassuring – with some caveats. The best way to verify long-term stability would be to stockpile supplies, let them sit for years, and even decades, and then test them. Americans can thank their government for doing just such testing – the Department of Defense/FDA Shelf Life Extension Program has been in place for over 20 years. It tested 122 different products, stored unopened and in their original containers, and found that about 88% are stable for at least one year after expiry with an average of 5 years after the expiry date. However, this was under ideal conditions – not typical use consumer use, where bottles are usually partially consumed, and partially exposed to moisture and light. Stability isn’t always a given. Epipen’s active ingredient degrades consistently after the expiration. (Though ProPublica points to a newer paper that suggests better stability.) So I’d never suggest people carry an expired Epi-Pen – but I wouldn’t hesitate to recommend its use in life-threatening anaphylactic situations where no other alternatives existed. Similarly, you may be less concerned about drug potency if you’re taking something like Excedrin for a headache, versus medication to treat epilepsy, where small changes in the dose delivered could affect drug levels. Because of sterility concerns, you should throw out an eye drop that has been open for several months, even if the expiry date still says it’s OK to use – that expiry date was for the unopened drug, not a bottle that’s been used. And if you leave your prescriptions to cook on the dash of your car in the hot sun, or freeze in the winter, (I have encountered both) speak with a pharmacist who may be able to get drug-specific stability data.
Conclusion: Drug expiration dates exist for a reason
There’s no single rule for expired drugs and supplements, owing to the variety of products, regulatory requirements, and other factors that can influence a product’s safety and efficacy. In general, expiry dates are conservative, and consumers can have confidence that drug labeling claims will be accurate up to, and in some cases well beyond, the labelled expiry date. But the reality is that we don’t store drugs under ideal circumstances. So when absolute certainty is required, stick to drug products that are not expired. When absolutely necessary, expired drugs are probably safe, however, the potency may be compromised. And before you flush or toss those expired drugs, find ways to dispose of them in a way that minimizes the environmental impact and potential for harm.
Photo from flickr users Brian Hansen and osseus under a CC licence.