Pharmacokinetics and Pharmacodynamics Following Repeat Dosing of neffy (Epinephrine Nasal Spray) Versus Intramuscular Injection During Induced Allergic Rhinitis.

Abstract

neffy (epinephrine nasal spray) is the first needle-free option for the treatment of severe allergic reactions. Seasonal allergic rhinitis with nasal obstruction may alter intranasal drug absorption, but its impact on nasal epinephrine is unclear. To compare pharmacokinetics and pharmacodynamics of repeated neffy dosing with intramuscular (IM) epinephrine under normal nasal conditions and following nasal allergen challenge (NAC)-induced allergic rhinitis, and to assess the effect of repeat-dose laterality METHODS: This was a phase 1, open-label, randomized, crossover study in 43 adults with seasonal allergic rhinitis. Subjects underwent 2 treatment periods under normal conditions (neffy 2.0 mg + 2.0 mg; IM 0.3 mg + 0.3 mg) and 3 periods after NAC. Under NAC, neffy was given to the same nostril (R/R) or opposite nostrils (R/L); IM was administered to contralateral thighs. Doses were separated by 10 minutes. Epinephrine concentrations, blood pressure, and heart rate were measured up to 240 minutes. Adverse events were recorded RESULTS: Across normal and NAC conditions, neffy resulted in a higher or comparable maximum plasma concentration, greater early (≤60-minute) partial area under the curves, and a faster time to maximum plasma concentration versus IM. Under NAC, neffy R/R resulted in the highest sustained epinephrine exposure and pharmacodynamic responses, whereas neffy R/L was generally comparable to IM. All adverse events were mild; no serious adverse events occurred. Repeated dosing of neffy, including during NAC-induced allergic rhinitis, yields pharmacokinetic/pharmacodynamic profiles comparable or greater to IM epinephrine, supports same-nostril repeat dosing, and provides a well-tolerated, needle-free option for patients who may require a second dose.