At Last, a Nasal Epinephrine Spray

This summer, the US Food and Drug Administration (FDA) fast-tracked approval of the first-in-its-class nasal epinephrine (neffy). It’s a very welcome addition to our anaphylaxis treatment armamentarium. As the FDA announcement notes, patients with anaphylaxis at times “delay or avoid” anaphylaxis “treatment due to fear of injections.” Neffy was approved on the basis of pharmacokinetic studies. In healthy volunteers, neffy achieved similar serum epinephrine levels, rises in blood pressure, and pulse compared with IM epinephrine. 
It was just a few days ago that I saw a new patient with fire ant anaphylaxis. The last time he tried to use an injectable epinephrine pen, he made two mistakes. First, he placed the wrong end against his thigh, and when it did not inject, he depressed it with his thumb — in other words, he injected his thumb with epinephrine. Of course, that cannot happen with neffy. 
I recall a few years ago, a child experienced anaphylaxis but the parent was hesitant to administer the EAI (epinephrine autoinjector). The parent drove to the emergency room but was delayed by traffic, and by the time they reached the ER, the patient had suffered a respiratory arrest and passed away. 
Patients are not the only ones who are hesitant to administer epinephrine. Some clinicians do not treat mild anaphylaxis appropriately. As an allergist, I see patients after-the-fact for diagnosis and management. Patients often tell me of systemic allergic reactions treated with IV antihistamines/corticosteroids and even sometimes with nebulized beta agonists, but not epinephrine. 
My opinion is that it’s not just needle phobia. As I mentioned, in my Medscape commentary “Injectable Epinephrine: An Epidemic of Misuse,” I believe it’s due to a misunderstanding of the guidelines and a sense that epinephrine is a potent medication to be used sparingly. Clinicians and patients must understand that epinephrine is a naturally occurring hormone and administration leads to serum levels seen under other natural circumstances (eg, stress — the fight-or-flight surge). The aforementioned article also includes a patient handout, “Don’t Fear Epinephrine,” which I encourage you to read and distribute. 
The potential benefits of neffy are clear: 
It should overcome fear of injection ergo being more likely to be used, and used earlier, by both patient/family member and clinicians.
It’s easier to carry than many larger devices (though not the AUVI-Q).
It cannot be injected incorrectly. 
Expiration is 8 months longer than the EAI.
There are no pharmacist substitutions (as there is no equivalent device).
As promising and beneficial as it is, I wonder about a few training issues. In the office, patients can be trained with a (reusable) injectable epinephrine trainer but not with a nasal spray device trainer in the office (an important alternative is a small model of a nose in the office for patient education). A training device should also be included in the neffy prescription, as with the EIA.
It’s more complicated than that neffy cannot be used with patients who have had nasal polyps or nasal surgery. It’s really about how much healthy nasal mucosa is required for absorption. Nasal surgery may be simple or complex. Nasal polyps may be obstructive or resolved with nasal steroid or biologic therapy. Nasal polyps affect 2% of the population, but 35% of pediatric food allergy (FA) patients develop allergic rhinitis (AR), and these AR symptoms present even when not triggered by FA. AR is present at baseline in patients with FA. How does this influence neffy absorption? For FA patients who have anaphylactic reactions with severe nasal reactions, neffy absorption could be further compromised, something that has not been studied. 
As we don’t yet know the comparative efficacy of neffy in anaphylactic episodes, it’s likely that patients, especially with more severe food sensitivities, will be prescribed both the nasal and IM devices. The question remains whether insurance will cover both. 
In “mild cases,” I suspect that doctors might be more inclined to prescribe neffy.
Delay in epinephrine use is frequent despite the clear indication during anaphylactic episodes, which in turn increases risk for mortality. Neffy will probably save many lives. 
Dr Gary Stadtmauer serves on the advisory board of Medscape. He is in private practice in New York City and is affiliated with the Mount Sinai School of Medicine.