What is the use of intranasal epinephrine (adrenaline)?

From the Guidelines

Intranasal epinephrine is not currently an FDA-approved or recommended route of administration for treating anaphylaxis or other conditions requiring epinephrine. The standard treatment for anaphylaxis remains injectable epinephrine, typically administered via an auto-injector (such as EpiPen, Auvi-Q, or generic equivalents) into the mid-outer thigh at a dose of 0.3mg for adults or 0.15mg for children 1. Intranasal delivery of epinephrine has been studied but has not demonstrated the reliable absorption, rapid onset of action, or consistent blood levels needed for emergency treatment of severe allergic reactions. The nasal mucosa's variable blood flow and potential congestion during allergic reactions make this route unpredictable. Additionally, epinephrine is rapidly metabolized when absorbed through mucous membranes, reducing its effectiveness. For these reasons, patients with severe allergies should continue to use prescribed injectable epinephrine auto-injectors and not attempt intranasal administration as a substitute.

Some key points to consider when administering epinephrine include:

• The importance of early administration in the treatment of anaphylaxis, as failure to administer epinephrine early has been implicated in anaphylaxis fatalities 1
• The potential for mild transient adverse effects, such as anxiety, fear, restlessness, headache, dizziness, palpitations, pallor, and tremor, as well as rare but severe adverse effects like ventricular arrhythmias, angina, myocardial infarction, pulmonary edema, sudden sharp increase in BP, and intracranial hemorrhage 1
• The need for repeated dosing after 5 to 15 minutes if symptoms persist or worsen, as up to 20% of patients may require more than one dose of epinephrine 1

It is essential to prioritize the use of injectable epinephrine auto-injectors over intranasal administration due to the unpredictable nature of intranasal absorption and the potential for reduced effectiveness. Research continues on alternative delivery methods, but currently, only injectable forms should be used in emergency situations.

From the FDA Drug Label

Epinephrine is a non-selective alpha and beta adrenergic agonist indicated: • For emergency treatment of allergic reactions (Type 1), including anaphylaxis, in adults and pediatric patients. (1.1) • To increase mean arterial blood pressure in adult patients with hypotension associated with septic shock. (1.2)

The indications for intranasal epinephrine are:

• Emergency treatment of allergic reactions (Type 1), including anaphylaxis, in adults and pediatric patients.
• Increasing mean arterial blood pressure in adult patients with hypotension associated with septic shock 2.

From the Research

Intranasal Epinephrine Administration

• Intranasal epinephrine administration is being investigated as a potential alternative route for anaphylaxis treatment 3, 4.
• A preliminary study found that significant systemic absorption of epinephrine via the intranasal route was observed only at a dose of 5 mg, which was comparable to intramuscular epinephrine administration 4.
• The study also found that the peak epinephrine concentrations and the time to reach them were not significantly different between intramuscular and 5-mg intranasal epinephrine administration 4.

Pharmacokinetic and Pharmacodynamic Comparison

• A comparative study found that intranasal epinephrine delivery resulted in a maximum concentration that was lower than or comparable to manual intramuscular epinephrine injection, but led to comparable increases in systolic blood pressure 5.
• The study also found that intranasal delivery of epinephrine increased systolic blood pressure more efficiently than manual intramuscular injection and epinephrine autoinjectors, despite lower maximum plasma concentrations 5.

Anaphylaxis Treatment

• Intramuscular epinephrine is the first-line treatment for anaphylaxis, and there are no absolute contraindications to its use 3, 6, 7.
• The standard treatment for anaphylaxis involves removal of the trigger, early administration of intramuscular epinephrine, supportive care, and a period of observation for potential biphasic reactions 6.
• Education about anaphylaxis and prompt treatment are critical for patients and their caregivers 7.