Adrenaline (epinephrine) nasal spray for severe allergic reactions

Background:
Adrenaline (epinephrine) is the first-line treatment for anaphylaxis. Intramuscular administration using an autoinjector has been widely recommended. A nasal spray formulation of adrenaline has been developed and is the first needle-free form of adrenaline approved for the emergency treatment of type I allergic reactions, including anaphylaxis.

Mechanism of action:
Adrenaline acts on alpha- and beta-adrenergic receptors, with effects on the sympathetic nervous system. These include bronchial smooth muscle relaxation and reduced histamine-induced vasodilation, which helps to reduce bronchospasm, wheezing, dyspnoea and hypotension.¹

Clinical trials:
The approval of intranasal adrenaline was based on extensive pharmacokinetic and pharmacodynamic studies in adult and paediatric patients, which demonstrated comparable profiles between intranasal spray and intramuscular injections of adrenaline,² although real-world evidence comparing the different preparations is currently limited.

A phase 3, open-label trial was conducted in Japanese patients aged 6 to 17 years with food allergy (n=15).³ Allergens included egg, milk, peanut, wheat and walnut. Patients underwent an oral food challenge and were enrolled if they demonstrated grade 2 anaphylaxis symptoms. Intranasal adrenaline was administered after the onset of gastrointestinal, respiratory or cardiovascular symptoms. Patients weighing 15 to less than 30 kg received a single dose of 1 mg adrenaline intranasally, and those weighing 30 kg or more received 2 mg of adrenaline intranasally. If symptoms persisted or worsened, and if additional treatments were deemed necessary, patients received standard treatments, such as antihistamines, beta₂ agonists and intravenous fluids. If a second dose of adrenaline was required, an intramuscular injection was used.

The primary endpoint was the change from baseline in main symptoms at 15 minutes, assessed using symptom grading.³ Secondary endpoints included the proportion of patients who did not require additional treatments, symptom severity, and time to resolution.

Symptoms improved within 5 minutes of intranasal adrenaline administration for all patients except one who experienced continuous tachycardia which could be attributed to the administration of adrenaline.³ No patient required a second adrenaline dose within 15 minutes of the initial intranasal dose. The median time to symptom resolution was 16 minutes. One patient experienced a recurrence of allergic symptoms (headache, dyspnoea, numbness of extremities) after 2 hours and 45 minutes, and consequently received intramuscular adrenaline. Seven patients required additional supportive treatments.

Retrospective data from an uncontrolled case series of 680 patients have been published by the sponsor.⁴ Data were collected via a survey of healthcare providers who had administered intranasal adrenaline in their clinics. Of these patients, 603 (88.7%) were effectively treated with a single dose of intranasal adrenaline for anaphylaxis symptoms during an oral food challenge or allergen immunotherapy; 77 patients (11.3%) required a second dose of adrenaline.⁴

Adverse effects:
It is uncommon to experience adverse effects following a single dose of intranasal adrenaline. Adverse effects have been reported after the administration of two 2 mg doses of adrenaline nasal spray, including throat irritation (18.8%), headache (17.6%), nasal discomfort (12.9%) and jitteriness (10.6%).¹

Dosage and administration:
Adrenaline nasal spray is available in 1 mg and 2 mg strengths. Each spray contains only one dose and should not be primed or tested before it is ready to be used. The recommended dosage depends on the person's body weight:¹

• Patients weighing 15 to less than 30 kg: one spray of adrenaline 1 mg into one nostril
• Patients weighing 30 kg or greater: one spray of adrenaline 2 mg into one nostril.

The nasal spray should be inserted into the nostril with the nozzle pointed straight toward the forehead. Patients should not sniff during or immediately after dosing. If any liquid drips out of the nose, a second dose may be needed.

If symptoms do not improve 5 minutes after the initial dose, a second dose should be administered using a new nasal spray, ideally in the same nostril.

Precautions:
There are no contraindications to administering adrenaline in an acute, life-threatening situation. It is not known whether structural and anatomical nasal conditions (e.g. polyps, history of nasal surgery) affect the absorption of intranasal adrenaline.¹

Use in pregnancy and breastfeeding:
Adrenaline is safe to use in pregnancy (Therapeutic Goods Administration pregnancy category A) and can be used in breastfeeding.

Place in therapy:
Adrenaline nasal spray is a needle-free option for the emergency treatment of severe allergic reactions, including anaphylaxis. For people with needle phobia or injection hesitancy, adrenaline nasal spray may encourage prompt administration at the first signs of a severe allergic reaction. Some patients may find a nasal spray more compact and easier to use than autoinjectors (pens), but clinical experience with intranasal adrenaline is currently limited.⁵

Prescribers should consider age, weight, reaction severity and caregiver availability when choosing between intranasal and intramuscular adrenaline. The safety and effectiveness of intranasal adrenaline have not been established in people weighing less than 15 kg or in children under 4 years of age. In these people, smaller dose adrenaline autoinjectors should be used.⁶

Intranasal adrenaline has not been compared with intramuscular adrenaline in patients with previous severe anaphylaxis with hypotension (more common in those with insect venom allergy), or patients who have previously required more than one dose of adrenaline to treat anaphylaxis. Given the lack of evidence, access to an adrenaline autoinjector is recommended for these people.⁵

Practice points:
Patients, and ideally their close associates (e.g. family members, caregivers, teachers), should be clearly instructed on how and when to administer adrenaline, including how to recognise the signs of anaphylaxis. For children under 12 years old, caregivers should administer or supervise administration. Urgent medical care should always be sought immediately after administering adrenaline to allow clinical monitoring and in case further treatment is required.

Adrenaline nasal spray is a single-use product and should be discarded and replaced immediately after use. It is recommended that patients always carry 2 nasal sprays in case of a severe allergic reaction.

This new drug comment was finalised on 17 February 2026. It was prepared by Sherilyn Wong, Clinical Editor, Australian Prescriber, and reviewed by Louis Nguyen, Paediatric Transplant and Cellular Therapies Pharmacist, Sydney Children's Hospital.

At the time this new drug comment was prepared, the Australian Public Assessment Report was not available from the Therapeutic Goods Administration. The sponsor did not provide the Clinical Evaluation Report.

This article is peer reviewed.

 

References

1. Therapeutic Goods Administration. Australian Product Information - NEFFY adrenaline (epinephrine) nasal spray vial Department of Health, Disability and Ageing; 2025. [cited 2026 Jan 19]
2. Ellis AK, Casale TB, Kaliner M, Oppenheimer J, Spergel JM, Fleischer DM, et al. Development of neffy, an Epinephrine Nasal Spray, for Severe Allergic Reactions. Pharmaceutics 2024;16.
3. Ebisawa M, Takahashi K, Takahashi K, Yanagida N, Sato S, Lieberman J, et al. Epinephrine Nasal Spray Improves Allergic Symptoms in Patients Undergoing Oral Food Challenge, Phase 3 Trial. J Allergy Clin Immunol Pract 2025;13:2787-94.
4. Casale TB, Spergel JM, Bernstein DI, Tanimoto S. Real-world data on the effectiveness of neffy in clinical practice-update. Ann Allergy Asthma Immunol 2025;135(5):S2.
5. British Society for Allergy & Clinical Immunology. BSACI EURneffy Statement. 2025. [cited 2026 Jan 20]
6. Australasian Society of Clinical Immunology and Allergy. How to give adrenaline (epinephrine) devices. 2026. [cited 2026 Jan 20]

 

The new drug comments in Australian Prescriber are prepared by the editors and reviewed by subject matter experts. Some of the views expressed on newly approved products should be regarded as preliminary, as there may be limited published data at the time of publication, and little experience in Australia of their safety or efficacy. Before new drugs are prescribed, it is important that more detailed information is obtained from the approved product information, a medicines information centre or some other appropriate source.

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