FLUENZ nasal spray suspension

Influenza vaccine (live attenuated, nasal)

Reassortant influenza virus* (live attenuated) of the following strains**:

A/<Official strain> (H1N1) like strain (<actual strain>)                          10^7.0±0.5 FFU***

A/<Official strain> (H3N2) like strain (<actual strain>)                          10^7.0±0.5 FFU***

B/<Official strain> like strain (<actual strain>)                                      10^7.0±0.5 FFU***

................................................................................................................per 0.2 ml dose

* propagated in fertilised hens' eggs from healthy chicken flocks.

** produced in VERO cells by reverse genetic technology. This product contains genetically modified organisms (GMOs).

*** fluorescent focus units

This vaccine complies with the WHO recommendation (Northern Hemisphere) and EU decision for the 20XX/20XX season.

The vaccine may contain residues of the following substances: egg proteins (e.g. ovalbumin) and gentamicin.

For a full list of excipients, see section 6.1.

Nasal spray, suspension

The suspension is colourless to pale yellow, clear to opalescent. Small white particles may be present.

Prophylaxis of influenza in individuals 24 months to less than 18 years of age.

The use of FLUENZ should be based on official recommendations.

Children and adolescents from 24 months:

0.2 ml (administered as 0.1 ml per nostril).

For children who have not previously been vaccinated against seasonal influenza, a second dose should be given after an interval of at least 4 weeks.

FLUENZ should not be used in infants and toddlers below 24 months of age because of safety concerns (see section 4.4).

Method of administration

Immunisation must be carried out by nasal administration.

DO NOT INJECT FLUENZ.

See section 6.6 for administration instructions.

Hypersensitivity to the active substances, to any of the excipients (e.g. gelatin; see section 6.1), to gentamicin (a possible trace residue), to eggs or to egg proteins (e.g. ovalbumin).

Children and adolescents who are clinically immunodeficient due to conditions or immunosuppressive therapy such as: acute and chronic leukaemias; lymphoma; symptomatic HIV infection; cellular immune deficiencies; and high-dose corticosteroids. FLUENZ is not contraindicated for use in individuals with asymptomatic HIV infection; or individuals who are receiving topical/inhaled corticosteroids or low-dose systemic corticosteroids or those receiving corticosteroids as replacement therapy, e.g. for adrenal insufficiency.

Children and adolescents younger than 18 years of age receiving salicylate therapy because of the association of Reye's syndrome with salicylates and wild-type influenza infection.

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

FLUENZ should not be administered to children and adolescents with severe asthma or active wheezing because these individuals have not been adequately studied in clinical studies.

Do not administer FLUENZ to infants and toddlers younger than 12 months. In a clinical study, an increase in hospitalisations was observed in infants and toddlers younger than 12 months after vaccination (see section 4.8). It is not recommended to administer FLUENZ to infants and toddlers 12-23 months of age. In a clinical study, an increased rate of wheezing was observed in infants and toddlers 12-23 months of age after vaccination (see section 4.8).

Vaccine recipients should be informed that FLUENZ is an attenuated live virus vaccine and has the potential for transmission to immunocompromised contacts. Vaccine recipients should attempt to avoid, whenever possible, close association with severely immunocompromised individuals (e.g. bone marrow transplant recipients requiring isolation) for 1-2 weeks following vaccination. Peak incidence of vaccine virus recovery occurred 2-3 days post-vaccination in clinical studies. In circumstances where contact with severely immunocompromised individuals is unavoidable, the potential risk of transmission of the influenza vaccine virus should be weighed against the risk of acquiring and transmitting wild-type influenza virus.

FLUENZ should under no circumstances be injected.

No data exist regarding the safety of intranasal administration of FLUENZ in children with unrepaired craniofacial malformations.

Do not administer FLUENZ to children and adolescents younger than 18 years of age receiving salicylate therapy (see section 4.3). Do not use salicylates in children and adolescents younger than 18 years of age for 4 weeks after vaccination unless medically indicated as Reye's syndrome has been reported following the use of salicylates during wild-type influenza infection.

The co-administration of FLUENZ with the live attenuated vaccines: measles, mumps, rubella, varicella, and orally-administered poliovirus has been studied. No clinically meaningful changes in immune responses to measles, mumps, varicella, orally-administered poliovirus or FLUENZ have been observed. The immune response to rubella vaccine was significantly altered. However, this alteration might not be of clinical relevance with the two dose immunisation schedule of the rubella vaccine.

The co-administration of FLUENZ with inactivated vaccines has not been studied.

The concurrent use of FLUENZ with antiviral agents that are active against influenza A and/or B viruses has not been evaluated. However, based upon the potential for influenza antiviral agents to reduce the effectiveness of FLUENZ, it is recommended not to administer the vaccine until 48 hours after the cessation of influenza antiviral therapy. Administration of influenza antiviral agents within two weeks of vaccination may affect the response of the vaccine.

If influenza antiviral agents and FLUENZ are administered concomitantly, revaccination should be considered when appropriate.

Pregnancy

There are limited data from the use of FLUENZ in pregnant women.

While animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity, FLUENZ is not recommended during pregnancy.

Breastfeeding

It is not known whether FLUENZ is excreted in human milk. Therefore, as some viruses are excreted in human milk, FLUENZ should not be used during breastfeeding.

Fertility

No data exist regarding the possible effects of FLUENZ on male and female fertility.

The vaccine is unlikely to have an effect on the ability to drive and use machines.

Safety data regarding use of FLUENZ have been compiled from over 28,500 children and adolescents 2 to 17 years of age from clinical studies and over 52,500 children and adolescents from post-authorisation safety studies. Additional experience has occurred with marketed use of this vaccine.

Although safety in children and adolescents with mild to moderate asthma has been established, data in children with other pulmonary diseases or with chronic cardiovascular, metabolic or renal diseases are limited. In studies of adults in which a high percentage of individuals had underlying chronic medical conditions, the safety profile of FLUENZ was comparable to the safety profile observed in individuals without these conditions.

The most common adverse reaction observed in clinical studies was nasal congestion/rhinorrhoea.

Adverse reaction frequencies are reported as:

Very common ( 1/10)

Common ( 1/100 to < 1/10)

Uncommon ( 1/1,000 to < 1/100)

Very rare (< 1/10,000)

Immune system disorders

Uncommon: Hypersensitivity reactions (including facial oedema, urticaria and very rare anaphylactic reactions)

Metabolism and nutrition disorders

Very common: Decreased appetite

Nervous system disorders

Very common: Headache

Respiratory, thoracic, and mediastinal disorders

Very common: Nasal congestion/rhinorrhoea

Uncommon: Epistaxis

Skin and subcutaneous tissue disorders

Uncommon: Rash

Musculoskeletal and connective tissue disorders

Common: Myalgia

General disorders and administration site conditions

Very common: Malaise

Common: Pyrexia

In an active-controlled clinical study (MI-CP111), an increased rate of hospitalisations (for any cause) through 180 days after final vaccination dose was observed in infants and toddlers 6-11 months of age (6.1% FLUENZ versus 2.6% injectable influenza vaccine). The rate of hospitalisations was not increased in FLUENZ recipients 12 months and older. In the same study, an increased rate of wheezing through 42 days was observed in infants and toddlers 6-23 months of age (5.9% FLUENZ versus 3.8% injectable influenza vaccine). The rate of wheezing was not increased in FLUENZ recipients 24 months and older. FLUENZ is not indicated for use in infants and toddlers younger than 24 months (see section 4.4).

Very rare reports of Guillain-Barré syndrome and exacerbation of symptoms of Leigh syndrome (mitochondrial encephalomyopathy) have also been observed in the post-marketing setting.

There have been occasional reports of administration of twice the recommended dose of FLUENZ in the post-marketing setting. The adverse reactions reported were similar to those seen with the recommended single dose of FLUENZ.

Pharmacotherapeutic group: Influenza vaccines, influenza live attenuated; ATC Code: J07BB03

The influenza virus strains in FLUENZ are (a) cold-adapted (ca); (b) temperature-sensitive (ts); and (c) attenuated (att). As a result, they replicate in the nasopharynx and induce protective immunity.

Efficacy

FLUENZ has been administered to over 30,000 individuals in controlled clinical studies over multiple years, in various regions and using different vaccine strains.

Paediatric studies

FLUENZ's efficacy data in the paediatric population consist of 9 controlled studies comprising over 20,000 infants and toddlers, children and adolescents, conducted during 7 influenza seasons. Four placebo-controlled studies included second season revaccination. FLUENZ has demonstrated superiority in 3 active-controlled studies with injectable influenza vaccine. See Table 1 and 2 for a summary of efficacy results in the paediatric population.

Table 1 FLUENZ Efficacy in Placebo Controlled Paediatric Studies

Table 2 FLUENZ Relative Efficacy in Active-controlled Paediatric Studies with Injectable Influenza Vaccine

Adult studies

Several studies against placebo have shown that FLUENZ may have some efficacy in adults. However, a conclusion on clinical benefit of this vaccine in adults could not be made given that results observed in some studies versus injectable influenza vaccines were suggestive of a lower efficacy of FLUENZ.

Not applicable.

Non-clinical data with FLUENZ reveal no special hazard for humans based on conventional non-clinical studies of repeated dose toxicity, reproduction and developmental toxicity, local tolerance, and neurovirulence.

Sucrose

Dibasic potassium phosphate

Monobasic potassium phosphate

Gelatin (porcine, Type A)

Arginine hydrochloride

Monosodium glutamate monohydrate

Water for injections

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

18 weeks.

Store in a refrigerator (2°C – 8°C).

Do not freeze.

Protect from light.

FLUENZ is supplied as a 0.2 ml suspension in a single-use nasal applicator (Type 1 glass), with nozzle (polypropylene with polyethylene transfer valve), nozzle tip-protector cap (synthetic rubber), plunger rod, plunger-stopper (butyl rubber), and a dose-divider clip.

Pack size of 1 or 10.

Not all pack sizes may be marketed.

Administration

FLUENZ IS FOR NASAL USE only.

• DO NOT USE WITH A NEEDLE. Do not inject.

• FLUENZ is administered as a divided dose in both nostrils.

• After administering half of the dose in one nostril, administer the other half of the dose in the other nostril immediately or shortly thereafter.

• The patient can breathe normally while the vaccine is being administered – there is no need to actively inhale or sniff.

• Refer to the FLUENZ administration diagram (Figure 1) for step-by-step administration instructions.

Figure 1 FLUENZ Administration

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

MedImmune, LLC

Lagelandseweg 78

6545 CG Nijmegen

Netherlands

(Tel) +31 24 371 7310

EU/1/10/661/001

EU/1/10/661/002

27 January 2011

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