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Fluarix Tetra

Last Updated on eMC 07-Jul-2016 View changes  | GlaxoSmithKline UK Contact details

 This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions.

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/California/7/2009 (H1N1)pdm09 - like strain (A/Christchurch/16/2010, NIB-74xp)

15 micrograms HA**

A/Hong Kong/4801/2014 (H3N2) - like strain (A/Hong Kong/4801/2014, NYMC X-263B)

15 micrograms HA**

B/Brisbane/60/2008 - like strain (B/Brisbane/60/2008, 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 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 2016/2017 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 3 years of age for the prevention of influenza disease caused by the two influenza A virus subtypes and the two influenza B virus types contained in the vaccine.

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 36 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 3 years: the safety and efficacy of Fluarix Tetra in children less than 3 years 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 should be postponed in patients with febrile illness or acute infection.

4.4 Special warnings and precautions for use

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

No interaction studies have been performed. 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.

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 two clinical studies, healthy adults 18 years of age and older and healthy children 3 to 17 years of age were administered Fluarix Tetra (more than 3,000 adults and 900 children) or GlaxoSmithKline trivalent influenza vaccine, Fluarix (more than 1,000 adults and 900 children).

Similar rates of solicited adverse events were observed in recipients of Fluarix Tetra and Fluarix.

In all age groups the most frequently reported local adverse reaction after vaccination was injection site pain (36.4% 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%).

List of adverse reactions

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

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

Metabolism and nutrition disorders

Common: appetite loss1

Psychiatric disorders

Very common: irritability1

Nervous system disorders

Common: drowsiness1, headache

Uncommon: dizziness2

Gastrointestinal disorders

Common: gastrointestinal symptoms (including nausea, vomiting, diarrhoea and/or abdominal pain)

Skin and subcutaneous tissue disorders

Uncommon: rash3

Musculoskeletal and connective tissue disorders

Very common: myalgia

Common: arthralgia

General disorders and administration site conditions

Very common: injection site pain, fatigue

Common: injection site redness4, injection site swelling4, shivering, fever

Uncommon: injection site hematoma2, injection site pruritus

1reported as a solicited symptom in subjects less than 6 years of age

2reported in adult subjects

3reported in subjects 3 years to 17 years of age

4very common in subjects 3 years to 17 years of age

In addition, the following adverse reactions were reported in previous Fluarix trials:

Skin and subcutaneous tissue disorders

Common: sweating

General disorders and administration site conditions

Common: injection site induration

Post-marketing data

The following adverse events that have been observed for Fluarix during post-marketing surveillance may occur in patients receiving Fluarix Tetra post-approval, as all three of the influenza strains contained in Fluarix are included in Fluarix Tetra.

Blood and lymphatic system disorders

Rare: transient lymphadenopathy

Immune system disorders

Rare: allergic reactions (including anaphylactic reactions)

Nervous system disorders

Rare: neuritis, acute disseminated encephalomyelitis, Guillain-Barré syndrome*

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

Skin and subcutaneous tissue disorders

Rare: urticaria, pruritus, erythema, angioedema

General disorders and administration site conditions

Rare: influenza-like illness, malaise

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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard

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 types) contained in the vaccine.

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

Specific levels of hemagglutination-inhibition (HI) antibody titer post-vaccination with inactivated influenza virus vaccines have not been correlated with protection from influenza illness but the HI antibody titers 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

Immunogenicity of Fluarix Tetra versus Fluarix

Clinical studies performed in adults (D-QIV-001 and D-QIV-008) and in children 3 years to 17 years of age (D-QIV-003) assessed the non-inferiority of Fluarix Tetra versus Fluarix for HI Geometric mean antibody titer (GMT) at Day 21 (for adults) and at Day 28 (for children) and HI seroconversion rate (4-fold rise in reciprocal titer or change from undetectable [< 10] to a reciprocal titer of ≥ 40).

In all studies, the immune response elicited by Fluarix Tetra against the three strains in common was non-inferior to Fluarix. Fluarix Tetra elicited a superior immune response against the additional B strain included in Fluarix Tetra compared to Fluarix.

Adults 18 years of age and older

In clinical study D-QIV-008, approximately 1,800 adults 18 years of age and older received a single dose of Fluarix Tetra and approximately 600 subjects received a single dose of Fluarix.

Table 1: Post-vaccination GMT and seroconversion rates:

Adults 18 years of age and older

Fluarix Tetra

N=1809

Fluarix1

N=608

GMT (95% confidence interval)

A/H1N1

201.1 (188.1;215.1)

218.4 (194.2;245.6)

A/H3N2

314.7 (296.8;333.6)

298.2 (268.4;331.3)

B (Victoria)2

404.6 (386.6;423.4)

393.8 (362.7;427.6)

B (Yamagata)3

601.8 (573.3;631.6)

386.6 (351.5;425.3)

Seroconversion rate (95% confidence interval)

A/H1N1

77.5% (75.5;79.4)

77.2% (73.6;80.5)

A/H3N2

71.5% (69.3;73.5)

65.8% (61.9;69.6)

B (Victoria)

58.1% (55.8;60.4)

55.4% (51.3;59.4)

B (Yamagata)

61.7% (59.5;64.0)

45.6% (41.6;49.7)

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

2recommended strain by WHO during the season 2010-2011

3additional B strain contained in Fluarix Tetra recommended in season 2008-2009

Post-vaccination seroprotection rates (Day 21 reciprocal titer of ≥ 40) for Fluarix Tetra were 91.3% against A/H1N1, 96.8% against A/H3N2, 98.8% against B (Victoria) and 91.8% against B (Yamagata).

In clinical study D-QIV-001 (vaccine composition of 2007-2008 season), post-vaccination seroprotection rates for Fluarix Tetra were 92.3% against A/H1N1, 97.1% against A/H3N2, 97.1% against B (Victoria) and 98.1% against B (Yamagata).

Children 3-17 years of age

In clinical study (D-QIV-003), approximately 900 children from 3-17 years of age received one or two doses of Fluarix Tetra or Fluarix, respectively.

Table 2: Post-vaccination GMT and seroconversion rates:

Children 3 years to 17 years of age

Fluarix Tetra

N=791

Fluarix1

N=818

GMT (95% confidence interval)

A/H1N1

386.2 (357.3;417.4)

433.2 (401.0;468.0)

A/H3N2

228.8 (215.0;243.4)

227.3 (213.3;242.3)

B (Victoria)2

244.2 (227.5;262.1)

245.6 (229.2;263.2)

B (Yamagata)3

569.6 (533.6;608.1)

224.7 (207.9;242.9)

Seroconversion rate (95% confidence interval)

A/H1N1

91.4% (89.2;93.3)

89.9% (87.6;91.8)

A/H3N2

72.3% (69.0;75.4)

70.7% (67.4;73.8)

B (Victoria)

70.0% (66.7;73.2)

68.5% (65.2;71.6)

B (Yamagata)

72.5% (69.3;75.6)

37.0% (33.7;40.5)

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

2recommended strain by WHO during the season 2010-2011

3additional B strain contained in Fluarix Tetra recommended in season 2008-2009

Post-vaccination seroprotection rates for Fluarix Tetra were 96.6% against A/H1N1, 98.0% against A/H3N2, 97.3% against B (Victoria) and 99.2% against B (Yamagata).

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 below table 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)

Attack Rates (n/N)1

Vaccine Efficacy (95% CI2)

N

n

%

%

LL3

UL

Antigenically matched, culture-confirmed Influenza4

Fluarix

5,103

49

1.0

66.9

51.9

77.4

Placebo

2,549

74

2.9

-

-

-

All culture-confirmed Influenza (Matched, Unmatched and Untyped)5

Fluarix

5,103

63

1.2

61.6

46.0

72.8

Placebo

2,549

82

3.2

-

-

-

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

Adults 18 years to 64 years

Fluarix1

N=291

GMT (95% confidence interval)

A/H1N1

541.0 (451.0;649.0)

A/H3N2

133.2 (114.6;154.7)

B (Victoria)

242.8 (210.7;279.7)

Seroconversion rate (95% confidence interval)

A/H1N1

76.3% (71.0;81.1)

A/H3N2

73.9% (68.4;78.8)

B (Victoria)

85.2% (80.6;89.1)

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).

The European Medicines Agency has deferred the obligation to submit the results of studies with Fluarix Tetra in one or more subsets of the paediatric population in the prevention of influenza disease caused by the two influenza A virus subtypes and the two influenza B virus types contained in the vaccine. (see Section 4.2 for information on paediatric use).

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, α-tocopheryl hydrogen succinate, polysorbate 80, octoxinol 10 and 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

0.5 ml suspension in prefilled syringe (Type I glass) with a plunger stopper (grey butyl rubber) with fixed or separate or without needles in the following pack sizes:

- with fixed needle: pack sizes of 1 or 10

- with 1 separate needle: pack sizes of 1 or 10

- with 2 separate needles: pack size of 1

- without needle: pack size 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 without a fixed needle

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

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

7. Marketing authorisation holder

SmithKline Beecham Limited

980 Great West Road

Brentford

Middlesex

TW8 9GS

Trading as:

GlaxoSmithKline UK

Stockley Park West

Uxbridge

Middlesex

UB11 1BT

8. Marketing authorisation number(s)

PL 10592/0302

9. Date of first authorisation/renewal of the authorisation

Date of first authorisation: 21 March 2013

Date of latest renewal:

10. Date of revision of the text

15 June 2016

Company contact details

GlaxoSmithKline UK

Company image
Address

Stockley Park West, Uxbridge, Middlesex, UB11 1BT

Fax

+44 (0)208 990 4328

Medical Information e-mail
Telephone

0800 221 441

E-mail
Customer Care direct line

0800 221 441

Before you contact this company: often several companies will market medicines with the same active ingredient. Please check that this is the correct company before contacting them. Why?

Active ingredients

influenza vaccine (split virion, inactivated)

Legal categories

POM - Prescription Only Medicine

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