Pharmacokinetic and pharmacodynamic comparison of epinephrine, administered intranasally and intramuscularly: An integrated analysis

Abstract

Background: Manual intramuscular epinephrine injection is the standard of care for treating severe allergic reactions and anaphylaxis. Epinephrine autoinjectors were approved on the basis of the assumption that their pharmacokinetic and pharmacodynamic profiles are equivalent to manual intramuscular injection; however, although there is emerging evidence for product-related differences in pharmacokinetic profiles, very little is known about the comparative pharmacodynamic profiles.

Objective: To compare pharmacokinetic and pharmacodynamic profiles of epinephrine delivered through manual intramuscular injection, autoinjectors, and intranasal spray.

Methods: This integrated analysis was based on data from 4 randomized cross-over phase 1 trials that compared the pharmacokinetics and pharmacodynamics of epinephrine using manual intramuscular epinephrine 0.3 mg injection, epinephrine 0.3 mg autoinjectors (Symjepi and EpiPen), and epinephrine 1 mg intranasal spray (neffy).

Results: Data from 175 participants showed that although neffy (1.0 mg intranasal spray) resulted in a maximum concentration (258 pg/mL) that was lower than or comparable with manual epinephrine intramuscular injection (254 pg/mL), Symjepi (438 pg/mL) and EpiPen (503 pg/mL), it led to comparable increases in systolic blood pressure (maximum effect [E_max], 16.9, 10.9, 14.9, and 18.1 mm Hg, respectively). The effect of neffy on diastolic blood pressure was also markedly more pronounced than that of other products (E_max, 9.32, 5.51, 5.78, and 5.93 mm Hg, respectively).

Conclusion: Intranasal delivery of epinephrine using neffy increases systolic blood pressure more efficiently than do manual intramuscular injection and epinephrine autoinjectors, despite lower maximum plasma concentrations.