Marcus Shaker, MD, a professor of pediatrics and medicine at the Dartmouth Geisel School of Medicine

Marcus Shaker, MD

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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.

Early Introduction, Rescue Refeeding, and Home OIT: Reframing Pediatric Food Allergy Management

No Testing Required: Reframing Early Allergy Introduction

 in infancy, one of the most persistent misconceptions is that allergy testing must come first. Marcus Shaker, MD, of Dartmouth Geisel School of Medicine at Dartmouth Health Children’s, pushed back on that assumption in his Eastern Allergy Conference (EAC) 2026 presentation, emphasizing that no testing is required before early introduction of allergenic foods in most cases.

No allergy testing is required before early introduction of allergenic foods

Early introduction should be pursued with small amounts, advancing as tolerated; any reaction warrants a pause and physician consultation

Children who develop food allergies may be strong candidates for rescue refeeding via early food immunotherapy, which carries a low rate of severe reactions

Home-based OIT models, including Dartmouth's published approach, can improve access and cost-effectiveness

The best general approach: feed early and feed often—but with open communication between families and clinicians throughout

Using a case-based approach, Shaker walked through the case of a child with a suspected egg allergy as a clinical illustration. While further evaluation with a board-certified allergist-immunologist would be appropriate before additional egg exposure, he noted that peanut introduction could proceed without testing. Families could try a small amount, approximately a sixteenth of a teaspoon of peanut flour mixed into a soft food, advancing as tolerated. If any reaction occurs, the guidance is clear: pause and seek evaluation.

“There's very good data that this is a safe and effective approach with a low rate of severe reactions, even safer in infants,” Shaker told HCPLive. “We have health economic data that [shows immunotherapy] can save potentially millions or even billions of dollars over time.”

Rescue Refeeding: A Viable Path When Allergy Develops

For children who develop food allergies, Shaker emphasized that a diagnosis is no longer a one-way door to indefinite avoidance. In 2026, he noted, early food immunotherapy represents a viable "rescue refeeding" approach, with strong supporting evidence for both safety and efficacy.

Oral immunotherapy in early childhood is effective and safe in preschoolers, with particular safety advantages in young infants.

 Shaker described the rate of severe reactions as low and characterized the evidence base as solid.

For families of a child with a confirmed egg allergy, Shaker outlined a collaborative path: working with a board-certified allergist-immunologist to review and implement a rescue refeeding protocol as a long-term partnership, rather than a discrete intervention.

The Dartmouth Spoon Sheet Approach: Home Multi-Food OIT

Shaker referenced Dartmouth's own published experience as an example of how immunotherapy can be made more accessible. The Dartmouth Spoon Sheet Home OIT Program evaluated children with food allergies receiving oral immunotherapy, with a meaningful proportion receiving multi-food OIT that included peanut, tree nut, or milk.

The program is designed to address equity and access barriers, particularly relevant in rural settings where repeated clinic visits for dose escalation can be prohibitive. Repeated clinic visits for food oral immunotherapy can limit equity and access in rural locations, and home protocols are cost-effective.

Shaker said that the role of the clinician is not simply to convey data but to meet families where they are emotionally. He cited Sir William Osler—"The practice of medicine is an art, not a trade; a calling, not a business; a calling in which your heart will be exercised equally with your head"—as a framing device for the conversation about food allergy management.

Read part 1 of our interview with Shaker here: 

Early Allergen Introduction in Infants: Reducing Food Allergy Risk Without Routine Testing

Shaker M. Food Allergy Prevention and Rescue Refeeding in 2026. Session presented at the Eastern Allergy Conference (EAC) 2026 in Palm Beach, Florida, on May 28.

Chua GT, Mack DP, Shaker MS, Chan ES. Oral food immunotherapy in patients with atopic dermatitis. 

2024;133(3):278-283. doi:10.1016/j.anai.2024.05.022

Shaker M, Hughes S. Real-World Multi-Food Home Oral Immunotherapy Using Daily Micro-Dose Schedules Has Low Rates of Adverse Reactions. 

Journal of Allergy and Clinical Immunology

doi:https://doi.org/10.1016/j.jaci.2023.11.394

Videos

At EAC 2026, Dartmouth Children's Health allergist Marcus Shaker, MD, outlined a framework built on shared decision-making for families navigating food allergy in infancy.

in Palm Beach, Florida, Marcus Shaker, MD, from Dartmouth Geisel School of Medicine, Dartmouth Health Children’s, highlighted one of the most important shifts in modern 

 prevention, which is the move toward early introduction of allergenic foods in infancy.

, Shaker emphasized that translating research findings into everyday clinical practice remains a challenge for both healthcare providers and families.

Using a case-based approach, he explored a common scenario: a child with a family history of food allergy whose parents are unsure when and how to introduce allergenic foods.

 The discussion centered on helping clinicians offer evidence-based guidance while acknowledging the realities and anxieties that many families face.

Early introduction of allergenic foods can reduce the risk of developing food allergies.

Routine allergy testing before first exposure is not recommended for most infants.

Avoiding foods based solely on test results may lead to unnecessary dietary restrictions.

Why Routine Allergy Testing Before Food Introduction Is Not Recommended for Most Infants

A key theme of Shaker’s presentation was that routine pre-introduction allergy testing is generally not required before introducing common allergenic foods. He noted that several landmark studies demonstrated a reduction in allergy risk when foods such as peanuts are introduced during infancy.

However, he cautioned against overinterpreting these findings. Although some infants may benefit from targeted evaluation, broad testing strategies can create confusion and unintended consequences. Positive test results do not always predict true clinical allergy, particularly in children who have never eaten the food in question.

Shaker explained that avoiding foods solely because of test results may prevent families from introducing foods that could be tolerated and potentially beneficial. Instead, decisions should be individualized, taking into account the child’s history, risk factors, and family circumstances.

Why Shared Decision-Making Is Key to Food Allergy Prevention Counseling

Shaker stressed the importance of shared decision-making. Parents bring their own values, preferences, and concerns to the discussion, and clinicians must balance scientific evidence with practical considerations.

He also noted that current practice parameters support a conditional recommendation for early allergen introduction, reflecting both the strength of the evidence and the need for flexibility in implementation.

For attendees, the message was clear: early introduction remains a valuable tool for food allergy prevention, but success depends on thoughtful communication, individualized care, and helping families navigate decisions with confidence.

Shaker M. Food Allergy Prevention and Rescue Refeeding in 2026. Poster presented at EAC 2026 on May 28.

Derman C. Early Peanut Introduction Guidelines Linked to Drop in Food Allergy Rates. HCPLive. Published on October 20, 2025. Accessed June 1, 2026. 

https://www.hcplive.com/view/early-peanut-introduction-guidelines-linked-drop-food-allergy-rates

Marcus Shaker, MD, discusses early allergen introduction, food allergy prevention, and the role of routine testing at EAC 2026.

Frequently asked questions (FAQ) about treating anaphylaxis:

When should I give my patients epinephrine for suspected anaphylaxis?

What’s the best observation period when treating anaphylaxis?

What test should I order for patients who experienced anaphylaxis?

Why should I instruct patients to call 911 after using an epinephrine auto-injector?

asked Marcus Shaker, MD, MSc, professor of pediatrics and medicine at the Geisel School of Medicine at Dartmouth, rapid-fire FAQ questions about the treatment of 

When should epinephrine be administered for suspected anaphylaxis?

 Right away. Epinephrine is the first-line treatment for suspected anaphylaxis.

What's the best observation period when treating anaphylaxis?

 The best observation period varies and depends on context and severity of anaphylaxis. For patients who have resolved non-severe anaphylaxis for at least an hour, the likelihood of recurrence of anaphylaxis is in the range of 5%.

What test should you order for patients who experienced anaphylaxis?

 The blood test is called the serum tryptase, and it can be very helpful in establishing a diagnosis.

Why do some patients need to call 911 even after using an epinephrine auto-injector?

 If symptoms are severe or don't immediately resolve or nearly resolve, patients may need additional epinephrine.

They may need additional support, including oxygen and IV fluid. Anaphylaxis can be severe and life-threatening, so if symptoms have not completely resolved or if they recur, patients should call 911 and seek care immediately.

2025 American College of Allergy, Asthma, & Immunology Annual Scientific Meeting

 in Orlando, Florida, from November 6 – 10, Shaker presented on misconceptions many people have surrounding epinephrine use in anaphylaxis management.

 According to Shaker, one of the most enduring myths both clinicians and patients have about epinephrine is that it is dangerous

“It's not,” Shaker told HCPLive during the meeting. “Epinephrine is the first-line treatment of anaphylaxis, and if you're having a severe allergic reaction, it is the recommended approach.”

Another misconception he listed was the necessity of calling 911 after administering epinephrine. Although patients may need to call 911 in certain situations, such as experiencing persistent or worsening symptoms, cardiovascular involvement, or a history of severe reactions, involving emergency services is not always necessary. Shaker said this misconception may result in patients not using their epinephrine to avoid a hospital visit. This myth can also feed the misbelief that epinephrine is dangerous.

At the conference, Shaker also discussed the nuanced approach clinicians must take when managing patients with a known trigger for anaphylaxis.

For instance, it may not be helpful to test a patient for peanut allergies if they are already 100% certain they have a peanut allergy. In this case, it would be more logical to shift the focus from diagnosis to treatment and preparedness.

Clinicians have many food allergy treatment options to select from, including oral and sublingual immunotherapy, biologics such as omalizumab, and a growing range of epinephrine delivery options. He said all of these options allow for richer discussions with patients and families about goals of care and management preferences.

Shaker M. Epinephrine Misconceptions Persist in Anaphylaxis Care, With Marcus Shaker, MD. HCPLive. November 7, 2025. 

https://www.hcplive.com/view/epinephrine-misconceptions-persist-anaphylaxis-care-marcus-shaker-md

Shaker M. When to Prescribe Epinephrine for Known Anaphylaxis Triggers, With Marcus Shaker, MD. HCPLive. November 7, 2025. 

https://www.hcplive.com/view/when-prescribe-epinephrine-known-anaphylaxis-triggers-marcus-shaker-md

Epinephrine is the primary treatment for suspected anaphylaxis and should be administered immediately. Observation periods vary based on the severity of the reaction, with a 5% recurrence rate for non-severe cases. Serum tryptase tests can aid in diagnosis. Patients should call 911 if symptoms persist or worsen after using an epinephrine auto-injector. Misconceptions about epinephrine's safety and the necessity of emergency services can hinder proper use. Clinicians should focus on treatment and preparedness, especially when triggers are known, and consider various allergy treatment options.

A quick guide for clinicians on epinephrine dosing, optimal observation periods, and the role of tryptase and other labs in anaphylaxis care.
