Sanofi Pasteur MSD Limited

INTANZA 15 microgram/strain suspension for injection

Influenza vaccine (split virion, inactivated)

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

A/California/7/2009 (H1N1) – derived strain used NYMC X-179A …………….15 micrograms HA**

A/Perth/16/2009 (H3N2) – like strain used NYMC X-187 derived from A/Victoria/210/2009 …………………………………………………………………………………….15 micrograms HA**

B/Brisbane/60/2008 ………………………………………………………………15 micrograms HA**

Per 0.1 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 2011/2012 season.

For the full list of excipients, see section 6.1.

INTANZA 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 injection.

Colourless and opalescent suspension.

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 INTANZA should be based on official recommendations.

Posology

Individuals 60 years of age and over: 0.1 ml.

Paediatric population

INTANZA 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.

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.

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 (see section 4.8).

INTANZA 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 INTANZA.

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

Interference with serological testing: See section 4.5.

INTANZA 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.

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

INTANZA has no or negligible influence on the ability to drive and use machines.

a. Summary of the safety profile

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

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 injection site.

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

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

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

After repetitive yearly injections the safety profile of INTANZA is similar to the previous injections.

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).

*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

Overdose is unlikely to have any untoward effect.

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 received 0.1 ml of INTANZA by intradermal route and 1,089 subjects over 60 years of age received 0.5 ml of a trivalent inactivated influenza vaccine administered by intramuscular route.

In this comparative trial the geometric mean titres (GMTs), seroprotection rate*, seroconversion or significant increase rate** and the geometric mean titre ratio (GMTR) for anti-HA antibody (measured by HI) were assessed according to predefined criteria.

Data were as follows (values in brackets show the 95% confidence intervals):

*Seroprotection = HI titre 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).

INTANZA 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 INTANZA 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.

INTANZA is as immunogenic as the comparator trivalent adjuvanted (MF-59 containing) vaccine in terms of GMT for each of the 3 influenza strains with the SRH method and for 2 strains with the HI method.

Not applicable

Non-clinical data revealed no special hazard for humans based on animal studies. The vaccine was immunogenic in mice and rabbits. In repeated-dose toxicity studies in rabbits there was no significant evidence of systemic toxicity. Nevertheless, single and repeated administrations led to transient local erythema and oedema. Genotoxicity and carcinogenic potential were not assessed because these studies are not appropriate for a vaccine. Fertility and toxicity studies to reproduction in females have not identified any specific potential hazard for humans.

Sodium chloride

Potassium chloride

Disodium phosphate dihydrate

Potassium dihydrogen phosphate

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.

Keep the syringe in the outer carton in order to protect from light.

0.1 ml of suspension in a pre-filled syringe (glass) with a Micro-Injection System, with attached micro-needle, equipped with an elastomer plunger stopper (chlorobutyl), a tip cap (thermoplastic elastomer and polypropylene) and a needle shielding system. Pack size of 1 or 10 or 20.

Not all pack sizes may be marketed.

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.

Micro-Injection System

Sanofi Pasteur MSD SNC, 8 rue Jonas Salk, F-69007 Lyon, France.

EU/1/08/505/004

EU/1/08/505/005

EU/1/08/505/006

Date of first authorisation: 24 February 2009

04/2012

Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu.