CELL-BASED QUADRIVALENT INFLUENZA VACCINE (SURFACE ANTIGEN INACTIVATED) SEQIRUS FOR INJECTION - summary of medicine characteristics

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

Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe.

Influenza vaccine, prepared in cell cultures

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

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

A/Hawaii/70/2019 (H1N1)pdm09-like strain (A/Nebraska/14/2019, wild type)

15 micrograms HA

A/Hong Kong/45/2019 (H3N2)-like strain (A/Delaware/39/2019, 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 2020/2021 season.

Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe may contain traces of betapropiolactone, 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.

Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe should be used in accordance with official recommendations.

4.2 Posology and method of administration

Posology

Adults and children from 2 years of age:

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 Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe 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, Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe 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 Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe. There are no data available on co-administration of Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe with other vaccines. Based on clinical experience with cell-based trivalent influenza vaccine (TIVc), Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe can be given at the same time as other vaccines.

4.6 Fertility, pregnancy and lactation

Pregnancy

There are limited data from the use of Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe in pregnant women. However, inactivated influenza vaccines can be used in all stages of pregnancy. For egg-derived influenza vaccines larger datasets on safety are available for the second and third trimester, compared with the first trimester; however, data from worldwide use of influenza vaccine do not indicate any adverse foetal and maternal outcomes attributable to the vaccine.

There are no reproductive and developmental toxicology studies with Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe. 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 Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe is excreted in human milk. No effects on breast fed newborn/infant are anticipated. Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe may be used 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

Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe 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 Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe in adults 18 years and older was evaluated in a randomised, controlled study (V130_01), in which 1334 subjects received Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe. Similar rates of solicited local and systemic adverse reactions were reported in subjects who received Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe and cell-based trivalent influenza vaccine comparator in this clinical trial.

The most commonly reported (>10%) reactions in subjects who received Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe 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 surveillance.

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 Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe 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 Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe (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 Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe. Children 4 to less than 9 years of age received one or two doses (separated by 4 weeks) of Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe 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 Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe 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 Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe (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 Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe. Children 2 to less than 9 years of age received one or two doses (separated by 28 days) of Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe 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 Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe 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

2 Myalgia 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 Y ellow 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

Non-clinical data reveal no special hazard for humans based on conventional studies of repeated dose toxicity and toxicity to reproduction and development.

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.

The Point, 29 Market Street,

Maidenhead SL6 8AA, UK