Leaflet EURNEFFY 2mg nasal spray, single-dose solution

EURneffy 1 mg nasal spray, solution in single-dose container

EURneffy 2 mg nasal spray, solution in single-dose container

EURneffy 1 mg nasal spray, solution in single-dose container

Each single-dose container delivers adrenaline (epinephrine) 1 mg in 100 microlitres.

EURneffy 2 mg nasal spray, solution in single-dose container

Each single-dose container delivers adrenaline (epinephrine) 2 mg in 100 microlitres.

Benzalkonium chloride 40 micrograms per single-dose container.

Sodium metabisulfite 5 micrograms per single-dose container.

For the full list of excipients, see section 6.1.

Nasal spray, solution

The solution is clear and colourless to pink brownish.

A solution with a pH of 3.0-5.5 and an osmolality of 325-560 mOsm/kg.

EURneffy is indicated in the emergency treatment of allergic reactions (anaphylaxis) due to insectstings or bites, foods, medicinal products and other allergens as well as idiopathic or exercise inducedanaphylaxis. Treatment is indicated for adults and children aged 4 years and over with a body weightof 15 kg or more.

This medicinal product should be administered at the first sign of a severe Type I allergic reaction.

The recommended initial dose in children aged 4 years and over weighing 15 kg to less than 30 kg is asingle nasal administration of 1 mg adrenaline.

The recommended initial dose in adults and children aged 4 years and over weighing 30 kg or more isa single nasal administration of 2 mg adrenaline.

The patient should be advised to immediately seek emergency medical assistance for close monitoringof the anaphylactic episode and in the event further treatment is required.

In the absence of clinical improvement after approximately 10 minutes, or if deterioration occurs orsymptoms reappear after the initial treatment, a second dose should be administered in the same nostriltogether with emergency medical help.

A maximum of 4 mg (two doses of 2 mg adrenaline) for adults and children aged 4 years and overweighing 30 kg or more may be given unless instructed by a medical professional to give additionaldoses.

A maximum of 2 mg (two doses of 1 mg adrenaline) for children aged 4 years or more weighing 15 kgto less than 30 kg may be given unless instructed by a medical professional to give additional doses. Itis recommended that patients should always carry two nasal sprays to treat an allergy emergency.

No pharmacokinetic (PK) data are available after nasal administration of adrenaline in patients aged65 years or older. No dose adjustment is required.

The safety and efficacy of EURneffy in children below 4 years of age and weighing less than 15 kghave not been established. No data are available.

For nasal use only.

This medicinal product is a ready-to-use, nasal spray, solution in single-dose container. It delivers itsentire dose upon activation. The nasal spray should not be primed and should not be sprayed in theeyes or mouth.

This medicinal product is for single use only and must be discarded and replaced immediately afteruse as it delivers only one dose.

Instructions for administration

Patients and caregivers should be counselled to carefully read the instructions for use in the packageleaflet for complete directions on how to properly administer this medicinal product (see section 4.4).

The patient/caregiver should be informed to seek emergency medical assistance immediately to haveclose monitoring of the anaphylactic episode and in the event further treatment is required.

* If symptoms get worse or reoccur after approximately 10 minutes, or if any error in dosingis suspected, a new nasal spray should be used to give a second dose in the same nostril.

* If a second dose is needed but not available, seek emergency medical assistanceimmediately.

* Patients should preferably lie flat with feet elevated but sit up if they have breathingdifficulties. Unconscious patients should be placed on their side in a recovery position.

For full instructions on the use of the medicinal product, see section 6.6.

None.

Instructions for patients at the time of prescribing

A physician who prescribes this medicinal product should take appropriate steps to ensure that thepatient understands the indication and use of the nasal spray thoroughly. The physician should reviewthe patient information leaflet and operating instructions of the nasal spray with the patient. Allpatients who are prescribed this medicinal product should be clearly instructed on how and when touse the product (see section 4.2). It is strongly advised to also educate the patient’s immediateassociates (e.g. parents, caregivers, teachers) on the correct use of this medicinal product in casesupport is needed in an emergency.

For children under 12 years of age, the caregiver should administer EURneffy or determine that thechild is properly instructed in the use of EURneffy and is fully capable of administration themselves.

Patients with a cold or a congested nose can use this medicinal product, even in these conditions,however the pharmacokinetic profile may be different (see section 5.2).

Warnings for patients about anaphylaxis

Patients should be instructed to recognise symptoms of systemic allergic reactions and anaphylaxisthat may occur within minutes after exposure and which may consist of flushing, apprehension,syncope, tachycardia, thready or unobtainable pulse associated with a fall in blood pressure,convulsions, vomiting, diarrhoea and abdominal cramps, involuntary voiding, wheezing, dyspnoea dueto laryngeal spasm, pruritus, rashes, urticaria, or angioedema. Patients with concomitant asthma maybe at increased risk of severe anaphylactic reaction.

In young children, symptoms of systemic allergic reactions and anaphylaxis resemble symptoms ofanaphylaxis in other age groups. The caregiver should be instructed to recognise symptoms ofsystemic allergic reactions and anaphylaxis that often consist of skin and/or gastrointestinal symptoms.

Recognition of symptoms can be challenging in young children as symptoms can mimic normalbehaviour (e.g. tongue thrusting, ear pulling, clinging to caregiver, cessation of playing, crying,spitting up/regurgitation after foods, increased secretions, loose stools, sleepiness/drowsiness afterfeeds, flushing with fever or crying spells, scratching, irritability) leading to misdiagnosis ofanaphylaxis if inappropriately interpreted.

Adrenaline is recommended for use at first signs or symptoms of severe allergy reactions leading toanaphylaxis. Patients should be instructed to always carry adrenaline in situations of potential risks.

The patient/caregiver should be informed about the possibility of biphasic anaphylaxis which ischaracterised by initial resolution followed by recurrence of symptoms some hours later. The patientshould be advised to always seek medical assistance immediately after any severe allergic reaction.

Populations at increased risks with the use of adrenaline

Extreme caution should be taken when administering adrenaline to patients who have a heart disease.

Use of adrenaline with medicinal products that may sensitise the heart to arrhythmias, e.g. digoxin,mercurial diuretics, or quinidine, ordinarily is not recommended (see section 4.5). Anginal pain maybe induced by adrenaline in patients with coronary insufficiency.

There is a risk of adverse reactions following adrenaline administration in patients with highintraocular pressure, severe renal impairment, prostatic adenoma leading to residual urine,hypercalcaemia, and hypokalaemia. In patients with Parkinson’s disease, adrenaline may be associatedwith a transient worsening of Parkinson’s symptoms such as rigidity and tremor.

Individuals with hyperthyroidism, cardiovascular disease, hypertension, or diabetes, elderlyindividuals, and pregnant women may be at greater risk of developing adverse reactions afteradrenaline administration (see sections 4.6 and 4.8).

Patients with these conditions, and/or any other persons who might be in a position to administer thismedicinal product to a patient experiencing a severe allergic reaction or anaphylaxis should becarefully instructed in regard to the circumstances under which this life-saving medicinal productshould be used.

This medicinal product contains benzalkonium chloride that may cause irritation or swelling inside thenose, especially if used for a long time.

Sodium metabisulphite

This medicinal product contains metabisulphite that may rarely cause severe hypersensitivity reactionsand bronchospasm.

Adrenaline and other medicinal products

Caution is indicated in patients receiving medicinal products that may sensitise the heart toarrhythmias, including digoxin, mercurial diuretics (e.g. chlormerodrin, merbaphen, mersalyl acid,meralluride, mercaptomerin, mercurophylline, merethoxylline procaine) or quinidine.

The effects of adrenaline may be potentiated by tricyclic antidepressants (e.g. imipramine) and monoamine oxidase inhibitors (MAO-inhibitors) (e.g. isocarboxazid, phenelzine, selegiline,tranylcypromine) and catechol-O-methyl transferase inhibitors (COMT-inhibitors) (e.g. entacapone,tolcapone, carbidopa-levodopa-entacapone, opicapone), thyroid hormones, theophylline, oxytocin,parasympatholytics (e.g. atropine, cyclopentolate, homatropine, hyoscine, tropicaminde), certainantihistamines (diphenhydramine, chlorpheniramine), levodopa, and alcohol.

Pressor effects of adrenaline

Pressor effects of adrenaline may be counteracted by rapidly acting vasodilators or alpha-adrenergic-blocking medicinal products such as phentolamine.

Adrenaline and insulin

Adrenaline inhibits the secretion of insulin, thus increasing the blood glucose level. It is unlikely ifgiven in an acute emergency that adrenaline would have any persistent effect on blood glucose levels,but for diabetic patients receiving adrenaline it may be necessary to increase their dose of insulin ororal hypoglycaemic medicinal products.

Adrenaline and beta-blocking medicinal products

The beta-stimulating effect of adrenaline may be inhibited by simultaneous treatment with beta-blocking medicinal products, e.g. propranolol.

There are no data on the effect of EURneffy in pregnant women.

A moderate amount of data on pregnant women (between 300-1 000 pregnancy outcomes) indicatesno malformation or feto/neonatal toxicity of adrenaline. While an endogenous substance and bloodlevels after administration of EURneffy are within normal physiologic ranges, adrenaline increasesblood pressure and heart rate which can impact the foetus.

Animal studies do not indicate reproductive toxicity (see section 5.3).

The use of this medicinal product may be considered during pregnancy, if necessary.

There are no data on the effect of adrenaline in breast-feeding women. However, EURneffy can beused in breast-feeding women.

It is unknown whether adrenaline/metabolites are excreted in human milk.

A risk to the newborns/infants cannot be excluded. However, due to its poor oral bioavailability andshort half-life, exposure is expected to be very low in the breastfed infants.

There are no data on the effect of EURneffy on human fertility.

Adrenaline is an endogenous substance and blood levels after administration of EURneffy are withinnormal physiological ranges and as such it is unlikely that there would be any detrimental effects onfertility.

EURneffy may have minor influence on the ability to drive and use machines due to adverse reactionsthat may occur after administration (see section 4.8); however it is not recommended that patients whoare experiencing an anaphylactic reaction drive or use machines since they may be impacted bysymptoms caused by the anaphylactic reaction.

The most frequently occurring adverse reactions following EURneffy administration are throatirritation, , headache, nasal discomfort and feeling jittery, all categorised as very common andreported by more than 1 out of per 10 patients.

Adverse reactions are summarised based on analysis of pooled safety data from primary PK/pharmacodynamic (PD) studies using EURneffy 1 mg and 2 mg in paediatric and adult healthyvolunteers, in patients with Type 1 allergies and in patients with allergic rhinitis. The adverse reactionsare ranked according to system organ class and frequency according to the following convention:

* Very common (≥ 1/10)

* Common (≥ 1/100 to < 1/10)

* Uncommon (≥ 1/1 000 to < 1/100)

* Rare (≥ 1/10 000 to < 1/1 000)

* Very rare (< 1/10 000)

* Not known (frequency cannot be estimated from the available data)

Table 1: Adverse reactions identified with EURneffy

System organ class Frequency Adversereaction

Psychiatric disorders Common Anxiety

Uncommon Euphoric mood

Nervousness

Not known Disorientation1

Memory impairment1

Panic reaction1

System organ class Frequency Adversereaction

Nervous system disorders Very common Headache

Common Tremor

Paraesthesia

Uncommon Dizziness

Head discomfort

Presyncope

Not known Psychomotor hyperactivity1

Somnolence1

Eye disorders Uncommon Lacrimation increased

Cardiac disorders Common Palpitations

Not known Angina1

Cardiac arrhythmias1,2

Stress cardiomyopathy1

Tachyarrhythmia1

Tachycardia1Ventricular ectopy1

Vascular disorders Not known Hypertension1

Vasoconstriction1

Respiratory, thoracic and Very common Nasal discomfortmediastinal disorders Throat irritation

Common Rhinorrhoea

Nasal oedema

Rhinalgia

Nasal congestion

Nasal pruritus

Uncommon Oropharyngeal pain

Sneezing

Intranasal paraesthesia

Paranasal sinus discomfort

Epistaxis

Nasal dryness

Dry throat

Upper respiratory tract congestion

Nasal mucosal disorder

Gastrointestinal disorders Uncommon Nausea

Paraesthesia oral

Salivary hypersecretion

Toothache

Gingival discomfort

Skin and subcutaneous tissue Uncommon Pruritusdisorders Not known Paraesthesia1

General disorders and Very common Feeling jitteryadministration site conditions Uncommon Chest discomfort

Energy increased

Feeling hot

Investigations Common Blood pressure increased

Heart rate increased

Uncommon Body temperature increased1 Adverse reactions that have not been observed in clinical studies with EURneffy, but are known tooccur with other adrenaline formulations including intravenous, intramuscular, and subcutaneousadministrations.

2 Cardiac arrhythmias may follow administration of adrenaline (see section 4.4).

In a clinical study of paediatric subjects, 80 subjects between 4 and 17 years of age weighing 15 kg ormore were treated with EURneffy. The most common adverse reactions in subjects weighing 15 kg toless than 30 kg treated with EURneffy 1 mg included: nasal congestion (19.0 %), upper respiratorytract congestion (14.3 %), dry throat, nasal dryness, and paraesthesia (each 9.5 %). The most commonadverse reactions in subjects weighing 30 kg or more treated with EURneffy 1 mg included: nasaldiscomfort and nasal mucosal disorder (each 19.2 %), and rhinalgia (7.7 %). The most commonadverse reactions in subjects weighing 30 kg or more treated with EURneffy 2 mg included: nasaldiscomfort, rhinorrhea and intranasal paraesthesia (19.0 %); sneezing (14.3 %); epistaxis, fatigue,feeling jittery, paraesthesia, and rhinalgia (9.5 %).

There were no clinically relevant differences in the safety between the paediatric and adult populationstreated with EURneffy.

Reporting suspected adverse reactions after authorisation of the medicinal product is important. Itallows continued monitoring of the benefit/risk balance of the medicinal product. Healthcareprofessionals are asked to report any suspected adverse reactions via the national reporting systemlisted in Appendix V.

Overdose of adrenaline may cause severe headaches, chest pain, dizziness, nausea, and blurred vision.

Significant overdoses or injection into a blood vessel can also cause cerebral haemorrhage resultingfrom a sharp rise in blood pressure. Fatalities may also result from pulmonary oedema because ofperipheral vascular constriction together with cardiac stimulation.

Pressor effects of adrenaline may be counteracted by rapidly acting vasodilators or alpha-adrenergicblocking medicinal products.

If an adrenaline overdose induces pulmonary oedema that interferes with respiration, treatmentconsists of a rapidly acting alpha-adrenergic blocking medicinal product such as phentolamine and/orintermittent positive-pressure respiration.

Adrenaline overdose can cause transient bradycardia followed by tachycardia, and these may beaccompanied by potentially fatal cardiac arrhythmias. Treatment of arrhythmias may consist ofadministration of beta-adrenergic blocking medicinal products.

Pharmacotherapeutic group: Cardiac therapy, adrenergic and dopaminergic agents

ATC code: C01CA24

Adrenaline is a nonselective agonist of all adrenergic receptors, including alpha- and beta-adrenergicreceptors. Binding to these receptors triggers a number of actions of sympathetic nerve system.

Through its action on alpha-adrenergic receptors, adrenaline lessens histamine induced vasodilation.

Adrenaline also reduces the vascular permeability induced by histamine that occurs duringanaphylaxis.

Adrenaline, through its action on beta-adrenergic receptors in bronchial smooth muscle, causesbronchial smooth muscle relaxation.

Adrenaline also alleviates pruritus, urticaria, and angioedema and may be effective in relievinggastrointestinal and genitourinary symptoms associated with anaphylaxis.

Four clinical pharmacology studies of EURneffy in adults and one clinical pharmacology study inpaediatric subjects who weigh 30 kg or more are described below.

Systolic blood pressure and pulse rate in healthy adult subjects (Study EPI 15)

Study EPI 15 was conducted in healthy adult subjects (N=42) that compared the PK and PD (i.e. pulserate (PR) and systolic blood pressure (SBP)) of adrenaline following:

* One nasal dose of EURneffy 2 mg to one intramuscular dose of adrenaline injection 0.3 mg(using a needle-syringe product and an auto-injector product).

* Two nasal doses of EURneffy 2 mg, administered 10 minutes apart, into either same naris oropposite nares to two intramuscular doses of adrenaline injection 0.3 mg (using an auto-injector) administered 10 minutes apart.

Results following one dose of all adrenaline products demonstrated an increase from baseline SBP and

PR as shown in Figure 1.

Figure 1: Median pulse rate (PR) and systolic blood pressure (SBP) change from baselinefollowing one dose of adrenaline in healthy subjects [Study EPI 15]

EURneffy 2 mg

Adrenaline 0.3 mg (Needle-syringe)

Adrenaline 0.3 mg (Autoinjector)

Time (minutes)

EURneffy 2 mg

Adrenaline 0.3 mg (Needle-syringe)

Adrenaline 0.3 mg (Autoinjector)

Time (minutes)

Results following two nasal doses of EURneffy (in the same naris or opposite nares) in comparison totwo intramuscular doses of adrenaline injection (using an autoinjector) showed a similar trend inmedian/mean SBP and PR responses.

Systolic blood pressure and pulse rate in adult patients with Type I allergy without anaphylaxis (Study

EPI 17)

Study EPI 17 was conducted in adult patients with Type I allergy without anaphylaxis (N=42) thatcompared the PK and PD of adrenaline following self-administered one nasal dose of EURneffy 2 mgto staff-administered one intramuscular dose of adrenaline injection 0.3 mg (using a needle-syringeproduct). In Study EPI 17, SBP and PR responses were assessed as a change from baseline over60 minutes. The SBP and PR responses results in Study EPI 17 were similar to those demonstrated in

Study EPI 15.

Median SBP Change from baseline Median PR Change from baseline (bpm)(mmHg)

Systolic blood pressure and pulse rate in adult patients with allergic rhinitis (Study EPI 16 and EPI18)

Study EPI 16 and Study EPI 18 were conducted in adult subjects with seasonal allergic rhinitis outsideof the allergy season. Subjects were required to have seasonal allergic rhinitis which was confirmedwith a nasal allergen challenge (NAC) during screening and did not have any allergy symptoms priorto treatment. Allergic rhinitis symptoms were induced by spraying the known allergen into thesubject’s nostrils in which a minimum Total Nasal Symptom Score of ≥ 5 out of 12, with a congestioncomponent of ≥ 2 out of 3 had to be reached.

Study EPI 16 enrolled 36 subjects. In this cross-over study, subjects received adrenaline as each of thefollowing:

* One nasal dose of EURneffy 2 mg without NAC.

* One nasal dose of EURneffy 2 mg after undergoing NAC to induce rhinitis/nasal congestion.

* One intramuscular dose of adrenaline injection 0.3 mg (using a needle syringe product)without NAC.

* One intramuscular dose of adrenaline injection 0.5 mg (using a needle syringe product)without NAC.

In Study EPI 16, SBP and PR responses were assessed as a change from baseline over 60 minutes.

Results showed the following:

* Median SBP and PR for EURneffy with NAC initially increased from baseline, but themedian responses were lower than the use of EURneffy without NAC after 5 to 15 minutespost-dose.

* Median SBP response for EURneffy with NAC was initially higher than the median SBPresponse for the intramuscular adrenaline injection without NAC through 20 minutes, afterwhich the median SBP response for EURneffy with NAC became comparable to theadrenaline injection without NAC through 60 minutes post-dose.

* Median PR response for EURneffy with NAC was initially higher than adrenaline injectionwithout NAC during the first 5 minutes post-dose, but then was numerically lower than themedian PR response for adrenaline injection without NAC through 60 minutes post-dose.

Study EPI 18 enrolled 43 subjects. In this cross-over study, subjects received two doses of adrenalineadministered 10 minutes apart as each of the following:

* Two nasal doses of EURneffy 2 mg (in the opposite nares (right(R)/left (L)) without NAC.

* Two intramuscular doses of adrenaline injections 0.3 mg (using a needle-syringe product; inthe opposite thigh (R/L)) without NAC.

* Two nasal doses of EURneffy 2 mg (either in the same naris (R/R) or opposite nares (R/L))after NAC to induce allergic rhinitis/nasal congestion.

* Two intramuscular doses of adrenaline injections 0.3 mg (using a needle-syringe product; inthe opposite thigh (R/L)) after NAC to induce allergic rhinitis/nasal congestion.

In Study EPI 18, SBP and PR responses were assessed as a change from baseline over 60 minutes.

Results showed the following:

Figure 2: Median change from baseline for systolic blood pressure (SBP) and pulse rate (PR)following two doses of adrenaline administered 10 minutes apart in right and left nares (R/L) orright and right nares (R/R) in subjects with allergic rhinitis with and without nasal allergenchallenge (NAC) [Study EPI 18]

EURneffy 2 mg twice R/L (without NAC)

EURneffy 2 mg twice R/R (with NAC)

Adrenaline IM 0.3 mg twice R/L (with NAC)

Time (minutes)

EURneffy 2 mg twice R/L (without NAC)

EURneffy 2 mg twice R/R (with NAC)

Adrenaline IM 0.3 mg twice R/L (with NAC)

Time (minutes)

Systolic blood pressure and pulse rate in paediatric patients with Type I allergy without anaphylaxis(Study EPI 10)

Study EPI 10 was a single-arm study conducted in paediatric patients who weighed either 15 kg to< 30 kg or 30 kg or more (age range: 4 to 17 years) with Type I allergy without anaphylaxis (N=80)that assessed the PK and PD of adrenaline following one nasal dose of EURneffy 0.65 mg, 1 mg or2 mg. Paediatric patients weighing 15 kg to < 30 kg were given either EURneffy 0.65 mg (N=12) or1 mg (N=21) and those 30 kg or more received either EURneffy 1 mg (N=26) or 2 mg (N=21). Themedian change in SBP and PR from baseline over the 60 minutes post-dose were significantly overbaseline, but numerically lower than in healthy adults who received the same dose of EURneffy in

Study EPI 15. See section 5.2 for information on PK results in the paediatric population.

Median SBP change (mmHg) Median PR change (bpm)

The European Medicines Agency has deferred the obligation to submit the results of studies with

EURneffy in one or more subsets of the paediatric population in the treatment of allergic reactions (seesection 4.2 for information on paediatric use).

Following one nasal dose of EURneffy 2 mg, the geometric mean plasma adrenaline concentration-time profile was overall within the range of that following one intramuscular dose of adrenalineinjection 0.3 mg (using a needle-syringe product and an auto-injector product) 60 minutes post-dose.

The integrated PK parameters of adrenaline are summarised in Table 2.

Table 2: Mean (CV%) and geometric mean plasma PK parameters following one or two doses ofadrenaline (integrated analysis)tmax (min) Cmax (pg/mL) AUClast (min*pg/mL)

Treatment N median(range) Mean Geometric Mean G eometric(% CV) mean (% CV) mean

EURneffy 2 mg78 20.5 (2 - 150) 485 (70.6) 361 40 900(HCP administration) (67.5) 32 600

EURneffy 2 mg(self-administration) 32 30 (10 - 240) 448 (67.1) 342 50 365(55.5) 41 077

EURneffy 2 mg 25.0 (2.5 - 35 500(paediatrics ≥ 30 kg) 16 120) 540 (70.7) 433 (76.3) 27 800

EURneffy 1 mg 20.0 (2.50- 35 100(paediatrics 15 - 30 kg) 21 61.5) 651 (64.2) 520 (57.3) 29 500

EURneffy 2 mg twice 86 000(L/R) 39 30 (6 - 150) 1 000 (93.1) 706 (77) 66 700

EURneffy 2 mg twice(R/R) 39 30 (4 - 150) 992 (75.3) 729 86 500(60.5) 69 900

Adrenaline 0.3 mg 17intramuscular 8 45 (3.9 -360) 277 (65.4) 234 27 900(38.7) 26 100

Adrenaline 0.3 mg 70 45 (6 - 180) 436 (48.8) 386 47 500intramuscular twice (32.6) 45 300

Adrenaline autoinjector 77 10 (2 - 45) 581 (75.6) 447 31 6000.3 mg (39.3) 29 200

Adrenaline autoinjector0.3 mg twice 78 20 (4 - 360) 754 (64.7) 630 55 000(47.9) 29 200

AUC: area under the curve; Cmax: the maximum observed concentration; CV: coefficient of variation;

Geo. mean: geometric mean; HCP: healthcare professional; ;L: left; N: number of subjects; R: right,tmax: the time it takes to reach the Cmax..

Adrenaline has a rapid onset of action after administration. Following nasal administration to healthyvolunteers, adrenaline was rapidly absorbed after both single and repeated dosing, with a time tomaximum plasma concentration in 20 to 30 minutes. In subjects with rhinitis (congestion and nasaloedema), adrenaline is absorbed more rapidly with the maximum concentration observed in about10 minutes.

Adrenaline is rapidly inactivated in the body, mostly in the liver by the enzymes catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO).

Much of a dose of adrenaline is excreted as metabolites in urine. Elimination is mainly via metabolismof the liver and sympathetic nerve endings, with a small amount excreted unchanged in the urine. Theplasma half-life following nasal administration is about 2 to 3 minutes.

Paediatric patients with Type I allergies without anaphylaxis (Study EPI 10)

Paediatric patients weighing 15 kg to < 30 kg (N=21) were given EURneffy 1 mg and those weighing30 kg or more (N=47) received either EURneffy 1 mg (N=26) or 2 mg (N=21). The PK of adrenalinein both weight classes in the paediatric patients were slightly higher than exposures seen with the samedose of EURneffy in adults, showing comparable absorption from EURneffy in children. In paediatricpatients with Type I allergies weighing 30 kg or more (age range: 8 to 17 years), following a single2 mg nasal dose of EURneffy, the geometric mean plasma adrenaline concentration time profile wassimilar to that of healthy adults receiving the same dose within 15 minutes post-dose (in a differentstudy) and then became slightly higher than that of healthy adults. A similar pattern was seen forpaediatric patients with Type I allergies weighing 15 to 30 kg (age range: 4 to 11 years), following asingle 1 mg nasal dose of EURneffy (see Table 2).

Nonclinical data carried out on EURneffy formulation and on adrenaline based on scientific literature,reveal no special hazard for humans based on conventional studies of safety pharmacology, repeateddose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction and development.

Sodium chloride

Dodecylmaltoside

Disodium edetate

Sodium metabisulphite (E 223)

Hydrochloric acid, concentrated (for pH-adjustment)

Sodium hydroxide (for pH-adjustment)

Water for injections

Not applicable.

EURneffy 1 mg2 years

EURneffy 2 mg30 months

This medicinal product does not require any special storage conditions.

If accidentally frozen, the nasal spray will not function. Allow the nasal spray to thaw at least onehour; do not use if the contents are still frozen or not completely thawed. Freezing does not affect theshelf life of the product.

Type I glass vials closed with a grey bromobutyl rubber stopper and then assembled into a Unit Dose

Sprayer device. The device is a non-pressurised dispenser delivering a single-dose nasal spray.

Pack size: Pack of 2 single-dose nasal sprays

Pack of 1 single-dose nasal spray

Not all pack sizes may be marketed.

A: To administer, the nasal spray should be removed from the packaging, by pulling open thepackaging (see Figure 1A).

(Figure 1A)

B: Hold the nasal spray with your thumb on the bottom of the plunger and a finger on either side ofthe nozzle (see Figure 1B).

* Do not pull or push on the plunger.

* Do not test or pre-spray; each nasal spray has only one dose.

(Figure 1B)

C: Insert the tip of nasal spray into a nostril until your fingers touch your nose (see Figure 1C).

* Keep the nozzle straight into the nose pointed toward your forehead.

* Do not angle the nasal spray to the inner or outer walls of the nose(Figure 1C)

D: Press the plunger up firmly until it snaps up and sprays into the nostril (see Figure 1D).

(Figure 1D)

Do not angle the nasal spray to the inner or outer walls of the nose.

Seek emergency medical assistance immediately to have close monitoring of the anaphylactic episodeand in the event further treatment is required.

If symptoms continue to worsen or reoccur after approximately 10 minutes, or of any error inadministration, use a new EURneffy nasal spray to give a second dose in the same nostril as the firstdose and seek urgent emergency medical assistance.

If accidentally frozen, the nasal spray will not function. Allow the nasal spray to thaw at least onehour; do not use if the contents are still frozen or not completely thawed. Freezing does not affect theshelf life of the product.

Any unused medicinal product or waste material should be disposed of in accordance with localrequirements.

ALK-Abelló A/S

Bøge Allé 6-82970 Hørsholm

Denmark

EU/1/24/1846/001

EU/1/24/1846/002

EU/1/24/1846/003

EU/1/24/1846/004

Date of first authorisation: 22 August 2024

Detailed information on this medicinal product is available on the website of the European Medicines

Agency https://www.ema.europa.eu