Epinephrine nasal spray achieves pharmacodynamic responses comparable with injections

Intranasal epinephrine produced pharmacodynamic results that were comparable with or higher than autoinjectors and manual injection, according to a study published in Annals of Allergy, Asthma & Immunology.

Specifically, the epinephrine nasal spray (neffy, ARS Pharmaceuticals) more efficiently increased blood pressure than other delivery systems despite lower maximum plasma concentrations, Sarina Tanimoto, MD, PhD, cofounder and chief medical officer of ARS Pharmaceuticals, and colleagues wrote.

The researchers analyzed data of 175 participants aged 19 to 55 years with balanced baseline characteristics such as age, sex and height from four randomized, open-label, single-dose phase 1 trials.

Patients received 1 mg of the intranasal epinephrine spray (n = 135), a 0.3 mg manual epinephrine intramuscular injection (n = 104), a 0.3 mg dose of epinephrine using Symjepi (Adamis Pharmaceuticals; n = 36) or EpiPen (Mylan/Viatris; n = 71) autoinjector or placebo (n = 70).

Researchers collected blood samples before dosing and up to 480 minutes afterward for pharmacokinetic analysis. They also measured systolic and diastolic blood pressure as well as heart rate for pharmacodynamic analysis before dosing and at various points up to 120 minutes afterward.

Mean maximum plasma concentration values after administration included 503 pg/mL for EpiPen, 438 pg/mL for Symjepi, 258 pg/mL for neffy and 254 pg/mL for manual injection, which the researchers called comparable.

Manual injection showed the longest median time to maximum concentration at 45 minutes, followed by Symjepi and neffy at 30 minutes each and EpiPen at 20 minutes.

Also, the researchers found that EpiPen, Symjepi and neffy had comparable increases in mean systolic blood pressure vs. time, although manual injection had a less pronounced change.

Mean systolic blood pressure maximum effects included 18.1 mm Hg for EpiPen, 16.9 mm Hg for neffy, 14.9 mm Hg for Symjepi and 10.9 mm Hg for manual injection. Also, manual injection had the longest time to maximum effect for systolic blood pressure at 30.5 minutes, with neffy at 21 minutes, EpiPen at 18 minutes and Symjepi at 16 minutes.

Only neffy conferred an increase in mean diastolic blood pressure over time. The other products resulted in decreases, with magnitudes of decreases after epinephrine injection greater than those observed after placebo.

At 9.32 mm Hg, neffy had the greatest mean maximum effect on diastolic blood pressure. Relative to this increase with neffy, increases were suppressed for the other products, including 5.51 mm Hg for manual injection, 5.78 mm Hg for Symjepi and 5.93 mm Hg for EpiPen.

Manual injection had the shortest time to maximum effect on diastolic blood pressure at 8.99 minutes, followed by 15 minutes for neffy, 18 minutes for Symjepi and 25 minutes for EpiPen.

EpiPen also had the highest peak mean heart rate vs. time, neffy had the second highest, followed by manual injection and then Symjepi. Mean maximum effect values included 13.6 bpm for neffy, 14.4 bpm for EpiPen and 12.8 bpm for manual injection, which the researchers called similar, whereas Symjepi had a maximum effect of 8.86 bpm.

Times to maximum effect in heart rate included 30 minutes for manual injection, 20 minutes for neffy, 16 minutes for Symjepi and 14 minutes for EpiPen.

Across all treatments, maximum plasma concentration appeared positively related to maximum effects for systolic blood pressure and heart rate, although this appeared limited to lower levels of maximum plasma concentration. Additional increases in maximum plasma concentration did not translate into increases in maximum effects once reaching approximately 500 pg/mL, the researchers continued.

As intranasal and injection epinephrine delivery methods varied in pharmacokinetic and pharmacodynamic effects, neffy achieved comparable or better pharmacodynamic effects than the other methods even with lower maximum plasma concentrations, the researchers concluded.