Epinephrine for Anaphylaxis: What Treatments are Available?

Epinephrine was first used as a medical treatment as early as 1901. But it wasn’t until 1987 that the U.S. Food and Drug Administration (FDA) approved it to treat severe allergic reactions, or anaphylaxis.

Epinephrine is now considered the first-line treatment for anaphylaxis. It’s the only medication that can stop or reverse the life-threatening symptoms of a severe allergic reaction.

For decades, epinephrine was mostly available to the public as a handheld auto-injector device. The medicine could also be drawn from a vial into a syringe for an epinephrine injection.

In recent years, new epinephrine administration options have emerged. Let’s explore each of the options, with their upsides and downsides.

First, what is anaphylaxis?

Anaphylaxis is a severe allergic reaction, usually to a certain food, insect sting, medication or latex. It comes on swiftly and can turn deadly in minutes.

When exposed to an allergen or an allergen is ingested, the immune system over-reacts in people at risk for anaphylaxis. The body is flooded with histamine in an effort to combat the allergen. This sudden chemical release can lead to severe onset of symptoms and shock.

Symptoms involve more than one body system: the skin, airways, stomach or heart. They may include hives, a swollen tongue, mouth or throat, and trouble breathing. Stomach distress, chest pain, nausea, vomiting and/or diarrhea are common. Blood flow problems, such as high blood pressure or low blodd pressure, are also possible. In severe cases, some people may feel faint or lose consciousness. Some may have cardiac or respiratory arrest, septic shock, or pulmonary edema.

Anaphylaxis requires emergency treatment: epinephrine. It is a dose of adrenaline that causes the constriction of blood vessels to raise blood pressure. This relaxes airway muscles and increases the heart rate. Epinephrine addresses symptoms within minutes. Give epinephrine first, and give it fast. This reduces the risk of hospitalization or death. Left untreated, anaphylaxis can be fatal.

Side effects of epinephrine use are minor and don’t last more than 30 minutes. These adverse effects may include a fast or irregular heartbeat, sweating, nausea, or dizziness.

How is epinephrine given for anaphylaxis?

Several options are now available for epinephrine emergency treatment. Most people are familiar with epinephrine auto-injectors. A dose of epinephrine can also come in a vial that is drawn into a syringe for injection into the muscle (IM), skin, or in an IV.

More recently, an epinephrine nasal spray earned approval in the U.S. market. And a new epinephrine sublingual (under the tongue) film is expected to be available soon.

Epinephrine auto-injector

This is a self-injectable epinephrine medication. It comes with the epinephrine pre-filled in a device that has an injectable syringe, and the needle attached. The injection site is the outer thigh.

Note: You may sometimes hear these devices called “EpiPens®.” This refers to a specific brand of auto-injector. Several brands of epinephrine auto-injectors are available on the market.

Instructions for use may vary by brand. For example, the amount of time to hold the injection may differ for each device. So it is important to familiarize yourself with your brand. One device – AUVI-Q® – includes a voice prompt that talks you through the injection.

Epinephrine auto-injectors are fast and easy to use. They are a little bulky but also small enough that they can easily be carried, even in a pocket. The downside is that, for anyone even a little bit wary of needles, there may be some reluctance and hesitation to give the injection. Any delay in giving epinephrine increases the risk of hospitalization or death.

Another potential downside is the cost if the device is not covered by insurance. For example, the cost of a two-pack of EpiPens is priced at more than $600. Some manufacturers introduced generic versions of epinephrine auto-injectors. These are priced lower than branded products, costing about $150 to $300 per two-pack.

Epinephrine nasal spray

The epinephrine nasal spray called neffy® was approved by FDA in 2024. It is a needle-free alternative to the auto-injector. The epinephrine is given directly into the nostril instead of by needle. It temporarily loosens the spaces between the nasal cells, allowing for fast absorption.

The neffy prescription consists of two single-dose nasal sprays. Each device is a single dose taken in one nostril. A second dose (using a new nasal spray in the same nostril) may be taken if there is no improvement in symptoms or symptoms worsen or come back.

The nasal spray is also fast and easy to use. It is small enough that it is carried, including in a pocket if no carry case is available. For people who are fearful of needles, this route of administration is an effective alternative to auto-injectors.

What about the cost? People who have private health insurance that covers neffy can pay $25 for each prescription. People without insurance or coverage for epinephrine can get neffy for $199 via BlinkRX and GoodRx.

More epinephrine nasal spray products are expected to arrive on the market soon.

Epinephrine vial or pre-filled syringe

Epinephrine vials are available to the public. The medication must first be drawn into a syringe that has a needle attached. The process of filling the syringe with the epinephrine solution can take time and delay treatment. It may be difficult to do by yourself, especially if you’re nervous and/or experiencing symptoms. Sometimes several doses are in a vial.

Epinephrine vials are most often used in the hospital setting. They are administered by trained nurses and doctors. The epinephrine is given in the muscle or intravenously.

Epinephrine pre-filled syringes with the correct dose are also available. But some do not come with the needle attached. Instead, you must attach it yourself. Then it can be injected into the thigh. This process adds the extra step of attaching the needle, which can delay treatment.

Some syringe kits do have a pre-filled syringe with the needle attached. Ask your doctor for an epinephrine syringe that has the needle attached.

Epinephrine vials and pre-filled syringes are a much cheaper alternative to epinephrine auto-injectors. A vial of epinephrine and syringes/needles can be purchased for around $20. This method may take a bit longer. But it is highly effective in treating anaphylaxis when administered correctly.

Epinephrine sublingual (under the tongue) film

A strip of film containing epinephrine is a potential new treatment option. It is undergoing review in clinical studies. FDA is expected to consider approval of the treatment sometime in 2025-26.

The strip of film, branded as Anaphylm™, is about the size of a postage stamp. It is placed under the tongue, where it dissolves on contact. The strip weighs less than an ounce. It comes in a package that is like a credit card, so it can be carried safely in a pocket or wallet.

Clinical studies of Anaphylm have shown it can provide quick and sustained levels of epinephrine. Research has also shown it can address symptoms in as fast as 2 minutes and resolve them by 12 minutes.

Can’t afford epinephrine? Here’s what you can do

If you have health insurance, contact your insurance company to find out what epinephrine devices are covered under your plan. Most Medicare and Medicaid plans cover epinephrine devices.

What if you are not insured, or your insurance plan does not cover the epinephrine device you want? Check out our “What If I Can’t Afford Epinephrine?” webpage to review your options. For example, you can learn how to compare prices at pharmacies or find out how to get coupons or discounts. You can also ask your doctor about epinephrine generics.

Reviewed by:
Purvi Parikh, MD, FACAAI, is an adult and pediatric allergist and immunologist at Allergy and Asthma Associates of Murray Hill in New York City. She is on faculty as Clinical Assistant Professor in both departments of Medicine and Pediatrics at New York University School of Medicine.

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