Mechanism of Action of Neffy (Epinephrine Nasal Spray)
Neffy works by delivering epinephrine intranasally to activate alpha and beta adrenergic receptors, producing rapid increases in blood pressure and heart rate, with pharmacodynamic effects comparable to or better than injectable epinephrine products despite lower peak plasma concentrations. 1, 2
Composition and Delivery System
Neffy consists of three FDA-approved components:
- Epinephrine (active ingredient)
- Intravail A3 (absorption enhancer)
- Unit Dose Spray (UDS) delivery device 1
This formulation allows for needle-free intranasal administration of epinephrine, which is particularly beneficial for patients who are reluctant to use injection devices due to needle phobia.
Pharmacokinetic Profile
Neffy delivers epinephrine with a pharmacokinetic profile that differs from injectable products:
- Mean peak plasma concentration (Cmax) of 481 pg/mL, which falls between EpiPen (753 pg/mL) and manual intramuscular injection (339 pg/mL) 2
- In an integrated analysis, Neffy 1.0 mg showed a maximum concentration of 258 pg/mL, which was lower than or comparable to manual epinephrine intramuscular injection (254 pg/mL), Symjepi (438 pg/mL), and EpiPen (503 pg/mL) 3
- In pediatric patients, Neffy 1 mg and 2 mg resulted in slightly higher maximum concentrations (651 pg/mL and 690 pg/mL, respectively) compared to adults (481 pg/mL) 4
Pharmacodynamic Effects
Despite its different pharmacokinetic profile, Neffy demonstrates robust pharmacodynamic effects:
- Produces more pronounced increases in pharmacodynamic parameters compared to EpiPen or manual injection when dosed both once and twice 2
- Leads to comparable or greater increases in systolic blood pressure (Emax of 16.9 mm Hg) compared to manual epinephrine intramuscular injection (10.9 mm Hg), Symjepi (14.9 mm Hg), and EpiPen (18.1 mm Hg) 3
- Shows more pronounced effects on diastolic blood pressure (Emax of 9.32 mm Hg) compared to other products (5.51-5.93 mm Hg) 3
- Activation of alpha and beta adrenergic receptors is confirmed by increased pulse rate and blood pressure observed as early as one minute following administration 1
Age-Related Differences
- Pediatric patients show a less pronounced increase in systolic blood pressure compared to adults
- Minimal differences in diastolic blood pressure are observed in pediatric patients
- Heart rate effects are similar between pediatric and adult subjects 4
Clinical Implications
Neffy provides a needle-free alternative for epinephrine delivery that may improve patient compliance in emergency situations:
- Addresses barriers to epinephrine use such as fear of needles, low prescription fulfillment rates, and failure to carry autoinjectors
- May reduce dosing hesitancy, potentially decreasing the risk of delayed epinephrine administration which is associated with increased morbidity and mortality 1, 2
- Provides pharmacodynamic responses that are comparable to or better than approved injection products, suggesting it will be safe and effective for treating severe allergic reactions including anaphylaxis 1, 2, 3
The development of Neffy represents an important advancement in the treatment of severe allergic reactions by providing an alternative delivery method that maintains the critical pharmacological effects of epinephrine while potentially improving accessibility and use in emergency situations.