- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions.
|A/California/7/2009 (H1N1)pdm09 - like strain (A/Bolivia/559/2013, MEDI 255962)||107.0±0.5 FFU***|
|A/Hong Kong/4801/2014 (H3N2) - like strain (A/New Caledonia/71/2014, MEDI 263122)||107.0±0.5 FFU***|
|B/Brisbane/60/2008 - like strain (B/Brisbane/60/2008, MEDI 228030)||107.0±0.5 FFU***|
|B/Phuket/3073/2013 - like strain (B/Phuket/3073/2013, MEDI 254977)||107.0±0.5 FFU***............ per 0.2 ml dose|
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 Tetra should not be used in infants and toddlers below 24 months of age because of safety concerns regarding increased rates of hospitalisation and wheezing in this population (see section 4.8).
Method of administrationImmunisation must be carried out by nasal administration. Do not inject Fluenz Tetra. Fluenz Tetra 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. See section 6.6 for administration instructions.
PregnancyThere are limited data from the use of Fluenz Tetra in pregnant women. There was no evidence of significant maternal adverse outcomes in 138 pregnant women who had a record of receiving trivalent Fluenz in a US-based health insurance claims database. In 27 reports of Fluenz administration to pregnant women from the US Vaccine Adverse Event Reporting System, 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 Tetra is not recommended during pregnancy.
Breast-feedingIt is not known whether Fluenz Tetra is excreted in human milk. Therefore, as some viruses are excreted in human milk, Fluenz Tetra should not be used during breast-feeding.
FertilityNo data exist regarding the possible effects of Fluenz Tetra on male and female fertility.
Summary of the safety profileThe safety experience with trivalent Fluenz is relevant to the use of Fluenz Tetra because Fluenz Tetra (influenza vaccine -live attenuated, nasal) is identical to Fluenz with the only difference being the addition of a fourth strain (a second B strain) to Fluenz Tetra. Safety data regarding use of Fluenz Tetra are based on data from Fluenz Tetra clinical studies in 1,382 children and adolescents 2 to 17 years of age, Fluenz clinical studies in over 29,000 children and adolescents 2 to 17 years of age and Fluenz post-authorisation safety studies in over 84,000 children and adolescents 2 to 17 years of age. Additional experience has occurred with marketed use of Fluenz.In clinical studies, the safety profile of Fluenz Tetra was similar to the safety profile of Fluenz. The most common adverse reaction observed in clinical studies was nasal congestion/rhinorrhoea.
List of adverse reactionsAdverse reaction frequencies are reported 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)
Immune system disordersUncommon: Hypersensitivity reactions (including facial oedema, urticaria and very rare anaphylactic reactions)
Metabolism and nutrition disordersVery common: Decreased appetite
Nervous system disordersVery common: Headache
Respiratory, thoracic and mediastinal disordersVery common: Nasal congestion/rhinorrhoea Uncommon: Epistaxis
Skin and subcutaneous tissue disordersUncommon: Rash
Musculoskeletal and connective tissue disordersCommon: Myalgia
General disorders and administration site conditionsVery common: MalaiseCommon: PyrexiaIn 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 24 months and older. Fluenz Tetra is not indicated for use in infants and toddlers younger than 24 months (see section 4.2). 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 with Fluenz.
Reporting of suspected adverse reactionsReporting 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:
United KingdomYellow Card Scheme Website: www.mhra.gov.uk/yellowcard
Clinical studiesClinical experience with Fluenz is relevant to Fluenz Tetra because both vaccines are manufactured using the same process and have overlapping compositions.
Fluenz efficacyFluenz'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
|Study Number||Region||Age Rangea||Number of Study Participantsb||Influenza Season||Efficacy(95% CI)cMatched strains||Efficacy(95% CI)cAll strains regardless of match|
|D153-P502||Europe||6 to 35 M||1,616||2000-2001||85.4% (74.3, 92.2)||85.9% (76.3, 92.0)|
|2001-2002||88.7% (82.0, 93.2)||85.8% (78.6, 90.9)|
|D153-P504||Africa, Latin America||6 to 35 M||1,886||2001||73.5% (63.6, 81.0)d||72.0% (61.9, 79.8)d|
|2002||73.6% (33.3, 91.2)||46.6% (14.9, 67.2)|
|D153-P513||Asia/Oceania||6 to 35 M||1,041||2002||62.2% (43.6, 75.2)||48.6% (28.8, 63.3)|
|D153-P522||Europe, Asia/Oceania, Latin America||11 to 24 M||1,150||2002-2003||78.4% (50.9, 91.3)||63.8% (36.2, 79.8)|
|D153-P501||Asia/Oceania||12 to 35 M||2,764||2000-2001||72.9% (62.8, 80.5)||70.1% (60.9, 77.3)|
|2001-2002||84.3% (70.1, 92.4)e||64.2% (44.2, 77.3)e|
|AV006||USA||15 to 71 M||1,259||1996-1997||93.4% (87.5, 96.5)||93.4% (87.5, 96.5)|
|1997-1998||100% (63.1, 100)||87.1% (77.7, 92.6)f|
|Study Number||Region||Age Rangea||Number of Study Participants||Influenza Season||Improved Efficacy(95% CI)bMatched strains||Improved Efficacy(95% CI)bAll strains regardless of match|
|MI-CP111||USA, Europe, Asia/Oceania||6 to 59 M||7,852||2004-2005||44.5% (22.4, 60.6) fewer cases than injectable||54.9% (45.4, 62.9)cfewer cases than injectable|
|D153-P514||Europe||6 to 71 M||2,085||2002-2003||52.7% (21.6, 72.2) fewer cases than injectable||52.4% (24.6, 70.5)dfewer cases than injectable|
|D153-P515||Europe||6 to 17 Y||2,211||2002-2003||34.7% (3.9, 56.0) fewer cases than injectable||31.9% (1.1, 53.5) fewer cases than injectable|
Chronic conditionsAlthough 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 a study (D153-P515) of children 6 to 17 years of age with asthma (trivalent 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 (trivalent 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. In studies of adults in which a high percentage of individuals had underlying chronic medical conditions, the safety profile of trivalent Fluenz was comparable to the safety profile observed in individuals without these conditions.
ImmunocompromisedIn 24 HIV-infected children and 25 HIV-negative children 1 through 7 years of age, and in 243 HIV-infected children and adolescents 5 through 17 years of age receiving stable anti-retroviral therapy, 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 trivalent 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 randomized 1:1 to trivalent 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. The effectiveness of Fluenz and Fluenz Tetra in preventing influenza illness in immunocompromised individuals has not been evaluated. Fluenz Tetra immunogenicityA multicenter, randomised, double-blind, active-controlled, non-inferiority study was conducted to assess the immunogenicity of Fluenz Tetra compared to Fluenz (active control) in children and adolescents 2-17 years of age. A total of 2,312 children and adolescents were randomised by site at a 3:1:1 ratio to receive either Fluenz Tetra or one of two formulations of comparator vaccine Fluenz, each containing a B strain that corresponded to one of the two B strains in Fluenz Tetra (a B strain of the Yamagata lineage and a B strain of the Victoria lineage). Immunogenicity was evaluated by comparing geometric mean titres (GMTs) of strain-specific serum haemagglutination inhibition (HAI) antibodies post dosing. Fluenz Tetra demonstrated immunologic non-inferiority to the two formulations of Fluenz as the upper bound for each of the four 95% CIs for the post-dose strain-specific GMT HAI antibody ratios was ≤ 1.5.
Adult studiesSeveral 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.
|Check expiry dateProduct must be used before date on applicator label.||Prepare the applicatorRemove rubber tip protector. Do not remove dose-divider clip at the other end of the applicator.||Position the applicatorWith the patient in an upright position, place the tip just inside the nostril to ensure Fluenz Tetra is delivered into the nose.|
|Depress the plungerWith a single motion, depress plunger as rapidly as possible until the dose-divider clip prevents you from going further.||Remove dose-divider clipFor administration in the other nostril, pinch and remove the dose-divider clip from plunger.||Spray in other nostrilPlace the tip just inside the other nostril and with a single motion, depress plunger as rapidly as possible to deliver remaining vaccine.|
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