FLUCELVAX TETRA 15UG/0.5ML DOSE SUSPENSION FOR INJECTION - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Flucelvax Tetra – suspension for injection in pre-filled syringe

Influenza vaccine (surface antigen, inactivated, prepared in cell cultures)

2. QUALITATIVE AND QUANTITATIVECOMPOSITION

Influenza virus surface antigens (haemagglutinin and neuraminidase), inactivated, of the following strains*:

A/Wisconsin/588/2019 (H1N1)pdm09-like strain (A/Washington/19/2020, wild type) 15 micrograms HA

A/Cambodia/e0826360/2­020 (H3N2)-like strain (A/Tasmania/503/2020, wild type) 15 micrograms HA

B/Washington/02/2019-like strain (B/Darwin/7/2019, wild type) 15 micrograms HA

B/Phuket/3073/2013-like strain (B/Singapore/INFTT-16–0610/2016, wild type) 15 micrograms HA per 0.5 ml dose

*

**

propagated in Madin Darby Canine Kidney (MDCK) cells haemagglutinin

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

Flucelvax Tetra may contain traces of beta-propiolactone, cetyltrimethy­lammonium bromide, and polysorbate 80.

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Suspension for injection in pre-filled syringe (injection).

Clear to slightly opalescent liquid.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Prophylaxis of influenza in adults and children from 2 years of age.

Flucelvax Tetra should be used in accordance with official recommendations.

4.2 Posology and method of administration

Posology

Adults and children from 2 years of age:

a Children less than 9 years of age who have not been previously vaccinated against influenza, should

receive a second dose.

The safety and efficacy of Flucelvax Tetra in children from birth to less than 2 years of age has not

been established.

Method of administration

For intramuscular injection only.

The preferred site for injection is the deltoid muscle of the upper arm. Young children with

insufficient deltoid mass should be vaccinated in the anterolateral aspect of the thigh.

The vaccine must not be injected intravenously, subcutaneously or intradermally and must not be

mixed with other vaccines in the same syringe.

For instructions on the handling of the vaccine before administration, see section 6.6.

4.3 Contraindications

Hypersensitivity to the active substance, to any of the excipients listed in section 6.1, or to possible

trace residues such as beta-propiolactone, cetyltrimethy­lammonium bromide, and polysorbate 80.

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.

Appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic event following the administration of the vaccine.

Vaccination should be postponed in patients with acute febrile illness until the fever is resolved.

As with all injectable vaccines, Flucelvax Tetra must be administered with caution to individuals with thrombocytopenia or a bleeding disorder since bleeding may occur following an intramuscular

administration.

Syncope (fainting) can occur following, or even before, any vaccination 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.

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

to prevent influenza.

A protective immune response may not be elicited in all vaccine recipients.

4.5 Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed with Flucelvax Tetra. Concomitant administration of Flucelvax Tetra with other vaccines has not been studied in trials conducted by Seqirus. Based on clinical experience with cell-based trivalent influenza vaccine (TIVc), Flucelvax Tetra can be given at the same time as other vaccines. If Flucelvax Tetra is to be used at the same time as another vaccine, it should be administered at separate injection sites and preferably on different limbs. It should be noted that the adverse reactions may be intensified.

Data assessed by the MHRA that support concomitant administration of influenza vaccines with COVID-19 vaccines (but at separate injection sites) are based on the ComFluCOV study [EudraCT Number: 2021–001124–18], which investigated concomitant administration in adults of Flucelvax Tetra with COVID-19 mRNA Vaccine BNT162b2 (Pfizer/BioNTech) and COVID-19 Vaccine AstraZeneca. The data show that the antibody responses are unaffected and that the reactogenicity profile is acceptable.

4.6 Fertility, pregnancy and lactation

Pregnancy

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

A prospective Pregnancy Exposure Registry was conducted in the Unites States (US) and data were collected from 665 women vaccinated with Flucelvax Tetra during 3

Northern Hemisphere influenza seasons (2017–18 to 2019–20), of whom 28% were exposed during their first trimester. Based on pregnancy outcomes and predefined infant safety outcomes, there was no evidence of adverse foetal, newborn or pregnancy outcomes attributable to the vaccine during any stage of pregnancy. Of 665 exposed pregnancies, 659 resulted in live births, with 667 infants born. There were no stillbirths. Prevalence rates for the infant outcomes of low birth weight (5.8%), preterm birth (9.2%) and major congenital malformations (1.9%), were below the rates reported in the general US population of 8.3%, 10.2% and 2.8%, respectively.

There have been no reproductive and developmental toxicology studies with Flucelvax Tetra. Reproductive and developmental toxicology data from cell-based trivalent influenza vaccine (TIVc) do not predict an increased risk of developmental abnormalities.

Breast-feeding

It is unknown whether Flucelvax Tetra is excreted in human milk. No effects on breast fed newborn/infant are anticipated. Flucelvax Tetra may be given during lactation.

Fertility

No human fertility data are available. Animal data, with cell-based trivalent influenza vaccine (TIVc), have not shown effects on female fertility. Male fertility has not been assessed in animals.

4.7 Effects on ability to drive and use machines

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

4.8 Undesirable effects

Summary of the safety profile

The safety of Flucelvax Tetra in adults 18 years and older was evaluated in a randomised, controlled

study (V130_01), in which 1334 subjects received Flucelvax Tetra. Similar rates of solicited local and

systemic adverse reactions were reported in subjects who received Flucelvax Tetra and cell-based

trivalent influenza vaccine comparator in this clinical trial.

The most commonly reported (>10%) reactions in subjects who received Flucelvax

Tetra were pain at

the injection site (34%), headache (14%), fatigue (14%), myalgia (14%), erythema (13%) and

induration (10%).

The incidence of some adverse reactions were considerably lower among subjects > 65 years of age

when compared to subjects 18 to < 65 years of age (see table below).

Tabulated list of adverse reactions

Adverse reactions reported are listed according to the following frequency categories:

Very common

(>1/10); Common (>1/100 to <1/10); Uncommon (>1/1,000 to <1/100), not known (cannot be estimated

from the available data).

Table 1: Adverse reactions reported following vaccination in adults 18 years and older in clinical trials and post-marketing surveilance.

1 Reported as Common in the elderly population 65 years of age and older

2 Reported as Uncommon in the elderly population 65 years of age and older

3 Adverse reactions reported from post-marketing surveillance

Paediatric population (2 to less than 18 years of age)

The safety of Flucelvax Tetra in children 2 to less than 18 years of age has been evaluated in two

clinical studies, V130_03 and V130_12. In the randomised, controlled study

V130_03, 1159

paediatric subjects received Flucelvax Tetra (584 subjects 9 to <18 years; 575 subjects 4 to <9 years).

Children 9 to less than 18 years of age received a single dose of Flucelvax Tetra.

Children 4 to less

than 9 years of age received one or two doses (separated by 4 weeks) of Flucelvax Tetra based on

determination of the subject’s prior influenza vaccination history. In this age group, 235 paediatric

subjects received one dose and 340 subjects received two doses. Similar rates of solicited local and

systemic adverse reactions were reported in subjects who received Flucelvax Tetra and cell-based

trivalent influenza vaccine comparator in this clinical trial.

In the multinational, randomised, observer-blind study V130_12, the safety population included a total

of 2255 children 2 to less than 18 years of age who received Flucelvax Tetra (580 subjects 2 to < 6

years; 564 subjects 6 to < 9 years; 1111 subjects 9 to < 18 years). Children 9 to less than 18 years of

age received a single dose of Flucelvax Tetra. Children 2 to less than 9 years of age received one or

two doses (separated by 28 days) of Flucelvax Tetra based on determination of the subject’s prior

influenza vaccination history.

The most common local and systemic adverse reactions reported in either study is described below by

paediatric sub-group.

The most common (>10%) local and systemic adverse reactions after one dose reported in paediatric

subjects of 9 to < 18 years of age were injection site pain (58%), headache (22%), erythema (19%),

fatigue (18%), myalgia (16%), and induration (15%).

The most common (>10%) local and systemic adverse reactions after any vaccination in children 6 to

less than 9 years of age were pain at the injection site (61%), injection site erythema (25%), injection site induration (19%), fatigue (16%), headache (16%) and injection site ecchymosis (11%).

The most common (>10%) local and systemic adverse reactions after any vaccination in children 2 to

less than 6 years of age were tenderness at the injection site (54%), injection site erythema (23%),

sleepiness (21%), irritability (19%), injection site induration (15%), change in eating habits (14%) and

injection site ecchymosis (11%).

Compared to adults 18 years of age and older, paediatric subjects generally reported higher rates of local

and systemic adverse reactions.

In children who received a second dose of Flucelvax Tetra the incidence of adverse reactions following

the second dose of vaccine was similar or slightly lower to that observed with the first dose.

The frequency of adverse reactions in children 2 to less and 18 years of age in these clinical studies are

described in Table 2 below.

Table 2: Solicited adverse reactions reported in clinical studies in children 2 to < 18

years of age

1 The youngest age range in study V130_03 was 4 to < 6 years

2Myalgia reported with a frequency of Common (3% and 6%) in children 6 to < 9 and 9 to < 18 years, respectively,

in study V130_12

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 or search for MHRA Yellow Card in the Google Play or Apple App

Store.

4.9 Overdose

5   PHARMACOLOGICAL PROPERTIES

5.1   Pharmacodynamic properties

5.2 Pharmacokinetic properties

Not applicable.

5.3 Preclinical safety data

6   PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sodium chloride

Potassium chloride

Magnesium chloride hexahydrate

Disodium phosphate dihydrate

Potassium dihydrogen phosphate

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

12 months

6.4 Special precautions for storage

Store in a refrigerator (2°C – 8°C).

Do not freeze.

Keep the pre-filled syringe in the outer carton in order to protect from light.

6.5 Nature and contents of container

0.5 ml suspension in pre-filled syringes (type I glass), with a plunger stopper (bromobutyl rubber),

with or without needle.

Pack of 1 pre-filled syringe, with or without needle

Pack of 10 pre-filled syringes, with or without needles.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Shake before use. After shaking, the normal appearance of the vaccine is a clear to slightly opalescent

suspension.

The vaccine should be visually inspected for particulate matter and discoloration prior to

administration. In the event of any foreign particulate matter and/or variation of physical aspect is

observed, do not administer the vaccine.

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

requirements.

7 MARKETING AUTHORISATION HOLDER

Seqirus UK Ltd.

Point, 29 Market Street,

Maidenhead SL6 8AA, UK