4.1. Therapeutic indications

Fluenz is indicated for active immunisation for the prevention of influenza disease in children and adolescents from 2 years to less than 18 years of age.

Fluenz should be used in accordance with official recommendations.

4.2. Posology and method of administration

Posology

Children and adolescents from 2 years to <18 years of age

The recommended dose is 0.2 ml, administered as 0.1 ml in each nostril.

For children 2 to 8 years of age who have not previously been vaccinated against seasonal influenza, a second dose should be given after an interval of at least 4 weeks.

Infants and toddlers <2 years of age

Fluenz should not be used in infants and toddlers below 2 years of age because of safety concerns regarding increased rates of hospitalisation and wheezing in this population (see section 4.8).

Method of administration

For nasal use only.

Fluenz should under no circumstances be injected.

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.

For detailed instructions on preparation and administration, see section 6.6.

4.3. Contraindications

• Hypersensitivity to the active substances or, to any of the excipients listed in section 6.1 or to gentamicin (a possible trace residue).

• Severe allergic reaction (e.g. anaphylaxis) to eggs or to egg proteins (e.g. ovalbumin).

• Children and adolescents with clinical immunodeficiency 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 (see section 4.5).

4.4. Special warnings and precautions for use

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Hypersensitivity and anaphylaxis

As with most vaccines, appropriate medical treatment and supervision should always be readily available to manage an anaphylactic event or serious hypersensitivity event following the administration of Fluenz.

Concurrent illness and chronic conditions.

Fluenz should not be administered to children and adolescents with severe asthma or who are currently wheezing, because these individuals have not been adequately studied in clinical studies (see section 4.8).

Administration of Fluenz should be postponed in individuals suffering from severe acute febrile illness or acute infection. The presence of a minor infection and/or low-grade fever should not result in the deferral of vaccination.

Vaccination should also be postponed in individuals with nasal blockage, due to the potential for reduced vaccine uptake and the absence of efficacy data in this population. The presence of mild symptoms of a common cold without nasal blockage should not result in the deferral of vaccination.

Immunocompromised individuals

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. The effectiveness of Fluenz preventing influenza disease in immunocompromised individuals has not been evaluated (see section 4.8).

General

Fluenz should under no circumstances be injected.

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

4.5. Interaction with other medicinal products and other forms of interaction

Fluenz must not be administered to children and adolescents receiving salicylate therapy (see section 4.3). Salicylates should not be used in children and adolescents 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.

Fluenz can be administered concomitantly with the live attenuated vaccines: measles, mumps, rubella, varicella, and orally‑administered poliovirus.

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 based on clinical judgement.

4.6. Fertility, pregnancy and lactation

Pregnancy

There is a moderate amount of data from the use of Fluenz in pregnant women. There was no evidence of significant maternal adverse outcomes in 138 pregnant women who had a record of receiving Fluenz in a US‑based health insurance claims database.

In more than 300 case reports in the AstraZeneca safety database of vaccine administration to pregnant women, no unusual patterns of pregnancy complications or foetal outcomes were observed.

While animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity, and post‑marketing data offer some reassurance in the event of inadvertent administration of the vaccine, Fluenz is not recommended during pregnancy.

Breast‑feeding

Limited available evidence suggests that Fluenz is not excreted in breastmilk. However, because there are limited data to assess the effects on the breast‑fed infant and as some viruses are excreted in human milk, Fluenz should not be used during breast‑feeding.

Fertility

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

4.7. Effects on ability to drive and use machines

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

4.8. Undesirable effects

Summary of the safety profile

Safety data regarding use of Fluenz are based on data from Fluenz clinical studies in over 29 000 children and adolescents 2 to 17 years of age, Fluenz post‑authorisation safety studies in over 84 000 children and adolescents 2 to 17 years of age, and data from influenza vaccine (live attenuated, nasal) tetravalent clinical studies in over 2 000 children and adolescents 2 to 17 years of age. Additional experience has occurred with marketed use of Fluenz and /or influenza vaccine (live attenuated, nasal) tetravalent.

In clinical studies, the safety profile of Fluenz and influenza vaccine (live attenuated, nasal tetravalent were similar.

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

Tabulated list of adverse reactions

Adverse reaction frequencies are organised by MedDRA System Organ Class (SOC). Within each SOC, adverse reactions are arranged by decreasing frequency and then by decreasing seriousness. Frequencies of occurance of adverse reactions are defined as:

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) and not known (cannot be estimated from available data).

Table 1 Adverse reactions

MedDRA SOC

Adverse reaction

Frequency

Immune system disorders

Hypersensitivity reactions (including facial oedema, urticaria)

Uncommon

Anaphylactic reactions

Very rare

Metabolism and nutrition disorders

Decreased appetite

Very common

Nervous system disorders

Headache

Common

Guillain‑Barré syndrome

Not knowna

Respiratory, thoracic and mediastinal disorders

Nasal congestion/rhinorrhoea

Very common

Epistaxis

Uncommon

Skin and subcutaneous tissue disorders

Rash

Uncommon

Musculoskeletal and connective tissue disorders

Myalgia

Common

General disorders and administration site conditions

Malaise

Very common

Pyrexia

Common

Congenital, familial, and genetic disorders

Exacerbation of symptoms of Leigh syndrome (mitochondrial encephalomyopathy)

Not knowna

a Post‑marketing experience

Paediatric population

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). Most hospitalisations were due to gastrointestinal and respiratory tract infections and occurred more than 6 weeks post vaccination. 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 2 years and older. Fluenz is not indicated for use in infants and toddlers younger than 2 years (see section 4.2).

Concurrent illness and chronic conditions

In a study (D153‑P515) of children 6 to 17 years of age with asthma (Fluenz: n=1 114, trivalent injectable influenza vaccine: n=1 115), there were no significant differences between treatment groups in the incidence of asthma exacerbations, mean peak expiratory flow rate, asthma symptom scores, or night‑time awakening scores. The incidence of wheezing within 15 days after vaccination was lower in Fluenz recipients relative to inactivated vaccine recipients (19.5% vs. 23.8%, P=0.02).

In a study of children and adolescents 9 to 17 years of age with moderate to severe asthma (Fluenz: n=24, placebo: n=24), the primary safety criterion, change in percent predicted forced expiratory volume in 1 second (FEV1) measured before and after vaccination, did not differ between treatment arms.

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, or other underlying chronic medical conditions are limited. In a study of adults 60 years of age and older (n=3 242), a high percentage of individuals had underlying chronic medical conditions (87%), including cardiac disorders (15%), respiratory, thoracic and mediastinal disorders (13%), and diabetes mellitus (9.6%). The safety profile of Fluenz in these individuals was comparable to the safety profile observed in individuals without these conditions.

Immunocompromised individuals

In HIV‑infected children (n=24) and HIV‑negative children (n=25) 1 through 7 years of age, and in HIV‑infected children and adolescents 5 through 17 years of age receiving stable anti‑retroviral therapy (Fluenz: n=122, trivalent injectable vaccine: n=121), the frequency and duration of vaccine virus shedding were comparable to that seen in healthy individuals. No adverse effects on HIV viral load or CD4 counts were identified following Fluenz administration.

Twenty mild to moderately immunocompromised children and adolescents 5 through 17 years of age (receiving chemotherapy and/or radiation therapy or who had recently received chemotherapy) were randomised 1:1 to Fluenz or placebo. Frequency and duration of vaccine virus shedding in these immunocompromised children and adolescents were comparable to that seen in healthy children and adolescents.

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 or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Overdose with Fluenz is unlikely due to its presentation as a single pre‑filled nasal applicator. Administration of a higher than recommended dose of Fluenz was reported rarely and the adverse reaction profile was comparable to that observed with the recommended dose of Fluenz.