Q:

4/2/2014
Every once in a while I have a patient ask what to do after they have inadvertently left their EpiPen/Auvi-Q in the car overnight when the temps were either very hot or below freezing. Should they always replace the device, or is one night exposure to extreme temperatures OK?

A:

Thank you for your inquiry.

The question you asked is one that is commonly discussed, but unfortunately, one which does not have a definitive answer. There are very little data in the literature regarding the stability of epinephrine in an automatic epinephrine injector exposed to temperatures outside the recommended range. I know of none that have looked at the effect of one day of storage out of this range. There is one study of which I am aware by Dr. Simons and colleagues (see abstract copied below) that has addressed this issue in terms of longer periods of time.

I have also copied below the instructions for storage (suggested ranges of temperature) to assure stability of the injectors for both the EpiPen and the Auvi-Q. As you can see, they are relatively similar instructions.

However, in practice, it is quite common for patients to be forced to store their injectors in temperature ranges outside of those recommended by the package insert. The manner in which one handles this, however, is based upon experience and clinical judgment without any evidence-based guidelines. Thus the only opinion I can offer you is not based on either consensus recommendation, or evidence-based, published literature.

However, unless the epinephrine in the autoinjector has frozen (and requires re-thawing), I would not replace an injector after one night or day of storage outside the recommended range.

Thank you again for your inquiry and we hope this response is helpful to you.

Long-term stability of epinephrine dispensed in unsealed syringes for the first-aid treatment of anaphylaxis
Annals of Allergy, Asthma & Immunology
Volume 102, Issue 6, June 2009, Pages 500–503
Background: When epinephrine autoinjectors are unavailable or unaffordable, patients at risk for anaphylaxis in the community are sometimes provided with an unsealed syringe containing a premeasured epinephrine dose for use in first-aid treatment of anaphylaxis episodes.
Objectives: To study the stability of epinephrine solution in unsealed syringes under conditions of high ambient temperature, low vs high humidity, and light vs dark.
Methods: Forty unsealed syringes each containing an epinephrine dose of 0.3 mg (as a 1-mg/mL epinephrine solution) were stored at 38°C for 5 months, with 10 syringes at each of 4 different standardized storage conditions: dark and light at low (15%) humidity and dark and light at high (95%) humidity. Duplicate syringes were removed monthly from each storage environment and analyzed for epinephrine content vs control syringes.
Results: The epinephrine dose, expressed as the percentage remaining of the mean control dose, was below compendial limits (90% to 115% of label claim) by 3 months after storage at 38°C and low humidity and by 4 months after storage at 38°C and high humidity. Light had no significant effect.
Conclusion: In hot climates, if an unsealed syringe prefilled with an epinephrine dose is provided for the first-aid treatment of anaphylaxis, it should be replaced every few months on a regular basis with a new syringe containing a fresh dose of epinephrine.

Storage and Stability
Always store EpiPen® or EpiPen® Jr in the carrier tube with the blue safety release on until you need to use it. Store at 25°C (77°F); EXCURSIONS PERMITTED TO 15° - 30°C (59 ° - 86°F).

Do not refrigerate. Protect from light. Periodically check to make sure the solution in the auto-injector is not brown in color. Replace if it is discolored or contains a precipitate.

16.2 Storage and Handling
Epinephrine is light sensitive and should be stored in the outer case provided to protect it from light. Store at 20°-25°C (68°-77°F); excursions permitted to 15°-30°C (59°-86°F). Do not refrigerate. Before using, check to make sure the solution in the auto-injector is clear and colorless. Replace the auto-injector if the solution is discolored, cloudy, or contains particles.

Sincerely,
Phil Lieberman, M.D.

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