1. NAME OF THE MEDICINAL PRODUCT

Fluarix Tetra suspension for injection in pre-filled syringe

Influenza vaccine (split virion, inactivated)

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Influenza virus (inactivated, split) of the following strains*:

A/Victoria/2570/2019 (H1N1)pdm09 - like strain (A/Victoria/2570/2019, IVR-215)

15 micrograms HA**

A/Cambodia/e0826360/2020 (H3N2) - like strain (A/Tasmania/503/2020, IVR-221)

15 micrograms HA**

B/Washington/02/2019 - like strain (B/Washington/02/2019, wild type)

15 micrograms HA**

B/Phuket/3073/2013 - like strain (B/Phuket/3073/2013, wild type)     

per 0.5 ml dose

• * propagated in fertilized hens’ eggs from healthy chicken flocks

• * * haemagglutinin

This vaccine complies with the World Health Organisation (WHO) recommendation (northern hemisphere) and EU recommendation for the 2021/2022 season.

Excipients with known effect

This product contains approximately 3.75 mg of sodium chloride and approximately 1.3 mg of disodium phosphate dodecahydrate per dose (see section 4.4).

This product contains approximately 0.2 mg of potassium dihydrogen phosphate and approximately 0.1 mg of potassium chloride per dose (see section 4.4).

Fluarix Tetra may contain traces of eggs (such as ovalbumin, chicken proteins), formaldehyde, gentamicin sulphate and sodium deoxycholate which are used during the manufacturing process (see section 4.3).

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Suspension for injection in pre-filled syringe.

The suspension is colourless and slightly opalescent.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Fluarix Tetra is indicated for active immunisation of adults and children from 6 months of age for the prevention of influenza disease caused by the two influenza A virus subtypes and the two influenza B virus lineages contained in the vaccine (see section 5.1).

The use of Fluarix Tetra should be based on official recommendations.

Annual revaccination with the current vaccine is recommended because immunity declines during the year after vaccination, and because circulating strains of influenza virus might change from year to year.

4.2 Posology and method of administration

Posology

Adults: 0.5 ml

Paediatric population

Children from 6 months onwards: 0.5 ml.

For children aged < 9 years, who have not previously been vaccinated against influenza, a second dose should be given after an interval of at least 4 weeks.

Children less than 6 months: the safety and efficacy of Fluarix Tetra in children less than 6 months have not been established.

Method of administration

Immunisation should be carried out by intramuscular injection.

Precautions to be taken before handling or administering the medicinal product

For instructions for preparation of the medicinal product before administration, see section 6.6.

4.3 Contraindications

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1 or to any component that may be present as traces such as eggs (ovalbumin, chicken proteins), formaldehyde, gentamicin sulphate and sodium deoxycholate.

Immunisation shall be postponed in patients with febrile illness or acute infection.

4.4 Special warnings and precautions for use

Traceability

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

It is good clinical practice to precede vaccination by a review of the medical history (especially with regard to previous vaccination and possible occurrence of undesirable events) and a clinical examination.

As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of an anaphylactic event following the administration of the vaccine.

Antibody response in patients with endogenous or iatrogenic immunosuppression may be insufficient.

Fluarix Tetra is not effective against all possible strains of influenza virus. Fluarix Tetra is intended to provide protection against those strains of virus from which the vaccine is prepared and to closely related strains.

As with any vaccine, a protective immune response may not be elicited in all vaccinees.

Fluarix Tetra should under no circumstances be administered intravascularly.

As with other vaccines administered intramuscularly, Fluarix Tetra should be given with caution to individuals with thrombocytopenia or any coagulation disorder since bleeding may occur following an intramuscular administration to these subjects.

Syncope (fainting) can occur following, or even before, any vaccination especially in adolescents as a psychogenic response to the needle injection. This can be accompanied by several neurological signs such as transient visual disturbance, paraesthesia and tonic-clonic limb movements during recovery. It is important that procedures are in place to avoid injury from faints.

Interference with serological testing

See section 4.5.

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially “sodium-free”.

This medicine contains potassium, less than 1 mmol (39 mg) per dose, i.e. essentially “potassium-free”.

4.5 Interaction with other medicinal products and other forms of interaction

Fluarix Tetra can be concomitantly administered with pneumococcal polysaccharide vaccines in subjects aged 50 years and above (see section 5.1).

Fluarix Tetra can be concomitantly administered with adjuvanted herpes zoster vaccine (Shingrix) (see section 5.1).

If Fluarix Tetra is to be given at the same time as another injectable vaccine, the vaccines should always be administered at different injection sites.

The frequency of injection site pain reported in subjects vaccinated concomitantly with inactivated quadrivalent influenza vaccine (Fluarix Tetra) and 23-valent pneumococcal polysaccharide vaccine (PPV23) is similar to that observed with PPV23 alone, and higher compared to Fluarix Tetra alone.

Incidence of fatigue, headache, myalgia and shivering reported in subjects vaccinated concomitantly with Fluarix Tetra and Shingrix is similar to that observed with Shingrix alone, and higher compared to Fluarix Tetra alone.

Following influenza vaccination, false positive results in serology tests using the ELISA method to detect antibodies against HIV1, Hepatitis C and especially HTLV1 have been observed. The Western Blot technique disproves the false-positive ELISA test results. The transient false positive reactions could be due to the IgM response by the vaccine.

4.6 Fertility, pregnancy and lactation

Pregnancy

Inactivated influenza vaccines can be used in all stages of pregnancy. Larger datasets on safety are available for the second and third trimester, compared with the first trimester; however, data from worldwide use of inactivated influenza vaccines do not indicate any adverse foetal and maternal outcomes attributable to the vaccine.

Breast-feeding

Fluarix Tetra may be used during breast-feeding.

Fertility

No fertility data are available.

4.7 Effects on ability to drive and use machines

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

• 4.8 Undesirable effects

Clinical trials

Summary of the safety profile

In all age groups the most frequently reported local adverse reaction after vaccination was injection site pain (15.6% to 40.9%).

In adults 18 years of age and above, the most frequently reported general adverse reactions after vaccination were fatigue (11.1%), headache (9.2%) and myalgia (11.8%).

In subjects aged 6 to 17 years, the most frequently reported general adverse reactions after vaccination were fatigue (12.6%), myalgia (10.9%) and headache (8.0%).

In subjects aged 3 to 5 years, the most frequently reported general adverse reactions after vaccination were drowsiness (9.8%) and irritability (11.3%).

In subjects aged 6 months to 3 years, the most frequently reported general adverse reactions after vaccination were irritability/fus­siness (14.9%) and loss of appetite (12.9%).

Tabulated list of adverse reactions

Adverse reactions reported for Fluarix Tetra in the different age groups are listed per dose according to the following frequency categories:

Adults

A clinical study with Fluarix Tetra in adults has evaluated the incidence of adverse reactions in subjects >18 years who received one dose of Fluarix Tetra (N = 3,036) or Fluarix (trivalent influenza vaccine) (N = 1,010).

The following adverse reactions per dose have been reported:

1Reported as unsolicited adverse reaction

2Reported in previous Fluarix trials

Children aged 6 months to <18 years

Two clinical studies evaluated the reactogenicity and safety of Fluarix Tetra in children who received at least one dose of Fluarix Tetra or a control vaccine.

One study enrolled children 3 to <18 years of age who received Fluarix Tetra (N = 915) or Fluarix (N = 912). The second study enrolled children 6 to <36 months of age who received Fluarix Tetra (N = 6,006) or a non-influenza vaccine control (N = 6,012) (see section 5.1).

The following adverse reactions per dose have been reported:

N/A=Not solicited in this age group

N/R=Not reported

1Reported as unsolicited adverse reaction

2Reported in previous Fluarix trials

Post-marketing data

The following adverse reactions have been observed for Fluarix and/or Fluarix Tetra during postmarketing surveillance1.

1Three of the influenza strains contained in Fluarix are included in Fluarix Tetra.

Spontaneous reports of Guillain-Barre syndrome have been received following vaccination with Fluarix and Fluarix Tetra; however, a causal association between vaccination and Guillain-Barre syndrome has not been established.

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

Overdosage is unlikely to have any untoward effect.

• 5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Influenza vaccine, ATC Code: J07BB02

Mechanism of action

Fluarix Tetra provides active immunisation against four influenza virus strains (two A subtypes and two B lineages) contained in the vaccine.

Fluarix Tetra induces humoral antibodies against the haemagglutinins. These antibodies neutralise influenza viruses.

Specific levels of haemagglutination-inhibition (HI) antibody titre post-vaccination with inactivated influenza virus vaccines have not been correlated with protection from influenza illness but the HI antibody titres have been used as a measure of vaccine activity. In some human challenge studies, HI antibody titres of >1:40 have been associated with protection from influenza illness in up to 50% of subjects.

Pharmacodynamic effects

Efficacy in children 6-35 months of age:

The efficacy of Fluarix Tetra was evaluated in clinical study D-QIV-004, a randomised, observerblind, non-influenza vaccine-controlled trial conducted during influenza seasons 2011 to 2014. Healthy subjects aged 6 through 35 months were randomized (1:1) to receive Fluarix Tetra (N = 6,006) or a non-influenza control vaccine (N = 6,012). They were administered 1 dose (in case of history of influenza vaccination) or 2 doses, approximately 28 days apart.

Efficacy of Fluarix Tetra was assessed for the prevention of reverse transcription polymerase chain reaction (RT-PCR)-confirmed influenza A and/or B disease (moderate to severe and of any severity) due to any seasonal influenza strain. Starting 2 weeks post-vaccination until the end of the influenza season (approximately 6 months later), nasal swabs were collected following an influenza like event, and tested for influenza A and/or B by RT-PCR. All RT-PCR-positive specimens were further tested for viability in cell culture and to determine whether the viral strains matched those in the vaccine.

Fluarix Tetra met the predefined criteria for primary and secondary vaccine efficacy objectives presented in Table 1.

Table 1: Fluarix Tetra: Attack rates and vaccine efficacy in children 6–35 months of age (ATP (according to protocol) cohort for efficacy – time to event)

CI: Confidence Interval

• 1Children received age appropriate non-influenza vaccine control

• 2Number of subjects included in the ATP cohort for efficacy – time to event. This cohort included subjects who met all eligibility criteria, who were followed for efficacy and complied with the study protocol until the episode.

• 3Number of subjects who reported at least one case in the reporting period

• 42-sided 97.5% confidence interval

• 52-sided 95% confidence interval

• 6 Influenza disease of any severity was defined as an episode of influenza-like illness (ILI, i.e. fever >38°C with any of the following: cough, runny nose, nasal congestion, or breathing difficulty) or a consequence of influenza virus infection [acute otitis media (AOM) or lower respiratory illness (LRI)].

• 7 Moderate to severe influenza was a subset of any influenza disease, with any of the following: fever >39°C, physician-diagnosed AOM, physician-diagnosed lower respiratory tract infection, physician-diagnosed serious extra-pulmonary complications, hospitalisation in the intensive care unit, or supplemental oxygen required for more than 8 hours.

Exploratory analyses were conducted on the Total Vaccinated Cohort including 12,018 subjects (N = 6,006 for Fluarix Tetra, N = 6,012 for control). Fluarix Tetra was efficacious in the prevention of moderate to severe influenza caused by each of the 4 strains (Table 2), even when there was significant antigenic mismatch with 2 of the vaccine strains (A/H3N2 and B/Victoria).

Table 2: Fluarix Tetra: Attack rates and vaccine efficacy for RT-PCR confirmed moderate to severe disease by Influenza A subtypes and Influenza B lineages in children 6–35 months of age (Total Vaccinated Cohort)

1Infants received age appropriate non-influenza vaccine control

2Number of subjects included in the Total Vaccinated cohort

3Number of subjects who reported at least one case in the reporting period

4 to 7Proportion of antigenic matching strains was 84.8%, 2.6%, 14.3% and 66.6%, for A/H1N1, A/H3N2, B/Victoria, and B/Yamagata, respectively.

Additionally, for RT-PCR confirmed cases of any severity, Fluarix Tetra reduced the risk of visits to the general practitioner by 47% (Relative Risk (RR): 0.53 [95% CI: 0.46; 0.61], i.e., 310 versus 583 visits) and to the emergency room by 79% (RR: 0.21 [95% CI: 0.09; 0.47], i.e., 7 versus 33 visits). The use of antibiotics was reduced by 50% (RR: 0.50 [95% CI: 0.42; 0.60], i.e., 172 versus 341 subjects).

Efficacy in adults 18-64 years of age

A clinical study performed in more than 7,600 subjects in the Czech Republic and Finland evaluated the efficacy of Fluarix to prevent culture-confirmed influenza A and/or B cases for vaccine antigenically matched strains.

Subjects were monitored for influenza-like illness to be confirmed by culture (see table 3 for results). Influenza-like illness was defined as at least one general symptom (fever >37.8°C and/or myalgia) and at least one respiratory symptom (cough and/or sore throat).

Table 3: Attack rates and Vaccine Efficacy against Illness associated with evidence of influenza A or B Infection in adults 18 to 64 years of age (Total Vaccinated Cohort)

1n/N: number of case/total number of subjects

2CI: Confidence Interval

3LL: Lower Limit

4There were no vaccine matched culture-confirmed cases of A/New Caledonia/20/1999 (H1N1) or

B/Malaysia/2506/2004 influenza strains with Fluarix or placebo

5Of the 22 additional cases, 18 were unmatched and 4 were untyped; 15 of the 22 cases were A (H3N2) (11 cases with Fluarix and 4 cases with placebo).

In this study, immunogenicity was also evaluated.

Table 4: Post-vaccination GMT and seroconversion rates

1containing A/H1N1, A/H3N2 and B (Victoria lineage)

Post-vaccination seroprotection rates were 97.6% against A/H1N1, 86.9% against A/H3N2 and 96.2% against B (Victoria).

Immunogenicity in children and adults:

Immunogenicity of Fluarix Tetra was evaluated in terms of HI Geometric mean antibody titre (GMT) at 28 days after the last dose (children) or Day 21 (adults) and HI seroconversion rate (4fold rise in reciprocal titre or change from undetectable [< 10] to a reciprocal titre of > 40).

In study D-QIV-004 (children 6–35 months), the evaluation was performed in a sub-cohort of 1,332 children (753 in the Fluarix Tetra group and 579 in the control group). The results are presented in Table 5.

The effect of a 2-dose priming schedule in D-QIV-004 was evaluated by assessing the immune response after revaccination one year later with 1 dose of Fluarix Tetra in study D-QIV-009. This study demonstrated that 7 days post-vaccination, immune memory in children 6 to 35 months of age had been elicited for all four vaccine strains.

Immunogenic non-inferiority of Fluarix Tetra was assessed versus Fluarix in children in study D-QIV-003 (approximately 900 children 3 to < 18 years of age in each treatment group who received one or two doses of either vaccine) and adults in study D-QIV-008 (approximately 1,800 subjects 18 years of age and older received 1 dose of Fluarix Tetra and approximately 600 subjects received 1 dose of Fluarix). In both studies, Fluarix Tetra elicited an immune response against the three strains in common that was non-inferior to Fluarix and a superior immune response against the additional B strain included in Fluarix Tetra. The results are presented in Table 5.

Table 5: Fluarix Tetra: Post-vaccination GMT and seroconversion rates (SCR) in children (6–35 months; 3 to < 18 years) and adults 18 years or older (According to Protocol Cohort)

N = Number of subjects with post-vaccination results available (for GMT)

N’ = Number of subjects with both pre- and post-vaccination results available (for SCR) 1non-influenza vaccine control

• 2results from the immunogenicity subcohort

• 3 B (Yamagata) strain was not included in Fluarix

Concomitant administration with pneumococcal polysaccharide vaccines:

In clinical study D-QIV-010 involving 356 adults >50 years of age at risk for complications of influenza and pneumococcal diseases, subjects received Fluarix Tetra and 23-valent pneumococcal polysaccharide vaccine (PPV23) either concomitantly or separately. For all four Fluarix Tetra vaccine strains and the six pneumococcal serotypes (1, 3, 4, 7F, 14, and 19A) in PPV23 evaluated in the pre-specified primary analysis, the immune response was non-inferior between the two treatment groups. Based on a descriptive analysis for six additional pneumococcal vaccine serotypes (5, 6B, 9V, 18C, 19F, and 23F), the immune response was comparable between groups, with 91.7% to 100% and 90.7% to 100% of subjects attaining seroprotective antibody levels against these serotypes in the separate and concomitant administration group respectively.

Concomitant administration with adjuvanted herpes zoster vaccine (Shingrix):

In clinical study Zoster-004, 828 adults > 50 years of age were randomised to receive 2 doses of Shingrix 2 months apart, administered either concomitantly at the first dose (N=413) or non-concomitantly (N=415) with one dose of Fluarix Tetra. The antibody responses to each vaccine were similar, whether administered concomitantly or non-concomitantly. Furthermore, immunological non-inferiority between concomitant and non-concomitant administration was demonstrated for all four strains included in Fluarix Tetra in terms of HI antibody GMTs.

5.2 Pharmacokinetic properties

Not applicable.

5.3 Preclinical safety data

Non-clinical data reveal no special hazards for humans based on conventional studies of acute toxicity, local tolerance, repeated dose toxicity and reproductive/de­velopmental toxicity.

• 6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sodium chloride

Disodium phosphate dodecahydrate

Potassium dihydrogen phosphate

Potassium chloride

Magnesium chloride hexahydrate a-tocopheryl hydrogen succinate Polysorbate 80

Octoxinol 10

Water for injections

6.2 Incompatibilities

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

6.3 Shelf life

1 year

• 6.4 Special precautions for storage

Store in a refrigerator (2 °C – 8 °C).

Do not freeze.

Store in the original package in order to protect from light.

6.5 Nature and contents of container

• – with 1 needle: pack sizes of 1 or 10

• – with 2 needles: pack size of 1

• – without needle: pack sizes of 1 or 10

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

The vaccine should be allowed to reach room temperature before use.

Shake before use. Inspect visually prior to administration.

Instructions for administration of the vaccine presented in pre-filled syringe

To attach the needle to the syringe, refer to the below drawing.

Syringe

• 1. Holding the syringe barrel in one hand (avoid holding the syringe plunger), unscrew the syringe cap by twisting it anticlockwise.

• 2. To attach the needle to the syringe, twist the needle clockwise into the syringe until you feel it lock (see picture).

• 3. Remove the needle protector, which on occasion can be a little stiff.

• 4. Administer the vaccine.

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

7. MARKETING AUTHORISATION HOLDER

8. MARKETING AUTHORISATION NUMBER(S)

[To be completed nationally]

9. DATE OF FIRST AUTHORISATION / RENEWAL OF THE AUTHORISATION

Date of first authorisation:

Date of latest renewal:

[To be completed nationally]

10. DATE OF REVISION OF THE TEXT

1. NAME OF THE MEDICINAL PRODUCT

Fluarix Tetra suspension for injection in pre-filled syringe

Influenza vaccine (split virion, inactivated)

2021/2022 season

2. STATEMENT OF ACTIVE SUBSTANCE(S)

WHO/EU recommended strains for 2021/2022 season (northern hemisphere):

A/Victoria/2570/2019 (H1N1)pdm09 – like strain 15 micrograms HA*

A/Cambodia/e0826360/2­020 (H3N2) – like strain 15 micrograms HA*

B/Washington/02/2019 – like strain 15 micrograms HA*

B/Phuket/3073/201­3 – like strain 15 micrograms HA*

*haemagglutinin

3. LIST OF EXCIPIENTS

Sodium chloride, disodium phosphate dodecahydrate, potassium dihydrogen phosphate, potassium chloride, magnesium chloride hexahydrate, a-tocopheryl hydrogen succinate, polysorbate 80, octoxinol 10 and water for injections

4. PHARMACEUTICAL FORM AND CONTENTS

Suspension for injection in a pre-filled syringe:

1 pre-filled syringe without needle

1 dose (0.5 ml)

1 pre-filled syringe + 1 needle

1 dose (0.5 ml)

1 pre-filled syringe + 2 needles

1 dose (0.5 ml)

10 pre-filled syringes without needle

10 × 1 dose (0.5 ml)

10 pre-filled syringes + 10 needles

10 × 1 dose (0.5 ml)

• 5. METHOD AND ROUTE(S) OF ADMINISTRATION

Intramuscular use

Read the package leaflet before use.

Shake before use.

• 6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED

OUT OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children

• 7. OTHER SPECIAL WARNING(S), IF NECESSARY

For use in adults and children from 6 months of age

• 8. EXPIRY DATE

EXP

• 9. SPECIAL STORAGE CONDITIONS

Store in a refrigerator

Do not freeze

Store in the original package in order to protect from light

• 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 [To be completed nationally]

• 12. MARKETING AUTHORISATION NUMBER(S) [To be completed nationally]

• 13. BATCH NUMBER

Lot

• 14. GENERAL CLASSIFICATION FOR SUPPLY

• 15. INSTRUCTIONS ON USE

• 16. INFORMATION IN BRAILLE

Justification for not including Braille accepted

• 17. UNIQUE IDENTIFIER – 2D BARCODE 2D barcode carrying the unique identifier included.

• 18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC

SN

NN

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

• 1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Fluarix Tetra Influenza vaccine 2021/2022 season IM

• 2. METHOD OF ADMINISTRATION

• 3. EXPIRY DATE

EXP

• 4. BATCH NUMBER

Lot

• 5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 1 dose (0.5 ml)

• 6. OTHER

PACKAGE LEAFLET

Package leaflet: Information for the user

Fluarix Tetra suspension for injection in pre-filled syringe

This leaflet has been written assuming the person receiving the vaccine is reading it, but it can be given to adolescents and children so you may be reading it for your child.

Read all of this leaflet carefully before you or your child start receiving this vaccine 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 or pharmacist.

• – This vaccine has been prescribed for you or your child only. Do not pass it on to others.

• – If you or your child get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

• 1. What Fluarix Tetra is and what it is used for

• 2. What you need to know before you use Fluarix Tetra

• 3. How Fluarix Tetra is given

• 4. Possible side effects

• 5. How to store Fluarix Tetra

• 6. Contents of the pack and other information

1. what fluarix tetra is and what it is used for

Fluarix Tetra is a vaccine. This vaccine helps to protect you against influenza (flu), particularly in subjects who run a high risk of associated complications. The use of Fluarix Tetra should be based on official recommendations.

When a person is given the vaccine Fluarix Tetra, the immune system (the body’s natural defence system) will produce its own protection (antibodies) against the disease. None of the ingredients in the vaccine can cause flu.

Flu is a disease that can spread rapidly and is caused by different types of strains that can change every year. Therefore, this is why you might need to be vaccinated every year. The greatest risk of catching flu is during the cold months between October and March. If you were not vaccinated in the autumn, it is still sensible to be vaccinated up until the spring since you run the risk of catching flu until then. Your doctor will be able to recommend the best time to be vaccinated. Fluarix Tetra will protect you against the four strains of virus contained in the vaccine from about 2 to 3 weeks after the injection.

The incubation period for flu is a few days, so if you are exposed to flu immediately before or after your vaccination, you could still develop the illness.

The vaccine will not protect you against the common cold, even though some of the symptoms are similar to flu.

2. what you need to know before you use fluarix tetra

To make sure that Fluarix Tetra is suitable for you, it is important to tell your doctor or pharmacist if any of the points below apply to you. If there is anything you do not understand, ask your doctor or pharmacist to explain.

Do not use Fluarix Tetra

• – If you are allergic to the active substances or any of the other ingredients of this medicine (listed in section 6) or any components that may be present in very small amounts such as eggs (ovalbumin or chicken proteins), formaldehyde, gentamicin sulphate or sodium deoxycholate.

• – If you have an illness with a high temperature or acute infection, the vaccination shall be postponed until after you have recovered.

Warnings and precautions

Talk to your doctor or pharmacist before you receive Fluarix Tetra:

• – if you have a poor immune response (immunodeficiency or taking medicines affecting the immune system).

• – if, for any reason, you have a blood test within a few days following a flu vaccination. This is because false positive blood test results have been observed in a few patients who had recently been vaccinated.

• – if you have a bleeding problem or bruise easily.

Your doctor will decide if you should receive the vaccine.

Fainting can occur (mostly in adolescents) following, or even before, any needle injection, therefore tell the doctor or nurse if you fainted with a previous injection.

As with all vaccines, Fluarix Tetra may not fully protect all persons who are vaccinated.

Other medicines and Fluarix Tetra

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Fluarix Tetra can be given at the same time as other vaccines by using separate limbs.

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.

Your doctor/pharmacist will be able to decide if you should receive Fluarix Tetra. Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Fluarix Tetra has no or negligible influence on the ability to drive or use machines.

Fluarix Tetra contains sodium

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially “sodium free”.

Fluarix Tetra contains potassium

This medicine contains potassium, less than 1 mmol (39 mg) per dose, i.e. essentially “potassium-free”.

3. How Fluarix Tetra is given

Adults receive one 0.5 ml dose.

Use in children:

Children from 6 months and older receive one 0.5 ml dose.

If your child is younger than 9 years of age and has not been previously vaccinated against flu, a second dose should be given after at least 4 weeks.

Method and/or route of administration

Your doctor will administer the recommended dose of the vaccine as an injection into the muscle. If you have any further questions on the use of this product, ask your doctor or pharmacist.

4. possible side effects

Like all medicines, this vaccine can cause side effects, although not everybody gets them.

During clinical trials, the following side effects have been observed.

Side effects that occurred in children 6 to 36 months of age

Very common (these may occur with more than 1 in 10 doses of the vaccine):

• Loss of appetite
• Irritability
• Drowsiness
• Pain at the injection site
• Redness at the injection site

Common (these may occur with up to 1 in 10 doses of the vaccine):

• Fever
• Swelling at the injection site

Side effects that occurred in children 3 to 6 years of age

Very common (these may occur with more than 1 in 10 doses of the vaccine):

• Pain at the injection site
• Redness at the injection site
• Swelling at the injection site
• Irritability

Common (these may occur with up to 1 in 10 doses of the vaccine):

• Loss of appetite
• Drowsiness
• Fever

Uncommon (these may occur with up to 1 in 100 doses of the vaccine):

• Rash
• Itching at the injection site

Side effects that occurred in children 6 to 18 years of age

Very common (these may occur with more than 1 in 10 doses of the vaccine):

• Aching muscles
• Pain at the injection site
• Redness at the injection site
• Swelling at the injection site
• Fatigue

Common (these may occur with up to 1 in 10 doses of the vaccine):

• Feeling sick, diarrhoea, vomiting, stomach pain
• Headache
• Joint pain
• Shivering
• Fever

Uncommon (these may occur with up to 1 in 100 doses of the vaccine):

• Rash
• Itching at the injection site

Side effects that occurred in adults >18 years of age

Very common (these may occur with more than 1 in 10 doses of the vaccine):

• Local reactions: pain
• Fatigue
• Muscular pain (myalgia)

Common (these may occur with up to 1 in 10 doses of the vaccine):

• Headache
• Feeling sick, diarrhoea, vomiting, stomach pain
• Joint pain (arthralgia)
• Fever, shivering
• Local reactions: redness, swelling

Uncommon (these may occur with up to 1 in 100 doses of the vaccine):

• Bruising (haematoma), itching (pruritus) around the area where the vaccine is injected
• Dizziness

In addition, side effects that occurred during clinical studies in subjects from 3 years of age with Fluarix (trivalent influenza vaccine) were:

Common (these may occur with up to 1 in 10 doses of the vaccine):

• Hardness (induration) around the area where the vaccine is injected
• Sweating

These reactions usually disappear within 1–2 days without treatment.

Next to the above side effects, the following side effects occurred occasionally during general use of Fluarix and/or Fluarix Tetra:

• allergic reactions:

• – leading to medical emergency with a failure of the circulatory system to maintain adequate blood flow to the different organs (shock) in rare cases,

• – swelling most apparent in the head and neck, including the face, lips, tongue, throat or any other part of the body (angioedema) in very rare cases.

• skin reactions that may spread throughout the body including itchiness (pruritus, urticaria) and redness (erythema) of the skin
• neurological disorders that may result in stiff neck, confusion, numbness, pain and weakness of the limbs, loss of balance, loss of reflexes, paralysis of part or all the body (encephalomyelitis, neuritis, Guillain-Barre syndrome)
• temporary swelling of the glands in the neck, armpit or groin (transient lymphadenopathy)
• flu-like symptoms, generally feeling unwell (malaise)

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes 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 fluarix tetra

Keep this vaccine out of the sight and reach of children.

Do not use this vaccine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of that month.

Store in a refrigerator (2°C – 8°C).

Do not freeze.

Store in the original package in order to protect from light.

Do not throw away any medicines via wastewater or household waste. 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 Fluarix Tetra contains

The active substance is : Influenza virus (inactivated, split) of the following strains*: A/Victoria/2570/2019 (H1N1)pdm09 – like strain (A/Victoria/2570/2019, IVR-215)

15 micrograms HA

A/Cambodia/e0826360/2­020 (H3N2) – like strain (A/Tasmania/503/2020, IVR-221)

15 micrograms HA B/Washington/02/2019 – like strain (B/Washington/02/2019, wild type) 15 micrograms HA** B/Phuket/3073/2013 – like strain (B/Phuket/3073/201­3, wild type) 15 micrograms HA**

per 0.5 ml dose

• * propagated in fertilised hens’ eggs from healthy chicken flocks

• * * haemagglutinin

This vaccine complies with the World Health Organisation (WHO) recommendation (northern hemisphere) and EU recommendation for the 2021/2022 season.

The other ingredients are : sodium chloride, disodium phosphate dodecahydrate, potassium dihydrogen phosphate, potassium chloride, magnesium chloride hexahydrate, a-tocopheryl hydrogen succinate, polysorbate 80, octoxinol 10 and water for injections.

What Fluarix Tetra looks like and contents of the pack

Fluarix Tetra is a suspension for injection in pre-filled syringe (0.5 ml) with or without needles in the following pack sizes:

• – with 1 needle: pack sizes of 1 or 10

• – with 2 needles: pack size of 1

• – without needle: pack sizes of 1 or 10.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

[To be completed nationally]

This medicinal product is authorised in the Member States of the EEA under the following names:

This leaflet was last revised in

The following information is intended for healthcare professional only:

As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of an anaphylactic event following the administration of the vaccine.

Immunisation should be carried out by intramuscular injection.

Fluarix Tetra should under no circumstances be administered intravascularly.

Fluarix Tetra may be given at the same time as other vaccines. Immunisation should be carried out on separate limbs.

The vaccine should be allowed to reach room temperature before use.

Shake before use. Inspect visually prior to administration.

Instructions for administration of the vaccine presented in pre-filled syringe

To attach the needle to the syringe, refer to the drawing.

Syringe

• 1. Holding the syringe barrel in one hand (avoid holding the syringe plunger), unscrew the syringe cap by twisting it anticlockwise.

• 2. To attach the needle to the syringe, twist the needle clockwise into the syringe until you feel it lock (see picture).

• 3. Remove the needle protector, which on occasion can be a little stiff.

• 4. Administer the vaccine.

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

• 7. MARKETING AUTHORISATION HOLDER

• 8. MARKETING AUTHORISATION NUMBER(S)

[To be completed nationally]

• 9. DATE OF FIRST AUTHORISATION / RENEWAL OF THE AUTHORISATION

Date of first authorisation:

Date of latest renewal:

[To be completed nationally]

• 10. DATE OF REVISION OF THE TEXT

[To be completed nationally]

LABELLING

PARTICULARS TO APPEAR ON THE OUTER PACKAGING PRE-FILLED SYRINGE

• 1. NAME OF THE MEDICINAL PRODUCT

Fluarix Tetra suspension for injection in pre-filled syringe

Influenza vaccine (split virion, inactivated)

2021/2022 season

• 2. STATEMENT OF ACTIVE SUBSTANCE(S)

WHO/EU recommended strains for 2021/2022 season (northern hemisphere):

A/Victoria/2570/2019 (H1N1)pdm09 – like strain 15 micrograms HA*

A/Cambodia/e0826360/2­020 (H3N2) – like strain 15 micrograms HA*

B/Washington/02/2019 – like strain 15 micrograms HA*

B/Phuket/3073/201­3 – like strain 15 micrograms HA*

haemagglutinin

• 3. LIST OF EXCIPIENTS

Sodium chloride, disodium phosphate dodecahydrate, potassium dihydrogen phosphate, potassium chloride, magnesium chloride hexahydrate, a-tocopheryl hydrogen succinate, polysorbate 80, octoxinol 10 and water for injections

• 4. PHARMACEUTICAL FORM AND CONTENTS

Suspension for injection in a pre-filled syringe:

1 pre-filled syringe without needle

1 dose (0.5 ml)

1 pre-filled syringe + 1 needle

1 dose (0.5 ml)

1 pre-filled syringe + 2 needles

1 dose (0.5 ml)

10 pre-filled syringes without needle

10 × 1 dose (0.5 ml)

10 pre-filled syringes + 10 needles

10 × 1 dose (0.5 ml)

• 5. METHOD AND ROUTE(S) OF ADMINISTRATION

Intramuscular use

Read the package leaflet before use.

Shake before use.

• 6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED

OUT OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children

• 7. OTHER SPECIAL WARNING(S), IF NECESSARY

For use in adults and children from 6 months of age

• 8. EXPIRY DATE

EXP

• 9. SPECIAL STORAGE CONDITIONS

Store in a refrigerator

Do not freeze

Store in the original package in order to protect from light

• 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 [To be completed nationally]

• 12. MARKETING AUTHORISATION NUMBER(S) [To be completed nationally]

• 13. BATCH NUMBER

Lot

• 14. GENERAL CLASSIFICATION FOR SUPPLY

• 15. INSTRUCTIONS ON USE

• 16. INFORMATION IN BRAILLE

Justification for not including Braille accepted

• 17. UNIQUE IDENTIFIER – 2D BARCODE 2D barcode carrying the unique identifier included.

• 18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC

SN

NN

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

• 1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Fluarix Tetra Influenza vaccine 2021/2022 season IM

• 2. METHOD OF ADMINISTRATION

• 3. EXPIRY DATE

EXP

• 4. BATCH NUMBER

Lot

• 5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 1 dose (0.5 ml)

• 6. OTHER

PACKAGE LEAFLET

Package leaflet: Information for the user

Fluarix Tetra suspension for injection in pre-filled syringe

This leaflet has been written assuming the person receiving the vaccine is reading it, but it can be given to adolescents and children so you may be reading it for your child.

Read all of this leaflet carefully before you or your child start receiving this vaccine 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 or pharmacist.

• – This vaccine has been prescribed for you or your child only. Do not pass it on to others.

• – If you or your child get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

• 1. What Fluarix Tetra is and what it is used for

• 2. What you need to know before you use Fluarix Tetra

• 3. How Fluarix Tetra is given

• 4. Possible side effects

• 5. How to store Fluarix Tetra

• 6. Contents of the pack and other information

1. what fluarix tetra is and what it is used for

Fluarix Tetra is a vaccine. This vaccine helps to protect you against influenza (flu), particularly in subjects who run a high risk of associated complications. The use of Fluarix Tetra should be based on official recommendations.

When a person is given the vaccine Fluarix Tetra, the immune system (the body’s natural defence system) will produce its own protection (antibodies) against the disease. None of the ingredients in the vaccine can cause flu.

Flu is a disease that can spread rapidly and is caused by different types of strains that can change every year. Therefore, this is why you might need to be vaccinated every year. The greatest risk of catching flu is during the cold months between October and March. If you were not vaccinated in the autumn, it is still sensible to be vaccinated up until the spring since you run the risk of catching flu until then. Your doctor will be able to recommend the best time to be vaccinated. Fluarix Tetra will protect you against the four strains of virus contained in the vaccine from about 2 to 3 weeks after the injection.

The incubation period for flu is a few days, so if you are exposed to flu immediately before or after your vaccination, you could still develop the illness.

The vaccine will not protect you against the common cold, even though some of the symptoms are similar to flu.

2. what you need to know before you use fluarix tetra

To make sure that Fluarix Tetra is suitable for you, it is important to tell your doctor or pharmacist if any of the points below apply to you. If there is anything you do not understand, ask your doctor or pharmacist to explain.

Do not use Fluarix Tetra

• – If you are allergic to the active substances or any of the other ingredients of this medicine (listed in section 6) or any components that may be present in very small amounts such as eggs (ovalbumin or chicken proteins), formaldehyde, gentamicin sulphate or sodium deoxycholate.

• – If you have an illness with a high temperature or acute infection, the vaccination shall be postponed until after you have recovered.

Warnings and precautions

Talk to your doctor or pharmacist before you receive Fluarix Tetra:

• – if you have a poor immune response (immunodeficiency or taking medicines affecting the immune system).

• – if, for any reason, you have a blood test within a few days following a flu vaccination. This is because false positive blood test results have been observed in a few patients who had recently been vaccinated.

• – if you have a bleeding problem or bruise easily.

Your doctor will decide if you should receive the vaccine.

Fainting can occur (mostly in adolescents) following, or even before, any needle injection, therefore tell the doctor or nurse if you fainted with a previous injection.

As with all vaccines, Fluarix Tetra may not fully protect all persons who are vaccinated.

Other medicines and Fluarix Tetra

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Fluarix Tetra can be given at the same time as other vaccines by using separate limbs.

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.

Your doctor/pharmacist will be able to decide if you should receive Fluarix Tetra. Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Fluarix Tetra has no or negligible influence on the ability to drive or use machines.

Fluarix Tetra contains sodium

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially “sodium free”.

Fluarix Tetra contains potassium

This medicine contains potassium, less than 1 mmol (39 mg) per dose, i.e. essentially “potassium-free”.

• 3. How Fluarix Tetra is given

  Adults receive one 0.5 ml dose.

Use in children:

Children from 6 months and older receive one 0.5 ml dose.

If your child is younger than 9 years of age and has not been previously vaccinated against flu, a second dose should be given after at least 4 weeks.

Method and/or route of administration

Your doctor will administer the recommended dose of the vaccine as an injection into the muscle. If you have any further questions on the use of this product, ask your doctor or pharmacist.

4. possible side effects

Like all medicines, this vaccine can cause side effects, although not everybody gets them.

During clinical trials, the following side effects have been observed.

Side effects that occurred in children 6 to 36 months of age

Very common (these may occur with more than 1 in 10 doses of the vaccine):

• Loss of appetite
• Irritability
• Drowsiness
• Pain at the injection site
• Redness at the injection site

Common (these may occur with up to 1 in 10 doses of the vaccine):

• Fever
• Swelling at the injection site

Side effects that occurred in children 3 to 6 years of age

Very common (these may occur with more than 1 in 10 doses of the vaccine):

• Pain at the injection site
• Redness at the injection site
• Swelling at the injection site
• Irritability

Common (these may occur with up to 1 in 10 doses of the vaccine):

• Loss of appetite
• Drowsiness
• Fever

Uncommon (these may occur with up to 1 in 100 doses of the vaccine):

• Rash
• Itching at the injection site

Side effects that occurred in children 6 to 18 years of age

Very common (these may occur with more than 1 in 10 doses of the vaccine):

• Aching muscles
• Pain at the injection site
• Redness at the injection site
• Swelling at the injection site
• Fatigue

Common (these may occur with up to 1 in 10 doses of the vaccine):

• Feeling sick, diarrhoea, vomiting, stomach pain
• Headache
• Joint pain
• Shivering
• Fever

Uncommon (these may occur with up to 1 in 100 doses of the vaccine):

• Rash
• Itching at the injection site

Side effects that occurred in adults >18 years of age

Very common (these may occur with more than 1 in 10 doses of the vaccine):

• Local reactions: pain
• Fatigue
• Muscular pain (myalgia)

Common (these may occur with up to 1 in 10 doses of the vaccine):

• Headache
• Feeling sick, diarrhoea, vomiting, stomach pain
• Joint pain (arthralgia)
• Fever, shivering
• Local reactions: redness, swelling

Uncommon (these may occur with up to 1 in 100 doses of the vaccine):

• Bruising (haematoma), itching (pruritus) around the area where the vaccine is injected
• Dizziness

In addition, side effects that occurred during clinical studies in subjects from 3 years of age with Fluarix (trivalent influenza vaccine) were:

Common (these may occur with up to 1 in 10 doses of the vaccine):

• Hardness (induration) around the area where the vaccine is injected
• Sweating

These reactions usually disappear within 1–2 days without treatment.

Next to the above side effects, the following side effects occurred occasionally during general use of Fluarix and/or Fluarix Tetra:

• allergic reactions:

• – leading to medical emergency with a failure of the circulatory system to maintain adequate blood flow to the different organs (shock) in rare cases,

• – swelling most apparent in the head and neck, including the face, lips, tongue, throat or any other part of the body (angioedema) in very rare cases.

• skin reactions that may spread throughout the body including itchiness (pruritus, urticaria) and redness (erythema) of the skin
• neurological disorders that may result in stiff neck, confusion, numbness, pain and weakness of the limbs, loss of balance, loss of reflexes, paralysis of part or all the body (encephalomyelitis, neuritis, Guillain-Barre syndrome)
• temporary swelling of the glands in the neck, armpit or groin (transient lymphadenopathy)
• flu-like symptoms, generally feeling unwell (malaise)

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes 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 fluarix tetra

Keep this vaccine out of the sight and reach of children.

Do not use this vaccine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of that month.

Store in a refrigerator (2°C – 8°C).

Do not freeze.

Store in the original package in order to protect from light.

Do not throw away any medicines via wastewater or household waste. 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 Fluarix Tetra contains

The active substance is : Influenza virus (inactivated, split) of the following strains: A/Victoria/2570/2019 (H1N1)pdm09 – like strain (A/Victoria/2570/2019, IVR-215)

15 micrograms HA

A/Cambodia/e0826360/2­020 (H3N2) – like strain (A/Tasmania/503/2020, IVR-221)

15 micrograms HA B/Washington/02/2019 – like strain (B/Washington/02/2019, wild type) 15 micrograms HA** B/Phuket/3073/2013 – like strain (B/Phuket/3073/201­3, wild type) 15 micrograms HA**

per 0.5 ml dose

• * propagated in fertilised hens’ eggs from healthy chicken flocks

• * * haemagglutinin

This vaccine complies with the World Health Organisation (WHO) recommendation (northern hemisphere) and EU recommendation for the 2021/2022 season.

The other ingredients are : sodium chloride, disodium phosphate dodecahydrate, potassium dihydrogen phosphate, potassium chloride, magnesium chloride hexahydrate, a-tocopheryl hydrogen succinate, polysorbate 80, octoxinol 10 and water for injections.

What Fluarix Tetra looks like and contents of the pack

Fluarix Tetra is a suspension for injection in pre-filled syringe (0.5 ml) with or without needles in the following pack sizes:

• – with 1 needle: pack sizes of 1 or 10

• – with 2 needles: pack size of 1

• – without needle: pack sizes of 1 or 10.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

[To be completed nationally]

This medicinal product is authorised in the Member States of the EEA under the following names:

This leaflet was last revised in

The following information is intended for healthcare professional only:

As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of an anaphylactic event following the administration of the vaccine.

Immunisation should be carried out by intramuscular injection.

Fluarix Tetra should under no circumstances be administered intravascularly.

Fluarix Tetra may be given at the same time as other vaccines. Immunisation should be carried out on separate limbs.

The vaccine should be allowed to reach room temperature before use.

Shake before use. Inspect visually prior to administration.

Instructions for administration of the vaccine presented in pre-filled syringe

To attach the needle to the syringe, refer to the drawing.

• 1. Holding the syringe barrel in one hand (avoid holding the syringe plunger), unscrew the syringe cap by twisting it anticlockwise.

• 2. To attach the needle to the syringe, twist the needle clockwise into the syringe until you feel it lock (see picture).

• 3. Remove the needle protector, which on occasion can be a little stiff.

• 4. Administer the vaccine.