INFLUENZA VACCINE TETRA MYL SUSPENSION FOR INJECTION IN PRE-FILLED SYRINGE - 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

Influenza vaccine Tetra MYL, suspension for injection in pre-filled syringe (influenza vaccine, surface antigen, inactivated).

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

* 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.

For a full list of excipients see section 6.1.

Influenza vaccine Tetra MYL may contain traces of eggs (such as ovalbumin, chicken proteins), formaldehyde, cetyltrimethy­lammonium bromide, polysorbate 80 or gentamicin, which are used during the manufacturing process (see section 4.3).

3 PHARMACEUTICAL FORM

Suspension for injection in pre-filled syringe.

A colourless clear liquid, filled in single-dose syringes.

4.1 Therapeutic indications

Prophylaxis of influenza, especially those who run an increased risk of associated complications.

Influenza vaccine Tetra MYL is indicated in adults and children from 6 months of age.

The use of Influenza vaccine Tetra MYL should be based on official recommendations.

4.2 Posology and method of administration

Posology

Adults: 0.5 ml.

Paediatric population

Children from 6 months to 17 years of age: 0.5 ml.

Children less than 9 years of age, who have not previously been vaccinated with a seasonal influenza vaccine: a second dose of 0.5 ml should be given after an interval of at least 4 weeks.

Infants less than 6 months of age: the safety and efficacy of Influenza vaccine Tetra MYL have not been established.

Method of Administration

Immunisation should be carried out by intramuscular or deep subcutaneous injection. The preferred sites for intramuscular injection are the anterolateral aspect of the thigh (or the deltoid muscle if muscle mass is adequate) in children 6 months through 35 months of age, or the deltoid muscle in children from 36 months of age and adults.

Precautions to be taken before handling or administrating 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, 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, cetyltrimethy­lammonium bromide, polysorbate 80 or gentamicin.

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.

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.

Influenza vaccine Tetra MYL should under no circumstances be administered intravascularly.

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

Anxiety-related reactions, including vasovagal reactions (syncope), hyperventilation or stress-related reactions 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.

Influenza vaccine Tetra MYL is not effective against all possible strains of influenza virus. Influenza vaccine Tetra MYL 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 vaccines.

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

Interference with serological testing: see section 4.5.

This medicine 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 Influenza vaccine Tetra MYL is given at the same time as other vaccines, immunisation should be carried out on separate limbs. It should be noted that the adverse reactions may be intensified.

The immunological response may be diminished if the patient is undergoing immunosuppressant treatment.

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 influenza vaccine do not indicate any adverse foetal and maternal outcomes attributable to the vaccine.

Breast-feeding

Influenza vaccine Tetra MYL may be used during breast-feeding.

Fertility

No fertility data are available.

4.7 Effects on ability to drive and use machines

Influenza vaccine Tetra MYL has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

a. Summary of the safety profile

The safety of Influenza vaccine Tetra MYL was assessed in three clinical trials.

In two clinical studies, healthy adults 18 years of age and older, and healthy children 3 to 17 years of age were administered Influenza vaccine Tetra MYL or trivalent influenza vaccine Influvac.

In a third study, the safety of Influenza vaccine Tetra MYL was assessed in healthy children from 6 months to 35 months of age administered Influenza vaccine Tetra MYL or a non-influenza vaccine control.

In both children studies, children from 6 months to 8 years of age received one or two doses of Influenza vaccine Tetra MYL depending on their influenza vaccination history.

Most reactions usually occurred within the first 3 days following vaccination and resolved spontaneously within 1 to 3 days after onset. The intensity of these reactions was generally mild.

In all age groups, the most frequently reported local adverse reaction after vaccination observed in the clinical studies for Influenza vaccine Tetra MYL was vaccination site pain.

The most frequently reported general adverse reactions after vaccination observed in the clinical studies for Influenza vaccine Tetra MYL in adults and children from 6 to 17 years of age were fatigue and headache, and for children from 3 to 5 years of age drowsiness, irritability and loss of appetite.

The most frequently reported general adverse reactions after vaccination observed in the clinical studies for Influenza vaccine Tetra MYL in children from 6 months to 35 months            of           age            were            irri­tability/fussi­ness. Similar rates of solicited adverse reactions were observed in recipients of Influenza vaccine Tetra MYL and trivalent influenza vaccine Influvac.

The rates of solicited systemic adverse reactions were similar in recipients of Influenza vaccine Tetra MYL and the non-influenza vaccine, whereby the rates of solicited local adverse reactions were lower in recipients of Influenza vaccine Tetra MYL.

b. Tabulated summary of adverse reactions

The following undesirable effects are considered at least possibly related to Influenza vaccine Tetra MYL and have either been observed during the clinical trials with Influenza vaccine Tetra MYL or are resulting from post-marketing experience with Influenza vaccine Tetra MYL and/or the trivalent influenza vaccine Influvac.

The following frequencies apply:

very common (£1/10); common (£1/100, <1/10); uncommon (£1/1,000, <1/100); and not known (adverse reactions from post-marketing experience; cannot be estimated from the available data).

Adults and elderly

Paediatric population

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

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:

Influenza vaccine Tetra MYL provides active immunisation against four influenza virus strains: an A/(H1N1) strain, an A/(H3N2) strain, and two B strains (one from each lineage; B/(Victoria) and B/(Yamagata)). Influenza vaccine Tetra MYL, manufactured according to the same process as trivalent influenza vaccine Influvac, 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.

An immune response is generally obtained within 2 to 3 weeks. The duration of postvaccinal immunity to homologous strains or to strains closely related to the vaccine strains varies but is usually 6–12 months.

Pharmacodynamic effects:

Efficacy of Influenza vaccine Tetra MYL in children 6 – 35 months of age:

The efficacy of Influenza vaccine Tetra MYL was evaluated in_a randomized, observer-blind, non-influenza vaccine-controlled study (INFQ3003) conducted during 3 influenza seasons 2017 to 2019 in Europe and Asia. Healthy subjects aged 6 – 35 months received two doses of Influenza vaccine Tetra MYL_(N=1005) or noninfluenza control vaccine (N=995) approximately 28 days apart._The efficacy of Influenza vaccine Tetra MYL_was assessed for the prevention of reverse transcription polymerase chain reaction (RT-PCR) -confirmed influenza A and/or B disease due to any influenza strain. All RT-PCR-positive specimens were further tested for viability in cell culture and to determine whether the circulating viral strains matched those in the vaccine.

Table: Efficacy in children 6 – 35 months of age

Vaccine efficacy: proportion of influenza cases prevented by the vaccination

N=number of subjects vaccinated

n=number of influenza cases

CI=confidence interval

Immunogenicity of Influenza vaccine Tetra MYL :

Clinical studies performed in adults of 18 years of age and older (INFQ3001) and children of 3 to 17 years of age (INFQ3002) assessed the safety and immunogenicity of Influenza vaccine Tetra MYL and its non-inferiority to trivalent influenza vaccine Influvac for the postvaccination HI Geometric mean antibody titer (GMT).

In both studies the immune response elicited by Influenza vaccine Tetra MYL against the three strains in common was non-inferior to trivalent influenza vaccine Influvac. Influenza vaccine Tetra MYL elicited a superior immune response against the additional B strain included in Influenza vaccine Tetra MYL_compared to trivalent influenza vaccine Influvac.

Adults 18 years of age and older:

In clinical study INFQ3001, 1,535 adults of 18 years of age and older received a single dose of Influenza vaccine Tetra MYL and 442 subjects received a single dose of trivalent Influvac:

Table: Post-vaccination GMT and Seroconversion rates

N= number of subjects included in immunogenicity analysis

Containing A/H1N1, A/H3N2 and B (Yamagata lineage)

Containing A/H1N1, A/H3N2 and B (Victoria lineage)

3recommended B strain by WHO for the season 2014–2015 NH for trivalent vaccines

4additional recommended B strain by WHO for season 2014–2015 NH for quadrivalent vaccines

Paediatric population

Children 3 – 17 years of age:

In clinical study INFQ3002, 402 children of 3 to 17 years of age received one or two doses of Influenza vaccine Tetra MYL and 798 children received one or two doses of trivalent Influvac based on their influenza vaccination history.

Table: Seroconversion rates

N= number of subjects included in immunogenicity analysis

Containing A/H1N1, A/H3N2 and B (Yamagata lineage)

Containing A/H1N1, A/H3N2 and B (Victoria lineage)

3recommended B strain by WHO for the season 2016–2017 NH for trivalent vaccines

Additional recommended B strain by WHO for season 2016–2017 NH for quadrivalent vaccines

Children 6 months – 35 months of age:

In clinical study INFQ3003 the immunogenicity of Influenza vaccine Tetra MYL was evaluated in terms of seroconversion rates across 3 influenza seasons.

Table: Seroconversion rates

N= number of subjects included in immunogenicity analysis

’containing recommended strains by WHO for respective season for quadrivalent vaccines

5.2 Pharmacokinetic properties

Not applicable.

5.3 Preclinical safety data

Non-clinical data revealed no special hazard for humans based on conventional studies of repeat dose and local toxicity, reproductive and developmental toxicity and safety pharmacology studies.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Potassium chloride, potassium dihydrogen phosphate, disodium phosphate dihydrate, sodium chloride, calcium chloride dihydrate, magnesium chloride hexahydrate 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 for injection in prefilled syringe with or without needle (glass, type I), pack of 1 or 10.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

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

Shake before use. Inspect visually prior to administration.

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