This information is intended for use by health professionals

1. Name of the medicinal product

INACTIVATED INFLUENZA VACCINE (SPLIT VIRION) BP, suspension for injection in prefilled syringe.

Influenza vaccine (split virion, inactivated).

2. Qualitative and quantitative composition

Influenza virus (inactivated, split) of the following strains*:

• A/Michigan/45/2015 (H1N1)pdm09 - like strain (A/Michigan/45/2015, NYMC X-275)

............................................................................................................................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/60/2008, 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 recommendations (Northern Hemisphere) and EU decision for the 2017/2018 season.

For the full list of excipients, see Section 6.1.

INACTIVATED INFLUENZA VACCINE (SPLIT VIRION) BP may contain traces of eggs, such as ovalbumin, and of neomycin, formaldehyde and octoxinol- 9, which are used during the manufacturing process (see Section 4.3).

3. Pharmaceutical form

Suspension for injection in prefilled syringe.

The vaccine, after shaking gently, is a slightly whitish and opalescent liquid.

4. Clinical particulars
4.1 Therapeutic indications

Prophylaxis of influenza.

INACTIVATED INFLUENZA VACCINE (SPLIT VIRION) BP is indicated in adults and children from 6 months of age.

The use of INACTIVATED INFLUENZA VACCINE (SPLIT VIRION) BP should be based on official recommendations.

4.2 Posology and method of administration

Posology

Adults: 0.5 ml.

Paediatric population

Children from 36 months onwards: 0.5 ml.

Children from 6 months to 35 months: 0.25 ml. Clinical data are limited. See Section 6.6 for more information on administration of 0.25 ml dose.

If this is required by national recommendations, 0.5 ml may be given.

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

Children less than 6 months: the safety and efficacy of INACTIVATED INFLUENZA VACCINE (SPLIT VIRION) BP in children less than 6 months have not been established. No data are available.

Method of administration

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

For adults and children from 36 months of age: the preferred site for intramuscular injection is the deltoid muscle.

For children from 12 to 35 months of age: the preferred site for intramuscular injection is the anterolateral aspect of the thigh (or the deltoid muscle if muscle mass is adequate).

For children from 6 to 11 months of age: the preferred site for intramuscular injection is the anterolateral aspect of the thigh.

Precautions to be taken before handling or administering the medicinal product

For instructions on 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, formaldehyde and octoxinol-9.

Vaccination should be postponed in case of moderate or severe febrile disease or acute disease.

4.4 Special warnings and precautions for use

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.

INACTIVATED INFLUENZA VACCINE (SPLIT VIRION) BP should under no circumstances be administered intravascularly.

As with other vaccines administered intramuscularly, the vaccine should be administered with caution to subjects with thrombocytopenia or a bleeding disorder since bleeding may occur following an intramuscular administration to these subjects.

Syncope (fainting) can occur following, or even before, any vaccination as a psychogenic response to the needle injection. Procedures should be in place to prevent injury from fainting and manage syncopal reactions.

As with any vaccine, vaccination with INACTIVATED INFLUENZA VACCINE (SPLIT VIRION) BP may not protect 100% of susceptible individuals.

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

INACTIVATED INFLUENZA VACCINE (SPLIT VIRION) BP 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 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 inactivated influenza vaccines do not indicate any adverse foetal and maternal outcomes attributable to the vaccine.

Breastfeeding

INACTIVATED INFLUENZA VACCINE (SPLIT VIRION) BP may be used during breastfeeding.

Fertility

No fertility data are available.

4.7 Effects on ability to drive and use machines

INACTIVATED INFLUENZA VACCINE (SPLIT VIRION) BP has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

a. Summary of the safety profile

In clinical trials approximately 10,300 individuals from 6 months of age received INACTIVATED INFLUENZA VACCINE (SPLIT VIRION) BP.

Depending on immunization history and the age of the children, the dosage and the number of doses were different (see Paediatric population in subsection b. Tabulated list of adverse reactions).

Most of adverse reactions usually occurred within the first 3 days following injection of INACTIVATED INFLUENZA VACCINE (SPLIT VIRION) BP, resolved spontaneously within 3 days after onset. The intensity of these reactions as mild to moderate.

The most frequently reported injection site reaction within 7 days following injection of INACTIVATED INFLUENZA VACCINE (SPLIT VIRION) BP was injection site pain in all population.

The most frequently reported systemic reaction within 7 days following injection of INACTIVATED INFLUENZA VACCINE (SPLIT VIRION) BP was headache in adults, elderly and children from 9 to 17 years of age, myalgia in children from 3 to 8 years, fever in children from 24 to 35 months of age and irritability in children from 6 to 23 months of age.

b. Tabulated list of adverse reactions

The data below summarize the frequencies of the adverse reactions that were recorded following vaccination with INACTIVATED INFLUENZA VACCINE (SPLIT VIRION) BP during clinical trials and worldwide post-marketing experience.

Adverse events are ranked under headings of frequency using the following convention:

Very common (≥1/10);

Common (≥1/100 to <1/10);

Uncommon (≥1/1,000 to <1/100);

Rare (≥1/10,000 to <1/1,000);

Very rare (<1/10,000),

Not known (cannot be estimated from available data).

Adult and elderly

The safety profile is based on data:

- from clinical trials in more than 5,000 adults and 4,400 elderly over 60 years of age,

- from worldwide post-marketing experience in the overall population (*).

ADVERSE REACTIONS

FREQUENCY

Blood and Lymphatic System Disorders

Lymphadenopathy (1)

Uncommon

Transient thrombocytopenia

Not known*

Immune System Disorders

Allergic reactions such as drug hypersensitivity (2), dermatitis atopic (2), urticaria (2, 5), oropharyngeal pain, asthma (1), rhinitis allergic (2), rhinorrhea (1), conjunctivis allergic (2)

Uncommon

Allergic reactions such as swelling face, pruritus (2, 5), erythema, rash, flushing (3), oral mucosal eruption (3), paraesthesia oral (3), throat irritation, dyspnea (2, 5), sneezing, nasal obstruction (2), upper respiratory tract congestion (2), ocular hyperaemia (2)

Rare

Allergic reactions such as rash erythematous, angioedema, shock

Not known*

Nervous System Disorders

Headache

Very common

Dizziness (7), somnolence (7)

Uncommon

Hypoaesthesia (2), paresthesia

Rare

Neuralgia, convulsions, encephalomyelitis, neuritis, Guillain Barré Syndrome

Not known*

Vascular disorders

Vasculitis such as Henoch-Schonlein purpura, with transient renal involvement in certain cases

Not known*

Gastrointestinal Disorders

Diarrhea, nausea

Uncommon

Abdominal pain (2), vomiting

Rare

Skin and Subcutaneous System Disorders

Hyperhidrosis (1)

Uncommon

Metabolism and Nutrition Disorders

Decreased appetite

Rare

Musculoskeletal and Connective Tissue Disorders

Myalgia

Very common

Arthralgia (1)

Uncommon

General Disorders and Administration Site Conditions

Injection site pain, malaise (4)

Very common

Fever (6), shivering, injection site erythema, injection site induration, injection site swelling/oedema

Common

Asthenia (1), fatigue, injection site ecchymosis, injection site pruritus, injection site warmth (1), injection site discomfort

Uncommon

Flu-like symtoms (2), injection site exfoliation (3), injection site hypersensitivity (2)

Rare

(1) Rare in elderly

(2) Reported during clinical trials in adults

(3) Reported during clinical trials in elderly

(4) Common in elderly

(5) Not known in elderly

(6) Uncommon in elderly

(7) Rare in adults

Paediatric population

Depending on immunization history, children from 6 months to 8 years received one or two doses of INACTIVATED INFLUENZA VACCINE (SPLIT VIRION) BP. Children/adolescents from 9 to 17 years of age received one dose.

Children from 6 to 35 months of age received the 0.25 ml formulation, and children from 3 years of age received the 0.5 ml formulation.

Children/adolescents from 3 to 17 years of age:

The safety profile is based on data:

- from clinical trials in 363 children from 3 to 8 years and in 296 children/adolescents from 9 to 17 years of age,

- from worldwide post-marketing experience in the overall population (*).

In children from 3 to 8 years of age, the most frequently reported reactions within 7 days following injection of INACTIVATED INFLUENZA VACCINE (SPLIT VIRION) BP were injection site pain (59.1%), injection site erythema/redness (30.3%), myalgia (25.0%), malaise (22.3%) and injection site swelling/oedema (22.1%).

In children/adolescents from 9 to 17 years of age, the most frequently reported reactions within 7 days following injection of INACTIVATED INFLUENZA VACCINE (SPLIT VIRION) BP were injection site pain (65.3%), headache (28.6%) and myalgia (27.6%).

ADVERSE REACTIONS

FREQUENCY

Blood and Lymphatic System Disorders

Lymphadenopathy (1, 6)

Uncommon

Transient thrombocytopenia

Not known*

Immune System Disorders

Allergic reactions such as urticaria, rash, pruritus (1, 6), oropharyngeal pain (1)

Uncommon

Allergic reactions such as rash erythematous, dyspnea, angioedema, shock

Not known*

Nervous System Disorders

Headache

Very common

Dizziness (2)

Uncommon

Neuralgia, paresthesia, convulsions, encephalomyelitis, neuritis and Guillain Barré Syndrome

Not known*

Vascular disorders

Vasculitis such as Henoch-Schonlein purpura, with transient renal involvement in certain cases

Not known*

Gastrointestinal Disorders

Diarrhea (1), abdominal pain (1)

Uncommon

Musculoskeletal and Connective Tissue Disorders

Myalgia

Very common

General Disorders and Administration Site Conditions

Injection site pain, injection site erythema, injection site swelling/oedema, injection site induration (3), malaise, shivering (4)

Very common

Fever, injection site ecchymosis (5)

Common

Injection site pruritus, injection site warmth (2), injection site discomfort (2), crying (1), asthenia (2), fatigue

Uncommon

(1) Reported during clinical trials in children from 3 to 8 years old

(2) Reported during clinical trials in children/adolescents from 9 to 17 years old

(3) Common in children/adolescents from 9 to 17 years old

(4) Common in children from 3 to 8 years old

(5) Uncommon in children/adolescent from 9 to 17 years old

(6) Not known in children/adolescents from 9 to 17 years old

Children from 6 to 35 months of age:

The safety profile is based on data:

- from clinical trials in 101 children from 6 to 35 months of age,

- from worldwide post-marketing experience in the overall population (*).

The most frequently reported reactions within 7 days following injection of INACTIVATED INFLUENZA VACCINE (SPLIT VIRION) were irritability (50.9%), injection site tenderness (36.6%), injection site erythema (34.0%), abnormal crying (34.0%), fever (29.0%) and appetite lost (28.3%).

ADVERSE REACTIONS

FREQUENCY

Blood and Lymphatic System Disorders

Transient thrombocytopenia, lymphadenopathy

Not known*

Immune System Disorders

Allergic reactions such as pruritus, rash erythematous, urticaria, dyspnea, angioedema, shock

Not known*

Metabolism and nutrition Disorders

Appetite lost (1)

Very common

Psychiatric Disorders

Crying abnormal (1), irritability (1)

Very common

Nervous System Disorders

Headache (2), drowsiness (1)

Very common

Paresthesia, convulsions, encephalomyelitis

Not known*

Vascular disorders

Vasculitis such as Henoch-Schonlein purpura, with transient renal involvement in certain cases

Not known*

Gastrointestinal Disorders

Diarrhea, vomiting (1)

Common

Musculoskeletal and Connective Tissue Disorders

Myalgia (2)

Very common

General Disorders and Administration Site Conditions

Injection site tenderness, injection site erythema, , injection site induration, injection site ecchymosis, injection site swelling/oedema, fever

Very common

Shivering (2)

Common

(1) Reported in children from 6 to 23 months old

(2) Reported in children from 24 to 35 months old

c. Other special populations

Although only a limited number of subjects with co-morbidities were enrolled, studies conducted in renal transplant patients, asthmatic patients, or children from 6 months to 3 years of age with medical conditions being at especially high risk of developing serious flu-related complications showed no major differences in terms of safety profile of INACTIVATED INFLUENZA VACCINE (SPLIT VIRION) BP in these populations.

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.

4.9 Overdose

Cases of administration of more than the recommended dose (overdose) have been reported with INACTIVATED INFLUENZA VACCINE (SPLIT VIRION) BP. When adverse reactions were reported, the information was consistent with the known safety profile of INACTIVATED INFLUENZA VACCINE (SPLIT VIRION) BP described in Section 4.8.

5. Pharmacological properties
5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Influenza vaccine, ATC code: J07BB02

An antibody immune response is generally induced within 2 to 3 weeks. The duration of postvaccinal induced immunity varies but is usually 6-12 months.

5.2 Pharmacokinetic properties

Not applicable.

5.3 Preclinical safety data

Not applicable.

6. Pharmaceutical particulars
6.1 List of excipients

Buffer solution:

• Sodium chloride

• Potassium chloride

• 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

1 year.

6.4 Special precautions for storage

Store in a refrigerator (2°C – 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 of suspension in prefilled syringe (type I glass) with attached needle, equipped with a plunger stopper (elastomer chlorobromobutyl or chlorobutyl or bromobutyl) – pack size of 1, 10, 20 or 50.

0.5 ml of suspension in prefilled syringe (type I glass) without needle, equipped with a plunger stopper (elastomer chlorobromobutyl or chlorobutyl or bromobutyl) – pack size of 1, 10, 20 or 50.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

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

Shake before use. Inspect visually prior to administration.

The vaccine should not be used if foreign particles are present in the suspension.

Instructions for administration of 0.25 ml in children from 6 months to 35 months

When one dose of 0.25 ml is indicated, in order to eliminate half of the volume of the 0.5 ml syringe, the syringe should be held in an upright position and the plunger stopper should be pushed until it reaches the fine black line printed on the syringe. The remaining volume of 0.25 ml should be injected. See also Section 4.2.

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

7. Marketing authorisation holder

Sanofi Pasteur Europe

14 Espace Henry Vallée

69007 Lyon

FRANCE

Distributed in the UK by:

Sanofi

One Onslow Street

Guildford

Surrey

GU1 4YS

8. Marketing authorisation number(s)

PL 46602/0002

9. Date of first authorisation/renewal of the authorisation

First authorization: 20 March 1998

Renewal of authorization: 30 December 2007

10. Date of revision of the text

16th March 2018