This information is intended for use by health professionals

1. Name of the medicinal product

Influenza Vaccine (split virion, inactivated)

Suspension for injection, pre-filled syringe

2. Qualitative and quantitative composition

Influenza virus* (inactivated with β-Propiolactone, split) of the following strains:

A/Michigan/45/2015 (H1N1) pdm09 - like strain (A/Singapore/GP1908/2015, IVR-180A)

15 micrograms HA**

A/Hong Kong/4801/2014 (H3N2) - like strain (A/Hong Kong/4801/2014, NYMC X-263B)

15 micrograms HA**

B/Brisbane/60/2008 – like strain (B/Brisbane/46/2015, wild type)

15 micrograms HA**

per 0.5 ml dose.

* propagated in fertilised hens' eggs from healthy chicken flocks

** haemagglutinin

This vaccine complies with the WHO recommendation (Northern Hemisphere) and EU decision for the 2017/2018 season.

For the full list of excipients, see section 6.1.

Influenza Vaccine (split virion, inactivated) may contain traces of eggs such as ovalbumin and residues of neomycin and polymyxin, which are used during the manufacturing process (see section 4.3).

3. Pharmaceutical form

Suspension for injection in a pre-filled syringe.

Clear to slightly opaque liquid with some sediment that resuspends upon shaking.

4. Clinical particulars
4.1 Therapeutic indications

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

Influenza Vaccine (split virion, inactivated) is indicated in adults and children from 5 years of age.

The use of Influenza Vaccine (split virion, inactivated) should be based on official recommendations.

4.2 Posology and method of administration

Posology

Adults:

0.5 ml

Paediatric population

Children from 5 years onwards:

0.5 ml

For children aged less than 9 years, who have not previously been vaccinated, a second dose should be given after an interval of at least 4 weeks.

Method of administration

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

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), neomycin, polymyxin.

Immunisation shall be postponed in patients with febrile illness or acute infection.

4.4 Special warnings and precautions for use

Paediatric population

During the 2010 Southern Hemisphere influenza season, there was an unexpected increase in reports of fever and febrile convulsions in children aged less than 5 years following seasonal influenza vaccination with this product. Febrile convulsions were reported uncommonly (i.e. reporting frequency estimated to be in the range ≥1/1000 to < 1/100)*.

An increased number of reports of fever was also reported in the age group 5 to less than 9 years. Therefore in this age group a decision to vaccinate with Influenza Vaccine (split virion, inactivated) should be based on careful consideration of potential benefits and risks in the individual.

On the basis of the increased risk of febrile convulsions in children less than 5 years of age, the vaccine indication has been restricted to use in adults and children from 5 years of age only.

(*estimated from epidemiological investigations).

As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of an anaphylactic event following administration of the vaccine.

Influenza Vaccine (split virion, inactivated) should under no circumstances be administered intravascularly.

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

Interference with serological testing

(See section 4.5)

4.5 Interaction with other medicinal products and other forms of interaction

Influenza Vaccine (split virion, inactivated) may be 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 serological 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 inactivated influenza vaccines do not indicate any adverse foetal and maternal outcomes attributable to the vaccine. An animal study conducted with Influenza Vaccine (split virion, inactivated) did not indicate reproductive toxicity (see section 5.3).

Breastfeeding

Influenza Vaccine (split virion, inactivated) may be used during breastfeeding.

Fertility

An animal study conducted with Influenza Vaccine (split virion, inactivated) did not indicate adverse effects on female fertility (see section 5.3).

4.7 Effects on ability to drive and use machines

Influenza Vaccine (split virion, inactivated) has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

Adverse reactions observed from clinical trials

Adult and Elderly populations

Summary of the safety profile

In clinical trials, a single dose of Influenza Vaccine (split virion, inactivated) has been administered to, and safety information collected for, 11,104 adults aged 18 to less than 65 years and 630 elderly aged 65 years or older. Clinical data are presented from 3 clinical trials; two placebo-controlled trials in adults (CSLCT-FLU-05-09 and CSLCT-USF-06-28) and one comparator-controlled trial in elderly (CSLCT-USF-07-41).

The safety assessment was similar for the three trials. Local (injection-site) adverse reactions and systemic adverse events were solicited for 5 days after vaccination. Unsolicited adverse events were collected for 21 days after vaccination.

The frequency of solicited local adverse reactions and systemic adverse events, and related unsolicited adverse events, are presented according to the Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class and frequency for adults from 18 years of age (Table 1). Among the trials, there were no vaccine-related deaths or vaccine-related serious adverse events reported.

For adults and elderly, the most frequently reported related unsolicited adverse events across the three clinical trials were reactogenicity event (3.0%), headache (1.1%) and arthralgia (1.1%).

Tabulated list of adverse reactions

Table 1 Solicited local adverse reactions, solicited systemic adverse events and related unsolicited adverse events by MedDRA System Organ Class and category of frequency in adults 18 years of age and older

System Organ class

Very common

1/10

Common

≥1/100 to <1/10

Uncommon

≥1/1,000 to <1/100

Nervous system disorders

Headache a

Headache b, c

Gastrointestinal disorders

Nausea a,b

Vomiting a,b

Musculoskeletal and connective tissue disorders

Myalgia/general muscle ache a

Myalgia/general muscle ache b

Arthralgiac

General disorders and administration site conditions

Injection site tenderness a,b

Injection site pain a,b

Malaise a

Injection site erythema/ redness a,b

Injection site swelling/ induration a,b

Chills/ shivering a,b

Pyrexia/fever a

Injection site ecchymosis/ bruising a

Malaise b

Reactogenicity eventc

Pyrexia/fever b

Injection site ecchymosis/ bruising b

No solicited local adverse reactions or systemic adverse events were categorized as Rare (≥1/10,000, <1/1,000), or Very rare (<1/10,000).

a Solicited local adverse reactions or systemic adverse avents in adults 18 to < 65 years.

b Solicited local adverse reactions or systemic adverse events in elderly ≥ 65 years.

c Related unsolicited adverse event.

Paediatric population

Summary of the safety profile

In clinical trials, Influenza Vaccine (split virion, inactivated) has been administered to, and safety information collected for, 3,009 children aged 6 months to less than 18 years. The exposure includes 1,601 children aged 6 months to less than 5 years, 756 children aged 5 years to less than 9 years and 652 children aged 9 years to less than 18 years. Clinical safety data for Influenza Vaccine (split virion, inactivated) in children has been evaluated from 3 clinical trials; a comparator-controlled trial (CSLCT-USF-07-36) and two open label, uncontrolled trials (CSLCT-USF-06-29 and CSLCT-FLU-04-05). Children aged 6 months to less than 9 years received one or two vaccinations as determined by previous vaccination history.

The safety assessment was similar for the three paediatric trials. Local (injection site) and systemic adverse events were solicited for 7 days after vaccination. Unsolicited adverse events were collected for 30 days after vaccination.

In children aged 5 to less than 9 years who received Influenza Vaccine (split virion, inactivated) in the comparator-controlled trial, the rate of malaise after dose 1 was 24% as compared to 13% who received the comparator, and the rate of diarrhoea after dose 2 was 13% as compared to 6% who received the comparator. In the same trial, the rate of fever after the first dose of Influenza Vaccine (split virion, inactivated) in children aged 5 to less than 9 years was 16% as compared to 8% in children who received the comparator. The rate of fever in children aged 9 to less than 18 years following a single dose of Influenza Vaccine (split virion, inactivated) was 6% as compared to 4% in children who received the comparator.

Across the paediatric clinical trials, erythema was reported more often in children 5 to less than 9 years compared to children 9 to less than 18 years after a single dose (23% vs 17% in the comparator-controlled trial; 24% vs 17% in the open label trials). In contrast, headache was less often reported in children 5 to less than 9 years compared to children 9 to less than 18 years after a single dose (21% vs 27% in the comparator-controlled trial; 16% vs 27% in the open label trials). In children 5 to less than 9 years, systemic adverse events were reported less often after dose 2 than dose 1. Among the paediatric trials, there were no vaccine-related deaths or vaccine-related serious adverse events reported in this age cohort.

The frequency of solicited local adverse reactions and systemic adverse events, and related unsolicited adverse events are presented according to the MedDRA System Organ Class and frequency (Table 2) for children 5 years of age and older, consistent with the current age indication for Influenza Vaccine (split virion, inactivated).

For children aged 5 to less than 9 years, the most frequently reported related unsolicited adverse events across the three clinical trials were cough (3.5%), upper respiratory tract infection (2.9%), rhinitis (2.2%) and rhinorrhoea (2.2%). For children aged 9 to less than 18 years, the most frequently reported related unsolicited adverse events across the three clinical trials were cough (2.8%), oropharyngeal pain (2.4%) and nasal congestion (2.4%).

Tabulated list of adverse reactions

Table 2: Solicited local adverse reactions, solicited systemic adverse events and related unsolicited adverse events by MedDRA System Organ Class and category of frequency in children aged 5 to less than 18 years

System Organ class

Very common

1/10

Common

1/100 to <1/10

Infections and infestations

Upper respiratory tract infectionc

Rhinitisc

Nasopharyngitisc

Nervous system disorders

Headache

Headachec

Respiratory, thoracic and mediastinal disorders

Coughc,d

Oropharyngeal painc,d

Nasal congestionc

Rhinorrhoeac

Pharyngolaryngeal Painc

Gastrointestinal disorders

Nausea / vomiting a

Diarrhoea a

Loss of appetite b

Vomiting/diarrhoea b

Abdominal pain upperc

Abdominal painc

Musculoskeletal and connective tissue disorders

Myalgia/general muscle ache

General disorders and administration site conditions

Injection site pain

Injection site erythema/redness

Malaise a

Irritability b

Injection site swelling/induration

Pyrexia/fever

Injection site pruritisc

Pyrexiac

Influenza-like illnessc

Irritabilityc

No solicited local adverse reactions or systemic adverse events were categorized as Uncommon (≥1/1,000, <1/100), Rare(≥1/10,000, <1/1,000), or Very rare (<1/10,000).

a Solicited systemic adverse events collected in trials CSLCT-USF-07-36 and CSLCT-USF-06-29.

b Solicited systemic adverse events collected in trial CSLCT-FLU-04-05.

c Related unsolicited adverse event in children aged 5 to < 9 years.

d Related unsolicited adverse event in children aged 9 to < 18 years.

Adverse reactions reported from post-marketing surveillance

The following adverse events have been spontaneously reported during post-marketing use of Influenza Vaccine (split virion, inactivated) and are in addition to the events observed during clinical trials. The adverse events reported are presented below according to System Organ Class:

Blood and lymphatic system disorders

Thrombocytopenia, transient lymphadenopathy

Immune system disorders

Allergic or immediate hypersensitivity reactions including anaphylactic shock

Nervous system disorders

Neuralgia, paraesthesia, convulsions (including febrile convulsions), encephalomyelitis, neuritis or neuropathy and Guillain-Barré syndrome

Vascular disorders

Vasculitis which may be associated with transient renal involvement

Skin and subcutaneous tissue disorders

Pruritus, urticaria and rash

General disorders and administration site conditions

Cellulitis and large injection site swelling

Influenza-like illness

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.

Tel: Freephone 0808 100 3352

Website: www.mhra.gov.uk/yellowcard

4.9 Overdose

Overdosage is unlikely to have any untoward effects.

5. Pharmacological properties
5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Influenza vaccine, ATC Code: J07B B02

Seroprotection 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 to 12 months.

5.2 Pharmacokinetic properties

Evaluation of pharmacokinetic properties is not required for vaccines.

5.3 Preclinical safety data

In a reproductive and developmental toxicity study, the effect of Influenza Vaccine (split virion, inactivated) on embryo-foetal and pre-weaning development was evaluated in pregnant rats. No adverse effects on mating, female fertility, pregnancy, parturition, lactation parameters, and embryo-foetal or pre-weaning development were observed. There were no vaccine-related foetal malformations or other evidence of teratogenesis.

6. Pharmaceutical particulars
6.1 List of excipients

Sodium chloride

Anhydrous disodium phosphate

Sodium dihydrogen phosphate dihydrate

Potassium chloride

Potassium dihydrogen phosphate

Calcium chloride

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

15 months.

6.4 Special precautions for storage

Store in a refrigerator (2°C to 8°C). Do not freeze.

Keep the 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 syringe (Type I glass) with plunger stopper (chlorobutyl rubber) with or without attached needle in pack sizes of 1 or 10. The syringe with attached needle may be supplied with or without needle-trap.***

Not all pack sizes may be marketed.

***See section 6.6 for instructions for use.

6.6 Special precautions for disposal and other handling

The vaccine should be allowed to reach room temperature before use. Shake before use. After shaking, the vaccine should appear as a homogenous suspension. The vaccine must be inspected visually prior to administration and should not be used if there is any variation of physical appearance (see section 3).

Influenza Vaccine (split virion, inactivated) is presented as a single use syringe and any unused medicinal product or waste material should be disposed of in accordance with local requirements.

For administration using the syringe with attached needle and needle-trap, refer to the diagrams below.

1-2: Bend the orange plastic needle-trap toward the side.

3-4: Remove the translucent plastic needle-shield cover and grey needle-shield and perform the injection. Intramuscular administration of Influenza Vaccine should be undertaken by injection into the deltoid muscle of the upper arm.

5: Place the orange needle-trap against a stable, hard surface and then press down the trap by bending the syringe. Continue the motion until the needle is bent by approximately 90 degrees and the needle audibly clicks into the trap.

6: The needle is now secured for safe disposal in accordance with local requirements.

7. Marketing authorisation holder

Seqirus GmbH

Emil-von-Behring-Strasse 76

35041 Marburg

Germany

8. Marketing authorisation number(s)

PL 22236/0001

9. Date of first authorisation/renewal of the authorisation

19 April 2005 / 29 March 2009

10. Date of revision of the text

06/2017

Ref: gxEZ 16_0