David Golden, MD, clinical associate professor of medicine at Johns Hopkins University School of Medicine.

David Golden, MD

Featured: David Golden, MD (top), Marcus Shaker, MD (bottom left), and Jacqueline Ross, MD (bottom right)

A patient who’s terrified of needles now has a legitimate needle-free option for treating 

: epinephrine nasal spray (neffy), approved on August 9, 2024.

However, if this patient were to ask whether the guidelines favor epinephrine nasal spray, the honest answer is not quite yet. 

When people ask, “Do I recommend Neffy?” Golden knows they are really asking the following:

“Guidelines don't happen overnight,” David B.K. Golden, MD, associate professor of medicine at Johns Hopkins and co-chair of the 2023 practice parameter update in anaphylaxis, told

. “First of all, they take 1 to 3 years to develop. When something new comes on the market, there's not going to be a guideline for it, and that guideline may not happen for years."

About 3 years ago, in December 2023, an updated anaphylaxis practice parameter was published in the Annals of Allergy, Asthma, & Immunology.

 This update focused on 7 key areas: diagnosis, infants and toddlers, community settings, epinephrine autoinjectors, beta-blockers and ACE inhibitors, mast cell disorders, and perioperative anaphylaxis.

At this time, epinephrine autoinjectors were strongly recommended for high-risk patients. The update advised clinicians to deliver an epinephrine autoinjector at the first sign of expected anaphylaxis, not preemptively before symptoms arrive. Clinicians could choose between Adrenaclick, Auvi-Q, EpiPen, EpiPen Jr, Twinject, Adrenalin, and Symjepi.

Epinephrine Nasal Spray Outperforms in Patient Preference, Efficacy Data

With the approval of epinephrine nasal spray, clinicians gained another treatment option: 1 delivered without a needle. A randomized crossover study presented at the 2026 American Academy of Allergy, Asthma, & Immunology (AAAAI) annual meeting in Philadelphia, found that 88% of 90 participants preferred the intranasal device over injectable epinephrine.

Patients preferred the intranasal spray for its needle-free design, ease of use, portability, and the sense that bystanders could administer it more easily in an emergency. Nearly all participants (98%–100%) rated its size, weight, and temperature flexibility favorably.

Epinephrine nasal spray also works just as quickly as any other epinephrine, taking about 5 minutes to take effect.

 A large real-world analysis showed that epinephrine nasal spray performed as effectively as epinephrine injections with success rates of 89.9% and 88.9%, respectively.

“Pharmacokinetic studies have been done, and these are the studies that look at epinephrine drug levels. Epinephrine drug levels are very similar whether epinephrine is delivered by the nasal route or by the intramuscular route,” Marcus Shaker, MD, from Dartmouth Health, told 

Neffy's pharmacokinetic profile fell within the range of the approved injectable products, with a mean peak plasma concentration of 481 pg/mL, which is higher than manual intramuscular epinephrine injection (339 pg/mL) but lower than EpiPen (753 pg/mL). Both single and double doses of epinephrine nasal spray produced greater pharmacodynamic effects than either EpiPen or manual injection.

Still, epinephrine only helps if it's actually used. In 2023, only 3.2 million of the 20 million patients treated for severe reactions filled an auto-injector prescription, and about half consistently carried one.

“We know that there have been many reports of incorrect use of auto injectors, often leading to significant injuries,” Golden said. “Every product has potential usability and reliability questions.”

Fill rates for neffy aren't yet available, but ARS Pharmaceuticals reported > 5000 prescriptions written as of May 2025, about 8 months after approval.

2025 Delphi Consensus on Anaphylaxis Treatment

Although the official anaphylaxis practice parameters have not been updated since the approval of epinephrine nasal spray, and may not be for some time, informal recommendations have started to emerge. In December 2025, a Delphi panel of 34 experts developed consensus recommendations for treating acute allergic reactions.

“The number 1 question that I get when patients leave our emergency departments, when we prescribe them an autoinjector, is: When should I administer epinephrine? What symptoms should I administer epinephrine for?” first author Timothy E. Dribin, MD, from the division of emergency medicine at Cincinnati Children’s Hospital Medical Center, told 

“It's a very complicated answer because there's no consensus on what symptoms warrant epinephrine and what symptoms do not warrant epinephrine.”

The panel reached consensus recommending epinephrine in 21 of 24 scenarios, with strongest agreement for reactions involving multiple organ systems or isolated severe respiratory or cardiovascular symptoms.

 Mild isolated cutaneous or GI symptoms did not warrant it, and moderate mucocutaneous symptoms alone lacked consensus. The recommendations did not mention epinephrine nasal spray, nor did they recommend any epinephrine form over another.

“Epinephrine is no different for these different forms,” Golden pointed out. “The only recommendation that's strong for epinephrine is that it should be used as the first and most important treatment for anaphylaxis... From there on, it's all conditional recommendations.”

To earn a strong recommendation, Golden said double-blind, placebo-controlled, randomized trials would need to show clear superiority of 1 treatment over the other. However, that isn’t possible in anaphylaxis research.

“There's never been any proof that epinephrine works,” Golden said. “You can't really do a controlled trial of epinephrine because you can't tell someone [with] anaphylaxis: ‘Well, we're going to give you placebo, and compare it to someone else who gets epinephrine.’ That would not be a good thing to do. Conditional recommendations are recommendations that have good evidence to support them, but not the best evidence, and it leaves some room for question[s] about what every doctor wants to prescribe.”

Golden also offered advice on what not to do: prescribe antihistamines for anaphylaxis and wait to see if it improves. Jacqueline Ross, MD, a physician at Allergy Partners of New Jersey, emphasized this too in an interview with 

 She said allergists still need to re-educate patients on the 2023 parameter update, which states epinephrine should be the first-line treatment.

“Antihistamines are not only not first-line in anaphylaxis or allergic reactions, [but] they aren't really a part of the standard therapy at this time,” Ross said. “We need to be identifying anaphylaxis early and administering this life-saving device.”

Epinephrine Nasal Spray and Cold or Respiratory Infection Questions

Golden estimated that it will be 3 to 5 years before a formal anaphylaxis update. In the time before anaphylaxis receives updated practice parameters, clinicians may have questions about newer epinephrine options.

“Patients have wondered, ‘Hey, I have a cold or an upper respiratory tract infection, will the nasal epinephrine work just as well?’ Oppenheimer and colleagues did a study in 2024, which also provided really good reassurance around this question,” Shaker said. The study showed that having an upper respiratory tract infection did not have a significant impact on the way epinephrine nasal spray works.

Golden’s 3 Epinephrine Questions: “Will It Work? Can I Trust It? Is It Dangerous?”

“When doctors ask me, ‘Do I recommend?’ ‘What should I prescribe?’ what they're really [asking] is: Will it work? Can I trust it? Is it dangerous? I always address those questions with patients and with doctors:

 Yes, it's FDA-approved, and everything we know about it is that it's going to work the same as any other epinephrine.

 No, epinephrine is not a dangerous drug. The only thing that's dangerous is not using it when you should.”

Smith T. FDA Approves Epinephrine Nasal Spray for Emergency Treatment of Allergic Reactions. HCPLive. Published August 9, 2024. Accessed July 23, 2026. 

https://www.hcplive.com/view/fda-approves-epinephrine-nasal-spray-for-emergency-treatment-of-allergic-reactions

Golden DBK, Wang J, Waserman S, et al. Anaphylaxis: A 2023 practice parameter update. 

Epinephrine (injection route). Mayo Clinic. Accessed July 23, 2026. 

https://www.mayoclinic.org/drugs-supplements/epinephrine-injection-route/description/drg-20072429

Mack D. Epinephrine Nasal Spray Shows Strong Patient Preference, With Douglas Mack, MD. HCPLive. Published March 12, 2026. Accessed July 23, 2026. 

https://www.hcplive.com/view/epinephrine-nasal-spray-shows-strong-patient-preference-douglas-mack-md

Smith T. Thomas B. Casale, MD: Discussing New Findings on Neffy for Urticaria Flares. HCPLive. Published February 26, 2024. Accessed July 23, 2026. 

https://www.hcplive.com/view/thomas-casale-md-discussing-new-findings-neffy-for-urticaria-flares

Clayton J. How Long Does It Take for an EpiPen to Work? Pharmacist-Backed Answers to 7 EpiPen FAQs. Goodrx. Published October 8, 2024. 

https://www.goodrx.com/epinephrine-epipen/how-long-does-it-take-for-an-epipen-to-work?srsltid=AfmBOoqOP8_jxjrW-kpl1koiW5IjfwFllvKV8SUfdS4E56OFMYeHrQa4

Casale T. Epinephrine Nasal Spray Shows Comparable Efficacy to Injection, With Thomas Casale, MD. HCPLive. Published September 15, 2025. Accessed July 23, 2026. 

https://www.hcplive.com/view/epinephrine-nasal-spray-shows-comparable-efficacy-to-injection-with-thomas-casale-md

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. 

ARS Pharmaceuticals Reports First Quarter 2025 Financial Results and Highlights Progress in U.S. Commercial Launch of neffy® (epinephrine nasal spray). ARS Pharma. Published May 14, 2025. Accessed July 23, 2026. 

https://ir.ars-pharma.com/news-releases/news-release-details/ars-pharmaceuticals-reports-first-quarter-2025-financial-results

Dribin T. International Consensus on Epinephrine Use, With Timothy E. Dribin, MD. HCPLive. Published February 25, 2026. Accessed July 23, 2026. 

https://www.hcplive.com/view/international-consensus-epinephrine-use-timothy-e-dribin-md

Oppenheimer J, Casale TB, Camargo CA Jr, et al. "Upper respiratory tract infections have minimal impact on neffy's pharmacokinetics or pharmacodynamics." 

https://www.jaci-inpractice.org/article/S2213-2198(24)00263-0/fulltext

Articles

Epinephrine nasal spray (neffy) offers a needle-free option for emergency treatment of anaphylaxis, but formal practice parameters typically lag new approvals by years. Current anaphylaxis guidance continues to emphasize prompt epinephrine as first-line therapy, historically via autoinjectors, and discourages delaying treatment with antihistamines. Emerging data show strong patient preference for intranasal delivery, rapid onset, comparable real-world effectiveness to injection, and pharmacokinetic/pharmacodynamic profiles within or exceeding approved injectable ranges. Underuse and carrying nonadherence remain major gaps.

Allergists explain what's settled about epinephrine nasal spray, what's not, and how to counsel patients before anaphylaxis guidelines catch up.

Epinephrine Nasal Spray Is Here. Updated Anaphylaxis Guidelines Aren't.

Expanding Epinephrine Options to Reduce Barriers, Improve Early Use

Part 4 of the special report explores one of the most rapidly evolving areas in 

 care: the expanding range of epinephrine delivery options and their potential to overcome long-standing barriers to timely treatment. Panelists reviewed both currently available products and emerging alternatives that may reshape how patients carry and use epinephrine.

The discussion began with a review of injectable options. In the United States, epinephrine autoinjectors are available in 0.1 mg, 0.15 mg, and 0.3 mg doses, while a 0.5 mg autoinjector is available in Europe but not yet in the US. Golden noted that this raises concerns about underdosing in larger adults and underscores the importance of promptly administering a second 0.3 mg dose if symptoms do not improve. Using weight-based dosing (0.01 mg/kg), a 0.3 mg dose is theoretically appropriate for a patient weighing approximately 30 kg (66 pounds), highlighting the need for repeat dosing in adolescents and adults with severe reactions.

Both experts emphasized that syringe-and-needle intramuscular epinephrine remains appropriate in healthcare settings, where dosing can be precisely tailored, even though autoinjectors achieve faster absorption in pharmacokinetic studies. However, many of the persistent gaps in anaphylaxis outcomes stem not from pharmacology but from human factors, including fear of needles, reluctance to carry devices, uncertainty about diagnosis, and hesitation to use epinephrine early.

The panel highlighted the significance of newly approved and emerging non-injectable options. Golden described the first FDA-approved intranasal epinephrine spray (neffy), which has been on the market for over a year.1 Because placebo-controlled anaphylaxis trials are not feasible, approval relied on pharmacokinetic data demonstrating plasma epinephrine levels comparable to existing intramuscular products.2 The nasal spray falls within the therapeutic range between manual intramuscular injection and autoinjectors, and early real-world experience has been encouraging.

The experts discussed additional products in development, including other nasal formulations and a sublingual oral film (Anaphylm) using a prodrug approach to overcome epinephrine’s absorption challenges.3 Lieberman noted that many patients strongly prefer oral medications, making a sublingual option particularly appealing if efficacy is maintained. Newer formulations may also offer practical benefits such as longer shelf life and greater temperature stability.

In closing, Golden and Lieberman returned to the core message of the entire series. Improving anaphylaxis outcomes requires earlier epinephrine use, fewer barriers to administration, and abandoning outdated reliance on antihistamines and corticosteroids in acute care. As Lieberman summarized succinctly: “Epinephrine, epinephrine. Let's stop using steroids for anaphylaxis, and let's use epinephrine early on and get rid of barriers to use.”

, a board certified allergist/immunologist from Cleveland Clinic Children’s Hospital.

, an associate professor from the College of Medicine - Memphis, department of pediatrics, and division of peds pulmonology at the University of Tennessee Health Science Center. He is also a practicing physician at LeBonheur Children’s Hospital, current chair of the food allergy committee for the American College of Allergy, Asthma, and Immunology, and is co-chair of the Joint Task Force for Practice Parameters.

, associate professor of medicine (part-time) at Johns Hopkins, co-chair of the Joint Task Force on Practice Parameters for allergy, and division chief for allergy-immunology at Sinai Hospital of Baltimore and Franklin Square Hospital in Baltimore.

Disclosures include Novartis Pharmaceuticals, Regeneron Pharmaceuticals, BioCryst, GlaxoSmithKline, Amgen, GENZYME Corporation, AstraZeneca Pharmaceuticals, and LEO Pharma for Schroer; Novartis Pharmaceuticals, ABBVIE, Genentech, Aquestive Therapeutics for Lieberman; and Phadia US and Genentech USA for Golden.

Greenhawt M, Schroer B, Kraft C, et al. One Year Later: How Intranasal Epinephrine Is Changing Emergency Allergy Treatment. HCPLive. Published on August 8, 2025. Accessed on February 10, 2026. 

https://join.hcplive.com/view/one-year-later-how-intranasal-epinephrine-is-changing-emergency-allergy-treatment

Smith T. FDA Approves Epinephrine Nasal Spray for Emergency Treatment of Allergic Reactions. HCPLive. Published on August 9, 2024. Accessed on February 10, 2026. 

Golden D. Anaphylm Remains Promising for Anaphylaxis Despite FDA CRL, With David Golden, MD. HCPLive. Published on February 3, 2026. Accessed on February 10, 2026. 

https://www.hcplive.com/view/anaphylm-remains-promising-anaphylaxis-despite-fda-crl-david-golden-md

Videos

Part 4 highlights how expanding epinephrine delivery options can reduce barriers, support earlier administration, and improve real-world anaphylaxis outcomes.

Recognizing, Managing Anaphylaxis in Infants

Part 3 of the special report turns to an increasingly important and nuanced topic: identifying and managing 

in infants. As early food introduction becomes standard practice, clinicians are encountering allergic reactions at younger ages, making infant-specific guidance more clinically relevant than ever.

Jay Lieberman, MD, opened the discussion by noting that while most reactions seen during early food introduction are mild and not anaphylaxis, the overall number of reactions has increased. This naturally raises the likelihood of encountering true anaphylaxis in infants. Unlike older children or adults, infants cannot verbalize classic symptoms such as throat tightness or oral itching, which complicates recognition and increases reliance on observable signs and caregiver intuition.

Both Lieberman and David Golden, MD, emphasized that infant anaphylaxis often presents through behavioral and nonspecific symptoms. These can include unusual or inconsolable fussiness, lethargy, persistent crying, tongue thrusting, ear pulling, and changes in appearance that parents frequently recognize before clinicians do. Although the current practice parameters still recommend using standard anaphylaxis criteria, the 2024 update acknowledges that it is reasonable to incorporate these infant-specific behavioral cues when assessing reactions in this age group.

From a management standpoint, the experts stressed that treatment principles in infants are fundamentally the same as in older patients. Epinephrine remains first-line therapy, and hesitation around dosing should not delay treatment. Golden highlighted that although autoinjectors are labeled for children above certain weight thresholds, the guidelines clearly support using whatever epinephrine dose is available, even in very small infants, because treating anaphylaxis takes precedence over concerns about relative dosing.

Lieberman reinforced this point succinctly: if a 0.1 mg device is available, use it; if only a 0.15 mg device is on hand, use that instead. Fear of “overdosing” should never prevent timely epinephrine administration in an infant with a concerning reaction.

The panel also noted emerging efforts to align updated infant recognition criteria, newer epinephrine delivery options, and post-epinephrine observation guidance into revised anaphylaxis action plans. The discussion concluded with a broader reminder that education is central to infant anaphylaxis care. Prescribing epinephrine alone is insufficient; clinicians must also teach caregivers how to recognize visual and auditory signs of systemic allergic reactions and when—and how—to act.

Golden DBK, Wang J, Waserman S, et al. Anaphylaxis: A 2023 practice parameter update. 

In this segment, experts emphasize the importance of giving an infant experiencing anaphylaxis epinephrine at whatever dose may be available rather than delaying treatment.


Delinking Epinephrine Use From Mandatory ED Visits

Part 2 of the special report focuses on one of the most practice-changing elements of the 2024 

 guideline update: whether patients must automatically go to the emergency department after using epinephrine.

David Golden, MD, explained that for decades, patients were universally instructed to seek emergency care after any epinephrine use, a message reinforced by package inserts and clinical dogma. However, during early COVID-19, patients and clinicians were reluctant to send otherwise stable individuals to emergency departments. Interim guidance developed during that period prompted a careful re-review of the evidence, ultimately leading to a permanent change in the 2024 practice parameters.

The updated guidance states that if epinephrine is administered promptly, the reaction is not severe, symptoms resolve, and the patient remains well, an emergency department visit is not always necessary. Golden emphasized that most anaphylaxis cases are mild to moderate, that approximately 90% respond to a single dose of epinephrine, and that biphasic reactions are uncommon, generally occurring in 5% to 10% of cases and often associated with delayed treatment.

By delinking epinephrine use from automatic emergency care, clinicians can reduce fear that delays treatment. Golden stressed that patients should focus on the reaction itself, not on meeting strict diagnostic criteria or worrying about the consequences of using epinephrine. The updated parameters explicitly note that epinephrine can be given even if anaphylaxis criteria are not fully met, and that giving epinephrine does not retrospectively confirm that the reaction was anaphylaxis.

The experts said factors such as patient comfort, access to emergency care, availability of a second epinephrine dose, presence of a caregiver, and individual risk factors all influence whether observation at home is appropriate. Severe presentations, such as hypotension, loss of consciousness, or significant respiratory distress, still warrant urgent medical evaluation.

The discussion concludes by reinforcing that the goal of the updated guidance is not to discourage emergency care, but to remove barriers to early epinephrine use. By shifting control to patients and families and tailoring decisions to individual circumstances, the 2024 update aims to improve outcomes while reducing unnecessary fear and hesitation.

In the second part of the special report, panelists delink epinephrine use from mandatory emergency department visits.