Fluenz® TetraA guide for immunisation teams2021-2022 influenza season

Prescribing information can be found on page 18.

flu: an Unwanted Guest

August 2021 GB-29940

This guide is produced and funded by AstraZeneca and is intended for UK immunisation teams.

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Please remember Fluenz Tetra has a maximum shelf life of 18 weeks.1

Please check the expiry date (day, month, year) on individual sprayers before administration.1

Discard any unused vaccine at the end of the vaccination season to prevent the use of expired vaccine.1

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ContentsIntroducing Fluenz Tetra 4 Key facts 4 Fluenz Tetra presentation 5 How is Fluenz Tetra produced? 6 What are the childhood cohorts for the 2021-2022 flu season? 7 Who can/cannot receive Fluenz Tetra? 8 Vaccine uptake in recent flu seasons 9 Vaccine effectiveness 10 Fluenz Tetra tolerability 10 What support resources are available? 12

The importance of vaccination against flu 13 Why vaccinate children? 13 What are the 2021-2022 uptake targets? 14 Other frequently asked questions 15

References 16Prescribing information 18

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Introducing Fluenz TetraKey factsFluenz Tetra is indicated for the prophylaxis of influenza in children and adolescents from 24 months to less than 18 years of age.1 The use of Fluenz Tetra should be based on official recommendations.1

Fluenz Tetra is administered as a spray directly into the nose of the recipient (once in each nostril).1 For further administration information, please refer to the Summary of Product Characteristics and also the resources on www.fluenztetra.co.uk.

Fluenz Tetra is a live attenuated intranasal influenza (flu) vaccine.1 Attenuated means that the live flu virus strains in Fluenz Tetra are weakened – they are also cold-adapted and temperature-sensitive.1,2 This means that the viruses are adapted to cold so that they multiply in the lower temperatures in the nasopharynx to induce protective immunity.1,3

Annual strainsThe WHO recommends that the quadrivalent vaccines for use in the 2021-2022 northern hemisphere influenza season contain the following:4

• An A/Victoria/2570/2019 (H1N1)pdm09-like virus;

• An A/Cambodia/e0826360/2020 (H3N2)-like virus;

• A B/Washington/02/2019 (B/Victoria lineage) -like virus; and

• A B/Phuket/3073/2013 (B/Yamagata lineage) -like virus

This vaccine complies with the WHO recommendation (Northern Hemisphere) and EU decision for the 2021/22 season.1,4

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Fluenz Tetra presentationSupplied as a 0.2 ml suspension in a single-use nasal applicator.1 Each pack of 10 vaccine applicators1 is 106 mm (length) by 176 mm (width) by 29 mm (depth).5

If you have any questions about Fluenz Tetra, please contact AstraZeneca Medical Information on 0800 783 0033 or email: Medical.InformationUK@astrazeneca.com, or visit: medicalinformation.astrazeneca.co.uk

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How is Fluenz Tetra produced?

DeliveriesOct-JanDeliveries continue to the end customer; majority of vaccination takes place

Sept-OctEvery batch to be used in the UK is tested and then released by an independent laboratory; Public Health England open ordering; deliveries begin

Testing & ReleaseAugSummary of Product Characteristics for current strains issued by regulators

JulClinical trials to ensure safety and immune response to vaccine

PlanningNov-MarCollection of global data from prior season; assess strain performance

Feb-MarWHO identifies virus strains for inclusion in next season’s vaccine

ProductionJan-JulBulk vaccine manufacturing of each individual strain; testing of potency

May-SeptStrains are added together to make final bulk vaccine; sprayers filled

For illustrative purposes only; these timings are approximate and may vary year-on-year

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*For definitions of clinically at-risk please refer to Chapter 19 of The Green Book.2 Age eligibility as of July 2021.

What are the childhood cohorts for the 2021-2022 flu season?The NHS Seasonal Flu Immunisation Programme offers a free nasal spray flu vaccine to all eligible children in England aged 2 and 3 years old, school children in Reception to Year 11, and those clinically at risk aged 2-17 years.*6 There may be some variance across the UK within the other devolved nations: please check the respective communications for Wales, Northern Ireland and Scotland.

If a child is not eligible for the nasal spray flu vaccine, they maybe offered an alternative injectable vaccine.6

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Who can/cannot receive Fluenz Tetra?Fluenz Tetra is indicated for prophylaxis of influenza in children and adolescents from 24 months to <18 years of age.1 The use of Fluenz Tetra should be based on official recommendations.1

Contraindications for Fluenz Tetra are as follows:1

• Hypersensitivity to the active substances, to any of the excipients listed in section 6.1 of the Summary of Product Characteristics (e.g. gelatine), or to gentamicin (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 or immunosuppressive therapy such as: acute and chronic leukaemias; lymphoma; symptomatic HIV infection; cellular immune deficiencies; and high-dose corticosteroids

• Children and adolescents younger than 18 years of age receiving salicylate therapy because of the association of Reye’s syndrome with salicylates and wild-type influenza infection

Fluenz Tetra is not contraindicated for use in individuals with asymptomatic HIV infection; or individuals who are receiving topical/inhaled corticosteroids or low-dose systemic corticosteroids or those receiving corticosteroids as replacement therapy, e.g. for adrenal insufficiency.

For further details, please also see the Pre-administration checklist for Fluenz Tetra for healthcare professionals, downloadable from www.fluenztetra.co.uk*

* This website has been developed and funded by AstraZeneca.

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Other warnings and precautions for use:1

Close association with severely immunocompromised individuals (e.g. bone marrow transplant recipients requiring isolation) should be avoided for vaccine recipients as far as possible for 1–2 weeks following vaccination.1

Flu antivirals may potentially affect the efficacy of the vaccine.1 Therefore, the vaccine should not be administered until at least 48 hours after flu antivirals are stopped.1 Flu antivirals may also affect the response to the vaccine if taken in the two weeks following vaccination.1

Severe asthma and active wheezing: Fluenz Tetra should not be administered to children and adolescents with severe asthma or active wheezing because these individuals have not been adequately studied in clinical studies.1

Salicylate therapy: Children or adolescents receiving salicylate therapy must not be given Fluenz Tetra as there is an association between the use of salicylates and Reye’s syndrome during influenza infection.1 For the same reason, salicylates must not be given for 4 weeks following vaccination unless medically indicated.1

Gelatine: This nasal spray flu vaccine contains a highly processed form of gelatine (porcine, derived from pigs),1 which is used globally in many essential medicines.7 Very sensitive scientific tests have shown that the flu vaccine

does not contain any detectable DNA from pigs. This analysis indicates that the gelatine is so degraded that the original source cannot be identified.8

Some faith groups accept the use of porcine gelatine in medical products7 – the decision is, of course, up to the parents or guardians of your patient. For further information about porcine gelatine and the nasal influenza vaccine, see Vaccines and porcine gelatine: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/751199/Vaccines_porcine_gelatine.pdf.

Pregnancy and breast-feeding: Fluenz Tetra is not recommended during pregnancy and should not be used during breast-feeding.1

Vaccine uptake in recent flu seasonsIn the 2020-21 season in England, an estimated 3,342,578 out of 5,416,670 eligible children in school (reception and years 1-7 combined) were vaccinated with an influenza vaccine,* giving a vaccine uptake of 61.7%, compared with 60.4% in 2019-20 (reception and years 1-6).9*

For 2-3 year olds vaccinated in GP surgeries, an estimated 56% were vaccinated in the 2020-21 season. This compares with 43.8% in the 2019-20 season.10*

* This figure includes children who were vaccinated with either LAIV (nasal spray) or IIV (an injection given to those unsuitable for a nasal spray vaccine)

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Vaccine effectivenessDue to the changing nature of influenza viruses, WHO monitors their epidemiology worldwide and makes recommendations on the strains to be included for the forthcoming winter (for both the northern and southern hemispheres).2,11 Influenza vaccines are then manufactured using virus strains which are in line with these recommendations.2,4

The effectiveness of flu vaccines varies from year to year, depending on variables such as the closeness of the match between the composition of a vaccine and the circulating strains, the type of vaccine and the age of the individual being vaccinated.2

Detailed information on the vaccine effectiveness of Fluenz Tetra can be found here: https://www.gov.uk/government/ publications/influenza-vaccine-effectiveness-seasonal-estimates. Since the programme started in 2013, Public Health England (PHE) has recommended the nasal spray flu vaccine as part of the childhood influenza vaccination programme.6

Fluenz Tetra safetyFluenz Tetra was licensed based on trivalent Fluenz vaccine safety data.1 The safety data for Fluenz is relevant to Fluenz Tetra because both use the same manufacturing process. The only difference between them is the addition of a fourth influenza strain (a second B strain) to Fluenz Tetra.1

In clinical studies, the safety profile of Fluenz Tetra was similar to that of Fluenz.1 Safety data regarding the use of Fluenz Tetra are based on data from Fluenz Tetra clinical studies in 2,231 children and adolescents 2 to 17 years of age, Fluenz clinical studies in over 29,000 children and adolescents 2 to 17 years of age and Fluenz post-authorisation safety studies in over 84,000 children and adolescents 2 to 17 years of age.1 Additional experience has occurred with marketed use of Fluenz.1

Common adverse reactions which occur in between 1 in 10 and 1 in 100 recipients, are:1

• Fever

• Muscle pain

• Headache

Occurrences of Guillain-Barré syndrome and worsening of Leigh syndrome (mitochondrial encephalomyopathy) have been reported very rarely with Fluenz Tetra (both occur in fewer than 1 in 10,000 recipients).1

Very common adverse reactions occurring in at least 1 in 10 recipients, are:1

• Nasal congestion/rhinorrhoea

• Decreased appetite

• Malaise

Uncommon adverse reactions, which occur in between 1 in 1,000 and 1 in 100, are:1

• Epistaxis

• Rash and hypersensitivity reactions

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For more detailed information on adverse reactions, please refer to the SmPC: https.//www.medicines.org.uk/emc/product/3296/smpc2. Adverse events should be reported. Reporting forms and information can be found at https://yellowcard.mhra.gov.uk. Adverse events should also be reported to AstraZeneca by visiting https://aereporting.astrazeneca.com or by calling 0800 783 0033.

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What support resources are available?There is a wide range of support materials available to download or order from our patient and HCP websites:

www.sharegoodtimesnotflu.co.uk*

Comprehensive flu and vaccination information and resources for parents and immunisation teams, including educational videos and animations.

www.fluenztetra.co.uk*

A hub for immunisation teams to download or order a range of items:

• A wide range of materials, including flu vaccine awareness materials for parents/guardians is available. They include:

• Patient leaflet (plus translations in Welsh, Polish, Punjabi, Urdu, Bengali and Gujarati)

• Children’s educational activity sheet

• Guide for practice managers and headteachers

• Fluenz Tetra guide for immunisation teams

• Pre-administration checklist for Fluenz Tetra

• Administration guide for Fluenz Tetra

• Post-administration information tear-off pad to provide to patients

• Post-vaccination stickers for patients

• Teaching and learning toolkit with versions for Early Years, Foundation Stage and Key Stages 1 and 2

*These websites have been developed and funded by AstraZeneca.

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The importance of vaccination against fluWhy vaccinate children?Seasonal flu has an annual incidence rate estimated at 5%–10% in adults and 20%–30% in children, globally.12

Flu can cause serious illness and even death.13 Young children are at risk of catching flu and bear a substantial, yet under-recognised burden, due to frequent complications and hospitalisations.13,14

As well as those with existing health problems, healthy children are also susceptible to flu and its associated complications, such as pneumonia and middle ear infections (otitis media).13,15,16

Children, particularly those of school age, contribute considerably to the spread of flu to their nursery and school friends, families and communities.17,18

Influenza causes absenteeism and lost productivity, with children missing school or day care and their parents or guardians missing work.19

A study across 14 flu seasons from 1995–2009 used Clinical Practice Research Datalink (CPRD) and Public Health England data to show the burden of flu in primary care.20 Seasonal mean estimates of flu-attributable GP consultations in

the UK were 857,996 for respiratory disease* (including middle-ear infection), of which around 75% were for Influenza A.20

The highest rates of GP consultations for Influenza A were seen in children <5 years old, compared to other age groups.20

Mathematical modelling in a study showed that vaccinating as few as 50% of 2 to 18 year olds with live attenuated influenza virus (LAIV) could result in a substantial reduction (up to 84%) in the annual number of GP consultations resulting from influenza A and B infections.21

A dynamic transmission model showed that paediatric vaccination of 2 to 18 year olds appears to be a highly cost-effective intervention that directly protects those targeted for vaccination, with indirect protection extending to both the very young and the elderly.21

Public Health England states that vaccinating children each year not only helps to protect children themselves but there will be reduced transmission across all age groups, lessening levels of flu overall and reducing the burden of flu across the population.22

* GP consultations were logged using READ codes combined into respiratory diagnoses consistent with recognised ICD-10 groupings. Flu-attributable consultations included all disorders in the ICD-10 respiratory disease chapter, otitis media, and selected presenting symptom codes that were used in some GP surgeries in lieu of specifying a clinical diagnosis.20

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* There may be some variance across the UK within the other devolved nations: please check the respective communications for Wales, Northern Ireland and Scotland.

What are the 2021-2022 uptake targets?NHS England is aiming to achieve vaccine uptake rates, to a target of at least 70% in eligible pre-school children, and at least 70% in eligible school-aged children.*6

Other frequently asked questionsFor answers to questions asked frequently by immunisation teams and their patients, please see www.fluenztetra.co.uk/faqs.* Examples include:Further questions immunisation teams may have:

• What can I do to improve vaccination uptake?

• How effective has the vaccination programme been since it was launched?

• Can Fluenz Tetra be co-administered with other live vaccines?

• Once Fluenz Tetra has been removed from the fridge, can it be returned to the fridge for later use?

• How and when should I order Fluenz Tetra?

• What training is available for Fluenz Tetra administration?

• Expired Fluenz Tetra has been inadvertently administered. What should I do?

Questions patients/guardians may ask:

• Is Fluenz Tetra the only vaccine against flu?

• Does Fluenz Tetra contain thiomersal?

• Is there any latex in the Fluenz Tetra applicator?

• What are the symptoms of flu vs the common cold?

• My child was vaccinated last year. Do they need a vaccination this year?

• Could my child get flu after being vaccinated?

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* This website has been developed and funded by AstraZeneca.

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1 Fluenz Tetra nasal spray suspension Influenza vaccine (live attenuated, nasal) Summary of Product Characteristics. Available at: https://www.medicines.org.uk/emc/product/3296/smpc.

2 Department of Health. Immunisation Against Infectious Disease. (The Green Book.) Chapter 19: Influenza. London: The Stationery Office. April 2019. Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/796886/GreenBook_Chapter_19_Influenza_April_2019.pdf.

3 Murphy BR, Coelingh K. Viral Immunol. 2002;15(2):295-323.

4 World Health Organization. Influenza. Recommended composition of influenza virus vaccines for use in the 2021-2022 northern hemisphere influenza season. 26 February 2021. Available at: https://www.who.int/publications/m/item/recommended-composition-of-influenza-virus-vaccines-for-use-in-the-2021-2022-northern-hemisphere-influenza-season.

5 Fluenz Tetra. Facts about Fluenz Tetra. Available at: https://www.fluenztetra.co.uk/content/dam/open-digital/fluenztetra/en/training/3-0.html.

6 Whitty C, Doyle Y & Powis S. National flu immunisation programme 2021 to 2022 letter. Available at: https://www.gov.uk/government/publications/national-flu-immunisation-programme-plan/national-flu-immunisation-programme-2021-to-2022-letter.

7 Public Health England: Vaccines and porcine gelatine: 2019. Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/824013/PHE_vaccines_porcine_gelatine.pdf.

8 Public Health England. The children’s flu vaccination programme, the nasal flu vaccine. Fluenz and porcine gelatine. Your questions answered. December 2014. Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/386842/2902998_PHE_FluPorcine_QAforParents_FINAL_CT.pdf.

9 Public Health England. Seasonal flu vaccine uptake in children of school age: winter 2020 to 2021. Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/995616/Childhood_flu_annual_report_2020_to_2021.pdf.

10 Public Health England. Seasonal flu vaccine uptake in GP patients: winter season 2020 to 2021. Available at https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/996033/Annual-Report_SeasonalFlu-Vaccine_GPs_2020_to_2021.pdf.

11 World Health Organization. Influenza (Seasonal). 6 November 2018. Available at: https://www.who.int/news-room/fact-sheets/detail/influenza-(seasonal).

12 International Federation of Pharmaceutical Manufacturers & Associations. Seasonal Influenza. Available at: https://www.ifpma.org/subtopics/seasonal-influenza-2/.

13 Centers for Disease Control and Prevention. Children & influenza. Last reviewed October 2019. Available at: https://www.cdc.gov/flu/highrisk/children.htm.

14 Usonis V et al. BMC Infect Dis. 2010;10:168 doi:10.1186/ 1471-2334-10-168.

15 Principi N et al. Archives of Disease in Childhood. 2004;89:1002-1007.doi: 10.1136/adc.2003.045401.

16 Heikkinen T et al. Eur J Pediatr. 2006;165(4):223-228 doi: 10.1007/s00431-005-0040-9.

17 Principi N et al. Pediatr Infect Dis J. 2003;22(10):S207–10.doi:10.1097/01.inf.0000092188.48726.e4.

18 Neuzil KM et al. Arch Pediatr Adolesc Med. 2002;156(10):986-991.

19 Ambrose CS, Antonova EN. Eur J Clin Microbiol Infect Dis.2014;33(4):569-575 doi: 10.1007/s10096-013-1986-6.

20 Fleming DM et al. Epidemiol Infect. 2016;144:537-547 doi: 10.1017/S0950268815001119.

21 Pitman RJ et al. Vaccine. 2012;30(6):1208-1224 doi: 10.1016/j.vaccine.2011.11.106.

22 Van-Tam J, Deputy Chief Medical Officer et al. The national flu immunisation programme 2019/20. 22 March 2019. Available at: https://www.england.nhs.uk/wp-content/uploads/2019/03/annual-national-flu-programme-2019-to-2020-1.pdf.

References

All website references were accessed in August 2021.

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Prescribing informationFLUENZ® TETRA nasal spray suspension Influenza vaccine (live attenuated, nasal)

Consult Summary of Product Characteristics before prescribing.

Indication: Prophylaxis of influenza in individuals 24 months to less than 18 years of age.

Presentation: Nasal spray, suspension.

Dosage and administration: 0.2ml (administered as 0.1ml per nostril). Children not previously vaccinated against seasonal influenza should be given a second dose after an interval of at least 4 weeks. Should not be used in individuals below 24 months of age because of safety concerns.

Method of administration: Nasal administration only. Do not inject Fluenz Tetra.

Contraindications: Hypersensitivity to the active substances, any of the excipients (e.g. gelatin), gentamicin (a possible trace residue), or eggs or to egg proteins (e.g. ovalbumin). Children and adolescents who are clinically immunodeficient due to conditions or immunosuppressive therapy: (acute and chronic leukaemias; lymphoma; symptomatic HIV infection; cellular immune deficiencies; and high-dose corticosteroids). Not contraindicated for use in individuals with asymptomatic HIV infection; or individuals who are receiving topical/inhaled corticosteroids or low-dose systemic corticosteroids or those receiving corticosteroids as replacement therapy, e.g. for adrenal insufficiency. Contraindicated in children and adolescents younger than 18 years of age receiving salicylate therapy because of the association of Reye’s syndrome with salicylates and wild-type influenza infection.

Warnings and precautions: Clearly record name and batch number of administered product to improve traceability. Medical treatment and supervision should always be readily available in case of an anaphylactic event following administration. Fluenz Tetra should not be administered to children and adolescents with severe asthma or active wheezing because these individuals have not been adequately studied in clinical studies. Do not administer to infants and toddlers below 24 months of age because of safety concerns regarding increased rates of hospitalisation and wheezing in this population. Vaccine recipients should be informed that Fluenz Tetra is an attenuated live virus vaccine and has the potential for transmission to immunocompromised contacts. Vaccine recipients should attempt to avoid, close association with severely immunocompromised individuals (e.g. bone marrow transplant recipients requiring isolation) for 1 2 weeks following vaccination. Where contact is unavoidable, the potential risk of transmission of the influenza vaccine virus should be weighed against the risk of acquiring and transmitting wild-type influenza virus. No data exists regarding the safety in children with unrepaired craniofacial malformations.

Drug interactions: Salicylates must not be used for 4 weeks following vaccination unless medically indicated. Co-administration of trivalent Fluenz with the live attenuated vaccines: No clinically meaningful changes in immune responses to measles, mumps, varicella, orally-administered poliovirus or trivalent Fluenz have been observed. Immune response to rubella vaccine was significantly altered. This might not be of clinical relevance with the two dose immunisation schedule of the rubella vaccine. Fluenz Tetra (influenza vaccine-live attenuated, nasal) is identical to trivalent Fluenz with the only difference being the addition of a fourth strain (a second B strain) to Fluenz Tetra. Co-administration of Fluenz Tetra with inactivated vaccines

has not been studied. Concurrent use with antiviral agents active against influenza A and/or B viruses has not been evaluated. Based upon the potential for influenza antiviral agents to reduce the effectiveness of Fluenz Tetra, it is recommended not to administer the vaccine until 48 hours after the cessation of influenza antiviral therapy. Administration of influenza antiviral agents within two weeks of vaccination may affect the response of the vaccine. If influenza antiviral agents and Fluenz Tetra are administered concomitantly, revaccination should be considered based on clinical judgment.

Fertility, Pregnancy and Lactation: Not recommended during pregnancy. Should not be used during breast-feeding. No data on the effects of Fluenz Tetra on male and female fertility.

Undesirable effects: Refer to SmPC for complete information on adverse reactions. Very common: decreased appetite, nasal congestion/rhinorrhoea, malaise. Common: headache, myalgia, pyrexia. Uncommon: hypersensitivity reactions (including facial oedema, urticaria and very rare anaphylactic reactions), epistaxis, rash. Very rare reports of Guillain-Barré syndrome and exacerbation of symptoms of Leigh syndrome (mitochondrial encephalomyopathy) have also been observed in the post-marketing setting.

Legal category: POM.

Marketing authorisation number: EU/1/13/887/004

Presentation & basic NHS cost: Fluenz Tetra nasal spray suspension pack of 10: £180.00

Marketing Authorisation Holder: AstraZeneca AB, SE-151 85 Södertälje, Sweden

Further information is available from: AstraZeneca UK Limited, 600 Capability Green, Luton, LU1 3LU, UK.

FLUENZ is a trademark of the AstraZeneca group of companies.

Date of preparation: 03/2020

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Adverse events should be reported. Reporting forms and information can be found at https://yellowcard.mhra.gov.uk. Adverse events should also be reported to AstraZeneca by visiting https://aereporting.astrazeneca.com or by calling 0800 783 0033.

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©AstraZeneca 2021 August 2021 GB-29940

flu: an Unwanted Guest

flu protection without an injection