Fluenz Tetra

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS



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1. NAME OF THE MEDICINAL PRODUCT

Fluenz Tetra nasal spray suspension
Influenza vaccine (live attenuated, nasal)

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

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

A/Guangdong-Maonan/SWL1536/2019 (H1N1)pdm09 - like strain
(A/Hawaii/66/2019, MEDI 326775) 107.0±0.5 FFU***

A/Hong Kong/2671/2019 (H3N2) - like strain 
(A/Hong Kong/2671/2019, MEDI 325078) 107.0±0.5 FFU***

B/Washington/02/2019 - like strain
(B/Washington/02/2019, MEDI 323797) 107.0±0.5 FFU***

B/Phuket/3073/2013 - like strain
(B/Phuket/3073/2013, MEDI 306444) 107.0±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 2020/2021 season.

The vaccine may contain residues of the following substances: egg proteins (e.g. ovalbumin) and 
gentamicin. The maximum amount of ovalbumin is less than 0.024 micrograms per 0.2 ml dose (0.12 
micrograms per ml).

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Nasal spray, suspension

The suspension is colourless to pale yellow, clear to opalescent with a pH of approximately 7.2. Small 
white particles may be present.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Prophylaxis of influenza in children and adolescents from 24 months to less than 18 years of age.

The use of Fluenz Tetra should be based on official recommendations.



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4.2 Posology and method of administration

Posology

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 administration

Immunisation 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.

4.3 Contraindications

- Hypersensitivity to the active substances, to any of the excipients listed in 
section 6.1 (e.g. gelatin), 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 Tetra 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.

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.

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 Tetra.



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Fluenz Tetra 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.

Vaccine recipients should be informed that Fluenz Tetra 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 Fluenz 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 Tetra should under no circumstances be injected.

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

4.5 Interaction with other medicinal products and other forms of interaction

Do not administer Fluenz Tetra to children and adolescents receiving salicylate therapy
(see section 4.3). Do not use salicylates 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.

The co-administration of trivalent 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. 
This observation with trivalent Fluenz is relevant to the use of Fluenz Tetra because Fluenz Tetra 
(influenza vaccine-liveattenuated, nasal) is identical to Fluenz with the only difference being the 
addition of a fourth strain (a second B strain) to Fluenz Tetra.

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

The concurrent use of Fluenz Tetra 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 Tetra, 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 Tetra 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 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 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.



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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-feeding

It 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.

Limited available evidence suggests that the trivalent Fluenz is not excreted in breastmilk. 

Fertility

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

4.7 Effects on ability to drive and use machines

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

4.8 Undesirable effects

Summary of the safety profile

The 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 2,231 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 reactions

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

Metabolism and nutrition disorders
Very common: Decreased appetite

Nervous system disorders
Common: Headache

Respiratory, thoracic and mediastinal disorders
Very common: Nasal congestion/rhinorrhoea



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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

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 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 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 national reporting system 
listed in Appendix V.

4.9 Overdose

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

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

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

Since 1985, two distinct lineages of influenza B viruses (Victoria and Yamagata) have circulated 
worldwide. Fluenz Tetra is a tetravalent vaccine that contains antigens for four influenza virus strains, 
an A/(H1N1) strain, an A/(H3N2) strain, and two B strains (one from each lineage). Fluenz Tetra is 
manufactured according to the same process as Fluenz. The influenza virus strains in Fluenz Tetra 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.

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


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Clinical studies

Clinical experience with Fluenz is relevant to Fluenz Tetra because both vaccines are manufactured 
using the same process and have overlapping compositions.

Paediatric studies

Fluenz efficacy
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

Study 
Number

Region
Age 

Rangea

Number of 
Study 

Participantsb

Influenza 
Season

Efficacy
(95% CI)c

Matched 
strains

Efficacy
(95% CI)c

All 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
a M=months.
b Number of study participants for year 1 efficacy analysis.
c Reduction in culture-confirmed influenza illness relative to placebo.
d Data presented for clinical trial D153-P504 are for study participants who received two doses of study vaccine. 
In previously unvaccinated study participants who received one dose in year 1, efficacy was 57.7% 
(95% CI: 44.7, 67.9) and 56.3% (95% CI: 43.1, 66.7), respectively, thus supporting the need for two doses 
of vaccine in previously unvaccinated children.
e In study participants who received 2 doses in year 1 and placebo in year 2, efficacy in year 2 was 56.2% 
(95% CI: 30.5, 72.7) and 44.8% (95% CI: 18.2, 62.9), respectively, in D153-P501, thus supporting the need for 
second-season revaccination.
f The primary circulating strain was antigenically dissimilar from the H3N2 strain represented in the vaccine; 
efficacy against the mismatched A/H3N2 strain was 85.9% (95% CI: 75.3, 91.9).



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

Study 
Number

Region
Age 

Rangea

Number of 
Study 

Participants

Influenza 
Season

Improved Efficacy
(95% CI)b

Matched strains

Improved 
Efficacy

(95% CI)b

All 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)c

fewer 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)d

fewer 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

a M=months. Y=years. Age range as described in the protocol for the study.
b Reduction in culture-confirmed influenza illness relative to injectable influenza vaccine.
c Fluenz demonstrated 55.7% (39.9, 67.6) fewer cases than injectable influenza vaccine in 3,686 infants and 
toddlers 6-23 months of age and 54.4% (41.8, 64.5) fewer cases in 4,166 children 24-59 months of age.
d Fluenz demonstrated 64.4% (1.4, 88.8) fewer cases than injectable influenza vaccine in 476 infants and 
toddlers 6-23 months of age and 48.2% (12.7, 70.0) fewer cases in 1,609 children 24-71 months of age.

Fluenz safety
Chronic conditions
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 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.

Immunocompromised
In 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 randomised 1:1 to trivalent Fluenz or placebo. Frequency and 



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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 immunogenicity
A multicentre, 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 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.

5.2 Pharmacokinetic properties

Not applicable.

5.3 Preclinical safety data

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

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sucrose
Dipotassium phosphate
Potassium dihydrogen phosphate
Gelatin (porcine, Type A)
Arginine hydrochloride
Monosodium glutamate monohydrate
Water for injections

6.2 Incompatibilities

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

6.3 Shelf life

18 weeks.

6.4 Special precautions for storage

Store in a refrigerator (2°C – 8°C).

Do not freeze.



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Keep the nasal applicator in the outer carton in order to protect from light.

Before use, the vaccine may be taken out of the refrigerator once for a maximum period of 12 hours at 
a temperature not above 25°C. Stability data indicate that the vaccine components are stable for 12
hours when stored at temperatures from 8°C to 25°C. At the end of this period, Fluenz Tetra should be 
used immediately or discarded.

6.5 Nature and contents of container

Fluenz Tetra 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.

6.6 Special precautions for disposal and other handling

Administration
Fluenz Tetra IS FOR NASAL USE ONLY.
 DO NOT USE WITH A NEEDLE. Do not inject.

 Do not use Fluenz Tetra if the expiry date has passed or the sprayer appears damaged, for 
example, if the plunger is loose or displaced from the sprayer or if there are any signs of 
leakage.

 Check the appearance of the vaccine before administration. The suspension should be colourless 
to pale yellow, clear to opalescent. Small white particles may be present.

 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.
 Refer to the Fluenz Tetra administration diagram (Figure 1) for step-by-step administration 

instructions.

Figure 1 Fluenz Tetra Administration



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Check expiry date
Product must be used 
before date on 
applicator label.

Prepare the applicator
Remove rubber tip 
protector. Do not remove 
dose-divider clip at the 
other end of the 
applicator.

Position the applicator
With the patient in an 
upright position, place 
the tip just inside the 
nostril to ensure Fluenz 
Tetra is delivered into 
the nose.

Depress the plunger
With a single motion, 
depress plunger as 
rapidly as possible
until the dose-divider 
clip prevents you from 
going further.

Remove dose-divider 
clip
For administration in the 
other nostril, pinch and 
remove the dose-divider 
clip from plunger.

Spray in other nostril
Place the tip just inside
the other nostril and 
with a single motion, 
depress plunger as 
rapidly as possible to 
deliver remaining 
vaccine.

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

7. MARKETING AUTHORISATION HOLDER

AstraZeneca AB
SE-151 85 Södertälje
Sweden

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/13/887/003 Top load carton assembly. 1 sprayer. 
EU/1/13/887/004 Top load carton assembly. 10 sprayers. 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 04 December 2013
Date of latest renewal: 20 November 2018

10. DATE OF REVISION OF THE TEXT

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

http://www.ema.europa.eu./


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ANNEX II

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) 
AND MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE 
SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT



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A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCES 
AND MANUFACTURER RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturer of the biological active substances

MedImmune, UK Limited
Plot 6, Renaissance Way
Boulevard Industry Park
Speke
Liverpool L24 9JW
United Kingdom

Name and address of the manufacturers responsible for batch release

MedImmune Pharma B.V.,
Lagelandseweg 78
Nijmegen, 6545CG
Netherlands

MedImmune, UK Limited
Plot 6, Renaissance Way
Boulevard Industry Park
Speke
Liverpool L24 9JW
United Kingdom

The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch.

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

Medicinal products subject to medical prescription.

 Official batch release

In accordance with Article 114 of Directive 2001/83/EC, the official batch release 
will be undertaken by a state laboratory or a laboratory designated for that purpose.

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION

 Periodic safety update reports (PSURs)

The requirements for submission of PSURs for this medicinal product are set out in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 
subsequent updates published on the European medicines web-portal.

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE 
SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT



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 Risk management plan (RMP)

The marketing authorisation holder (MAH) shall perform the required pharmacovigilance 
activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the 
marketing authorisation and any agreed subsequent updates of the RMP.

An updated RMP should be submitted:
 At the request of the European Medicines Agency;
 Whenever the risk management system is modified, especially as the result of new 

information being received that may lead to a significant change to the benefit/risk 
profile or as the result of an important (pharmacovigilance or risk minimisation) 
milestone being reached.

If the dates for submission of a PSUR and the update of a RMP coincide, they can be submitted at the 
same time.



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ANNEX III

LABELLING AND PACKAGE LEAFLET



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A. LABELLING



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING

PACK SIZE OF 1 SINGLE-USE NASAL APPLICATOR (IN A TRI-FOLD CARTON)
PACK SIZE OF 10 SINGLE-USE NASAL APPLICATORS

1. NAME OF THE MEDICINAL PRODUCT

Fluenz Tetra nasal spray suspension
Influenza vaccine (live attenuated, nasal)
2020/2021 season

2. STATEMENT OF ACTIVE SUBSTANCE(S)

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

A/Guangdong-Maonan/SWL1536/2019 (H1N1)pdm09 - like strain
(A/Hawaii/66/2019, MEDI 326775) 107.0±0.5 FFU***

A/Hong Kong/2671/2019 (H3N2) - like strain 
(A/Hong Kong/2671/2019, MEDI 325078)           107.0±0.5 FFU***

B/Washington/02/2019 - like strain
(B/Washington/02/2019, MEDI 323797)           107.0±0.5 FFU***

B/Phuket/3073/2013 - like strain
(B/Phuket/3073/2013, MEDI 306444)            107.0±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.
*** fluorescent focus units.

This vaccine complies with the WHO recommendations (Northern Hemisphere) and EU decision for 
the 2020/2021 season.

3. LIST OF EXCIPIENTS

Contains also: sucrose, dipotassium phosphate, potassium dihydrogen phosphate, gelatin (porcine, 
Type A), arginine hydrochloride, monosodium glutamate monohydrate, water for injections.

4. PHARMACEUTICAL FORM AND CONTENTS

Nasal spray, suspension
1 single-use nasal applicator (0.2 ml)
10 single-use nasal applicators (0.2 ml each)

5. METHOD AND ROUTE(S) OF ADMINISTRATION

For nasal use only. Do not inject.
Read the package leaflet before use.



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6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in a refrigerator.

Do not freeze.

Protect from light.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

AstraZeneca AB
SE-151 85 Södertälje
Sweden

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/13/887/003 Top load carton assembly. 1 sprayer.
EU/1/13/887/004 Top load carton assembly. 10 sprayers.

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY



19

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Justification for not including Braille accepted

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN



20

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

SINGLE-USE NASAL APPLICATOR

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Fluenz Tetra
Influenza vaccine
2020/2021 season

2. METHOD OF ADMINISTRATION

For nasal use only.

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

0.2 ml

6. OTHER



21

B. PACKAGE LEAFLET



22

Package leaflet: Information for the user

Fluenz Tetra nasal spray suspension
Influenza vaccine (live attenuated, nasal)

Read all of this leaflet carefully before the vaccine is given because it contains important 
information for you or your child.

- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor, nurse or pharmacist.
- This vaccine has been prescribed for you or your child only. Do not pass it on to others.
- If any of the side effects gets serious, talk to your doctor, nurse or pharmacist. This includes any 

possible side effects not listed in this leaflet. See section 4.

What is in this leaflet:

1. What Fluenz Tetra is and what it is used for
2. What you need to know before you are given Fluenz Tetra
3. How Fluenz Tetra is given
4. Possible side effects
5. How to store Fluenz Tetra
6. Contents of the pack and other information

1. What Fluenz Tetra is and what it is used for

Fluenz Tetra is a vaccine to prevent influenza (flu). It is used in children and adolescents 24 months to 
less than 18 years of age. Fluenz Tetra will help to protect against the four virus strains contained in 
the vaccine, and other strains closely related to them.

How Fluenz Tetra works

When a person is given the vaccine, the immune system (the body’s natural defence system) will 
produce its own protection against the influenza virus. None of the ingredients in the vaccine can 
cause the flu.

Fluenz Tetra vaccine viruses are grown in chicken eggs. Each year the vaccine targets four strains of 
influenza, following the annual recommendations by the World Health Organisation.

2. What you need to know before you are given Fluenz Tetra

You will not be given Fluenz Tetra:

 if you are allergic to gentamicin, gelatin or any of the other ingredients of this vaccine (listed in 
section 6 “Contents of the pack and other information”). 

 if you have ever had a severe allergic reaction to eggs or egg proteins. For signs of allergic 
reactions, see section 4 “Possible side effects”.

 if you have a blood disorder or a cancer that affects the immune system.
 if you have been told by your doctor that you have a weakened immune system as a result 

of a disease, medicine or other treatment.
 if you are already taking acetylsalicylic acid (a substance present in many medicines used 

to relieve pain and lower fever). This is because of the risk of a very rare but serious disease
(Reye’s syndrome).

If any of these apply, tell your doctor, nurse or pharmacist.



23

Warnings and precautions

Talk to your doctor, nurse or pharmacist before vaccination:
 if the child is less than 24 months of age. Children less than 24 months of age should not 

receive this vaccine because of the risk of side effects.
 if you have severe asthma or are currently wheezing.
 if you are in close contact with someone with a severely weakened immune system

(for example, a bone marrow transplant patient needing isolation).

If any of these apply, tell your doctor, nurse or pharmacist before vaccination. He or she will 
decide if Fluenz Tetra is suitable for you.

Other medicines, other vaccines and Fluenz Tetra

Tell your doctor, nurse or pharmacist if the person being vaccinated is taking, has recently taken or 
might take any other medicines, including medicines that do not require a prescription.
 Do not give acetylsalicylic acid (a substance present in many medicines used to relieve pain and 

lower fever) to children for 4 weeks after vaccination with Fluenz Tetra unless your doctor, 
nurse or pharmacist tells you otherwise. This is because of the risk of Reye’s syndrome, a very 
rare but serious disease that can affect the brain and liver.

 It is recommended that Fluenz Tetra is not given at the same time as influenza-specific 
antiviral medicines, such as oseltamivir and zanamivir. This is because the vaccine may work 
less effectively.

Your doctor, nurse or pharmacist will decide if Fluenz Tetra can be given at the same time as other 
vaccines.

Pregnancy and breast-feeding
 If you are pregnant, think you may be pregnant, plan to become pregnant soon or are 

breast-feeding, tell your doctor, nurse or pharmacist before receiving this vaccine. Fluenz 
Tetra is not recommended for women who are pregnant or are breast-feeding.

Driving and using machines
 Fluenz Tetra has no or negligible influence on the ability to drive and use machines.

3. How Fluenz Tetra is given

Fluenz Tetra will be administered under the supervision of a doctor, nurse or pharmacist.

Fluenz Tetra must only be used as a nasal spray.

Fluenz Tetra must not be injected.

Fluenz Tetra will be given as a spray in each nostril. You can breathe normally while you are given 
Fluenz Tetra. You do not need to actively inhale or sniff.

Dosage
The recommended dose for children and adolescents is 0.2 ml Fluenz Tetra, administered as 0.1 ml 
in each nostril. Children who have not previously had an influenza vaccine will receive a second, 
follow-up dose after an interval of at least 4 weeks. Follow your doctor, nurse or pharmacist’s
instructions about if and when your child should return for the second dose.

If you have any further questions on this vaccine, ask your doctor, nurse or pharmacist.



24

4. Possible side effects

Like all medicines, this vaccine can cause side effects, although not everybody gets them. In clinical 
studies with the vaccine, most side effects were mild in nature and short term.

Ask your doctor, nurse or pharmacist if you want more information about possible side effects from 
Fluenz Tetra.

Some side effects may be serious

Very rare
(may affect up to 1 in 10,000 people):
 severe allergic reaction: signs of a severe allergic reaction may include shortness of breath and 

swelling of the face or tongue.

Tell your doctor straight away or seek urgent medical care if you experience any of the effects 
above.

Other possible side effects of Fluenz Tetra

Very common
(may affect more than 1 in 10 people):
 runny or stuffy nose
 reduced appetite
 weakness

Common
(may affect up to 1 in 10 people):
 fever
 muscle aches
 headache

Uncommon
(may affect up to 1 in 100 people):
 rash
 nose bleed
 allergic reactions

Reporting of side effects
If you get any side effects, talk to your doctor, nurse or pharmacist. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine.

5. How to store Fluenz Tetra

Keep this vaccine out of the sight and reach of children.

Do not use this vaccine after the expiry date which is stated on the applicator label after the 
letters EXP.

Store in a refrigerator (2°C to 8°C). Do not freeze.

Keep the nasal applicator in the outer carton in order to protect from light.

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


25

Before use, the vaccine may be taken out of the refrigerator once for a maximum period of 12 hours at 
a temperature not above 25°C. If the vaccine has not been used after this 12 hour period, it should be
discarded.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how 
to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Fluenz Tetra contains

The active substances are:
Reassortant influenza virus* (live attenuated) of the following four strains**:

A/Guangdong-Maonan/SWL1536/2019 (H1N1)pdm09 - like strain
(A/Hawaii/66/2019, MEDI 326775) 107.0±0.5 FFU***

A/Hong Kong/2671/2019 (H3N2) - like strain 
(A/Hong Kong/2671/2019, MEDI 325078)            107.0±0.5 FFU***

B/Washington/02/2019 - like strain
(B/Washington/02/2019, MEDI 323797)            107.0±0.5 FFU***

B/Phuket/3073/2013 - like strain
(B/Phuket/3073/2013, MEDI 306444)            107.0±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 (World Health Organisation) recommendations
(Northern Hemisphere) and EU decision for the 2020/2021 season.

The other ingredients are sucrose, dipotassium phosphate, potassium dihydrogen phosphate, gelatin 
(porcine, Type A), arginine hydrochloride, monosodium glutamate monohydrate and water for
injections.

What Fluenz Tetra looks like and contents of the pack

This vaccine is presented as a nasal spray suspension in a single-use nasal applicator (0.2 ml) in a pack 
size of 1 and 10. Not all pack sizes may be available in your country.

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



26

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder: 

AstraZeneca AB
SE-151 85
Södertälje
Sweden

Manufacturer: 

MedImmune Pharma B.V.,
Lagelandseweg 78
Nijmegen, 6545CG
Netherlands

MedImmune, UK Limited
Plot 6, Renaissance Way
Boulevard Industry Park
Speke
Liverpool L24 9JW
United Kingdom

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder:

België/Belgique/Belgien
AstraZeneca S.A./N.V.
Tel: +32 2 370 48 11

Lietuva
UAB AstraZeneca Lietuva
Tel: +370 5 2660550

България
АстраЗенека България ЕООД
Тел.: +359 24455000

Luxembourg/Luxemburg
AstraZeneca S.A./N.V.
Tél/Tel: +32 2 370 48 11

Česká republika
AstraZeneca Czech Republic s.r.o.
Tel: +420 222 807 111

Magyarország
AstraZeneca Kft.
Tel.: +36 1 883 6500

Danmark
AstraZeneca A/S
Tlf: +45 43 66 64 62

Malta
Associated Drug Co. Ltd
Tel: +356 2277 8000

Deutschland
AstraZeneca GmbH
Tel: +49 41 03 7080

Nederland
AstraZeneca BV
Tel: +31 79 363 2222

Eesti
AstraZeneca
Tel: +372 6549 600

Norge
AstraZeneca AS
Tlf: +47 21 00 64 00

Ελλάδα
AstraZeneca A.E.
Τηλ: +30 210 6871500

Österreich
AstraZeneca Österreich GmbH
Tel: +43 1 711 31 0



27

España
AstraZeneca Farmacéutica Spain, S.A.
Tel: +34 91 301 91 00

Polska
AstraZeneca Pharma Poland Sp. z o.o.
Tel.: +48 22 245 73 00

France
AstraZeneca
Tél: +33 1 41 29 40 00

Portugal
AstraZeneca Produtos Farmacêuticos, Lda.
Tel: +351 21 434 61 00

Hrvatska
AstraZeneca d.o.o.
Tel: +385 1 4628 000

România
AstraZeneca Pharma SRL
Tel: +40 21 317 60 41

Ireland
AstraZeneca Pharmaceuticals (Ireland) DAC
Tel: +353 1609 7100

Slovenija
AstraZeneca UK Limited
Tel: +386 1 51 35 600

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
AstraZeneca AB, o.z.
Tel: +421 2 5737 7777

Italia
AstraZeneca S.p.A.
Tel: +39 02 98011

Suomi/Finland
AstraZeneca Oy
Puh/Tel: +358 10 23 010

Κύπρος
Αλέκτωρ Φαρμακευτική Λτδ
Τηλ: +357 22490305

Sverige
AstraZeneca AB
Tel: +46 8 553 26 000

Latvija
SIA AstraZeneca Latvija
Tel: +371 67377100

United Kingdom
AstraZeneca UK Ltd
Tel: +44 1582 836 836

This leaflet was last revised in.

Other sources of information
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.

------------------------------------------------------------------------------------------------------------------------

Instructions for healthcare professionals

The following information is intended for healthcare professionals only:

Fluenz Tetra is for nasal use only.
 Do not use with a needle. Do not inject.

 Do not use Fluenz Tetra if the expiry date has passed or the sprayer appears damaged, for 
example, if the plunger is loose or displaced from the sprayer or if there are any signs of 
leakage.

 Check the appearance of the vaccine before administration. The suspension should be colourless 
to pale yellow, clear to opalescent. Small white particles may be present.

http://www.ema.europa.eu./


28

 Fluenz Tetra is administered as a divided dose in both nostrils as described below. (See also, 
How Fluenz Tetra is given, in section 3).

 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.

Check expiry date
Product must be used 
before date on applicator 
label.

Prepare the applicator
Remove rubber tip 
protector. Do not remove 
dose-divider clip at the 
other end of the 
applicator.

Position the applicator
With the patient in an 
upright position, place 
the tip just inside the 
nostril to ensure Fluenz 
Tetra is delivered into 
the nose.

Depress the plunger
With a single motion, 
depress plunger as 
rapidly as possible until 
the dose-divider clip 
prevents you from going 
further.

Remove dose-divider 
clip
For administration in the 
other nostril, pinch and 
remove the dose-divider 
clip from plunger.

Spray in other nostril
Place the tip just inside 
the other nostril and 
with a single motion, 
depress plunger as 
rapidly as possible to 
deliver remaining 
vaccine.

See section 5 for advice on storage and disposal.


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCES AND MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET