Introduction
Anaphylaxis is a serious, systemic hypersensitivity reaction characterized by rapid onset and the potential for life-threatening progression within minutes. In many cases, symptoms escalate in seconds, turning an ordinary moment at a restaurant, school event, or family gathering into a medical emergency. If left untreated, anaphylaxis may lead to loss of consciousness, cardiac arrest, or death. According to the Allergy and Asthma network, approximately 1 in 20 Americans have experienced anaphylaxis. Among individuals with food allergies, 42% of children and 51% of adults report a history of severe reactions. The economic burden is also substantial, with an estimated $1.2 billion in annual direct medical costs in the United States, including roughly $294 million attributed to epinephrine prescriptions alone. Anaphylaxis is associated with approximately 225 deaths per year in the U.S., and notably, about half of all episodes occur at home.
Epinephrine remains the only medication capable of reversing the life-threatening symptoms of anaphylaxis and is universally recognized as the cornerstone of management. In theory, that makes the solution sound straight forward—recognize symptoms and administer epinephrine immediately. In practice, it’s more complicated. Despite clear guideline recommendations, epinephrine continues to be underutilized. In a nationwide survey conducted by Wood and colleagues, 52% of patients who had previously experienced anaphylaxis had never received a prescription for an epinephrine auto-injector (EAI), and 60% did not have one currently available. Barriers include needle phobia, fear and anxiety surrounding device use, lack of confidence in administration technique, and misconceptions that a prescription is unnecessary. Delayed administration is associated with more severe outcomes, including biphasic reactions and increased risk of fatality. When it comes to anaphylaxis, hesitation can be costly—timely epinephrine use is strongly correlated with improved survival.
This gap between what should happen and what actually happens has fueled interest in alternative delivery systems. Anaphylm, an investigational sublingual epinephrine film developed by Aquestive Therapeutics, is being studied as a potential alternative to injectable epinephrine products.The film is small and lightweight, designed to dissolve under the tongue without the need for water or swallowing, and is packaged in a compact, weather-resistant format. While still under regulatory review, the concept raises important questions for pharmacists—Could a needle-free option improve willingness to carry epinephrine? Would simpler administration reduce delays in real-world emergencies? As the landscape of anaphylaxis treatment evolves, pharmacists will play a critical role in evaluating emerging therapies and translating new options into safe, practical patient care.
Overview of Anaphylaxis
Hypersensitivity reactions are immune-mediated responses that result in tissue injury and clinical symptoms. They are classified into four types (I-IV) based on their underlying immunologic mechanism and timing of presentation. The chart below outlines the key features and common examples of each type.
As a type I hypersensitivity reaction, anaphylaxis represents the most acute and potentially life-threatening immune response. The table below highlights common triggers and causes that pharmacists should be aware of.
Recognizing and responding to anaphylaxis is a critical skill for all healthcare personnel. Prompt anaphylaxis treatment should be considered when a patient presents with generalized symptoms such as hives, or more serious, potentially life-threatening signs including hypotension, respiratory distress, significant swelling of the lips or tongue, or involvement of more than one body system. Other common clinical manifestations of anaphylaxis include:
- Respiratory—Sensation of throat closing, stridor (high-pitched sound while breathing), shortness of breath, wheezing, or cough
- Gastrointestinal—Nausea or vomiting, diarrhea, abdominal pain
- Cardiovascular—Dizziness or fainting, tachycardia, hypotension
- Skin mucosal—Generalized hives, itching, swelling of lips, face or throat
- Neurological—agitation, convulsions, acute change in mental status, sensation of impending doom
If a patient exhibits any of these signs, especially when multiple systems are involved, immediate recognition and intervention is essential. Prompt action can be lifesaving and prevents progression to severe or fatal outcomes. Here is what to do when anaphylaxis is suspected:
- Assess airway, breathing, and circulation (ABCs)
- Administer epinephrine immediately
- Call emergency medical services
- Place the patient in supine position
Current Epinephrine Options
When anaphylaxis occurs, epinephrine is the lifesaving first-line treatment, and timely administration is critical. The current FDA-approved epinephrine options are:
- Neffy® nasal spray by ARS Pharma
- EpiPen® / EpiPen Jr® or their generics
- Auvi-Q® Auto-Injector
- Authorized generic of Adrenaclick® by Amneal Pharmaceuticals
- Generic of EpiPen® / EpiPen Jr® by Teva Pharmaceuticals
- EpiPen® / EpiPen Jr® and authorized generics by Viatris (formerly Mylan)
Even with multiple options on the market, no form of epinephrine has been shown to be more or less effective than another. In practice, insurance coverage often determines which option a patient receives. Most auto-injectors and the nasal spray come in two packs to ensure a backup dose is available in case a second injection is needed or in case the first device malfunctions. The table below shows a comparison between the auto-injector and nasal spray version of epinephrine.
Despite the availability of multiple epinephrine options, there are several challenges to consider. Patients and caregivers may become confused when faced with different devices or administration instructions, and fear of needles can lead to hesitation or improper use. In fact, a study from the National Institute of Health found that EAIs are used incorrectly 35-45% of the time. Access and insurance coverage can also be limiting factors, particularly for nasal spray options, which are less widely covered.
While epinephrine can be lifesaving, it is important for patients and healthcare providers to be aware of potential side effects and what to expect after administration. Side effects include:
- Tachycardia
- Arrhythmias
- Palpitations
- Hypertension
- Headache
- Tremor, weakness
- Pallor, sweating
- Nausea and vomiting
- Nervousness and anxiety
- Pain, redness at the injection site
- Tissue necrosis (if extravasated)
What is Sublingual Epinephrine?
For decades, epinephrine has been the frontline defense against anaphylaxis, now it is getting a needle-free upgrade. A new oral form of epinephrine is currently in clinical development, representing the first and only oral delivery option for Type I allergic reactions, including anaphylaxis. This innovative formulation contains a prodrug of epinephrine that is designed to be portable while achieving rapid absorption through sublingual administration.
The oral epinephrine is about the size of a postage stamp and weighs less than an ounce. Its packaging is even thinner and smaller than the average credit card, making it easy to carry in a pocket. It can also withstand weather conditions like rain or sunlight.
Anaphylm offers several advantages to patients and providers including:
With oral epinephrine on the horizon, the future of anaphylaxis management could be more convenient, safer and patient-friendly than ever before.
Challenges and Considerations for Anaphylm
While oral epinephrine offers exciting benefits, there are some current limitations to be aware of. On January 30, 2026, the FDA issues Anaphylm a Complete Response Letter, meaning the product was not approved in its current form. The agency raised concerns about usability, including trouble opening the pouch and correctly placing the film under the tongue. Importantly, these issues were related to the packaging and administration, rather than the drug’s safety or efficacy.
The main issues involve practicality during emergency situations and the need for additional pharmacokinetic data. The company developing the product believes these concerns can be resolved quickly, with plans to resubmit as early as summer 2026. The FDA is requesting further information on packaging, labeling, and pharmacokinetics, and details on insurance coverage remain uncertain at this time.
Despite these hurdles, oral epinephrine remains a promising innovation that could significantly improve the accessibility and ease of anaphylaxis treatment once these issues are addressed.
The Final Consensus of Anaphylm for Patients
Anaphylaxis remains one of the most urgent and high-stakes emergencies pharmacists may encounter, and rapid access to epinephrine continues to be the mainstay of treatment. While current auto-injectors and nasal formulations are effective, challenges such as device confusion, administration errors, and access barriers still exist. Emerging innovations like oral epinephrine have the potential to reshape the future of anaphylaxis management by improving portability, ease of use, and patient confidence. As the treatment landscape continues to evolve, pharmacists will remain at the forefront to educate patients, navigate coverage barriers, and ensure that when seconds matter the most, lifesaving therapy is ready and within reach.
APPE Student, Hailey Montour
References
Allergy & Asthma Network. Anaphylaxis Statistics. Accessed February 26, 2026. https://allergyasthmanetwork.org/anaphylaxis/anaphylaxis-statistics/
Aquestive Therapeutics. Anaphylm®. Accessed February 26, 2026. https://aquestive.com/anaphylm/
Aquestive Therapeutics. Sublingual epinephrine (Anaphylm®) provides consistent pharmacokinetics in both adult and pediatric subjects. Accessed February 26, 2026. https://www.aquestivedata.com/pdfs/sublingual_epinephrine_anaphylm_provides_consistent_pharmacokinetics_in_both_adult_and_pediatric_subjects.pdf
Centers for Disease Control and Prevention (CDC). Recognizing and Responding to Anaphylaxis. Accessed February 26, 2026. https://www.cdc.gov/vaccines/covid-19/downloads/recognizing-responding-to-anaphylaxis-508.pdf
Food Allergy Research & Education (FARE). Epinephrine Options and Training. Accessed February 26, 2026. https://www.foodallergy.org/resources/epinephrine-options-and-training
Food Allergy Research & Education (FARE). What Epinephrine Option Is Best for You? Accessed February 26, 2026. https://aafa.org/wp-content/uploads/2026/02/what-epinephrine-option-is-best-for-you.pdf
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Ziyar A, Kwon J, Li A, Naderi A, Jean T. Improving epinephrine autoinjector usability and carriage frequency among patients at risk of anaphylaxis: a quality improvement initiative. BMJ Open Qual. 2022;11(3):e001742. doi:10.1136/bmjoq-2021-001742