Is there a nasal spray epinephrine (adrenaline) instead of the EpiPen (epinephrine auto-injector)?

Nasal Spray Epinephrine as an Alternative to EpiPen

Yes, there is now an FDA-approved nasal spray epinephrine called Neffy that serves as an alternative to the EpiPen for treating anaphylaxis in adults and children weighing at least 30 kg (66 pounds). 1

Available Nasal Epinephrine Products

• Neffy (epinephrine nasal spray) is the first non-injectable adrenaline delivery device approved in both Europe and the United States for emergency treatment of anaphylaxis. 1
• The device delivers epinephrine via intranasal dry powder formulation in a single-use, needle-free device. 2
• Neffy is licensed specifically for patients weighing ≥30 kg, which excludes most young children who would require the 0.15 mg EpiPen Jr dose. 1

Pharmacokinetic Advantages of Nasal Epinephrine

• Intranasal epinephrine absorption is faster than intramuscular EpiPen, offering a clinical advantage in the short therapeutic window for treating anaphylaxis. 3
• FMXIN002 (the investigational name for nasal epinephrine) at 3.2 mg achieved a median time to peak concentration (Tmax) of 2.5 minutes versus 9.0 minutes for EpiPen 0.3 mg IM. 3
• The time to reach clinically relevant plasma concentration (100 pg/mL) was significantly shorter: 1.0 minute for nasal spray versus 3.0 minutes for EpiPen (P < .02). 3
• In a dose-finding study, 91% of subjects achieved the clinical threshold of 100 pg/mL plasma epinephrine at 6 minutes after FMXIN002 4.0 mg compared to only 55% with IM autoinjector. 2

Practical Advantages

• The nasal spray is needle-free, pocket-size, user-friendly, and eliminates fear of needles, which is a significant barrier to EpiPen use. 3
• The device demonstrated remarkable stability: 2 years at room temperature in one study 3 and up to 5 years at 20±5°C in another 2, addressing the short shelf-life problem of traditional autoinjectors.
• No serious adverse events occurred in clinical trials; all events were mild, local, and self-resolved. 3, 2

Critical Limitations and Caveats

• Intramuscular epinephrine remains the guideline-recommended first-line treatment for anaphylaxis with the most established safety and efficacy data. 4, 5
• The nasal spray is NOT approved for children weighing <30 kg, who still require traditional EpiPen Jr (0.15 mg) or EpiPen (0.3 mg) based on weight. 1
• High pharmacokinetic variability (coefficient of variation) exists with nasal absorption, meaning individual responses may vary more than with IM injection. 3
• Nasal congestion or inflammation from allergen exposure may affect absorption, though paradoxically, one study showed that prior nasal allergen challenge actually increased absorption speed and amount. 3

Clinical Decision-Making Algorithm

For patients with confirmed anaphylaxis:

1. Use whichever epinephrine device is immediately available—Neffy or EpiPen—as rapid treatment is more important than route of administration. 4
2. Call 911 immediately after administering either device. 6, 4
3. Have a second dose available and administer if symptoms persist or recur after 5 minutes. 6, 4, 7
4. Position patient supine with legs elevated; never allow standing or walking. 7
5. Transport to emergency department even if symptoms resolve. 7

Important Clinical Context

• Delay in administering epinephrine is associated with anaphylaxis fatalities, making ease of use and patient willingness to carry/use the device paramount. 4
• Antihistamines and bronchodilators should never be relied upon as primary treatment—only epinephrine addresses life-threatening cardiovascular and respiratory manifestations. 8, 4
• There are no absolute contraindications to epinephrine in anaphylaxis, even in patients with cardiac disease or advanced age. 4, 5

Bottom Line for Prescribing

For patients ≥30 kg who refuse or cannot reliably use EpiPen due to needle phobia, the nasal spray represents a legitimate alternative that may improve treatment compliance and outcomes. 1 However, patients and caregivers must understand that IM epinephrine has decades of proven efficacy, while nasal epinephrine is newly approved with more limited real-world data. 5, 9 The best epinephrine device is the one the patient will actually carry and use when needed. 5