Treatment of Anaphylaxis

Epinephrine is the drug of choice for the emergency treatment of Type 1 allergic reactions to stinging and biting insects (e.g., bees, wasps, hornets, yellow jackets, fire ants, mosquitoes, and triatoma); idiopathic or exercise-induced anaphylaxis; foods; immunobiologicals, contrast media, and other drugs; and various other allergens (e.g., latex).3,4 No absolute contraindications exist to the use of epinephrine in the emergency treatment of acute anaphylactic reactions.3,4

It is of note that in 2016, the FDA changed its labeling standards for all single-entity epinephrine preparations such as those used in the treatment of anaphylaxis.4 Dosage strengths must now only be expressed in mg/mL. The labeling change was prompted by numerous reports of serious medication errors caused by confusion with ratio expressions (e.g., 1:1000, 1:2000, etc.). Pre-filled, single-use, epinephrine auto-injectors are available in convenient strengths and include:3,4

  • EpiPen Jr®
    • 0.15 mg/0.3 mL epinephrine injection, USP, pre-filled auto-injector (green label – Figure 4)3
  • EpiPen®
    • 0.3 mg/0.3 mL epinephrine injection, USP, pre-filled auto-injector (yellow label – Figure 5)3
Figure 4. EpiPen Jr®, 1.5 mg of epinephrine.
Photo showing EpiPen Jr®, 1.5 mg of epinephrine
Figure 5. EpiPen®, 0.3 mg of epinephrine.
Photo showing EpiPen®, 0.3 mg of epinephrine
  • Auvi-Q®
    • 0.1 mg/0.1 mL epinephrine injection, USP, pre-filled auto-injector (white and lavender outer case – Figure 6)3
    • 0.15 mg/0.15 mL epinephrine injection, USP, pre-filled auto-injector (blue outer case – Figure 7)3
    • 0.3 mg/0.3 mL epinephrine injection, USP, pre-filled auto-injector (red outer case – Figure 8)3
Figure 6. Auvi-Q, 0.1 mg of epinephrine.
Photo showing Auvi-Q, 0.1 mg of epinephrine
Figure 7. Auvi-Q, 0.15 mg of epinephrine.
Photo showing Auvi-Q, 0.15 mg of epinephrine
Figure 8. Auvi-Q, 0.3 mg of epinephrine.
Photo showing Auvi-Q, 0.3 mg of epinephrine

FDA-approved generic epinephrine injection formulations are also available in pre-filled, single-use, auto-injectors capable of delivering one dose of either 0.15 mg/0.15 mL or 0.3 mg/0.3 mL of epinephrine injection, USP (Figure 9).3 In 2017, the FDA also approved Symjepi®, a pre-filled, single-use syringe for manual injection containing 0.3 mg/0.3 mL of epinephrine, USP.3

Figure 9. Generic epinephrine auto-injectors: 0.15 mg and 0.3 mg.
Photo showing generic epinephrine auto-injectors: 0.15 mg and 0.3 mg

Some manufacturers of epinephrine auto-injectors supply an auto-injector trainer device (e.g., EpiPen Trainer Device - Figure 10; and AUVI-Q Trainer - Figure 11).3 The devices contain neither a needle nor epinephrine. It is prudent to practice with a trainer to ensure the safe use of the real auto-injector before an emergency occurs. Reliable information on the use of these trainer devices is available in the FDA-approved package insert of each product.3

Figure 10. EpiPen Trainer Device.
Photo showing EpiPen Auto-Injector Trainer Device
Figure 11. AUVI-Q Trainer.
Photo showing AUVI-Q Trainer

An anaphylactic reaction may occur within minutes after reexposure (previous sensitization is a prerequisite) to a specific allergen and consists of urticaria, pruritus, angioedema (e.g., swelling of the lips, eyelids, and tongue), wheezing, dyspnea, and hypotension.4,10,17 Although patients susceptible to anaphylaxis are instructed to always carry their epinephrine auto-injector with them, it should always be available in various fixed-dose formulations in every emergency kit.

The safe and effective use of epinephrine auto-injectors in the treatment of anaphylaxis in oral healthcare setting is predicated on familiarity with FDA-approved, individual drug-related, clinically relevant data and include the following general information:3,4

Step 1 - Select an auto-injector with the appropriate dosage strength predicated on the patient’s body weight:

  • Patients 7.5 to 15 kg (16.5 to 33 pounds)
    • 0.1 mg; with severe persistent anaphylaxis, repeat injection with an additional dose may be necessary in 15-20 minutes
  • Patients 15 to 30 kg (33 to 66 pounds)
    • 0.15 mg; with severe persistent anaphylaxis, repeat injection with an additional dose may be necessary in 15-20 minutes
  • Patients ≥30 kg (≥66 pounds)
    • 0.3 mg; with severe persistent anaphylaxis, repeat injection with an additional dose may be necessary in 15-20 minutes

Step 2 - Remove the auto-injector from its protective case.

  • Check to make sure the expiration date has not passed.
  • Confirm that the liquid inside the auto-injector is not discolored (i.e., not pinkish or brownish), cloudy, and is free of particles.

Step 3 - Grasp the auto-injector in the dominant hand, with thumb closest to the safety cap; and, with the other hand, remove the cap.

Step 4 - Hold the patient’s leg to keep it steady while injecting.

  • Place (jab) the needle end of the auto-injector at right angle against the anterolateral aspect of the thigh.
  • The needle is designed to go through clothing.

Step 5 – Press on the auto-injector firmly to release the needle and inject the epinephrine.

  • Keep auto-injector in place for ≈5 seconds.
  • Do not be alarmed if liquid is left in the auto-injector, the auto-injector is designed to release the proper dose.

Step 6 - Remove the auto-injector and massage the injection site for 10 seconds.

  • Some auto-injectors have a needle that retracts back into the case after use.
  • If the needle remains exposed, insert the injector (needle first) back into its case.

Step 7 - Immediately following the administration of epinephrine, the patient must be referred for additional medical care - Call 911.

  • Tell the dispatcher you just administered epinephrine to a patient to treat a suspected anaphylactic reaction.

Step 8 – With severe persistent anaphylaxis a repeat injection of epinephrine, with an additional auto-injector, may be necessary in 15-20 minutes.

  • More than two sequential doses of epinephrine should not be administered without direct medical supervision of the patient.

Step 9 – Do not discard the auto-injector.

  • Identify the site of injection and surrendered the auto-injector to EMS personnel.

ADRs may occur with the administration of therapeutic doses of epinephrine.4,10,17 Signs and symptoms, which usually subside rapidly with rest and recumbency, include restlessness, tremor, palpitations, tachycardia, sweating, nausea and vomiting, pallor, headache, dizziness, feelings of panic or anxiety, and respiratory difficulties. These signs and symptoms are more likely to occur in patients with high blood pressure (BP) and those with uncontrolled hyperthyroidism.4,10,17

Overdosage (and even therapeutic doses) of epinephrine may precipitate angina pectoris and/or produce ventricular arrhythmias in patients with heart disease (i.e., cardiac arrhythmias, coronary artery or organic heart disease), high BP, hyperthyroidism, and in patients who are on drugs that may sensitize the heart to the effects of epinephrine.3,4,17 While waiting for EMS, prepare to begin cardiopulmonary resuscitation (CPR) and automated external defibrillation.