IDflu - summary of medicine characteristics

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

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

A/Califomia/7/2009 (H1N1)pdm09 – like strain (A/Califomia/7/2009, NYMC X-179A)........­.............­.............­.............­.............­.............­.............­.............­.............­.............­.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)

Per 0.1 ml dose

• * propagated in fertilised hens’ eggs from healthy chicken flocks

• * * haemagglutinin

This vaccine complies with the WHO recommendations (Northe the 2016/2017 season.

For the full list of excipients, see section 6.1.

IDflu may contain residues of eggs such as ovalbumin and residues of neomycin, formaldehyde and octoxinol 9, which are used during the manufacturing process (see section 4.3).

Suspension for

Colourless and

4. CLINICAL PARTICULARS4.1 Therapeutic indications

Prophylaxis of influenza in individuals 60 years of age and over, especially in those who run an increased risk of associated complications.

The use of IDflu should be based on official recommendations.

4.2 Posology and method of administration

Posology

Individuals 60 years of age and over: 0.1 ml.

Paediatric population

IDflu is not recommended for use in children and adolescents below 18 years due to insufficient data on safety and efficacy.

Method of administration

Immunisation should be carried out by intradermal route.

The recommended site of administration is the region of the deltoid.

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 Contraindicationsays be accine (see

Hypersensitivity to the active substances, to any of the excipients listed in section 6.1, or to any residues such as eggs (ovalbumin, chicken proteins), neomycin, formaldehyde and octoxinol 9.

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

4.4 Special warnings and precautions for use

As with all injectable vaccines, appropriate medical treatment and supervision sho readily available in case of an anaphylactic event following the administration o section 4.8).

IDflu should under no circumstances be administered intravascularly.

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

Very limited data in immunocompromised patients are available for IDflu.

In case of presence of liquid at the injection site after vaccine administration, re-vaccination is not required.

Interference with serological testing: See s

4.5 Interaction with other medicinal products and other forms of interaction

IDflu 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.

ertility, pregnancy and lactation

This vaccine is intended for individuals 60 years of age and over. Therefore, this information is not applicable.

4.7 Effects on ability to drive and use machines

IDflu 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 IDflu has been assessed in 3 open-label randomised clinical trials, 3,372 vaccinees received an injection of IDflu.

Safety evaluation was performed for all subjects during the first 3 weeks following vaccination and serious adverse reactions were collected during six months of follow-up for 2,974 subjects (population of two out of the three clinical trials).

The most common reactions occurring after vaccine administration were local reactions at injecti site.

Apparent local reactions after intradermal administration were more frequent than after intramus administration of an adjuvanted or non-adjuvanted comparator vaccine.

Most reactions resolved spontaneously within 1 to 3 days after onset.

Systemic safety profile of IDflu is similar to the comparator vaccine, adjuvanted or non-adjuvanted, administered intramuscularly.

After repetitive yearly injections the safety profile of IDflu is similar

• b. Tabulated summary of adverse reactions

The data below summarizes the frequencies of the adverse reactions that were recorded following vaccination during clinical trials and worldwide post-marketing experience, 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 <1/1000); very rare (<1/10,000), not known (cannot be estimated from available data).

Organ class	Very common	Common	Uncommon	Rare	Very rare	Not known
Immune system disorders						Allergic reactions including generalized skin reactions such as urticaria, anaphylactic reactions, angioedem a, shock
Nervous system disorders	Headache			Paresthesia, neuritis		(XT
Skin and subcutaneous tissue disorders			Sweating	Pruritus, rash
Musculoskeletal and connective tissue disorders	Myalgia		Arthralgia	A w	V
General disorders and administration site conditions	Local reactions: redness*, induration swelling, pruritus, pain	Malaise, shivering, fever, Local reactions: ecchymosis	Fatigue	y

* In some cases, local redness lasted up to 7 days.

• c. Potential adverse events

Based on the experience with trivalent inactivated influenza vaccines administered by intramuscular or deep subcutaneous injection, the following events may be reported:

Blood and lymphatic system disorders

Transient thrombocytopenia, transient lymphadenopathy

Nervous system disorders

Neuralgia, febrile convulsions, neurological disorders, such as encephalomyelitis and Guillain-Barré syndrome

Vascular disorders

Vasculitis associated in very rare cases with transient renal involvement

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 national reporting system listed in

4.9 Overdose

Overdose is unlikely to have any untoward effect.

5. PHARMACOLOGICAL PROPERTIES5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Influenza vaccines, ATC code: J07BB02

Immunogenicity

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 6–12 months.

In a pivotal randomised comparative phase III trial, 2,606 subjects over 60 years of age re 0.1 ml of IDflu by intradermal route and 1,089 subjects over 60 years of age received 0.5 trivalent inactivated influenza vaccine administered by intramuscular rou­te.

In this comparative trial the geometric mean titres (GMTs), serop significant increase rate** and the geometric mean titre ratio (G (measured by HI) were assessed according to predefined criteria.

Data were as follows (values in brackets show the 95% confidence i

		Intra dermal >5gg
	A/H1N1	A/H3N2	B
	A/New Caledonia/ 20/99	A/Wisconsin/ 67/2005	B/Malaysia/ 2506/2004
	N = 2,585	N = 2,586	N = 2,582
Geometric mean of titre (1/dil)	81.7 (78.0 ; O5.6)	298.0 (282 ; 315)	39.9 (38.3 ; 41.6)
Seroprotection rate (%)	(75 3 ; 78.6)	93.3 (92.3 ; 94.3)	55.7 (53.8 ; 57.6)
Seroconversion or significant increase rate (%) * *	(.6.3<;-4o.6>	61.3 (59.3 ; 63.1)	36.4 (34.5 ; 38.3)
Geometric mean of titre ratio 4 (GMTR)	3.97 (3.77 ; 4.18)	8.19 (7.68 ; 8.74)	3.61 (3.47 ; 3.76)

Seroprotection =

40

** Seroconversion. = negative pre-vaccination HI titre and post vaccination HI titre > 40, Significant

increase = positive pre-vaccination HI titre and at least a 4-fold increase in post-vaccination HI titre GMTR: Geometric mean titre ratio of individual (post-/pre-vaccination titre).

IDflu is at least as immunogenic as the comparator trivalent inactivated influenza vaccine administered by intramuscular route for each of the 3 influenza strains in subjects from 60 years of age and over.

Across all three influenza strains, for the comparator intramuscular vaccine GMTs ranged between 34.8 (1/dil) and 181.0 (1/dil), seroprotection rates ranged between 48.9% and 87.9%, seroconversion or significant increase rates ranged between 30.0% and 46.9% and GMTRs ranged between 3.04 and 5.35-fold over baseline HI titres.

In a randomised comparative phase III trial, 398 subjects over 65 years of age received 0.1 ml of IDflu by intradermal route and 397 subjects over 65 years of age received 0.5 ml of a trivalent inactivated adjuvanted (MF-59 containing) influenza vaccine at the same dosage administered by intramuscular rou­te.

5.2 Pharmacokinetic properties

Not applicable

5.3 Preclinical safety data

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

6.2 Incompatibilities

6.2 Incompati­bilities

6.3 Shelf-life

6.3 Shelf-life

6.4 Special precautions for storage

6.4 Special precautions for storage

6.5 N

0.1 ml of suspension in a pre-filled syringe (glass) with a Micro-Injection System, with attached

o-needle, equipped with an elastomer plunger stopper (chlorobutyl), a tip cap (thermoplastic omer and polypropylene) and a needle shielding system. Pack size of 1 or 10 or 20.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

6.6 Special precautions for disposal and other handling

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

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

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

It is not necessary to shake the vaccine before use.

The Micro-Injection System for intradermal injection consists of a pre-filled syringe with a micro-needle (1.5 mm) and a needle shielding system.

The needle shielding system is designed to cover the micro-needle after use.

INSTRUCTION FOR USE

Please read the instructions before use

INGER

Once the micro-needle has been inserted, maintain a light pressure on the surface of the skin and inject using the index finger to push on the plunger.

The vein test is unnecessary.

5/ ACTIVATE NEEDLE SHIELD BY PUSHING FIRMLY ON PLUNGER

Remove the needle from the skin.

Orient the needle away from you and others.

With the same hand, push very firmly with the thumb on the plunger to activate the needle shield.

You hear a click and a shield comes out to cover the needle.

Immediately dispose of the system in the nearest sharps collector.

Injection is considered successful whether or not the presence of a wheal is observed.

In case of presence of liquid at the injection site after vaccine administration, revaccination is not required.

7. MARKETING AUTHORISATION HOLDER

Sanofi Pasteur SA, 2, avenue Pont Pasteur, F-69007 Lyon, France.

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/08/507/004

EU/1/08/507/005

EU/1/08/507/006

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 24 February 2009

Date of latest renewal: 24 February 2014