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

BACKGROUND: 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. OBJECTIVE: 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. CONCLUSIONS: 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.