Leaflet FLUENZ nasal spray, suspension

The most common adverse reaction is nasal congestion/rhinorrhoea (56.7%).

The following adverse reactions have been reported with influenza vaccines (live, nasal) trivalent andtetravalent during clinical studies and post-marketing experience. Adverse reactions are listed by

MedDRA System Organ Class (SOC). Within each SOC, adverse reactions are presented bydecreasing frequency. Within each frequency grouping, adverse reactions are presented in the order ofdecreasing seriousness. Frequencies of occurrence 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 Uncommon(including facial oedema,urticaria)

Anaphylactic reactions Very rare

Metabolism and nutrition Decreased appetite Very commondisorders

Nervous system disorders Headache Common

Syncope Not knowna

Guillain-Barré syndrome Not knowna

Respiratory, thoracic and Nasal congestion/rhinorrhoea Very commonmediastinal disorders Epistaxis Uncommon

Skin and subcutaneous tissue Rash Uncommondisorders

Musculoskeletal and Myalgia Commonconnective tissue disorders

Congenital, familial, and Exacerbation of symptoms of Not knownagenetic disorders Leigh syndrome (mitochondrialencephalomyopathy)

General disorders and Malaise Very commonadministration site conditions Pyrexia Commona Post-marketing experience

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 togastrointestinal and respiratory tract infections and occurred more than 6 weeks post vaccination. Therate 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 ofage (5.9% Fluenz versus 3.8% injectable influenza vaccine). The rate of wheezing was not increasedin Fluenz recipients 2 years and older. Fluenz is not indicated for use in infants and toddlers youngerthan 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, trivalentinjectable influenza vaccine: n=1 115), there were no significant differences between treatment groupsin the incidence of asthma exacerbations, mean peak expiratory flow rate, asthma symptom scores, ornight-time awakening scores. The incidence of wheezing within 15 days after vaccination was lowerin 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 forcedexpiratory volume in 1 second (FEV1) measured before and after vaccination, did not differ betweentreatment arms.

Although safety in children and adolescents with mild to moderate asthma has been established, datain 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 andolder (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 diabetesmellitus (9.6%). The safety profile of Fluenz in these individuals was comparable to the safety profileobserved in individuals without these conditions.

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-retroviraltherapy (Fluenz: n=122, trivalent injectable vaccine: n=121), the frequency and duration of vaccinevirus shedding were comparable to that seen in healthy individuals. No adverse effects on HIV viralload 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) wererandomised 1:1 to Fluenz or placebo. Frequency and duration of vaccine virus shedding in theseimmunocompromised children and adolescents were comparable to that seen in healthy children andadolescents.

Reporting suspected adverse reactions after authorisation of the medicinal product is important. Itallows continued monitoring of the benefit/risk balance of the medicinal product. Healthcareprofessionals are asked to report any suspected adverse reactions via the national reporting systemlisted in Appendix V.