EpiPen vs. Neffy: What You Need to Know

What Are EpiPen and Neffy?

EpiPen and Neffy are both medications used by people with severe life-threatening allergies. They are used to temporarily relieve severe allergic reactions known as “anaphylaxis” so that the affected person has time to get emergency medical help. The two products are similar in that they deliver a measured dose of the medication “epinephrine.” The main difference between the two is that EpiPen delivers the medication through an autoinjector, an intramuscular injection needle given in the leg, whereas Neffy is a needle-free nasal spray.

Epipen has been the standard life-saving device for anaphylactic reactions since 1983, so many readers may be familiar with this device. However, Neffy is a relatively new product, first approved by the United States (US) Food and Drug Administration (FDA) in August 2024. As such, people who have trusted their lives to EpiPen may have some concerns with the newer product. Is it as good as EpiPen? Is it as reliable as EpiPen? Is it right for me or my child? In this article, I'll answer those questions and more. I'll finish with a scorecard where I compare the two products.

What Is Anaphylaxis?

Anaphylaxis is a severe, potentially life-threatening allergic reaction that affects the whole body. It is rapid-onset, although it can rarely occur as a delayed reaction hours or days after exposure to the allergen.

Some of the most common allergens that may cause anaphylaxis include:

About 1-3% of the world population has an anaphylactic allergy, and the prevalence is increasing. Anaphylaxis can occur in anyone at any age, but it is more common in the younger population.

Anaphylaxis occurs because of the immune system’s hypersensitivity to a specific allergen that results in a cascade of chemicals being released. Some of these chemicals make the blood vessels dilated and leaky, which can cause a dangerous drop in blood pressure and leave the vital organs with an insufficient blood supply. As well, some of these chemicals cause constriction and swelling of the airways, which may make the person unable to get enough oxygen.

Figure 1. Typical symptoms of anaphylaxis.

The symptoms of anaphylaxis (see Figure 1) usually begin with a feeling of a lump in the throat and a need to constantly clear the throat. A hoarse voice, wheezing, and difficulty breathing usually rapidly follow. Inability to breathe, severe abdominal pain, muscle cramping, lightheadedness, loss of consciousness, and death may follow.

When people die from an anaphylactic reaction, it is usually because of an inability to breathe and shock (blood pressure too low to support life).

How Does Epinephrine Treat Anaphylaxis?

Epinephrine (also known as adrenaline) is a natural hormone produced by the adrenal glands (hormone-secreting organs that sit atop each kidney) in response to stress. Epinephrine causes the blood vessels to constrict, raises blood pressure, makes the heart beat faster, and opens up the airways. This is why we feel alert and ready to act in times of emergency or other stressful situations.

Epinephrine’s effects counter the low blood pressure and airway constriction that cause death in anaphylaxis. It begins working immediately, so relief from low blood pressure and breathlessness occurs right away. However, its effects are short-lived, lasting at most 20 to 30 minutes. As such, epinephrine should not be viewed as a cure. Rather, it should be seen as a temporary reprieve to buy the person time to get emergency medical attention.

The first hour after exposure to the allergen is the most crucial; about one-half of deaths occur during this time. This is why it is important for anyone with known or suspected anaphylactic allergies to always have at least two epinephrine treatment devices on hand at all times.

However, the first hour of the reaction is not the only time of concern. About 20% of cases occur in pulses, where even after successful treatment of the initial reaction, another reaction follows in 8 to 11 hours. This is why replacing an epinephrine device immediately after use is crucial.

All About EpiPen

Figure 2. The EpiPen device.

EpiPen has been the standard of care for emergency first aid for life-threatening allergies since the 1980s. They come as pre-loaded EpiPen syringes that are equipped with an “auto-injector” so that the user does not have to learn to draw up the medication and give themselves a traditional needle (figure 2). They are designed for the rapid use required for responding to a serious allergic reaction.

Epipen is available in adult and children's preparations; Epipen and Epipen Jr., respectively. They come in a two-pack carton (EPIPEN 2-PAK® and EPIPEN JR 2-PAK® cartons). Each carton contains a trainer unit that does not contain any medication or a needle. Viatris (the makers of EpiPen) offers a video on their website that demonstrates how to use the device.

EpiPen is intended for use by children and adults who weigh more than 66 lb. EpiPen Jr. is intended for individuals who weigh 33 to 66 lb.

All About Neffy

Figure 3. The Neffy devices.

Neffy is a new product, approved by the FDA for use in life-threatening allergies in August 2024. It is a needle-free nasal spray that delivers epinephrine for use as emergency first aid for anaphylaxis. It comes in a 2 mg dose for adults and children who weigh at least 66 lb, and a pediatric 1 mg dose for use by children aged 4 years and up and who weigh between 33 and 66 lb.

Neffy comes as a twin-pack, with each injector blister-packed. It is administered as a single spray in one nostril. If the first dose isn’t effective or a second dose is needed, the second dose is sprayed into the same nostril.

Differences Between EpiPen and Neffy

Shelf Life

The expiry date of any epinephrine device is clearly printed on the packaging and the product (Figure 4). The length of time left for the product may depend on how long it has spent on the shelf at the pharmacy. EpiPen has a shelf-life of 12 to 18 months. Neffy has a shelf-life of 2.5 years for the 2 mg dose and 2 years for the 1 mg dose.

The expiry date is usually printed as “EXP.” If the expiry date is given as a month and year (e.g., 12/27), then the product expires at the end of that month. For example, a product labeled EXP: 12/27 would expire on the last day of December 2027. Every person who uses a life-saving product like EpiPen or Neffy should note the expiry date and ensure they make arrangements to replace it before it expires.

Figure 4. Sample expiry date on an EpiPen device.

A 2019 research study demonstrated that EpiPen and its generics remain 100% effective for at least 6 months after their expiry date and up to 90% effective up to 30 months after the expiry date. However, this should not be taken as a reason to use expired products. These are life-saving devices, and taking chances can never be substantiated.

Cost

The cost of an EpiPen two-pack in the US without insurance is about $650 to $750 USD. Generic versions are usually cheaper, usually in the $340 to $400 range. There are discount programs that may cut the cost by as much as 50%. For example, membership-based discount programs may reduce brand-name EpiPens to about $359, and generic devices to $77 to $100.

EpiPens are usually covered by Medicare Part D, although a specific brand (usually generic) may be required.

Neffy costs about $701 and up for a twin-pack. Generic versions are not yet available. In general, Neffy is not covered by medicare part D at this time. However, individuals should check with their Medicare plan to see if it is covered and whether prior authorization is needed.

Sometimes further savings can be found by checking manufacturers’ websites for coupons, checking discount websites, and checking pharmacy websites for special deals. Many consumers also look to reputable Canadian pharmacies to purchase at a discount as well.

Effectiveness

There is more than 40 years of clinical experience with EpiPen, with millions of doses being used worldwide. Its effectiveness is beyond doubt. Neffy is a much newer product with a novel delivery method, so it is natural to be cautious about its effectiveness. However, the FDA has approved Neffy for use in the emergency treatment of anaphylaxis.

The FDA based its approval of Neffy on four clinical trials where the product was used on 175 adults who did not have anaphylaxis. That is not a shortcoming on the part of the FDA; testing Neffy on individuals who are experiencing anaphylaxis is not feasible because of the ethics and impracticality of inducing a life-threatening condition to test a product. Similarly, there are no clinical studies supporting the efficacy of EpiPen.

The clinical trials used by the FDA to confirm the efficacy of Neffy were based on measuring blood levels of epinephrine following use of the device. These studies confirmed that Neffy produces blood levels of epinephrine comparable to those produced by EpiPen. As well, Neffy was found to produce the same life-saving increases in blood pressure and heart rate as EpiPen.

The bottom line is that although there is a lack of clinical experience with Neffy compared to our extensive experience with EpiPen, it is reasonable to believe that Neffy works just as well.

Limitations for Use

Both products come with cautions that epinephrine, the drug in EpiPen and Neffy, may cause problems in people with certain health conditions and may interact with certain medications. However, Neffy comes with the additional warning that people with nasal polyps or a history of nasal surgery, or certain other nasal conditions, should consult with their physician before choosing Neffy because these conditions may affect absorption.

Side Effects

Both products may produce the typical side effects of epinephrine, which include a rapid heart rate, nausea, dizziness, headache, and a feeling of panic. However, Neffy has additional possible side effects due to the nasal route of administration. These may include: nose or throat irritation or pain, sneezing, and nosebleeds. EpiPen may produce redness, swelling, or tenderness at the injection site, but these are reported as a rare occurrence.

Ease of Carrying

Figure 6. One Neffy twin-pack, 2 mg dose.

Neffy comes in a convenient, easy-to-carry zip pouch with a carabiner clasp (Figure 6). It is smaller in size than an EpiPen two-pack. After-market storage and carry pouches are available for EpiPen, but these are an added expense.

Bottom Line

The table below compares Neffy with EpiPen, based on the various factors we've discussed.

Table. Comparison scorecard: EpiPen versus Neffy.

Notes:

*Both products have comparable costs, but the advantage is given to EpiPen because of the availability of generics and the wider insurance and Medicare coverage at this time.

**Both products are likely equally effective but given the limited clinical data for the use of Neffy in real-life situations and the very limited clinical experience with this new product, EpiPen is given the advantage.

Based on my scoring system, I give the nod to EpiPen as the more advantageous product at this time. However, product selection is personal and should be discussed with your physician. For example, some individuals may be fearful of the needle involved in EpiPen and may therefore absolutely wish to take advantage of the newly available Neffy nasal spray.