Practice Advances: A focus on neffy® (epinephrine nasal spray)

Key Learning Objectives

1. Educate physicians on the approved label and intended usage of neffy
2. Highlight how real-world survey findings and PK/PD data provide insight into neffy’s use and performance in practice
3. Showcase applicability and importance of approval based on current treatment options and unmet need

Introduction

neffy^® (epinephrine nasal spray) is an alpha- and beta-adrenergic receptor agonist indicated for emergency treatment of type I allergic reactions, including anaphylaxis, in adult and pediatric patients 4 years of age and older who weigh 15 kg or greater.¹ It delivers rapid epinephrine levels, with activation of adrenergic receptors occurring in less than 1 minute, without requiring inhalation. In a Phase 3 OFC study a single dose resulted in symptom resolution in all patients treated (N = 15).^1-3 neffy is the first and only FDA-approved needle-free option for administering epinephrine, which is its active ingredient.¹ Epinephrine has been used to treat allergic reactions for more than 100 years, and it currently is the only universally recommended first-line treatment for severe allergic reactions such as anaphylaxis, characterized by symptoms including difficulty breathing, hives, tachycardia, confusion, diarrhea, stomach cramps, dizziness, or unconsciousness.^1,2,4 Prompt use of epinephrine is essential at the first sign or symptom of a potentially severe allergic reaction, as anaphylaxis may initially present with subtle or less severe symptoms before rapidly progressing.² Epinephrine is effective for treating type 1 allergic reactions only when it is on-hand and administered quickly and correctly.²

IMPORTANT SAFETY INFORMATION (Brief)It is recommended that patients are prescribed and have immediate access to two neffy nasal sprays at all times. In the absence of clinical improvement or if symptoms worsen after initial treatment, administer a second dose of neffy in the same nostril with a new nasal spray starting 5 minutes after the first dose.

neffy is for use in the nose only.

Advise patients when to seek emergency medical assistance for close monitoring of the anaphylactic episode and in the event further treatment is required.

A continuation of the Important Safety Information is below.

Barriers to Epinephrine Administration

Multiple factors contribute to delayed or absent epinephrine use during severe allergic reactions, including not having the device readily accessible, needle phobia, concerns about emergency room visits, and lack of confidence.^2,5-7 Hesitation in using epinephrine carries significant risks.² The longer that there is a delay, that’s been associated with an increased risk of hospitalization, with an increased risk of abnormal vital signs and an increased risk of potentially having a biphasic reaction.^2,6 Recommendations for overcoming these barriers include patient education on allergic symptoms and when to treat, providing a customized action plan, emphasizing prompt epinephrine use without hesitation, demonstrating proper device technique, ensuring awareness of device expiration dates, and reviewing all of these details with returning patients at future visits.^6,8

Auto-injectors (EAIs) have traditionally been the primary method for administering epinephrine.⁹ However, real-world experience has shown that many individuals struggle with timely use: users report that EAIs can be cumbersome and inconvenient, and up to 83% of patients and caregivers either fail to administer or delay using an EAI during a severe allergic reaction.⁴ These challenges have underscored the importance of offering additional administration routes to support timely epinephrine delivery.²

As a needle-free epinephrine nasal spray, neffy may help address the apprehension and delay associated with use of EAIs, removing the risk of accidental injection, and improving ease with carrying the product, all of which could lead to better outcomes.⁴ In survey results, 76% of patients said they would be more likely to carry a needle-free option, and patients and caregivers said they would use a needle-free device earlier, reducing the time to dosing by 45%. In addition, almost half of patients currently not filling their epinephrine needle-injector prescription would be more likely to fill a prescription for a needle-free option.^10,11

This article provides an overview of neffy, including product characteristics, mechanism of action, efficacy and safety data, real-world evidence, and dosage and administration.

Composition and Mechanism of Action

neffy is available as single-dose nasal sprays with 0.1 mL solution that is comprised of 3 FDA-approved ingredients and components: either 1 mg or 2 mg epinephrine, which is the active ingredient; Intravail^® (dodecylmaltoside), which is a proprietary agent that helps enhance the bioavailability of intranasal drugs; and a single-dose sprayer that produces a spray pattern and droplet size that optimizes delivery of the spray to the turbinate.^1,2

Epinephrine

According to clinical guidelines and global agreement, epinephrine is considered the most effective treatment for anaphylaxis.² Epinephrine acts on 1) alpha-adrenergic receptors, which in turn decreases the vasodilation and vascular permeability that is associated with anaphylaxis, and 2) beta-adrenergic receptors, which relax bronchial smooth muscles and reduce bronchospasm, wheezing, and dyspnea that can occur with anaphylaxis. In addition, epinephrine may relieve pruritus, urticaria, angioedema. Because it can relax the smooth muscle of the stomach, intestine, uterus, and urinary bladder, the compound may also alleviate gastrointestinal and genitourinary symptoms.¹

Intravail^®

Intravail is an alkylsaccharide that enhances epinephrine absorption by changing mucosal viscosity and membrane fluidity, thereby loosening cell-to-cell junctions. It is water- and oil-soluble and does not irritate or harm mucosal membranes.² With Intravail, absorption of epinephrine does not appear to be limited by epinephrine’s vasoconstrictive effects, supporting consistent intranasal uptake. This allows neffy to achieve reliable epinephrine exposure without requiring manual intramuscular administration, which can sometimes result in variable delivery or device-related complications. Optimized absorption may also help reduce the risk of dosing errors or complications reported with injectable products.²

Single-dose sprayer

The device was designed for easy, intuitive use (hold, insert, press) without hesitation. In usability studies, 100% of adult and pediatric patients correctly administered neffy.^2,11

Safety and Tolerability

neffy offers a safety profile that avoids the complications associated with injectable products, such as serious infection in the skin or soft tissue (eg, necrotizing faciitis, myonecrosis), lacerations, bent needles, or imbedded needles.^1,12 neffy has been considered generally well tolerated and safe across all clinical studies. Adverse events that were noted in the clinical trials were generally mild in nature and resolved quickly. Using the 2-mg dose, the most commonly seen adverse events were nasal discomfort, headache, rhinorrhea, dizziness, nausea, vomiting throat irritation, feeling jittery, and tremor. Using the 1-mg dose, the most commonly seen adverse events were nasal congestion, upper respiratory tract congestion, dry throat, nasal dryness, and paresthesia. For slightly heavier children using the 2-mg dose, the most common adverse events seen were nasal discomfort, intranasal paresthesia, rhinorrhea, sneezing, epistaxis, paresthesia, fatigue, and feeling jittery. These are not all of the possible side effects with neffy.¹

For neffy, several studies as well as the PK/PD data and FDA-required bracketing support its approved use. PK/PD findings demonstrated reliable adrenergic receptor activation following intranasal administration, and bracketing confirmed that neffy’s epinephrine exposure falls between manual intramuscular injection (lower efficacy threshold) and EpiPen^® (upper safety threshold)—the range FDA uses to establish safety and effectiveness benchmarks for epinephrine products. These pharmacology data provide foundational context for understanding neffy’s use in clinical practice.¹

Real-World Evidence

Real-world evidence has demonstrated neffy’s efficacy for treatment of anapylaxis symptoms. Results from a phase 3 prospective study in pediatric patients experiencing anaphylaxis with an oral food challenge (OFC; N=15) showed a single dose of neffy 1 mg or 2 mg was associated with a 100% response rate.³ Several case report outcomes have also shown that neffy effectively treats severe allergic reactions in different settings.^13-15

To obtain real-world evidence, a survey was given to health care providers (HCPs) regarding outcomes following use of neffy. Of the 2947 HCPs who participated, 375 shared that they had used neffy in 680 patients; of those patients, 603 (88.7%) required only 1 dose of neffy for effective treatment and 77 (11.3%) required an additional dose of epinephrine. These findings (n=680) were similar to historical success rates (n=12,615) associated with approved injectable products.^{16, 20}

It is important to note the limitations; this was a non-controlled survey. There was also potential for recall bias because outcomes were self-reported. Safety and tolerability data were not collected.¹⁶

Administration

neffy is designed to be easy to use, and its use is easy to explain. It is a simple nasal spray and you push upwards. It can be done with no training required. Each neffy nasal spray unit contains a single dose with either 1 mg (for patients 15 kg to less than 30 kg) or 2 mg epinephrine (for patients 30 kg or greater). neffy is to be used in the nose only. Administration of neffy is as intuitive as 1) Hold, 2) Insert, and 3) Press, and the patient may be in any position. Specifically, the spray should be administered entirely in 1 nostril by inserting the nozzle until the fingers touch the nose, then the plunger should be pressed firmly to activate the spray. With administration, the right hand should be used for the right nostril and left hand for left nostril. The unit must be held straight and not angled, and the patient should not sniff while the spray is dispensed. In the absence of any clinical improvement or if symptoms worsen after the initial treatment, administer a second dose of neffy into the same nostril with the new nasal spray, starting about 5 minutes after the first dose. Advise patients when to seek emergency medical assistance for close monitoring of the anaphylactic episode and in the event further treatment is required. Of note, a neffy device should not be used for more than 1 administration. In addition, it’s recommended that patients are prescribed and have immediate access to 2 nasal sprays at all times.^1,

Precautions

Epinephrine can temporarily exacerbate underlying conditions or increase symptoms in patients with the following conditions: hyperthyroidism, Parkinson’s disease, diabetes, or renal impairment. Any form of epinephrine should be administered with caution in these patients, as well as in older adult patients and in patients who are pregnant. As a class effect, please administer neffy or any form of epinephrine with caution to patients who have underlying heart disease. Epinephrine may worsen angina pectoris or ventricular arrhythmias. Arrhythmias, including fatal ventricular fibrillation, have been reported, particularly in patients with underlying cardiac disease or who are taking cardiac glycosides, diuretics, or other antiarrhythmics.¹

Caution should be given when administering epinephrine concomitantly with certain drugs. Patients with certain medical conditions or who take certain medications for allergies, depression, thyroid disorders, diabetes, and hypertension may be at greater risk for adverse reactions, which is another class effect of epinephrine.¹

Absorption of neffy may be affected by underlying structural anatomical nasal conditions. Patients with conditions that affect the structure of the nose may be better suited for using an epinephrine product that is given by another route of administration.¹

Storage and Handling

neffy is stored in a carton that includes 2 blister packages, each of which contain a single-dose nasal spray of either 1 mg or 2 mg epinephrine.¹ neffy has an extremely small design.¹⁷ It’s the smallest device that’s available on the market at present.¹⁷ It’s compact, it’s lightweight, it’s easy to carry. That’s going to increase the chance that your patient is carrying it.⁴ If they increase the chance of carrying it, that means when they need to use it, they are more likely to have it with them.⁴ neffy has the longest shelf life of any epinephrine device on the market, which is about 30 months from date of manufacture, depending on the dose.¹⁷ This means less frequent refills for the patient. neffy should always be stored at room temperature but can tolerate high temperatures, up to 122 degrees F, as well as some exposure to the cold.^1,17 This sets neffy apart from other devices currently on the market.^1,17

Patient Access and Support

neffy is accessible to patients, with convenient availability at patients’ preferred pharmacies.Commercially-insured patients may pay as little as $0 with a copay card. All patients may benefit from having their prescription sent to Getneffy.com, which provides a patient prescribing service that helps patients find the best price for neffy using all of the available discounts and assist with any required insurance authorizations.¹⁸

Conclusion

neffy 1 mg (for patients 15 kg to less than 30 kg) and 2 mg epinephrine (for patients 30 kg or greater) is the first and only approved needle-free epinephrine product for type I allergic reactions, including anaphylaxis.¹

Several studies—including a prospective phase 3 trial, multiple case reports, and a survey—have provided real-world evidence for the efficacy of neffy in treating severe allergic reactions.^3,13-16

As neffy is intended for self-administration, it is important to educate and continually reinforce patients and caregivers on recognizing symptoms; when to use neffy; its proper use, including the process of nasal insertion, activation; repeat dosing; and when to seek emergency care.^1,19 Clinicians should ensure patients understand storage and handling guidance and should provide information on pertinent precautions, such as effects on certain underlying conditions and drug-drug interactions.¹ Shared decision-making is an important factor for prescribers to engage with their patients.⁸ Providers and patients should have a written and understood action plan, with all questions answered.⁸ These discussions are to build trust and to help young patients understand their care plan, symptom cascade, and the importance of continuous self-carrying and knowing when to use the epinephrine. Prescribers should also ask patients for their preferences regarding the form and delivery of epinephrine to increase the likelihood of using the medication.⁶ With appropriate use according to labeling, neffy offers a unique epinephrine administration option that may help to address the apprehension and delays associated with use of EAIs, thereby supporting timely therapy initiation at the first sign or symptom of severe allergic reaction and halting its progression.^1,2,4,17

INDICATION & IMPORTANT SAFETY INFORMATION

INDICATION
neffy is indicated for emergency treatment of type I allergic reactions, including anaphylaxis, in adult and pediatric patients aged 4 years and older who weigh 15 kg or greater.

IMPORTANT SAFETY INFORMATION

It is recommended that patients are prescribed and have immediate access to two neffy nasal sprays at all times. In the absence of clinical improvement or if symptoms worsen after initial treatment, administer a second dose of neffy in the same nostril with a new nasal spray starting 5 minutes after the first dose.

neffy is for use in the nose only.

Advise patients when to seek emergency medical assistance for close monitoring of the anaphylactic episode and in the event further treatment is required.

Absorption of neffy may be affected by underlying structural or anatomical nasal conditions.

Administer with caution to patients who have heart disease; epinephrine may aggravate angina pectoris or produce ventricular arrhythmias. Arrhythmias, including fatal ventricular fibrillation, have been reported, particularly in patients with underlying cardiac disease or taking cardiac glycosides, diuretics, or anti-arrhythmics.

The presence of a sulfite in neffy should not deter use.

neffy may alter nasal mucosa for up to 2 weeks after administration and increase systemic absorption of nasal products, including neffy.

Patients with certain medical conditions or who take certain medications for allergies, depression, thyroid disorders, diabetes, and hypertension, may be at greater risk for adverse reactions.

Epinephrine can temporarily exacerbate the underlying condition or increase symptoms in patients with the following: hyperthyroidism, Parkinson’s disease, diabetes, renal impairment. Epinephrine should be administered with caution in patients with these conditions, including elderly patients and pregnant women.

Most common adverse reactions are nasal discomfort, headache, rhinorrhea, dizziness, nausea, vomiting, throat irritation, nasal congestion, paresthesia, sneezing, upper respiratory tract congestion, epistaxis, rhinalgia, nasal dryness, dry throat, fatigue, and feeling jittery.

These are not all of the possible side effects of neffy. To report suspected adverse reactions, contact ARS Pharmaceuticals Operations, Inc. at 1-877-MY-NEFFY (877-696-3339) or FDA at 1-800-FDA-1088 or

www.fda.gov/medwatch.

Please see the full Prescribing Information

This program was made possible through the financial support of ARS Pharmaceuticals.

References

1. neffy. Prescribing Information. ARS Pharmaceuticals Operations, Inc; 2025. Accessed November 19, 2025. https://www.ars-pharma.com/wp-content/uploads/pdf/Prescribing_Information.pdf
2. Ellis AK, Casale TB, Kaliner M, et al. Development of neffy, an Epinephrine Nasal Spray, for Severe Allergic Reactions. Pharmaceutics. 2024;16(6):811. Published 2024 Jun 14. doi:10.3390/pharmaceutics16060811
3. Ebisawa M, Takahashi K, Takahashi KK, Yanagida N, Sato S, Lieberman J, et al. Epinephrine nasal spray improves allergic symptoms in patients undergoing oral food challenge, phase 3 trial. J Allergy Clin Immunol. 2025;13(10):2787-2794. https://doi.org/10.1016/j.jaip.2025.06.038.
4. Casale TB, Ellis AK, Nowak-Wegrzyn A, Kaliner M, Lowenthal R, Tanimoto S. Pharmacokinetics/pharmacodynamics of epinephrine after single and repeat administration of neffy, EpiPen, and manual intramuscular injection. J Allergy Clin Immunol. 2023;152(6):1587-1596. doi:10.1016/j.jaci.2023.08.007
5. Warren CM, Zaslavsky JM, Kan K, Spergel JM, Gupta RS. Epinephrine auto-injector carriage and use practices among US children, adolescents, and adults. Ann Allergy Asthma Immunol. 2018;121(4):479-489.e2. doi:10.1016/j.anai.2018.06.010
6. Golden DBK, Wang J, Waserman S, et al. Anaphylaxis: A 2023 practice parameter update. Ann Allergy Asthma Immunol. 2024;132(2):124-176. doi:10.1016/j.anai.2023.09.015
7. Glassberg B, Nowak-Wegrzyn A, Wang J. Factors contributing to underuse of epinephrine autoinjectors in pediatric patients with food allergy. Ann Allergy Asthma Immunol. 2021;126(2):175-179.e3. doi:10.1016/j.anai.2020.09.012
8. Anagnostou A, Abrams EM, Anderson WC 3rd, et al. Development of a validated, updated North American pediatric food allergy anaphylaxis management plan. Ann Allergy Asthma Immunol. 2025;135(1):71-78.e4. doi:10.1016/j.anai.2025.03.027
9. Oppenheimer J, Casale TB, Camargo CA Jr, Fleischer DM, Bernstein D, Lowenthal R, Tanimoto S. Upper respiratory tract infections have minimal impact on neffy’s pharmacokinetics or pharmacodynamics. J Allergy Clin Immunol Pract. 2024;12(6):1640-1643.e2. doi:10.1016/j.jaip.2024.02.038
10. Kaplan H, Rooney E, Tanimoto S, Lowenthal R. Epinephrine via needle-free device would be administered faster after symptoms: results of a patient/caregiver survey. Ann Allergy Asthma Immunol. 2022;125(5):S17.10.1016/j.anai.2022.08.549
11. ARS Pharmaceuticals Operations, Inc. neffy Core Visual Aid Training. Data on File. 2025
12. EPIPEN. Prescribing information. Viatris Specialty LLC; 2023. Accessed November 19, 2025.https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?type=display&setid=7560c201-9246-487c-a13b-6295db04274a
13. Rosenblum J, Puglisi G, Grillo J. First reported real world clinical anaphylaxis treated with neffy: a case series. Poster presented at: Eastern Allergy Conference Meeting; May 29-June 1, 2025; Palm Beach, FL.
14. Long C. The use of neffy (epinephrine nasal spray) to treat anaphylaxis during an oral food challenge. Poster presented at: Eastern Allergy Conference Meeting; May 29-June 1, 2025; Palm Beach, FL.
15. Doroudchi A, Modena B. Successful usage of intranasal epinephrine during in-office anaphylaxis, a case series of three pediatric patients in real-world setting. Poster presented at: Eastern Allergy Conference Meeting; May 29-June 1, 2025; Palm Beach, FL.
16. Casale T, Spergel J, Fleischer D, Tanimoto S. Real world data on the effectiveness of epinephrine nasal spray in clinical practice - update. Ann Allergy Asthma Immunol. 2025;135:S2-S4. doi:10.1016/j.anai.2025.10.018
17. ARS Pharmaceuticals Operations, Inc. neffy (Epinephrine Nasal Spray). Data on File.
18. ARS Pharmaceuticals Operations, Inc. Get neffy. Accessed November 20, 2025. https://getneffy.com/
19. Casale TB, Oppenheimer J, Kaliner M, Lieberman JA, Lowenthal R, Tanimoto S. Adult pharmacokinetics of self-administration of epinephrine nasal spray 2.0 mg versus manual IM epinephrine 0.3 mg by health care provider. J Allergy Clin Immunol Pract. 2024;12(2):500-502.e1. doi:10.1016/j.jaip.2023.11.006
20. Patel N, Chong KW, Yip AYG, Ierodiakonou D, Barta J, Boyle RJ, et al. Use of multiple epinephrine doses in anaphylaxis: a systematic review and meta-analysis. J Allergy Clin Immunol. 2021;148(5):1307-1315.

©2025 ARS Pharmaceuticals Operations, Inc. All rights reserved. “ARS Pharma, “neffy,” and the neffy logo are trademarks or registered trademarks of ARS Pharmaceuticals Operations, Inc.

NEF-US-0937I 12/2025