The EpiPen auto-injector retained substantial epinephrine for years after their expiration dates in a small study from California, with more than half of pens tested containing at least 90% of their stated amount of adrenaline. MedPage Today reports that researchers tested the potency of 40 expired EpiPen products (31 EpiPens and 9 EpiPen Jrs) collected from a single community clinic over a two-week period. The pens had expired one to 50 months prior to analysis.
The study led by Dr F Lee Cantrell and colleagues at the California Poison Control System – San Diego, Kaiser Permanente San Diego, University of California – San Francisco, found 65% of EpiPens (1 mg/mL epinephrine) and 56% of EpiPen Jrs (0.5 mg/mL epinephrine) contained at least 90% of the stated amount of the drug.
The findings suggest the need for revisiting the process for determining the shelf life of epinephrine auto-injectors, the researchers said, adding that "in the setting of outpatient anaphylaxis without other therapeutic alternatives, patients and caregivers should consider the potential benefits of using an expired EpiPen." But the report quotes Cantrell as saying that the take-away message from the study should not be that expiration dates on epinephrine auto-injectors can be ignored.
"The Food and Drug Administration says that most medications marketed in the US can contain 90% to 110% of the labeled concentration of the active ingredient, and, by that standard, the vast majority of the pens we tested were clinically potent," he said. "But the point is not to encourage people to use expired EpiPens."
Cantrell said larger studies are needed to confirm findings from both studies. If confirmed, the findings make a strong case for reconsidering current practices regarding drug expiration dating, he said. This may be especially timely, he added, given the dramatic price increases of many prescription drugs in recent years.
The report says in 2016, EpiPen manufacturer Mylan angered patients, their families, and public health groups when it raised the price of a twin pack of the auto-injector to more than $600. Critics noted that the actual cost of the epinephrine included in the auto-injector is about $1. The move proved so controversial that Mylan later announced that it would produce a generic version of the EpiPen at roughly half the cost, but critics complained that this was still too expensive for a life-saving drug with few alternatives.
"If we are trying to save healthcare dollars, and get this drug to the people who need it, revisiting the expiration dating process has broad scale implications," Cantrell said. He noted that while medications in the US typically have expiration dates of up to three years, EpiPens are often labeled with an expiration date of 18 months or even less.
The study also found that: all EpiPens that had expired up to 29 months prior to analysis (n=19) retained 89% or more of the listed epinephrine (range 89% to 100%): EpiPens expiring 35 to 49 months before analysis (n=10) retained 84% to 90% of their potency; two EpiPens that had expired 50 months prior to analysis retained 88% and 84% of their epinephrine, respectively: EpiPen Jrs expiring one to two months before testing retained 92% to 99% of their potency: two EpiPen Jrs examined seven months after their expiration date had 88% and 91% of their epinephrine remaining; and three EpiPen Jrs expiring 30 months prior to testing retained 81%, 82%, and 86% of their epinephrine.
"Our data show that EpiPen Products can retain substantial amounts of epinephrine well beyond their expiration dates," the researchers wrote. "Although we observed declining concentrations of epinephrine over time, we expect that the dose available 50 months after expiration would still provide a beneficial pharmacologic response."
Abstract
Background: Interest and outrage have been mounting over dramatic price increases for the emergency-use epinephrine autoinjection device EpiPen (Mylan). Since 2007, the price of this potentially lifesaving medication has risen more than 400%. This sharp increase has caused patients to ask health care practitioners whether they can use expired EpiPens because they cannot afford to replace them.
Objective: To determine whether EpiPens expired up to 50 months retain their stated potency.
Methods: Over 2 weeks, patients and practitioners at a community clinic were asked to provide unused, expired EpiPens. All pens were examined for color changes and expiration date. Two separate aliquots of each EpiPen's content were quantitatively analyzed for epinephrine concentrations by liquid chromatography (Agilent 1260 Infinity II LC, Agilent Technologies)–tandem mass spectrometry (Triple Quad 5500, AB SCIEX). Epinephrine was monitored using 2 transitions (mass–charge ratio, 184.1 to 107.0 and 184.1 to 166.0) and quantified by isotope dilution using epinephrine-d6 as an internal standard.
Authors
F Lee Cantrell; Patricia Cantrell; Anita Wen; Roy Gerona
[link url="http://www.medpagetoday.com/allergyimmunology/allergy/65124"]MedPage Today report[/link]
[link url="http://annals.org/aim/article/2625390/epinephrine-concentrations-epipens-after-expiration-date"]Annals of Internal Medicine abstract[/link]