FLUENZ suspension nose spray medication leaflet

Fluenz nasal spray suspension

Influenza vaccine (live, nasal)

Reassortant influenza virus* (live attenuated) of the following three strains**:

A/Victoria/4897/2022 (H1N1)pdm09-like strain(A/Norway/31694/2022, MEDI 369815) 107.0±0.5 FFU***

A/Thailand/8/2022 (H3N2)-like strain(A/Thailand/8/2022, MEDI 370626) 107.0±0.5 FFU***

B/Austria/1359417/2021-like strain(B/Austria/1359417/2021, MEDI 355292) 107.0±0.5 FFU***.................................................................................................................per 0.2 ml dose

* Propagated in fertilised hens’ eggs from healthy chicken flocks.

** Produced in VERO cells by reverse genetic technology. This product contains geneticallymodified organisms (GMOs).

*** Fluorescent Focus Units.

This vaccine complies with the WHO recommendation (Northern Hemisphere) and EU decision forthe 2024/2025 season.

The vaccine may contain traces of the following substances: egg proteins (e.g. ovalbumin) andgentamicin. The maximum amount of ovalbumin is less than 0.024 micrograms per 0.2 ml dose(0.12 micrograms per ml), see section 4.3.

For the full list of excipients, see section 6.1.

Nasal spray suspension

Colourless to pale yellow, clear to opalescent suspension with a pH of approximately 7.2. Small whiteparticles may be present.

Fluenz is indicated for active immunisation for the prevention of influenza disease in children andadolescents from 2 years to less than 18 years of age.

Fluenz should be used in accordance with official recommendations.

Children and adolescents from 2 years to <18 years of age

The recommended dose is 0.2 ml, administered as 0.1 ml in each nostril.

For children 2 to 8 years of age who have not previously been vaccinated against seasonal influenza, asecond dose should be given after an interval of at least 4 weeks.

Infants and toddlers <2 years of age

Fluenz should not be used in infants and toddlers below 2 years of age because of safety concernsregarding increased rates of hospitalisation and wheezing in this population (see section 4.8).

For nasal use only.

Fluenz should under no circumstances be injected.

Fluenz is administered as a divided dose in both nostrils. After administering half of the dose in onenostril, administer the other half of the dose in the other nostril immediately or shortly thereafter. Thepatient can breathe normally while the vaccine is being administered - there is no need to activelyinhale or sniff.

For detailed instructions on preparation and administration, see section 6.6.

* Hypersensitivity to the active substances or, to any of the excipients listed in section 6.1 or togentamicin (a possible trace residue).

* Severe allergic reaction (e.g. anaphylaxis) to eggs or to egg proteins (e.g. ovalbumin).

* Children and adolescents with clinical immunodeficiency due to conditions orimmunosuppressive therapy such as acute and chronic leukaemias, lymphoma, symptomatic

HIV infection, cellular immune deficiencies, and high-dose corticosteroids. Fluenz is notcontraindicated for use in individuals with asymptomatic HIV infection, or individuals who arereceiving topical/inhaled corticosteroids or low-dose systemic corticosteroids, or those receivingcorticosteroids as replacement therapy, e.g. for adrenal insufficiency.

* Children and adolescents younger than 18 years of age receiving salicylate therapy because ofthe association of Reye’s syndrome with salicylates and wild-type influenza infection (seesection 4.5).

In order to improve the traceability of biological medicinal products, the name and the batch numberof the administered product should be clearly recorded.

As with most vaccines, appropriate medical treatment and supervision should always be readilyavailable to manage an anaphylactic event or serious hypersensitivity event following theadministration of Fluenz.

Concurrent illness and chronic conditions.

Fluenz should not be administered to children and adolescents with severe asthma or who are currentlywheezing, because these individuals have not been adequately studied in clinical studies (see section4.8).

Administration of Fluenz should be postponed in individuals suffering from severe acute febrile illnessor acute infection. The presence of a minor infection and/or low-grade fever should not result in thedeferral of vaccination.

Vaccination should also be postponed in individuals with nasal blockage, due to the potential forreduced vaccine uptake and the absence of efficacy data in this population. The presence of mildsymptoms of a common cold without nasal blockage should not result in the deferral of vaccination.

Vaccine recipients should be informed that Fluenz is an attenuated live virus vaccine and has thepotential for transmission to immunocompromised contacts. Vaccine recipients should attempt toavoid, whenever possible, close association with severely immunocompromised individuals (e.g. bonemarrow transplant recipients requiring isolation) for 1-2 weeks following vaccination. Peak incidenceof vaccine virus recovery occurred 2-3 days post-vaccination in clinical studies. In circumstanceswhere contact with severely immunocompromised individuals is unavoidable, the potential risk oftransmission of the influenza vaccine virus should be weighed against the risk of acquiring andtransmitting wild-type influenza virus. The effectiveness of Fluenz preventing influenza disease inimmunocompromised individuals has not been evaluated (see section 4.8).

Fluenz should under no circumstances be injected.

No data exist regarding the safety of intranasal administration of Fluenz in children with unrepairedcraniofacial malformations.

Fluenz must not be administered to children and adolescents receiving salicylate therapy (seesection 4.3). Salicylates should not be used in children and adolescents for 4 weeks after vaccinationunless medically indicated, as Reye’s syndrome has been reported following the use of salicylatesduring wild-type influenza infection.

Fluenz can be administered concomitantly with the live attenuated vaccines: measles, mumps, rubella,varicella, and orally-administered poliovirus.

The co-administration of Fluenz with inactivated vaccines has not been studied.

The concurrent use of Fluenz with antiviral agents that are active against influenza A and/or B viruseshas not been evaluated. However, based upon the potential for influenza antiviral agents to reduce theeffectiveness of Fluenz, it is recommended not to administer the vaccine until 48 hours after thecessation of influenza antiviral therapy. Administration of influenza antiviral agents within two weeksof vaccination may affect the response of the vaccine.

If influenza antiviral agents and Fluenz are administered concomitantly, revaccination should beconsidered based on clinical judgement.

There is a moderate amount of data from the use of Fluenz in pregnant women. There was no evidenceof significant maternal adverse outcomes in 138 pregnant women who had a record of receiving

Fluenz in a US-based health insurance claims database.

In more than 300 case reports in the AstraZeneca safety database of vaccine administration to pregnantwomen, no unusual patterns of pregnancy complications or foetal outcomes were observed.

While animal studies do not indicate direct or indirect harmful effects with respect to reproductivetoxicity, and post-marketing data offer some reassurance in the event of inadvertent administration ofthe vaccine, Fluenz is not recommended during pregnancy.

Limited available evidence suggests that Fluenz is not excreted in breastmilk. However, because thereare limited data to assess the effects on the breast-fed infant and as some viruses are excreted in humanmilk, Fluenz should not be used during breast-feeding.

No data exist regarding the possible effects of Fluenz on male and female fertility.

Fluenz has no or negligible influence on the ability to drive and use machines.

Safety data regarding use of Fluenz are based on data from Fluenz clinical studies in over29 000 children and adolescents 2 to 17 years of age, Fluenz post-authorisation safety studies in over84 000 children and adolescents 2 to 17 years of age, and data from influenza vaccine (live attenuated,nasal) tetravalent clinical studies in over 2 000 children and adolescents 2 to 17 years of age.

Additional experience has occurred with marketed use of Fluenz and/or influenza vaccine (liveattenuated, nasal) tetravalent.

In clinical studies, the safety profile of Fluenz and influenza vaccine (live attenuated, nasal) tetravalentwere similar.

The most common adverse reaction observed in clinical studies was nasal congestion/rhinorrhoea.

Adverse reaction frequencies are organised by MedDRA System Organ Class (SOC). Within each

SOC, adverse reactions are arranged by decreasing frequency and then by decreasing seriousness.

Frequencies of occurance of adverse reactions are defined as: 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) and not known (cannot be estimated from available data).

Table 1 Adverse reactions

MedDRA SOC Adverse reaction Frequency

Immune system disorders Hypersensitivity reactions Uncommon(including facial oedema,urticaria)

Anaphylactic reactions Very rare

Metabolism and nutrition Decreased appetite Very commondisorders

Nervous system disorders Headache Common

Guillain-Barré syndrome Not knowna

Respiratory, thoracic and Nasal congestion/rhinorrhoea Very commonmediastinal disorders Epistaxis Uncommon

Skin and subcutaneous tissue Rash Uncommondisorders

Musculoskeletal and Myalgia Commonconnective tissue disorders

General disorders and Malaise Very commonadministration site conditions Pyrexia Common

Congenital, familial, and Exacerbation of symptoms of Not knownagenetic disorders Leigh syndrome (mitochondrialencephalomyopathy)a Post-marketing experience

In an active-controlled clinical study (MI-CP111), an increased rate of hospitalisations (for any cause)through 180 days after final vaccination dose was observed in infants and toddlers 6-11 months of age(6.1% Fluenz versus 2.6% injectable influenza vaccine). Most hospitalisations were due togastrointestinal and respiratory tract infections and occurred more than 6 weeks post vaccination. Therate of hospitalisations was not increased in Fluenz recipients 12 months and older. In the same study,an increased rate of wheezing through 42 days was observed in infants and toddlers 6-23 months ofage (5.9% Fluenz versus 3.8% injectable influenza vaccine). The rate of wheezing was not increasedin Fluenz recipients 2 years and older. Fluenz is not indicated for use in infants and toddlers youngerthan 2 years (see section 4.2).

Concurrent illness and chronic conditions

In a study (D153-P515) of children 6 to 17 years of age with asthma (Fluenz: n=1 114, trivalentinjectable influenza vaccine: n=1 115), there were no significant differences between treatment groupsin the incidence of asthma exacerbations, mean peak expiratory flow rate, asthma symptom scores, ornight-time awakening scores. The incidence of wheezing within 15 days after vaccination was lowerin Fluenz recipients relative to inactivated vaccine recipients (19.5% vs. 23.8%, P=0.02).

In a study of children and adolescents 9 to 17 years of age with moderate to severe asthma(Fluenz: n=24, placebo: n=24), the primary safety criterion, change in percent predicted forcedexpiratory volume in 1 second (FEV1) measured before and after vaccination, did not differ betweentreatment arms.

Although safety in children and adolescents with mild to moderate asthma has been established, datain children with other pulmonary diseases or with chronic cardiovascular, metabolic or renal diseases,or other underlying chronic medical conditions are limited. In a study of adults 60 years of age andolder (n=3 242), a high percentage of individuals had underlying chronic medical conditions (87%),including cardiac disorders (15%), respiratory, thoracic and mediastinal disorders (13%), and diabetesmellitus (9.6%). The safety profile of Fluenz in these individuals was comparable to the safety profileobserved in individuals without these conditions.

In HIV-infected children (n=24) and HIV-negative children (n=25) 1 through 7 years of age, and in

HIV-infected children and adolescents 5 through 17 years of age receiving stable anti-retroviraltherapy (Fluenz: n=122, trivalent injectable vaccine: n=121), the frequency and duration of vaccinevirus shedding were comparable to that seen in healthy individuals. No adverse effects on HIV viralload or CD4 counts were identified following Fluenz administration.

Twenty mild to moderately immunocompromised children and adolescents 5 through 17 years of age(receiving chemotherapy and/or radiation therapy or who had recently received chemotherapy) wererandomised 1:1 to Fluenz or placebo. Frequency and duration of vaccine virus shedding in theseimmunocompromised children and adolescents were comparable to that seen in healthy children andadolescents.

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 with Fluenz is unlikely due to its presentation as a single pre-filled nasal applicator.

Administration of a higher than recommended dose of Fluenz was reported rarely and the adversereaction profile was comparable to that observed with the recommended dose of Fluenz.

Pharmacotherapeutic group: Vaccines, influenza vaccines, ATC code: J07BB03

Fluenz is a trivalent vaccine that contains three cold-adapted (ca); temperature-sensitive (ts); andattenuated (att) influenza virus strains, an A/(H1N1) strain, an A/(H3N2) strain, and a B strain fromthe Victoria lineage. After intranasal administration, Fluenz replicates in the nasopharynx and inducesimmune responses against the three influenza strains contained in the vaccine.

Fluenz’s efficacy data in the paediatric population consist of 9 controlled studies comprising over20 000 infants and toddlers, children and adolescents, conducted during 7 influenza seasons. Fourplacebo-controlled studies included second season revaccination. Fluenz has demonstrated superiorityin 3 active-controlled studies with injectable influenza vaccine. See Table 2 and 3 for a summary ofefficacy results in the paediatric population.

Table 2 Fluenz efficacy after 2 doses against culture-confirmed influenza illness in placebocontrolled paediatric studies

Number of (95% CI)

Study Age Influenza (95% CI)a Region study all strainsnumber rangeb season matchedparticipants regardlessstrainsof match85.4% 85.9%

D153-P502 Europe 6 to 35 M 1 616 2000-2001(74.3, 92.2) (76.3, 92.0)

Africa,73.5% 72.0%

D153-P504 Latin 6 to 35 M 1 886 2001(63.6, 81.0)c (61.9, 79.8)c

America

Asia/ 62.2% 48.6%

D153-P513 6 to 35 M 1 041 2002

Oceania (43.6, 75.2) (28.8, 63.3)

Europe,

Asia/78.4% 63.8%

D153-P522 Oceania, 11 to 23 M 1 150 2002-2003(50.9, 91.3) (36.2, 79.8)

Latin

America

Asia/ 72.9% 70.1%

D153-P501 12 to 35 M 2 764 2000-2001

Oceania (62.8, 80.5) (60.9, 77.3)

AV006 USA 15 to 71 M 1 259c 93.4%1996-1997 N/A(87.5, 96.5)a Per protocol population, except where noted otherwise; none of the participants were previouslyvaccinated against influenzab Age range as described in the study protocol. M=months.c Data presented are for study participants who received two doses (ITT population).

In clinical studies AV006 and D153-P504, the efficacy of a single dose of Fluenz was evaluated inpreviously unvaccinated children aged 15-71 months (n=288) and aged 6-35 months (n=1 877). Theefficacy against culture-confirmed influenza caused by any matched strain was 88.8% (95% CI:

64.5, 96.5) and 57.7% (95% CI: 44.7, 67.9), respectively.

Fluenz efficacy estimates against all matched strains in children who received 2 doses in year 1 andrevaccination in year 2 was 100% (95% CI: 38.2, 100; n=1 110) in AV006, 84.3% (95% CI:

70.1, 92.4; n=1 265) in D153-P501, 88.7% (95% CI: 82.0, 93.2; n=1 090) in D153-P502 and 73.6%(95% CI: 33.3, 91.2; n=680) in D153-P504.

Fluenz efficacy estimates against all matched strains in children who received 2 doses in year 1 andplacebo in year 2 were lower: 56.2% (95% CI: 30.5, 72.7; n=1 253) in D153-P501 and 57.0%(95% CI: 6.1, 81.7; n=718) in D153-P504.

Table 3 Fluenz relative efficacy against culture-confirmed influenza illness inactive-controlled paediatric studies with injectable influenza vaccine

Improved

Improvedefficacy

Number of efficacy

Study Age Influenza (95% CI)

Region study (95% CI)numbera rangeb season all strainsparticipants matchedregardless ofstrainsmatch

USA, Europe, 44.5% 54.9%

MI-CP111 6 to 59 M 7 852c 2004-2005

Asia/Oceania (22.4, 60.6) (45.4, 62.9)de 52.7% 52.4%

D153-P514 Europe 6 to 71 M 2 085 2002-2003(21.6, 72.2) (24.6, 70.5)f34.7% 31.9%

D153-P515 Europe 6 to 17 Y 2 211g 2002-2003(3.9, 56.0) (1.1, 53.5)a Per protocol populationb Age range as described in the study protocol. M=months. Y=years.c Data presented are for study participants who received two doses if unvaccinated or vaccination history wasunknown, and one dose for those previously vaccinated.d Fluenz demonstrated 55.7% (39.9, 67.6) fewer cases than injectable influenza vaccine in 3 686 infants andtoddlers 6-23 months of age and 54.4% (41.8, 64.5) fewer cases in 4 166 children 24-59 months of age.e Data presented are for study participants with a history of recurrent respiratory tract infections who receivedtwo doses of intranasal influenza vaccine compared to those who received two doses of injectable influenzavaccine.f Fluenz demonstrated 64.4% (1.4, 88.8) fewer cases than injectable influenza vaccine in 476 infants andtoddlers 6-23 months of age and 48.2% (12.7, 70.0) fewer cases in 1 609 children 24-71 months of age.g Data presented are for study participants clinically diagnosed with asthma who received one dose ofintranasal influenza vaccine compared to those who received one dose of injectable influenza vaccine.

Not applicable.

Non-clinical data reveal no special hazard for humans based on conventional non-clinical studies ofrepeated dose toxicity, reproduction and developmental toxicity, local tolerance and neurovirulence.

Sucrose

Dipotassium phosphate

Potassium dihydrogen phosphate

Gelatin

Arginine hydrochloride

Monosodium glutamate monohydrate

Water for injections

In the absence of compatibility studies, this vaccine must not be mixed with other medicinal products.

15 weeks

Store in a refrigerator (2°C - 8°C).

Do not freeze.

Keep the nasal applicator in the outer carton in order to protect from light.

Before use, the vaccine may be taken out of the refrigerator once for a maximum period of 12 hours ata temperature not above 25°C. Stability data indicate that the vaccine components are stable for12 hours when stored at temperatures from 8°C to 25°C. At the end of this period, Fluenz should beused immediately or discarded.

Fluenz is supplied as a nasal spray suspension (0.2 ml) in a single-use nasal applicator (Type 1 glass),with nozzle (polypropylene with polyethylene transfer valve), nozzle tip-protector cap (syntheticrubber), plunger rod, plunger-stopper (butyl rubber) and a dose-divider clip.

Pack sizes of 1 or 10 nasal applicators.

Not all pack sizes may be marketed.

Fluenz is for single nasal use only.

* Do not use with a needle. Do not inject.

* Do not use Fluenz if the expiry date has passed or the sprayer appears damaged, for example, ifthe plunger is loose or displaced from the sprayer or if there are any signs of leakage.

* Check the appearance of the vaccine before administration. The suspension should be colourlessto pale yellow, clear to opalescent. Small white particles may be present.

* Fluenz is administered as a divided dose in both nostrils.

* After administering half of the dose in one nostril, administer the other half of the dose in theother nostril immediately or shortly thereafter.

* The patient can breathe normally while the vaccine is being administered - there is no need toactively inhale or sniff.

* Refer to the Fluenz administration diagram (Figure 1) for step-by-step administrationinstructions.

Figure 1: Fluenz Administration

Plunger stopper

Dose-divider clip

Nozzle tip protector

Plunger rod

Check expiry date Prepare the applicator Position the applicator

Product must not be Remove nozzle tip With the patient in anused after date on protector. Do not remove upright position, placeapplicator label. dose-divider clip at the the tip just inside theother end of the nostril to ensure Fluenzapplicator. is delivered into thenose.

Depress the plunger Remove dose-divider Spray in other nostril

With a single motion, clip Place the tip just insidedepress plunger as For administration in the the other nostril andrapidly as possible other nostril, pinch and with a single motion,until the dose-divider remove the dose-divider depress plunger asclip prevents you from clip from plunger. rapidly as possible togoing further. deliver remainingvaccine.

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

AstraZeneca AB

SE-151 85 Södertälje

Sweden

EU/1/24/1816/001

EU/1/24/1816/002

Date of first authorisation: 03 June 2024

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

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