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 2019/2020 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).

Suspension for injection in pre-filled syringe.

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

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

Influenza vaccine Tetra MYL is indicated in adults and children from 3 years of age.

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

Posology

Adults: 0.5 ml.

Paediatric population

Children from 3 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.

Children less than 3 years of age: the safety and efficacy of Influenza vaccine Tetra MYL in children have not been established.

Method of Administration

Immunisation should be carried out by intramuscular or deep subcutaneous injection.

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.

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.

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.

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.

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'.

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.

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.

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

a. Summary of the safety profile

The safety of Influenza vaccine Tetra MYL was assessed in two clinical trials in which 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. Children from 3 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.

Similar rates of solicited adverse reactions were observed in recipients of Influenza vaccine Tetra MYL and trivalent influenza vaccine Influvac.

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 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.

Overdosage is unlikely to have any untoward effect.

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:

Immunogenicity of Influenza vaccine Tetra MYL compared to trivalent Influvac:

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 for 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

N = number of subjects included in efficacy analysis

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

²containing 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: Post-vaccination GMT

N= number of subjects included in efficacy analysis

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

²containing A/H1N1, A/H3N2 and B (Victoria lineage)

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

⁴additional recommended B strain by WHO for season 2016-2017 NH for quadrivalent vaccines

The European Medicines Agency has deferred the obligation to submit the results of studies with Influenza vaccine Tetra MYL in one or more subsets of the paediatric population.

Not applicable.

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.

Potassium chloride, potassium dihydrogen phosphate, disodium phosphate dihydrate, sodium chloride, calcium chloride dihydrate, magnesium chloride hexahydrate and water for injections.

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

1 year.

Store in a refrigerator (+2°C to +8°C).

Do not freeze.

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

0.5 ml suspension for injection in prefilled syringe with / without needle (glass, type I), pack of 1 or 10.

Not all pack sizes may be marketed.

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.

Mylan Products Limited

20 Station Close

Potters Bar

Herts

EN6 1TL

UK

PL 46302/0056

Date of first authorisation: 25/07/2017

May 2019