What is the recommended interval between doses of EpiPen (epinephrine) in an emergency if symptoms do not improve?

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Last updated: February 26, 2025View editorial policy

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From the Guidelines

If symptoms of a severe allergic reaction (anaphylaxis) persist after using an EpiPen, you should administer a second dose after 5 to 15 minutes if emergency medical help has not yet arrived and symptoms are not improving or are worsening. This recommendation is based on the most recent and highest quality study available, which emphasizes the importance of prompt and repeated administration of epinephrine in the management of anaphylaxis 1. The study highlights that clinicians should administer additional doses of intramuscular epinephrine every 5 to 15 minutes if anaphylaxis signs or symptoms persist, and that there are no absolute contraindications to its use for anaphylaxis. Key points to consider when administering a second dose of EpiPen include:

  • Monitoring for continued difficulty breathing, persistent wheezing, severe dizziness, or loss of consciousness
  • Calling emergency services immediately after using the first EpiPen
  • Carrying two auto-injectors, as approximately 20% of patients require a second dose
  • Seeking immediate medical attention after using EpiPen, even if symptoms improve, as the effects are temporary and symptoms may return. It is also important to note that the management of anaphylaxis should be tailored to the individual patient's needs and medical history, and that other treatments such as antihistamines and glucocorticoids may be used as adjunctive therapy, but should not be administered before or in place of epinephrine 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION Anaphylaxis: Adults and Children 30 kg (66 lbs) or more: 0.3 to 0.5 mg (0.3 to 0.5 mL) intramuscularly or subcutaneously into anterolateral aspect of the thigh every 5 to 10 minutes as necessary Children 30 kg (66 lbs) or less: 0.01 mg/kg (0.01 mL/kg), up to 0.3 mg (0.3 mL), intramuscularly or subcutaneously into anterolateral aspect of the thigh every 5 to 10 minutes as necessary

The recommended interval between doses of EpiPen (epinephrine) in an emergency if symptoms do not improve is every 5 to 10 minutes as necessary 2.

From the Research

Recommended Interval Between Doses of EpiPen

The recommended interval between doses of EpiPen (epinephrine) in an emergency if symptoms do not improve is not explicitly stated in the provided studies. However, the studies suggest the following:

  • If symptoms of severe anaphylaxis fail to resolve following an initial dose of epinephrine, it is reasonable to administer a second dose 3.
  • Patients should be monitored for a biphasic reaction (i.e., recurrence of anaphylaxis without reexposure to the allergen) for four to 12 hours, depending on risk factors for severe anaphylaxis 4.
  • Prehospital treatment with epinephrine decreased the likelihood of receiving multiple doses of epinephrine in the ED 5.

Key Considerations

  • Epinephrine is the essential antianaphylactic drug in the pharmacologic treatment of anaphylaxis 6.
  • The use of epinephrine autoinjectors can be lifesaving in the first aid setting 3.
  • Patients who have survived an anaphylactic reaction should be thoroughly examined and an allergy diagnosis should be performed 6.

Administration of Epinephrine

  • Epinephrine should be administered intramuscularly, and only in very severe cases or under conditions of surgical interventions should intravenous application be tried 6.
  • The recommended dose of epinephrine for children is 0.01 mg per kilogram 7.
  • For infants at risk of anaphylaxis in the community, the Canadian Society of Allergy and Immunology recommends prescribing the 0.15 mg epinephrine autoinjector 7.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Anaphylaxis: Recognition and Management.

American family physician, 2020

Research

Evaluation of Prehospital Management in a Canadian Emergency Department Anaphylaxis Cohort.

The journal of allergy and clinical immunology. In practice, 2019

Research

Anaphylaxis: acute treatment and management.

Chemical immunology and allergy, 2010

Research

CSACI position statement: epinephrine auto-injectors and children < 15 kg.

Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology, 2015

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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