EpiPenThe above question is common from patients with a history of an allergic reaction seen for a repeat emergency department visit. The manufacturers of EpiPen caution not to use the pen beyond the expiration date, and if the drug solution becomes discolored (oxidation). But EpiPens are expensive! Is there harm in using the pen beyond the expiration date? What should we tell our patients?1

PICO Analysis

PICO AnalysisFinding
  • 34 EpiPens past their expiration date (1-90 months)
  • Most were not discolored and did not contain precipitate
ComparisonNon-outdated EpiPens
  • Adult EpiPen epinephrine bioavailability in rabbits’ blood after IM injection
    • Maximum Blood Concentration in expired EpiPens 10.8 ± 0.9 ng/mL
    • Maximum Blood Concentration in non-expired EpiPens 26.2 ± 6.9 ng/mL
    • Obvious significant difference in bioavailability (p<0.05)
  • Epinephrine content in outdated pens (%)
    • EpiPens (n=28): 51-102 vs. 105-111 in-date pens
    • EpiPen Jr (n=6): 55-93 vs. 86-114 in-date pens

2017 Update

The answer to the title’s question is perhaps more pertinent now than ever. Since this post in 2014, the price of EpiPen has unethically increased by more than 400%. This unnecessary price increase may interfere with our patients’ ability to obtain and refill EpiPen prescriptions on time. Emergency care providers may find themselves answering the title question more frequently than before.

An additional bench study was recently published addressing the potency of epinephrine in expired EpiPens.2 The authors collected 31 expired EpiPens and 9 EpiPen Junior autoinjectors. The expiration dates ranged between 1 and 50 months past the manufacturer expiration date. The concentration of active epinephrine ranged between 84 – 100%, with decreasing concentration over time.

Bottom Line

  1. Outdated Epipens start losing epinephrine once expired.
  2. A significant amount of epinephrine may still be present up to 90 months after the expiration date.
  3. We should always recommend in-date pens to be used and provide a new prescription or a refill if needed; however, as advocated by the publication article’s authors, if an expired, non-discolored EpiPen is the only out-of-hospital intervention available for an anaphylactic reaction, it should be used as the risk of harm is minimal with significant benefit.
Simons F, Gu X, Simons K. Outdated EpiPen and EpiPen Jr autoinjectors: past their prime? J Allergy Clin Immunol. 2000;105(5):1025-1030. [PubMed]
Cantrell F, Cantrell P, Wen A, Gerona R. Epinephrine Concentrations in EpiPens After the Expiration Date. Ann Intern Med. 2017;166(12):918-919. [PubMed]
Zlatan Coralic, PharmD

Zlatan Coralic, PharmD

Assistant Clinical Professor
Emergency Department Clinical Pharmacist
University of California, San Francisco (UCSF)
Zlatan Coralic, PharmD


Emergency Medicine Clinical Pharmacist. Views expressed here are my own. #FOAMed