Influenza vaccine TIV MYL suspension for injection in pre-filled syringe

Prophylaxis of influenza disease in adults and children from 6 months of age.

Influenza vaccine TIV MYL should be used in accordance with official recommendations.

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 TIV MYL have not been established. No data are available.

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 administering the medicinal product: see section 6.6

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.

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 TIV MYL should under no circumstances be administered intravascularly.

As with other vaccines administered intramuscularly, Influenza vaccine TIV 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 TIV MYL is not effective against all possible strains of influenza virus. Influenza vaccine TIV 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 vaccinees.

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

Interference with serological testing: see section 4.5.

Sodium and potassium content

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 TIV 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 fetal and maternal outcomes attributable to the vaccine.

Breast-feeding

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

Fertility

No fertility data are available.

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

a. Summary of safety profile

Data for Influvac sub-unit Tetra are relevant to Influenza vaccine TIV MYL sub-unit TIV because both vaccines are manufactured using the same process. The safety of Influenza vaccine TIV MYL was evaluated in several clinical trials and similar rates of solicited adverse reactions were observed in recipients of quadrivalent or trivalent formulations.

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 was vaccination site pain.

The most frequently reported systemic adverse reactions 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 systemic adverse reactions in children from 6 months to 35 months of age were irritability/fussiness.

In rare cases, allergic reactions may evolve to shock, angioedema (see section 4.4).

b. Tabulated summary of adverse reactions

The following undesirable effects have been observed during clinical trials with Influvac sub-unit Tetra or are resulting from post-marketing experience with Influenza vaccine TIV MYL sub-unit TIV and Influvac sub-unit Tetra with the following frequencies:

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 (including elderly)

Paediatric population (6 months to 17 years of age)

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 TIV MYL provides active immunisation against three influenza virus strains: an A/(H1N1) strain, an A/(H3N2) strain, and a B strain. It induces humoral antibodies against the haemagglutinins. These antibodies neutralise influenza viruses.

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

Data for Influvac sub-unit Tetra are relevant to Influenza vaccine TIV MYL because both vaccines are manufactured using the same process.

Efficacy and immunogenicity of Influenza vaccine TIV MYL in children 6 - 35 months of age

The efficacy of Influvac sub-unit Tetra was evaluated in a randomised, 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 Influvac sub-unit Tetra (N=1005) or non-influenza control vaccine (N=995) approximately 28 days apart. Vaccine efficacy 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

Table: Seroconversion rates in children 6 – 35 months of age

N= number of subjects included in immunogenicity analysis

¹containing recommended strains by WHO for respective season for quadrivalent vaccines

Immunogenicity of Influenza vaccine TIV MYL in children 3 – 17 years of age and adults (including elderly)

Clinical studies performed in adults (INFQ3001) and children of 3 to 17 years of age (INFQ3002) assessed the immunogenicity of Influvac sub-unit Tetra and its non-inferiority to trivalent Influenza vaccine TIV MYL formulations for the postvaccination HI Geometric mean antibody titres (GMT) and seroconversion rates. Children received one or two doses of vaccine based on their influenza vaccine history.

Table: Post-vaccination GMTs and seroconversion rates in adults

N= number of subjects included in immunogenicity 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

Table: Seroconversion rates in children 3 – 17 years of age

N= number of subjects included in immunogenicity 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

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 - 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 or 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.