1 ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 2 1. NAME OF THE MEDICINAL PRODUCT EURneffy 1 mg nasal spray, solution in single-dose container EURneffy 2 mg nasal spray, solution in single-dose container 2. QUALITATIVE AND QUANTITATIVE COMPOSITION 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. Excipients with known effect 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. 3. PHARMACEUTICAL FORM 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. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications EURneffy is indicated in the emergency treatment of allergic reactions (anaphylaxis) due to insect stings or bites, foods, medicinal products and other allergens as well as idiopathic or exercise induced anaphylaxis. Treatment is indicated for adults and children aged 4 years and over with a body weight of 15 kg or more. 4.2 Posology and method of administration Posology 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 a single nasal administration of 1 mg adrenaline. The recommended initial dose in adults and children aged 4 years and over weighing 30 kg or more is a single nasal administration of 2 mg adrenaline. The patient should be advised to immediately seek emergency medical assistance for close monitoring of the anaphylactic episode and in the event further treatment is required. 3 In the absence of clinical improvement after approximately 10 minutes, or if deterioration occurs or symptoms reappear after the initial treatment, a second dose should be administered in the same nostril together with emergency medical help. A maximum of 4 mg (two doses of 2 mg adrenaline) for adults and children aged 4 years and over weighing 30 kg or more may be given unless instructed by a medical professional to give additional doses. A maximum of 2 mg (two doses of 1 mg adrenaline) for children aged 4 years or more weighing 15 kg to less than 30 kg may be given unless instructed by a medical professional to give additional doses. It is recommended that patients should always carry two nasal sprays to treat an allergy emergency. Elderly No pharmacokinetic (PK) data are available after nasal administration of adrenaline in patients aged 65 years or older. No dose adjustment is required. Paediatric population The safety and efficacy of EURneffy in children below 4 years of age and weighing less than 15 kg have not been established. No data are available. Method of administration For nasal use only. This medicinal product is a ready-to-use, nasal spray, solution in single-dose container. It delivers its entire dose upon activation. The nasal spray should not be primed and should not be sprayed in the eyes or mouth. This medicinal product is for single use only and must be discarded and replaced immediately after use as it delivers only one dose. Instructions for administration Patients and caregivers should be counselled to carefully read the instructions for use in the package leaflet 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 have close 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 dosing is 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 assistance immediately. • Patients should preferably lie flat with feet elevated but sit up if they have breathing difficulties. 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. 4.3 Contraindications None. 4.4 Special warnings and precautions for use Instructions for patients at the time of prescribing A physician who prescribes this medicinal product should take appropriate steps to ensure that the patient understands the indication and use of the nasal spray thoroughly. The physician should review the patient information leaflet and operating instructions of the nasal spray with the patient. All patients who are prescribed this medicinal product should be clearly instructed on how and when to 4 use the product (see section 4.2). It is strongly advised to also educate the patient’s immediate associates (e.g. parents, caregivers, teachers) on the correct use of this medicinal product in case support is needed in an emergency. For children under 12 years of age, the caregiver should administer EURneffy or determine that the child 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 anaphylaxis that 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 due to laryngeal spasm, pruritus, rashes, urticaria, or angioedema. Patients with concomitant asthma may be at increased risk of severe anaphylactic reaction. In young children, symptoms of systemic allergic reactions and anaphylaxis resemble symptoms of anaphylaxis in other age groups. The caregiver should be instructed to recognise symptoms of systemic 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 normal behaviour (e.g. tongue thrusting, ear pulling, clinging to caregiver, cessation of playing, crying, spitting up/regurgitation after foods, increased secretions, loose stools, sleepiness/drowsiness after feeds, flushing with fever or crying spells, scratching, irritability) leading to misdiagnosis of anaphylaxis if inappropriately interpreted. Adrenaline is recommended for use at first signs or symptoms of severe allergy reactions leading to anaphylaxis. 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 is characterised by initial resolution followed by recurrence of symptoms some hours later. The patient should 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 may be induced by adrenaline in patients with coronary insufficiency. There is a risk of adverse reactions following adrenaline administration in patients with high intraocular pressure, severe renal impairment, prostatic adenoma leading to residual urine, hypercalcaemia, and hypokalaemia. In patients with Parkinson’s disease, adrenaline may be associated with a transient worsening of Parkinson’s symptoms such as rigidity and tremor. Individuals with hyperthyroidism, cardiovascular disease, hypertension, or diabetes, elderly individuals, and pregnant women may be at greater risk of developing adverse reactions after adrenaline 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 this medicinal product to a patient experiencing a severe allergic reaction or anaphylaxis should be carefully instructed in regard to the circumstances under which this life-saving medicinal product should be used. 5 Excipients with known effect Benzalkonium chloride This medicinal product contains benzalkonium chloride that may cause irritation or swelling inside the nose, especially if used for a long time. Sodium metabisulphite This medicinal product contains metabisulphite that may rarely cause severe hypersensitivity reactions and bronchospasm. 4.5 Interaction with other medicinal products and other forms of interaction Adrenaline and other medicinal products Caution is indicated in patients receiving medicinal products that may sensitise the heart to arrhythmias, 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 mono amine 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), certain antihistamines (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 if given 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 or oral 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. 4.6 Fertility, pregnancy and lactation Pregnancy 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) indicates no malformation or feto/neonatal toxicity of adrenaline. While an endogenous substance and blood levels after administration of EURneffy are within normal physiologic ranges, adrenaline increases blood 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. 6 Breast-feeding There are no data on the effect of adrenaline in breast-feeding women. However, EURneffy can be used 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 and short half-life, exposure is expected to be very low in the breastfed infants. Fertility 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 within normal physiological ranges and as such it is unlikely that there would be any detrimental effects on fertility. 4.7 Effects on ability to drive and use machines EURneffy may have minor influence on the ability to drive and use machines due to adverse reactions that may occur after administration (see section 4.8); however it is not recommended that patients who are experiencing an anaphylactic reaction drive or use machines since they may be impacted by symptoms caused by the anaphylactic reaction. 4.8 Undesirable effects Summary of safety profile The most frequently occurring adverse reactions following EURneffy administration are throat irritation, , headache, nasal discomfort and feeling jittery, all categorised as very common and reported by more than 1 out of per 10 patients. Tabulated list of adverse reactions 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 healthy volunteers, in patients with Type 1 allergies and in patients with allergic rhinitis. The adverse reactions are 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 Adverse reaction Psychiatric disorders Common Anxiety Uncommon Euphoric mood Nervousness Not known Disorientation 1 Memory impairment 1 Panic reaction 1 7 System organ class Frequency Adverse reaction Nervous system disorders Very common Headache Common Tremor Paraesthesia Uncommon Dizziness Head discomfort Presyncope Not known Psychomotor hyperactivity 1 Somnolence 1 Eye disorders Uncommon Lacrimation increased Cardiac disorders Common Palpitations Not known Angina 1 Cardiac arrhythmias 1,2 Stress cardiomyopathy 1 Tachyarrhythmia 1 Tachycardia 1 Ventricular ectopy 1 Vascular disorders Not known Hypertension 1 Vasoconstriction 1 Respiratory, thoracic and mediastinal disorders Very common Nasal discomfort 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 disorders Uncommon Pruritus Not known Paraesthesia 1 General disorders and administration site conditions Very common Feeling jittery Uncommon Chest discomfort Energy increased Fatigue Feeling hot Investigations Common Blood pressure increased Heart rate increased Uncommon Body temperature increased 1 Adverse reactions that have not been observed in clinical studies with EURneffy, but are known to occur with other adrenaline formulations including intravenous, intramuscular, and subcutaneous administrations. 2 Cardiac arrhythmias may follow administration of adrenaline (see section 4.4). 8 Paediatric population In a clinical study of paediatric subjects, 80 subjects between 4 and 17 years of age weighing 15 kg or more were treated with EURneffy. The most common adverse reactions in subjects weighing 15 kg to less than 30 kg treated with EURneffy 1 mg included: nasal congestion (19.0 %), upper respiratory tract congestion (14.3 %), dry throat, nasal dryness, and paraesthesia (each 9.5 %). The most common adverse reactions in subjects weighing 30 kg or more treated with EURneffy 1 mg included: nasal discomfort and nasal mucosal disorder (each 19.2 %), and rhinalgia (7.7 %). The most common adverse reactions in subjects weighing 30 kg or more treated with EURneffy 2 mg included: nasal discomfort, 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 populations treated with EURneffy. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V. 4.9 Overdose Symptoms 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 resulting from a sharp rise in blood pressure. Fatalities may also result from pulmonary oedema because of peripheral vascular constriction together with cardiac stimulation. Management Pressor effects of adrenaline may be counteracted by rapidly acting vasodilators or alpha-adrenergic blocking medicinal products. If an adrenaline overdose induces pulmonary oedema that interferes with respiration, treatment consists of a rapidly acting alpha-adrenergic blocking medicinal product such as phentolamine and/or intermittent positive-pressure respiration. Adrenaline overdose can cause transient bradycardia followed by tachycardia, and these may be accompanied by potentially fatal cardiac arrhythmias. Treatment of arrhythmias may consist of administration of beta-adrenergic blocking medicinal products. 5. PHARMACOLOGICAL PROPERTIES 5.1 Pharmacodynamic properties Pharmacotherapeutic group: Cardiac therapy, adrenergic and dopaminergic agents ATC code: C01CA24 Mechanism of action Adrenaline is a nonselective agonist of all adrenergic receptors, including alpha- and beta-adrenergic receptors. Binding to these receptors triggers a number of actions of sympathetic nerve system. 9 Pharmacodynamic effects Through its action on alpha-adrenergic receptors, adrenaline lessens histamine induced vasodilation. Adrenaline also reduces the vascular permeability induced by histamine that occurs during anaphylaxis. Adrenaline, through its action on beta-adrenergic receptors in bronchial smooth muscle, causes bronchial smooth muscle relaxation. Adrenaline also alleviates pruritus, urticaria, and angioedema and may be effective in relieving gastrointestinal and genitourinary symptoms associated with anaphylaxis. Clinical efficacy Four clinical pharmacology studies of EURneffy in adults and one clinical pharmacology study in paediatric 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. pulse rate (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 or opposite 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. 10 Figure 1: Median pulse rate (PR) and systolic blood pressure (SBP) change from baseline following one dose of adrenaline in healthy subjects [Study EPI 15] Results following two nasal doses of EURneffy (in the same naris or opposite nares) in comparison to two intramuscular doses of adrenaline injection (using an autoinjector) showed a similar trend in median/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) that compared the PK and PD of adrenaline following self-administered one nasal dose of EURneffy 2 mg to staff-administered one intramuscular dose of adrenaline injection 0.3 mg (using a needle-syringe product). In Study EPI 17, SBP and PR responses were assessed as a change from baseline over 60 minutes. The SBP and PR responses results in Study EPI 17 were similar to those demonstrated in Study EPI 15. Time (minutes) EURneffy 2 mg Adrenaline 0.3 mg (Needle-syringe) Adrenaline 0.3 mg (Autoinjector) Median PR Change from baseline (bpm) Median SBP Change from baseline (mmHg) EURneffy 2 mg Adrenaline 0.3 mg (Needle-syringe) Adrenaline 0.3 mg (Autoinjector) Time (minutes) 11 Systolic blood pressure and pulse rate in adult patients with allergic rhinitis (Study EPI 16 and EPI 18) Study EPI 16 and Study EPI 18 were conducted in adult subjects with seasonal allergic rhinitis outside of the allergy season. Subjects were required to have seasonal allergic rhinitis which was confirmed with a nasal allergen challenge (NAC) during screening and did not have any allergy symptoms prior to treatment. Allergic rhinitis symptoms were induced by spraying the known allergen into the subject’s nostrils in which a minimum Total Nasal Symptom Score of ≥ 5 out of 12, with a congestion component 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 the following: • 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 the median responses were lower than the use of EURneffy without NAC after 5 to 15 minutes post-dose. • Median SBP response for EURneffy with NAC was initially higher than the median SBP response for the intramuscular adrenaline injection without NAC through 20 minutes, after which the median SBP response for EURneffy with NAC became comparable to the adrenaline injection without NAC through 60 minutes post-dose. • Median PR response for EURneffy with NAC was initially higher than adrenaline injection without NAC during the first 5 minutes post-dose, but then was numerically lower than the median 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 adrenaline administered 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; in the 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; in the 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: 12 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) or right and right nares (R/R) in subjects with allergic rhinitis with and without nasal allergen challenge (NAC) [Study EPI 18] Paediatric population 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 or 2 mg. Paediatric patients weighing 15 kg to < 30 kg were given either EURneffy 0.65 mg (N=12) or 1 mg (N=21) and those 30 kg or more received either EURneffy 1 mg (N=26) or 2 mg (N=21). The median change in SBP and PR from baseline over the 60 minutes post-dose were significantly over baseline, 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) 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) Median PR change (bpm) 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) 13 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 (see section 4.2 for information on paediatric use). 5.2 Pharmacokinetic properties Absorption 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 adrenaline injection 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 of adrenaline (integrated analysis) Treatment N t max (min) median (range) C max (pg/mL) AUC last (min*pg/mL) Mean (% CV) Geometric mean Mean (% CV) Geometric mean EURneffy 2 mg (HCP administration) 78 20.5 (2 - 150) 485 (70.6) 361 40 900 (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 (paediatrics ≥ 30 kg) 16 25.0 (2.5 - 120) 540 (70.7) 433 35 500 (76.3) 27 800 EURneffy 1 mg (paediatrics 15 - 30 kg) 21 20.0 (2.50- 61.5) 651 (64.2) 520 35 100 (57.3) 29 500 EURneffy 2 mg twice (L/R) 39 30 (6 - 150) 1 000 (93.1) 706 86 000 (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 intramuscular 17 8 45 (3.9 -360) 277 (65.4) 234 27 900 (38.7) 26 100 Adrenaline 0.3 mg intramuscular twice 70 45 (6 - 180) 436 (48.8) 386 47 500 (32.6) 45 300 Adrenaline autoinjector 0.3 mg 77 10 (2 - 45) 581 (75.6) 447 31 600 (39.3) 29 200 Adrenaline autoinjector 0.3 mg twice 78 20 (4 - 360) 754 (64.7) 630 55 000 (47.9) 29 200 AUC: area under the curve; C max : the maximum observed concentration; CV: coefficient of variation; Geo. mean: geometric mean; HCP: healthcare professional; ;L: left; N: number of subjects; R: right, t max : the time it takes to reach the C max.. Adrenaline has a rapid onset of action after administration. Following nasal administration to healthy volunteers, adrenaline was rapidly absorbed after both single and repeated dosing, with a time to maximum plasma concentration in 20 to 30 minutes. In subjects with rhinitis (congestion and nasal oedema), adrenaline is absorbed more rapidly with the maximum concentration observed in about 10 minutes. 14 Biotransformation Adrenaline is rapidly inactivated in the body, mostly in the liver by the enzymes catechol-O- methyltransferase (COMT) and monoamine oxidase (MAO). Elimination Much of a dose of adrenaline is excreted as metabolites in urine. Elimination is mainly via metabolism of the liver and sympathetic nerve endings, with a small amount excreted unchanged in the urine. The plasma half-life following nasal administration is about 2 to 3 minutes. Paediatric population 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 weighing 30 kg or more (N=47) received either EURneffy 1 mg (N=26) or 2 mg (N=21). The PK of adrenaline in both weight classes in the paediatric patients were slightly higher than exposures seen with the same dose of EURneffy in adults, showing comparable absorption from EURneffy in children. In paediatric patients with Type I allergies weighing 30 kg or more (age range: 8 to 17 years), following a single 2 mg nasal dose of EURneffy, the geometric mean plasma adrenaline concentration time profile was similar to that of healthy adults receiving the same dose within 15 minutes post-dose (in a different study) and then became slightly higher than that of healthy adults. A similar pattern was seen for paediatric patients with Type I allergies weighing 15 to 30 kg (age range: 4 to 11 years), following a single 1 mg nasal dose of EURneffy (see Table 2). 5.3 Preclinical safety data 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, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction and development. 6. PHARMACEUTICAL PARTICULARS 6.1 List of excipients Sodium chloride Dodecylmaltoside Disodium edetate Benzalkonium chloride Sodium metabisulphite (E 223) Hydrochloric acid, concentrated (for pH-adjustment) Sodium hydroxide (for pH-adjustment) Water for injections 6.2 Incompatibilities Not applicable. 6.3 Shelf life EURneffy 1 mg 2 years 15 EURneffy 2 mg 30 months 6.4 Special precautions for storage 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 one hour; do not use if the contents are still frozen or not completely thawed. Freezing does not affect the shelf life of the product. 6.5 Nature and contents of container 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. 6.6 Special precautions for disposal and other handling Instructions for use A: To administer, the nasal spray should be removed from the packaging, by pulling open the packaging (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 of the 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 16 (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 episode and in the event further treatment is required. If symptoms continue to worsen or reoccur after approximately 10 minutes, or of any error in administration, use a new EURneffy nasal spray to give a second dose in the same nostril as the first dose and seek urgent emergency medical assistance. If accidentally frozen, the nasal spray will not function. Allow the nasal spray to thaw at least one hour; do not use if the contents are still frozen or not completely thawed. Freezing does not affect the shelf life of the product. Any unused medicinal product or waste material should be disposed of in accordance with local requirements. 17 7. MARKETING AUTHORISATION HOLDER ALK-Abelló A/S Bøge Allé 6-8 2970 Hørsholm Denmark 8. MARKETING AUTHORISATION NUMBER(S) EU/1/24/1846/001 EU/1/24/1846/002 EU/1/24/1846/003 EU/1/24/1846/004 9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION Date of first authorisation: 22 August 2024 10. DATE OF REVISION OF THE TEXT Detailed information on this medicinal product is available on the website of the European Medicines Agency https://www.ema.europa.eu 18 ANNEX II A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT 19 A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE Name and address of the manufacturer responsible for batch release ALK-Abelló A/S Venlighedsvej 10 2970 Hørsholm Denmark B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE Medicinal product subject to medical prescription. C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION • Periodic safety update reports (PSURs) The requirements for submission of PSURs for this medicinal product are set out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any subsequent updates published on the European medicines web-portal. D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT • Risk management plan (RMP) The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing authorisation and any agreed subsequent updates of the RMP. An updated RMP should be submitted: • At the request of the European Medicines Agency; • Whenever the risk management system is modified, especially as the result of new information being received that may lead to a significant change to the benefit/risk profile or as the result of an important (pharmacovigilance or risk minimisation) milestone being reached. • Additional risk minimisation measures Prior to the launch of EURneffy in each Member State the MAH must agree about the content and format of the educational programme, including communication media, distribution modalities, and any other aspects of the programme, with the National Competent Authority. The educational programme is aimed at preventing misuse of the medicinal product in the context of an emergency situation. The MAH shall ensure that in each Member State where EURneffy is marketed, all healthcare professionals and patients/carers who are expected to prescribe, dispense, use EURneffy have access to/are provided with the following educational information: • Physician educational material • Patient/caregivers information pack 20 Physician educational material: • The Summary of Product Characteristics • Training device • Healthcare professionals training material (training videos) o Training device to familiarise with use of EURneffy device o Indications in which EURneffy should be used o Detailed description of the administration procedures of EURneffy o Importance of seeking medical assistance when using EURneffy o Relevant information on the EURneffy single dose device and how to use it o Instructions on correct handling of EURneffy device o Need to always carry a second device in case of second dose would be required o Need to seek emergency medical assistance o Patient’s preparation for the procedure and subsequent monitoring o Management of early signs and symptoms of selected safety concerns, namely severe allergic reaction/anaphylaxis Patient/caregivers information pack: • Patient information leaflet • Training device provided by physician as needed • The patient/caregivers /digital information brochure/videos: o Indication in which EURneffy should be used including anaphylaxis/severe allergic reaction action plan o Information on how to identify a serious allergic reaction o A description of the correct use of EURneffy and the need to seek emergency medical assistance when using EURneffy o Detailed description of the modalities used for the self-administration of EURneffy o A description of the best course of action if second dose is needed o Need to always carry a second device in case of second dose would be required o Monitoring and guidance for actions following use of EURneffy 21 ANNEX III LABELLING AND PACKAGE LEAFLET 22 A. LABELLING 23 PARTICULARS TO APPEAR ON THE CARTON OUTER CARTON – 1 mg 1. NAME OF THE MEDICINAL PRODUCT EURneffy 1 mg nasal spray, solution in single-dose container adrenaline 2. STATEMENT OF ACTIVE SUBSTANCE Each single-dose container delivers 1 mg adrenaline in 100 microlitres. 3. LIST OF EXCIPIENTS Contains sodium metabisulphite and benzalkonium chloride. See leaflet for further information. 4. PHARMACEUTICAL FORM AND CONTENTS nasal spray, solution 2 single-dose nasal sprays 1 single-dose nasal spray 5. METHOD AND ROUTE OF ADMINISTRATION For nasal use only. Single use Read package leaflet before use QR code + eurneffy.eu Scan to Learn More 6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE SIGHT AND REACH OF CHILDREN Keep out of sight and reach of children who are not the intended user. 7. OTHER SPECIAL WARNING(S), IF NECESSARY 24 8. EXPIRY DATE EXP 9. SPECIAL STORAGE CONDITIONS 10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE 11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER ALK-Abelló A/S Bøge Allé 6-8 2970 Hørsholm Denmark 12. MARKETING AUTHORISATION NUMBER(S) EU/1/24/1846/003 EU/1/24/1846/004 13. BATCH NUMBER Lot 14. GENERAL CLASSIFICATION FOR SUPPLY 15. INSTRUCTIONS ON USE Seek emergency medical assistance immediately to have close monitoring of the anaphylactic episode and in the event further treatment is required. 16. INFORMATION IN BRAILLE EURneffy 1 mg 25 17. UNIQUE IDENTIFIER – 2D BARCODE 2D barcode carrying the unique identifier included. 18. UNIQUE IDENTIFIER - HUMAN READABLE DATA PC SN NN 26 MINIMUM PARTICULARS TO APPEAR ON BLISTERS/ STRIPS TRAY - 1 mg 1. NAME OF THE MEDICINAL PRODUCT EURneffy 1 mg nasal spray, solution in single-dose container adrenaline 2. NAME OF THE MARKETING AUTHORISATION HOLDER ALK-Abelló A/S 3. EXPIRY DATE EXP 4. BATCH NUMBER Lot 5. OTHER For nasal use only. Single use. Read the package leaflet before use. QR code + eurneffy.eu Learn More 27 MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS NASAL SPRAY - 1 mg 1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION EURneffy 1 mg nasal spray adrenaline For nasal use only 2. METHOD OF ADMINISTRATION Single use 3. EXPIRY DATE EXP 4. BATCH NUMBER Lot 5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 1 mg 6. OTHER ALK-Abelló A/S 28 PARTICULARS TO APPEAR ON THE CARTON OUTER CARTON – 2 mg 1. NAME OF THE MEDICINAL PRODUCT EURneffy 2 mg nasal spray, solution in single-dose container adrenaline 2. STATEMENT OF ACTIVE SUBSTANCE Each single-dose container delivers 2 mg adrenaline in 100 microlitres. 3. LIST OF EXCIPIENTS Contains sodium metabisulphite and benzalkonium chloride. See leaflet for further information. 4. PHARMACEUTICAL FORM AND CONTENTS nasal spray, solution 2 single-dose nasal sprays 1 single-dose nasal spray 5. METHOD AND ROUTE OF ADMINISTRATION For nasal use only. Single use Read package leaflet before use QR code + eurneffy.eu Scan to Learn More 6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE SIGHT AND REACH OF CHILDREN Keep out of sight and reach of children who are not the intended user. 7. OTHER SPECIAL WARNING(S), IF NECESSARY 29 8. EXPIRY DATE EXP 9. SPECIAL STORAGE CONDITIONS 10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE 11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER ALK-Abelló A/S Bøge Allé 6-8 2970 Hørsholm Denmark 12. MARKETING AUTHORISATION NUMBER(S) EU/1/24/1846/001 EU/1/24/1846/002 13. BATCH NUMBER Lot 14. GENERAL CLASSIFICATION FOR SUPPLY 15. INSTRUCTIONS ON USE Seek emergency medical assistance immediately to have close monitoring of the anaphylactic episode and in the event further treatment is required. 16. INFORMATION IN BRAILLE EURneffy 2 mg 30 17. UNIQUE IDENTIFIER – 2D BARCODE 2D barcode carrying the unique identifier included. 18. UNIQUE IDENTIFIER - HUMAN READABLE DATA PC SN NN 31 MINIMUM PARTICULARS TO APPEAR ON BLISTERS/ STRIPS TRAY - 2 mg 1. NAME OF THE MEDICINAL PRODUCT EURneffy 2 mg nasal spray, solution in single-dose container adrenaline 2. NAME OF THE MARKETING AUTHORISATION HOLDER ALK-Abelló A/S 3. EXPIRY DATE EXP 4. BATCH NUMBER Lot 5. OTHER For nasal use only. Single use. Read the package leaflet before use. QR code + eurneffy.eu Learn More 32 MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS NASAL SPRAY - 2 mg 1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION EURneffy 2 mg nasal spray adrenaline For nasal use only 2. METHOD OF ADMINISTRATION Single use 3. EXPIRY DATE EXP 4. BATCH NUMBER Lot 5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 2 mg 6. OTHER ALK-Abelló A/S 33 Intructions for use to be included within blister pack Instructions for use EURneffy nasal spray, solution in single-dose container adrenaline Before you need to use it, fully familiarise yourself with EURneffy, including when and how it should be used. EURneffy nasal spray Follow these instructions only when ready to use. A Remove EURneffy nasal spray from the packaging. Pull open the packaging to remove the EURneffy nasal spray. B Hold the nasal spray as shown. Hold the nasal spray with your thumb on the bottom of the plunger and one finger on either side of the nozzle. • Do not pull or push on the plunger • Do not test or pre-spray; each nasal spray has only one dose. C Insert the tip of nasal spray into a nostril until your fingers touch your nose. 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. Nozzle/Tip Plunger 34 D Press plunger up firmly until it snaps up and sprays into the nostril. Do not angle the nasal spray to the inner or outer walls of the nose. Seek emergency medical assistance Seek emergency medical assistance immediately to have close monitoring of the anaphylactic episode and in the event further treatment is required. Monitor patient symptoms If symptoms continue to worsen or reoccur after approximately 10 minutes, or if any dosing error, give a second dose using a new EURneffy nasal spray in the SAME nostril as the first dose and seek urgent emergency medical assistance. If necessary, you can lie down with feet raised. If this makes you breathless, you should sit up. Unconscious patients should be placed on their side in the recovery position. If symptoms do not resolve, you should, if possible, remain with another person until medical assistance arrives. 35 B. PACKAGE LEAFLET 36 Package leaflet: Information for the user EURneffy 1 mg nasal spray, solution in single-dose container EURneffy 2 mg nasal spray, solution in single-dose container adrenaline Read all of this leaflet carefully before you start using this medicine because it contains important information for you. - Keep this leaflet. You may need to read it again. - If you have any further questions, ask your doctor, pharmacist or nurse. - This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours. - If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4. What is in this leaflet 1. What EURneffy is and what it is used for 2. What you need to know before you use EURneffy 3. How to use EURneffy 4. Possible side effects 5. How to store EURneffy 6. Contents of the pack and other information 1. What EURneffy is and what it is used for EURneffy contains the active substance adrenaline (epinephrine) which is an adrenergic medicine (medicine that has an effect on the sympathetic nervous system, the part of the nervous system that increases heart rate, blood pressure, breathing rate, and pupil size). EURneffy is used in adult and children aged 4 years and over with a body weight of 15 kg or more for the emergency treatment of allergic reactions, including anaphylaxis (sudden, severe and sometimes life-threatening allergic reactions), to insect stings or bites, foods, medicines and other allergens (substances that cause an allergy) as well as idiopathic anaphylaxis (the cause of anaphylaxis is not known) or anaphylaxis caused by exercise. EURneffy is intended for immediate self-administration by a person (or given to a person by a caregiver or medical professional) with a history or recognised risk of a severe allergic reaction that can lead to anaphylactic shock. The active substance in EURneffy, adrenaline, is a naturally occurring hormone released by the body in response to stress. It works directly on the cardiovascular (heart and blood circulation) and respiratory (lung) systems to stop the possible fatal effects of a severe allergic reaction that can lead to anaphylactic shock. In acute allergic reactions it improves blood pressure, heart function and breathing, and reduces tissue swelling. EURneffy is an emergency rescue therapy but you must seek emergency medical assistance immediately to have close monitoring of the anaphylactic episode and in the event further treatment is required. Always tell your friends and family that you carry EURneffy with you (see section 2 ‘Warnings and precautions’). 2. What you need to know before you use EURneffy Do not use EURneffy There is no known reason why anyone should not use EURneffy during an allergic emergency. 37 Warnings and precautions You, or anyone who may need to give EURneffy to you (such as a parent, caregiver or teacher), should be carefully instructed by your doctor or nurse on how and when to correctly use EURneffy (see the instructions for use in section 3 ‘How to use EURneffy’). Symptoms that signal the onset of an anaphylactic shock occur within minutes of exposure to the allergen and include: itching of the skin; raised rash (like a nettle rash); flushing; swelling of the lips, throat, tongue, hands and feet; wheezing; hoarseness; shortness of breath; nausea; vomiting; stomach cramps and; in some cases, loss of consciousness; apprehension, a fast heartbeat, fitting, diarrhoea (loose stools), loss of bladder control. Young children may not be able to describe their symptoms, such as itching, difficulty breathing or feeling faint. Some signs of anaphylaxis can be difficult to understand because they also occur in young children for other reasons; examples include behavioural changes, such as tongue thrusting, ear pulling, clinging to the caregiver, cessation of playing, crying, spitting up/vomiting after eating, increased drooling or running nose, loose stools, sleepiness/drowsiness after eating, flushing with fever or crying, scratching and irritability. Use EURneffy at the first signs or symptoms of a severe allergic reaction. Symptoms of anaphylaxis can reoccur within 72 hours of the initial episode, even without new exposure to the allergen that triggered the allergic reaction. You must make sure you understand the reason EURneffy has been prescribed for you. You should be confident that you know exactly how and when to use EURneffy. Explain how to use EURneffy to your family, carers, co-workers or teachers. They will need to know how to use it before you suffer an anaphylactic reaction. If you are at risk of a severe allergic reaction, you should always keep EURneffy with you. Patients with a history or a recognised risk of a severe allergic reaction that can lead to anaphylactic shock should have quick access to EURneffy. If you have asthma, you may be at increased risk of a severe allergic reaction. Anyone who has an episode of anaphylaxis should see their doctor about testing for substances they may be allergic to, so these can be strictly avoided in future. It is important to be aware that an allergy to one substance can lead to allergies to a number of related substances. Populations with an increased risk of side effects from the use of adrenaline You may have a greater risk of developing side effects with EURneffy if you: - have cardiovascular disease (disease affecting the heart and blood circulation) - have increased pressure in your eyes - have reduced renal (kidney) function - have prostatic adenoma (a benign (not cancer) condition in which an overgrowth of prostate tissue pushes against the urethra and the bladder, blocking the flow of urine) - have hypercalcaemia (high blood calcium levels) - have hypokalaemia (low blood potassium levels) - have Parkinson’s disease - have hyperthyroidism (an overactive thryoid gland) - have hypertension (high blood pressure) - have diabetes - are elderly - are pregnant (see section 2 ‘Pregnancy, breast-feeding and fertility’). Talk to your doctor if any of the above conditions apply to you, or if you are not sure. 38 Children Do not give this medicine to children below 4 years of age weighing less than 15 kg. The safety and efficacy of this medicinal product are unknown in children below 4 years of age weighing less than 15 kg. Other medicines and EURneffy Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This is especially important if you take any of the following as they may reduce the effect of adrenaline: • Alpha and beta-blocking medicines, e.g. propranolol. • Medicines that counteract the pressor effects of adrenaline (vasodilators or alpha- adrenergic-blocker, e.g. phentolamine). You must also tell your doctor or pharmacist if you take any of the following as they may increase the risk of side effects of adrenaline: • Medicines that may make the heart sensitive to arrhythmias (abnormal or irregular heartbeat), such as digoxin, mercurial diuretics (medicines that increase urine production which act mainly on the transport of sodium) (e.g. chlormerodrin, merbaphen, mersalyl acid, meralluride, mercaptomerin, mercurophylline, merethoxylline procaine) or quinidine. • Antidepressants such as tricyclic antidepressants, e.g. imipramine, or monoamine oxidase inhibitors (MAO inhibitors) (e.g. isocarboxazid, phenelzine, selegiline, tranylcypromine). • Medicines for the treatment of Parkinson’s disease such as catechol-O-methyl transferase inhibitors (COMT inhibitors) (e.g. entacapone, tolcapone, carbidopa-levodopa-entacapone, opicapone) and levodopa. • Medicines for thyroid disease such as levothyroxine. • Medicines that make you breathe more easily; used for asthma (theophylline). • Medicines used in labour (oxytocin). • Medicines used to treat allergies such as diphenhydramine or chlorpheniramine (antihistamines). • Medicines that act on the nervous system (parasympatholytics) (e.g. atropine, cyclopentolate, homatropine, hyoscine, tropicaminde). Patients with diabetes should carefully monitor their glucose levels after they use EURneffy, as adrenaline can reduce the amount of insulin made by the body, thus increasing the blood glucose level. Pregnancy, breast-feeding and fertility If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. There is limited experience of the use of adrenaline during pregnancy. If you are pregnant, do not hesitate to use EURneffy in an emergency, since you and your baby’s lives may be in danger. Discuss this with your doctor if you are pregnant. It is expected that the amount of EURneffy that is passed through breast-feeding is very low. For the emergency treatment of anaphylaxis, EURneffy should be used in breast-feeding women in the same manner as for non-breast-feeding patients. EURneffy with alcohol Alcohol can increase the effects of adrenaline. Driving and using machines The ability to drive and use machines may be affected by symptoms that may occur following administration of this medicine. Do not drive if you are having an anaphylactic reaction. 39 EURneffy contains sodium metabisulphite and benzalkonium chloride This medicine contains sodium metabisulphite, which may cause severe allergic reactions (hypersensitivity) or breathing difficulty (bronchospasm). This medicine contains 0.04 mg benzalkonium chloride in each dose. Benzalkonium chloride may cause irritation or swelling inside the nose, especially if used repeatedly. 3. How to use EURneffy Always use EURneffy exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure. When to carry EURneffy You should always carry EURneffy with you or have it close at all times in the event of an allergic emergency. Always carry at least two EURneffy nasal sprays in the event a second dose is needed due to a mistake in taking the medicine or insufficient response after the first dose. Always tell your friends and family that you carry EURneffy with you. Dose The recommended dose for patients with a body weight of 30 kg or more, is a single-dose of EURneffy nasal spray delivering 2 mg of adrenaline. The maximum dose of adrenaline for the emergency treatment of allergic reactions is 4 mg, taken as two separate single-dose nasal sprays. Use in children The recommended dose for children aged 4 years and over with a body weight of 15 kg to less than 30 kg is a single nasal administration of 1 mg adrenaline. The maximum dose that may be given is 2 mg taken as two separate single-dose nasal sprays. The recommended dose for patients aged 4 years and over with a body weight of 30 kg or more is a single nasal administration of 2 mg adrenaline. The maximum dose that may be given is 4 mg taken as two separate single-dose nasal sprays. Method of administration EURneffy must be given nasally (in the nose) only. EURneffy is a ready-to-use single-dose nasal spray that delivers its entire content upon activation. EURneffy can be used even if you have a cold or a congested nose. Do not press the plunger before inserting the EURneffy nasal spray into a nostril, otherwise the single dose will be lost prior to use. EURneffy should only be given as a nasal spray into a nostril; do not spray EURneffy into the eyes or mouth. The instructions for use must be carefully followed in order to use EURneffy correctly. If you notice the signs of an acute allergic reaction (see section 2 Warnings and precautions), use EURneffy immediately. Seek emergency medical assistance immediately to have close monitoring of the anaphylactic episode and in the event further treatment is required. Ideal dosing is to use the dominant hand to hold the sprayer and administer to the same side nostril (e.g. for self-administration, right hand to right nostril; or left hand to left nostril; and for caregiver administration, right hand to left nostril and left hand to right nostril). Sometimes a single dose of EURneffy may not be sufficient to completely reverse the effects of a serious allergic reaction. If your symptoms have not improved or have deteriorated within 40 approximately 10 minutes after using the first nasal spray of EURneffy, either you or the person with you should give a second nasal spray of EURneffy in the same nostril as the first dose. The instructions for use given below must be followed. Instructions for use Before you need to use it, fully familiarise yourself with EURneffy, including when and how it should be used. EURneffy nasal spray Follow these instructions only when ready to use. A Remove EURneffy nasal spray from the packaging. Pull open the packaging to remove the EURneffy nasal spray. B Hold the nasal spray as shown. Hold the nasal spray with your thumb on the bottom of the plunger and one finger on either side of the nozzle. • Do not pull or push on the plunger • Do not test or pre-spray; each nasal spray has only one dose. Nozzle/Tip Plunger 41 C Insert the tip of nasal spray into a nostril until your fingers touch your nose. 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. D Press the plunger up firmly until it snaps up and sprays into the nostril. Do not angle the nasal spray to the inner or outer walls of the nose. Seek immediate medical attention after use Seek emergency medical assistance immediately to have close monitoring of the anaphylactic episode and in the event further treatment is required. Monitor patient symptoms If symptoms continue to worsen or reoccur after approximately 10 minutes, or in any error of dosing, use a new EURneffy nasal spray, to give a second dose in the SAME nostril as the first dose and seek urgent emergency medical assistance. If necessary, you can lie down with feet raised. If this makes you breathless, you should sit up. Unconscious patients should be placed on their side in the recovery position to prevent choking. If symptoms do not resolve, you should, if possible, remain with another person until medical assistance arrives. If you use more EURneffy than you should In case of an overdose of the adrenaline, you should always seek immediate medical help. Overdose may cause a sudden increase in blood pressure (with symptoms including headache or dizziness), bleeding in brain tissue, palpitations (forceful heartbeats that may be rapid or irregular), reduced blood flow and accumulation of fluid in the lungs (causing symptoms including difficulty breathing). You will need to be monitored. If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 42 4. Possible side effects Like all medicines, this medicine can cause side effects, although not everybody gets them. Tell your doctor or pharmacist if any of the following side effects occur or worsen. The following side effects are associated with the use of EURneffy nasal spray: Very common (may affect more than 1 in 10 people) - Nasal discomfort - Headache - Feeling jittery - Throat irritation Common (may affect up to 1 in 10 people) - Increased blood pressure - Palpitations (forceful heartbeats that may be rapid or irregular) - Rhinorrhoea (runny nose) - Anxiety - Nasal oedema (itching and burning pain of the nose. Nose feels swollen, hot and red) - Rhinalgia (nose pain) - Heart rate increased - Nasal congestion - Nasal pruritus (irritation or inflammation of the nose) - Paraesthesia (sensations like numbness, tingling, pins and needles) Uncommon (may affect up to 1 in 100 people) - Dizziness - Lacrimation increased (watery eyes) - Tremor (shaking) - Oropharyngeal pain (pain in the tongue, soft palate, the side and back walls of the throat and tonsils). - Nausea (feeling sick) - Intranasal paraesthesia (sensations like numbness, tingling, pins and needles in the nose) - Sneezing - Paranasal sinus discomfort (nasal obstruction and congestion, nasal discharge that is thick, opaque, and coloured, and facial pain or pressure) - Paraesthesia oral (sensations like numbness, tingling, pins and needles in the mouth or back of - the throat) - Salivary hypersecretion (drooling) - Toothache - Head discomfort - Nasal dryness - Nasal mucosal disorder (inflammation of the tissue that lines the nasal cavity) - Gingival discomfort (gum and mouth irritation) - Energy increased - Fatigue (feeling tired) - Feeling hot - Body temperature increased - Presyncope (feeling faint) - Euphoric mood - Nervousness - Pruritus (itching skin) - Epistaxis (nosebleed) - Chest discomfort - Dry throat - Upper respiratory tract congestion (stuffiness in the upper airways including nose and throat) 43 Reporting of side effects If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine. 5. How to store EURneffy Keep this medicine out of sight and reach of children who are not the intended user. Do not use this medicine after the expiry date which is stated on the nasal spray label after EXP. The expiry date refers to the last day of that month. This medicine does not require any special storage conditions. If accidentally frozen, the nasal spray will not function. Allow the nasal spray to thaw for at least one hour; do not use if the contents are still frozen or not completely thawed. Freezing does not affect the shelf life of the product. Do not throw away any medicines via wastewater. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment. 6. Contents of the pack and other information What EURneffy contains - The active substance is adrenaline (epinephrine). EURneffy 1 mg nasal spray: Each dose of nasal spray solution delivers 1 mg adrenaline in 100 μL. EURneffy 2 mg nasal spray: Each dose of nasal spray solution delivers 2 mg adrenaline in 100 μL. - The other ingredients are sodium chloride, dodecylmaltoside, disodium edetate, benzalkonium chloride, sodium metabisulphite (E 223), hydrochloric acid, concentrated (for pH-adjustment), sodium hydroxide (for pH-adjustment), water for injections (see section 2. ‘EURneffy contains sodium metabisulphite and benzalkonium chloride’). What EURneffy looks like and contents of the pack The EURneffy nasal spray, solution in single dose container is a non-pressurised dispenser delivering a single-dose spray containing the active substance in a clear and colourless to pink brownish solution. EURneffy is available in packs containing 1 or 2 single dose nasal sprays. Not all pack sizes may be marketed. Marketing Authorisation Holder ALK-Abelló A/S Bøge Allé 6-8 2970 Hørsholm Denmark Manufacturer ALK-Abelló A/S Venlighedsvej 10 2970 Hørsholm Denmark 44 For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder: België/Belgique/Belgien ALK-Abelló B.V. Tél/Tel: +32 (0)28990835 Lietuva ALK-Abelló A/S Tel: + 45 45747576 България ALK-Abelló A/S Teл.: + 45 45747576 Luxembourg/Luxemburg ALK-Abelló A/S Tél/Tel: + 45 45747576 Česká republika ALK Slovakia s.r.o. – odštěpný závod Tel: +420 233 312 907 Magyarország ALK-Abelló A/S Tel: + 45 45747576 Danmark ALK-Abelló Nordic A/S Tlf.: +45 38 16 70 70 Malta ALK-Abelló A/S Tel: + 45 45747576 Deutschland ALK-Abelló Arzneimittel GmbH Tel: +49 40 703845-0 Nederland ALK-Abelló B.V. Tel: +31 (0)365397840 Eesti ALK-Abelló A/S Tel: + 45 45747576 Norge ALK-Abelló Nordic Tlf: +47 99 44 60 40 Ελλάδα ALK-Abelló A/S Τηλ: + 45 45747576 Österreich ALK-Abelló Allergie-Service GmbH Tel: +43 732 38 53 72-0 España ALK-Abelló, S.A. Tel: +34 913276100 Polska ALK-Abelló A/S Tel.: + 45 45747576 France ALK Tél: (+33) 03 29 80 71 62 Portugal ALK-Abelló A/S Tel: + 45 45747576 Hrvatska ALK-Abelló A/S Tel: + 45 45747576 Ireland ALK-Abelló A/S Tel: + 45 45747576 România ALK-Abelló A/S Tel: + 45 45747576 Slovenija ALK-Abelló A/S Tel: + 45 45747576 Ísland ALK-Abelló A/S Sími: +45 45747576 Slovenská republika ALK Slovakia s.r.o. Tel: +421 2 546 503 71 Italia ALK-Abelló A/S Tel: + 45 45747576 Suomi/Finland ALK-Abelló Nordic A/S, sivuliike Suomessa/filial i Finland Puh/Tel: +358 (0)9 5842 2120 45 Κύπρος ALK-Abelló A/S Τηλ: + 45 45747576 Sverige ALK Nordic A/S, Danmark Filial Tel: +46 (0)300 - 185 45 Latvija ALK-Abelló A/S Tel: + 45 45747576 This leaflet was last revised in Detailed information on this medicine is available on the European Medicines Agency web site: https://www.ema.europa.eu.