Is Intranasal Adrenaline Effective for the Treatment of Anaphylaxis?
Date First Published:
July 17, 2026
Last Updated:
July 17, 2026
Report by:
Dr Tom Jaconelli, Honorary Senior Lecturer/Consultant in Emergency Medicine (York Hospital)
Search checked by:
Dr Steven Crane, Consultant in Emergency Medicine
Three-Part Question:
In [patients presenting with anaphylaxis] is [intranasal adrenaline as effective as intramuscular adrenaline] for [achieving rapid control of symptoms and signs]?
Clinical Scenario:
A 23-year-old male presents to the emergency department with symptoms and signs of anaphylaxis after being unable to self-administer adrenaline before
arrival, he is administered intramuscular adrenaline. Once he has clinically improved he asks whether he could be discharged with intranasal adrenaline due
to a reluctance to administer intramuscular adrenaline as he has a needle phobia. You wonder whether intranasal adrenaline is as clinically effective as
intramuscular adrenaline.
arrival, he is administered intramuscular adrenaline. Once he has clinically improved he asks whether he could be discharged with intranasal adrenaline due
to a reluctance to administer intramuscular adrenaline as he has a needle phobia. You wonder whether intranasal adrenaline is as clinically effective as
intramuscular adrenaline.
Search Strategy:
Embase 1974 to March 2026 and MEDLINE 1946 to March 2026 databases were searched using the Ovid Interface and the following search strategy: (Exp
Anaphylaxis/ OR anaphylaxis.mp.) AND ((Exp Administration, Intranasal/ OR intranasal.mp.) AND (Exp Injections, Intramuscular/ OR intramuscular.mp.))
AND (Exp Epinephrine/ OR adrenaline.mp. OR epinephrine.mp.)
Anaphylaxis/ OR anaphylaxis.mp.) AND ((Exp Administration, Intranasal/ OR intranasal.mp.) AND (Exp Injections, Intramuscular/ OR intramuscular.mp.))
AND (Exp Epinephrine/ OR adrenaline.mp. OR epinephrine.mp.)
Outcome:
Of 113 unique papers identified, 8 were directly relevant to the clinical outcome. Seven studies were case series, six of which were published only as
conference abstracts, and one was an open-label phase III study. 22 studies were also identified which assessed the pharmacodynamic and pharmacokinetic
properties, these were not analysed.
conference abstracts, and one was an open-label phase III study. 22 studies were also identified which assessed the pharmacodynamic and pharmacokinetic
properties, these were not analysed.
Relevant Paper(s):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| Epinephrine Nasal Spray Improves Allergic Symptoms in Patients Undergoing Oral Food Challenge, Phase 3 Trial Ebisawa et al 2025 Japan | 15 paediatric patients undergoing oral food challenge- induced anaphylaxis | Change from | • Median symptom resolution time | • Very small sample size (15 patients enrolled) • No blinding, placebo group or active comparator • Isolated to paediatric patients • Almost half of the patients received additional treatments • No direct comparison with standard treatment (IM adrenaline) • Controlled hospital setting • All patients had moderate symptoms so unable to assess response in severe anaphylaxis • Short follow-up duration • Industry-sponsored trial |
|
| baseline in main | was 16 minutes | ||||
| symptoms | • No patients required a second | ||||
| (improvement rate) | dose of IN adrenaline | ||||
| at 15 minutes | • One patient had a biphasic | ||||
| reaction needing IM adrenaline | |||||
| First reported allergen immunotherapy anaphylaxis treated with neffy nasal spray: A case series 2025 USA | 3 adult patients exposed to allergen immunotherapy | No predefined | • All had rapid symptom | For all case series: • Tiny sample size • No control group • Lack of standardisation of diagnostic criteria for anaphylaxis-many cases had mild symptoms • No predefined objective outcome measures • Potential selection bias due to data from clinics or supervised food challenge or immunotherapy treatment-supervised settings-not generalisable to emergency setting/prehospital setting • Potential publication bias due to case series • Observer bias from lack of blinding • No long term outcomes e.g. did any biphasic reactions occur • The study by Rosenblum was supported by a grant from the manufacturer of a intranasal adrenaline spray • The conference abstracts lack full reporting of methodology and peer review is limited |
|
| objective outcome | improvement after IN adrenaline | ||||
| measures | • Symptom relief occurred within | ||||
| minutes | |||||
| • 1 patient required a second dose | |||||
| of IN adrenaline | |||||
| • Observation after treatment was | |||||
| between 45-60 minutes and there | |||||
| was no recurrence | |||||
| A CASE SERIES OF INTRANASAL EPINEPHRINE FOR TREATMENT OF IN OFFICE ANAPHYLAXIS Sweha, L et al 2025 USA | 10 adult and paediatric patients cases of in-office anaphylaxis | No predefined | • 5 patients resolved with intranasal | ||
| objective outcome | adrenaline alone | ||||
| measures | • 2 patients resolved after IM and | ||||
| then intranasal adrenaline | |||||
| • 3 patients required an additional | |||||
| IM adrenaline dose after | |||||
| intranasal use | |||||
| EFFICACY OF INTRANASAL EPINEPHRINE FOR THE TREATMENT OF ANAPHYLAXIS FOLLOWING SUBCUTANEOUS ALLERGY IMMUNOTHERAPY Ogershok P et al 2025 USA | 6 adult and paediatric patients with immunotherapy -induced anaphylaxis | No predefined | • 6 patients improved after | ||
| outcome measures | intranasal adrenaline | ||||
| • Symptoms improved within 2–7 | |||||
| min | |||||
| • No patients needed a second | |||||
| dose of intranasal adrenaline | |||||
| REAL WORLD NEEDLE-FREE EPINEPHRINE EXPERIENCE IN AN ALLERGY CLINIC Todoric 2025 USA | 6 patients received intranasal adrenaline (4 undergoing food challenges and 2 receiving allergen immunotherapy) | 1 patient required a second dose | |||
| of intranasal adrenaline | |||||
| 5 patients resolved within 5 | |||||
| minutes after single intranasal | |||||
| dose | |||||
| Real-world Use of Intranasal Epinephrine During IgE-mediated Reactions Silvers S 2026 USA | 55 adult and paediatric patients who were reported to have anaphylaxis in an allergy clinical setting | No predefined | • 48 patients achieved symptom | ||
| outcome measures | resolution with a single intranasal | ||||
| adrenaline dose | |||||
| • 1 patient required a second | |||||
| intranasal adrenaline dose | |||||
| • 3 patients received IM adrenaline | |||||
| after IN adrenaline | |||||
| INTRANASAL EPINEPHRINE USE IN PEDIATRIC ANAPHYLAXIS DURING FOOD CHALLENGE: A CASE SERIES Rosenblum J et al 2025 USA | 7 paediatric patients who had anaphylaxis during oral food challenge | No predefined | • 2 patients improved after single | ||
| outcome measures | intranasal adrenaline dose | ||||
| • Symptom improvement reported | |||||
| within 5-10 minutes | |||||
| • No patients required a second | |||||
| dose or IM adrenaline | |||||
| CASE REPORT: THE USE OF EPINEPHRINE NASAL SPRAY TO TREAT ANAPHYLAXIS DURING ALLERGEN IMMUNOTHERAPY K. Kwak 2025 USA | 3 adult and paediatric patients of anaphylaxis due to allergen immunotherapy | No predefined | • 3 patients improved after a single | ||
| outcome measures | IN adrenaline dose | ||||
| • Symptom improvement: within 5 | |||||
| 15 min | |||||
| • Symptom resolution in 30–90 | |||||
| minutes | |||||
| • No patients required second dose | |||||
| or IM adrenaline |
Author Commentary:
Intramuscular adrenaline is the established first-line treatment for anaphylaxis9. It has been proposed that there are barriers to using intramuscular adrenaline
via autoinjectors including needle phobia and lack of proper training1. With this in mind studies have looked at the pharmacodynamic and pharmacokinetic
properties comparing the two ways of administering adrenaline and have shown in healthy volunteers that intranasal adrenaline produces plasma adrenaline
concentrations that are higher and more sustained than those achieved with intramuscular autoinjectors with a similar pharmacodynamic effect10. However,
concerns have been raised about analysing the pharmacological effects in healthy individuals, when in anaphylaxis the physiology will differ11. The twenty-two
pharmacokinetic and pharmacodynamic studies identified were excluded because they did not assess clinical outcomes and the clinical relevance of the
pharmacological findings remains uncertain.
The strongest evidence regarding real-world clinical effectiveness comes from an open-label phase III study1 which demonstrated symptomatic improvement
in 14 paediatric patients who had food challenge-induced anaphylaxis, with one patient requiring rescue intramuscular adrenaline. This study was severely
limited by a small sample size, inclusion of moderate reactions, controlled study setting and lack of a comparator group.
The remaining evidence is of small case series, mostly presented as conference abstracts. These demonstrate symptomatic improvement in many cases,
however several patients needed additional treatments including rescue intramuscular adrenaline. However, the findings are substantially limited by the
inherent weaknesses of uncontrolled case series.
Overall risk of bias across the included literature was high owing to uncontrolled study designs, small sample sizes, lack of blinding and potential for
publication bias. There are no direct comparative studies of intranasal adrenaline against intramuscular adrenaline, which remains the established first-line
treatment.
via autoinjectors including needle phobia and lack of proper training1. With this in mind studies have looked at the pharmacodynamic and pharmacokinetic
properties comparing the two ways of administering adrenaline and have shown in healthy volunteers that intranasal adrenaline produces plasma adrenaline
concentrations that are higher and more sustained than those achieved with intramuscular autoinjectors with a similar pharmacodynamic effect10. However,
concerns have been raised about analysing the pharmacological effects in healthy individuals, when in anaphylaxis the physiology will differ11. The twenty-two
pharmacokinetic and pharmacodynamic studies identified were excluded because they did not assess clinical outcomes and the clinical relevance of the
pharmacological findings remains uncertain.
The strongest evidence regarding real-world clinical effectiveness comes from an open-label phase III study1 which demonstrated symptomatic improvement
in 14 paediatric patients who had food challenge-induced anaphylaxis, with one patient requiring rescue intramuscular adrenaline. This study was severely
limited by a small sample size, inclusion of moderate reactions, controlled study setting and lack of a comparator group.
The remaining evidence is of small case series, mostly presented as conference abstracts. These demonstrate symptomatic improvement in many cases,
however several patients needed additional treatments including rescue intramuscular adrenaline. However, the findings are substantially limited by the
inherent weaknesses of uncontrolled case series.
Overall risk of bias across the included literature was high owing to uncontrolled study designs, small sample sizes, lack of blinding and potential for
publication bias. There are no direct comparative studies of intranasal adrenaline against intramuscular adrenaline, which remains the established first-line
treatment.
Bottom Line:
To date, there is insufficient evidence to determine whether intranasal adrenaline is as effective as intramuscular adrenaline in anaphylaxis. Intramuscular
adrenaline remains the recommended first-line treatment and standard of care for anaphylaxis.
adrenaline remains the recommended first-line treatment and standard of care for anaphylaxis.
Level of Evidence:
Level 3: Small numbers of small studies or great heterogeneity or very different population
References:
- Ebisawa et al. Epinephrine Nasal Spray Improves Allergic Symptoms in Patients Undergoing Oral Food Challenge, Phase 3 Trial
- . First reported allergen immunotherapy anaphylaxis treated with neffy nasal spray: A case series
- Sweha, L et al. A CASE SERIES OF INTRANASAL EPINEPHRINE FOR TREATMENT OF IN OFFICE ANAPHYLAXIS
- Ogershok P et al. EFFICACY OF INTRANASAL EPINEPHRINE FOR THE TREATMENT OF ANAPHYLAXIS FOLLOWING SUBCUTANEOUS ALLERGY IMMUNOTHERAPY
- Todoric. REAL WORLD NEEDLE-FREE EPINEPHRINE EXPERIENCE IN AN ALLERGY CLINIC
- Silvers S. Real-world Use of Intranasal Epinephrine During IgE-mediated Reactions
- Rosenblum J et al. INTRANASAL EPINEPHRINE USE IN PEDIATRIC ANAPHYLAXIS DURING FOOD CHALLENGE: A CASE SERIES
- K. Kwak. CASE REPORT: THE USE OF EPINEPHRINE NASAL SPRAY TO TREAT ANAPHYLAXIS DURING ALLERGEN IMMUNOTHERAPY