Thread by @DrJaclynnMoskow

When do drugs really expire?

Which ones take decades to degrade?

Why does the US government use secret expiration dates for pharmaceutical stockpiles — but make pharmacies & hospitals discard perfectly potent meds?

I went down a wild rabbit hole for us

In 2012, Dr. Lee Cantrell, a Cali pharmacist-toxicologist, finds a box of drugs that had been stashed away on a shelf for decades

He wonders if any of the meds are still effective

Most people stop at wonder — the scientifically-minded amongst us find a way to get an answer

Dr. Cantrell hits up a UC lab for some liquid chromatography & mass spectrometry

They analyze various meds that had expired 28 - 40 years prior

Very cool study

Study synopsis?

The average % of active ingredient still present compared to decades-old label:

• Acetaminophen — 100% remaining
• Hydrocodone — 100%
• Caffeine — 100%
• Methaqualone — 100%
• Codeine — 95%
• Phenobarbital — 94%
• Amphetamine — 49%
• Aspirin — 1%

The implications of these findings received press coverage a few times over the years — but public discussion always quickly dissipates

What incentive does pharma have to extend expiration dates!?

Imagine how much money pharma would lose if pharmacies, hospitals, & patients were to STOP routinely trashing & replacing large quantities of Rx & OTC meds

What would it take for the pharma-funded FDA to tell pharma to take that kind of monetary hit?

But the reality is, for decades, the US federal government has been quietly studying the true shelf-life of medications

They stockpile pharmaceuticals around the world for the military, as well as for “emergency preparedness” programs like the Strategic National Stockpile

Rather than throw out stockpiled drugs on assigned expiration dates, the government tests them

The Shelf Life Extension Program (SLEP) began in 1985 – a joint venture of DoD & FDA

State & local governments are not permitted to participate (despite having their own stockpiles)

When SLEP finds that a drug is still useful, they extend the expiration date for their stockpiles — but not for us consumers

In fact, they have a strict policy to never share drug testing results or extension decisions

Yes, they are gatekeeping efficiency in this case

Crazy

~20 years back, the AMA called SLEP out

In turn, SLEP released a single lone paper revealing a bit of what they know about the true shelf-life of carefully-stored pharmaceuticals

This disclosure, however, flew under the radar

Very few know of it

You are about to be in the few

SLEP divulged that they were able to extend the expiration date for 88% of 122 stockpiled drugs tested over a 20+ year period

They examined & reexamined potency, pH, ability to dissolve, water content, impurities, etc

Some meds tested “still good” since the program's inception

The tables in this SLEP paper are a bit tedious to digest, but I dug through them to compile us some lists

In their carefully-stored government stockpiles, the following drugs NEVER failed testing:

• Acetaminophen pseudoephedrine (capsules)
• Amoxicillin sodium (tablets)
• Amyl nitrite (inhalant)
• Ampicillin (capsules)
• Atropine sulfate-pralidoxime chloride (autoinjector)
• Benzonatate (capsules)
• Bretylium tosylate (solution)
• Bupivacaine HCl (solution)
• Calcium chloride (solution)
• Calcium glucepate (solution)
• Ceftriaxone sodium (powder) 
• Cephalexin (capsules)
• Chloroquine HCl (solution)
• Chlorpromazine HCl (solution)
• Cimetidine HCl (tablets)
• Ciprofloxacin (tablets & suspension)
• Dexamethasone sodium phosphate (syringe)
• Dextrose 10% (solution)
• Dextrose & NaCl (solution)
• Diphenhydramine HCl (syringe)
• Dobutamine HCl (solution)
• Doxycycline hyclate (capsules & powder)
• Edrophonium chloride (solution)
• Enflurane (liquid)
• Ephedrine sulfate (solution)
• Erythromycin lactobionate (powder)
• Fentanyl citrate (solution)
• Guaifenesin ER (tablets)
• Halothane (liquid)
• Hetastarch in NaCl (solution)
• Hexachlorophene cleansing (emulsion)
• Hydrocortisone sodium succinate (solution)
• Iothalamate meglumine (solution)
• Ketamine HCl (solution)
• Mafenide acetate (cream) 
• Mannitol (solution)
• Mebendazole (tablets)
• Meperidine HCl (solution)
• Mepivacaine HCl (cartridge)
• Morphine sulfate (syringe)
• Naloxone HCl (solution)
• Naproxen (tablets) 
• Neostigmine methylsulfate (solution)
• Oxacillin sodium (powder)
• Penicillin G benzathine (suspension)
• Phenylephrine HCl (solution)
• Phenytoin sodium (solution)
• Potassium iodide (granules & tablets)
• Povidone-iodine (ointment)
• Prochlorperazine edisylate (solution) 
• Promethazine HCl (solution)
• Protamine sulfate (powder)
• Sodium bicarbonate (solution)
• Sodium chloride (solution)
• Sodium nitrite (solution)
• Sodium thiosulfate (solution)
• Sulfisoxazole (tablets)
• Triamterene & hydrochlorothiazide (capsules)
• Tubocurarine chloride (solution)
• Undecylenic acid & zinc salt (powder)

Which drugs did SLEP find failed expiration testing more often than passed?

There were only 10:

• Albuterol (inhalant)
• Diphenhydramine HCl (spray)
• Epinephrine & lidocaine HCl (solution)
• Ergotamine tartrate & caffeine (tablets)
• Isoproterenol HCl (solution)
• Levarterenol bitartrate (solution)
• Mefloquine HCl (tablets)
• Penicillin G procaine (powder)
• Phenobarbital sodium (cartridge)
• Physostigmine salicylate (solution)

But, about epinephrine…

Dr. Cantrell recently tested 40 EpiPens, 1 - 50 months past expiration

All devices still contained 80%+ of their labeled concentration

About half contained 90%+

I would 100%+ use an expired EpiPen if I were going into anaphylaxis & it was all I had

What about insulin & nitroglycerin?

Not included in the SLEP study

Perhaps they didn’t want to waste resources testing meds already widely known to degrade

But in an emergency, I would use those expired, too

(& call for help!)

Quite interestingly, SLEP tested 4 drugs MUCH more often than they did any others:

1) Pyridostigmine bromide (nerve agent prophylaxis)

2) Atropine sulfate (nerve agent antidote)

3) Pralidoxime chloride (nerve agent antidote)

4) Ciprofloxacin (broad-spectrum antibiotic that can be used to treat anthrax)

In fact, over 50% of ALL tests conducted in the SLEP program during the study period were on these 4 drugs!

Remember, this info was published 19 years ago, during the 911-era

I am grateful to learn they were protecting us in this manner

(Veteran readers — ty for your service!! 🇺🇸🇺🇸🇺🇸)

What did SLEP find out about antidepressant stability?

Well,

They didn’t report examining them at all

Is this omission an indirect admission from the government?

Perhaps antidepressants really aren’t important for our military & public health?

I digress,

You may be wondering,

Say a med truly does expire & becomes less effective or ineffective — does it ever turn TOXIC?

Toxicity is almost unheard of

Once upon a time, I learned expired tetracycline can potentially degrade into a dangerous compound & cause kidney problems

Modern formulations are now designed to prevent this — but it is still theoretically possible with tetracycline specifically

There are also some theoretical reasons that the breakdown products of expired hydralazine & chlorpromazine could cause harm to the body — but there is no evidence it’s ever happened

Common sense will tell us that expired liquid meds & ointments may eventually grow bacteria &/or mold

Expired biologics like immunotherapies & vaccines may also pose increased risk as molecules denature / aggregate (according to… my brain) – potential for immune rxns & etc

Common sense will also tell us:

1) Meds that need a “propellant”, like an inhaler, may fail to dispense over time

2) Gelatin capsules will eventually break down

3) Hard tablet pills will live the longest

Yet, right now, almost all pharma meds expire within 1-3 years

So what’s the deal with this seemingly arbitrary selection of inaccurate, quick expiration dates?

When pharma submits a drug application to the FDA, they are required to assign an expiration date & include stability testing to show it can make it to said date

Picking a far-off expiration date delays getting a drug to market, pharma would need to sit around waiting to get test results

Speed is everything in business

and some pharma products are legit — patients need them now vs later

In theory, pharma could retest after drug approval & resubmit to extend dates

But the FDA does not require that they examine stability in this way

So, they don’t!

Retesting costs money

Extending expiration cuts into the profits that come from forcing repurchases

But what about the SLEP research? Why hasn’t it led to the FDA instructing pharma to extend expiration dates?

That would be too logical

SLEP uses their data to extend expiration in their stockpiles only

Extensions for “the rest of us” come from pharma’s testing data, not SLEP’s

This will generally only happen if pharma can’t keep up with demand in an ~emergency~

Examples:

• EpiPens in 2019

• Tamiflu per 2010 Swine Flu

• COVID vaccines during the marketing of a pandemic

But most of time, pharma can easily meet demand & perpetually supply new batches and make new sales

The result?

Hospitals, pharmacies, & patients collectively spend billions of dollars per year replacing perfectly potent, safe, useful drugs — prescription & over-the-counter

It’s illegal to export expired drugs — so donating them to countries in crisis isn’t permitted

The lol-WHO even issued an instruction manual on how to dispose of drug donations, including those “near expiry date”

There have been documented instances in which the unavailability of certain antibiotics led to the prescribing of broader-spectrum ones – which, in turn, led to increased antibiotic-resistant strains appearing in hospitals & communities

Disastrous & unnecessary

So, should the incoming FDA revisit pharma med expiration dates?

Our tax dollars have already funded decades-long research on this matter

SLEP has many of the drug-stability answers we need

Pharma prefers they continue to keep those answers to themselves

Lmk what YOU think

Link to share from top —

https://twitter.com/drjaclynnmoskow/status/1882103624266039641

Press coverage on Dr. Cantrell & SLEP:

ProPublica & Business Standard: “The Myth of Drug Expiration Dates”

Vox: “Are drug expiration dates meaningless?”

There are others as well

Deep dive into SLEP, by SLEP:

Khan SR, et al. United States Food and Drug Administration and Department of Defense shelf-life extension program of pharmaceutical products: progress and promise. J Pharm Sci. 2014 May;103(5):1331-6