Intranasal epinephrine: A potential substitute for injections?

Three studies initially scheduled for presentation at AAAAI 2020 demonstrated that epinephrine delivered intranasally was more rapidly absorbed and led to greater haemodynamic response compared with epinephrine delivered intramuscularly.

“[Intranasal] epinephrine (1 mg ARS-1) was bioequivalent (AUC*) to 0.3 mg intramuscular (IM) injection but was absorbed more rapidly resulting in a significantly improved haemodynamic response (increased systolic blood pressure [BP] and heart rate). ARS-1 … has promise as a needle-free alternative to IM epinephrine,” said the researchers.

In the first study (ARS-EPI07), 36 participants received one and two doses of intranasal epinephrine (1 mg) compared with one and two injections of IM epinephrine (0.3 mg) injected into the mid-anterolateral thigh. BP and heart rate were monitored every 5 minutes.

In the ARS-EPI03 study, 70 healthy adults were randomized to receive one or two doses of ARS-1 (1 mg), one or two doses of IM epinephrine 0.3 mg, or a single dose of IM epinephrine 0.5 mg. The participants underwent continuous electrocardiography and BP was assessed every 4 minutes.

In the ARS-EPI04 study, 36 patients with induced allergic rhinitis received ARS-1 (1 mg), IM epinephrine (0.3 and 0.5 mg), and subcutaneous epinephrine (0.3 mg).

The absorption of ARS-1 was faster than that of IM epinephrine. This led to a significant improvement in haemodynamic response – faster and greater increases in heart rate and systolic BP – with intranasal vs IM epinephrine. ARS-1 also had a bioequivalent exposure (AUC_0–t) to one or two doses of IM epinephrine (0.3 mg). [AAAAI 2020, abstract 240]

In the ARS-EPI03 study specifically, the two doses of intranasal and IM epinephrine 0.3 mg, given 5 minutes apart, demonstrated bioequivalency (AUC_0–t; ratio 102 and 95 percent for one dose and two doses, respectively). [AAAA1 2020, abstract 239]

ARS-1 was also more quickly absorbed than IM epinephrine, with a faster time to maximum concentration (t_max 20 vs 45 minutes). Assessment of absorption using time to 100 pg/mL and partial AUCs also demonstrated quicker absorption with ARS-1 vs IM epinephrine. 

This faster absorption led to quicker and greater increases in systolic BP and heart rate. However, peak epinephrine concentration (C_max) with ARS-1 was only greater than that of IM epinephrine 0.3 mg, with an approximately 16 percent lower C_max than IM epinephrine 0.5 mg.

“ARS-1 was well tolerated with mostly mild adverse events and no significant nasal pain or irritation,” said the researchers.

“There’s a stigma associated with needles, and fears over administrating epinephrine to oneself or someone else can cause delays in medication administration. These delays can lead to emergency situations that can put the patient in real danger,” said study author Professor Richard Lockey from the University of South Florida, Tampa, Florida, US.

“Based on these results, nasal spray epinephrine … could help to alleviate some of those delays in treatment,” he continued.

“Epinephrine nasal spray has shown promise in these completed studies,” said Lockey. “With a lack of serious AEs, comparable rates of absorption, and the consistent reliability when it comes to delivery, the ARS-1 product, which will be called Neffy, represents a step forward in patient care for the treatment of severe systemic allergic reactions to help prevent anaphylaxis,” he noted.