New Review Shows Epinephrine for Anaphylaxis is Safe in Correct Doses

Although adrenaline can cause mild and transient adverse events, new research finds this should not deter allergists from administering it in dire situations like anaphylaxis.¹

“This review article demonstrates that [intramuscular adrenaline is a safe option when given at an adequate dose in the context of anaphylaxis,” wrote investigators, led by Motohiro Ebisawa, Mfrom NHO Sagamihara National Hospital, in Japan.¹

Adrenaline has many misconceptions about its safety, and The American Academy of Allergy, Asthma, & Immunology debunked epinephrine myths: epinephrine is not dangerous, the needle is not large or painful, and antihistamines should not replace it.² The organization stated that epinephrine is safe and lifesaving, only causing short-lived adverse effects, such as anxiety, tremor, and fast heart rate. Epinephrine is available as a small, often pain-free needle, ranging from 0.29 to 1 itch.

Anaphylaxis is more than just itching and hives—it can lead to fatal vascular collapse or airway obstruction. In the US, 1 in 20 individuals face anaphylactic reactions, with 225 deaths per year.¹

National and international guidelines for anaphylaxis recommend immediate intramuscular injection of adrenaline into mid-anterolateral thigh as the first-line treatment. However, misconceptions surrounding epinephrine can result in improper administration.

The European Anaphylaxis Registers show only a small percentage of anaphylactic events are treated with adrenaline. Clinicians may rely on second-line treatments, including high-flow oxygen, intravenous fluids, inhaled short-acting bronchodilators, and nebulized adrenaline, or third-line antihistamines and corticosteroids, which have slower onset and peak plasma concentrations.

In this review, investigators provided an overview of the clinical use of adrenaline autoinjectors in the management of anaphylaxis, safety considerations, and the pharmacokinetic/pharmacodynamic profile of 3 autoinjectors.

The review found that adrenaline is safe when administered in the correct dose and route. However, a study reported that only 61% of physicians could accurately calculate the volume of adrenaline required when provided with the concentration and intended mass.

Intramuscular adrenaline (1 mg/mL) should be administered at a rate of 0.01 mL per kilogram of body weight up to a total of 0.5 mg per dose. This type of adrenaline can be repeatedly administered in short intervals of 5 – 10 minutes until the patient no longer has anaphylaxis.¹

As for intravenous adrenaline, the recommended dose for anaphylactic shock is 1 μg/kg in children and 0.1 mg of 0.1 mg/mL in adults. The intravenous dose for cardiac arrest is 1 mg of a 0.1 mg/mL concentration in adults.¹

Intramuscular adrenaline can lead to mild and transient adverse events, including tremors, palpitations, and anxiety. Other reported events include tachycardia, hypertension, dizziness, tremors, vomiting, and chest pain, but none were considered severe.

Recent guidelines from the Resuscitation Council of the UK have stated that intravenous infusion should be administered to patients with refractory anaphylaxis. Otherwise, these patients may be at risk of cardiovascular risks due to dosing errors. The review found overdoses of adrenaline can result in severe cardiovascular complications, such as myocardial ischemia, ventricular tachycardia, and myocardial infarction, among others.

Investigators noted they only observed adrenaline overdoses when it was administered as an intravenous bolus.

“This shows that even in an emergency setting, there is limited awareness on appropriate usage and route of administration of adrenaline,” investigators wrote. ¹“Education and training on usage aspects may help reduce [cardiovascular] complications and overdoses when using adrenaline to treat anaphylaxis.”

When delivered in correct doses, patients only experience mild adverse events, and auto-injectors do not cause additional events.

“Therefore, limiting adrenaline administration owing to anticipated side effects in an emergency circumstance like anaphylaxis would not be warranted,” investigators wrote.¹

EpiPen, Emerade, and Anapen all show strong pharmacokinetic/pharmacodynamic profiles; EpiPen 300 μg provides faster and greater early adrenaline exposure than intramuscular synringes, Emerade shows delayed absorption requiring higher doses, and Anapen 300 μg achieves high Cmax even in individuals with high STMD.

“The benefits of administering appropriate dose and choosing the [intramuscular] route substantially outweighs the risks,” investigators concluded.¹

References

1. Ebisawa M, Muraro A, Worm M, et al. Optimizing Adrenaline Administration in Anaphylaxis: Clinical Practice Considerations and Safety Insights. Clin Transl Allergy. 2025;15(8):e70085. doi:10.1002/clt2.70085

2. Epinephrine Myths Vs Facts. The American Academy of Allergy, Asthma, & Immunology. https://www.aaaai.org/Aaaai/media/Media-Library-PDFs/Conditions%20Treatments/Allergies/Epinephrine-MythFact_2.pdf . Accessed August 15, 2025.