Consumer medicine information

FluQuadri

Influenza virus vaccine, split virion, quadrivalent (inactivated)

BRAND INFORMATION

Brand name

FluQuadri

Active ingredient

Influenza virus vaccine, split virion, quadrivalent (inactivated)

Schedule

SUMMARY CMI

FluQuadri™

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor, nurse or pharmacist.

1. Why am I using FluQuadri?

FluQuadri is a vaccine. This vaccine helps to protect you against influenza (flu). FluQuadri is used to prevent flu in persons of 6 months of age and older.

For more information, see Section 1. Why am I using FluQuadri? in the full CMI.

2. What should I know before being given FluQuadri?

Do not use if you have ever had an allergic reaction to FluQuadri or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before being given FluQuadri? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with FluQuadri and affect how it works. Tell your doctor, nurse or pharmacist if you are taking, have recently taken or might take any other vaccines or medicines, including medicines obtained without a prescription.

For more information, see Section 3. What if I am taking other medicines? in the full CMI.

4. How is FluQuadri given?

FluQuadri is given by your doctor, nurse or pharmacist.

More instructions can be found in Section 4. How is FluQuadri given? in the full CMI.

5. What should I know about being given FluQuadri?

Things you should do	Tell your doctor, nurse or pharmacist after you or your child receive the vaccine have signs of allergic reactions that may include difficulty breathing, shortness of breath, swelling of the face, lips, throat or tongue, cold, clammy skin, palpitations, dizziness, weakness, fainting, rash or itching.
Looking after your medicine	FluQuadri is usually stored in the surgery or clinic, or at the pharmacy. However, if you need to store FluQuadri: keep in the fridge between 2-8°C. Do not freeze.

For more information, see Section 5. What should I know about being given FluQuadri? in the full CMI.

6. Are there any side effects?

Serious side effects can include severe allergic reactions, inflammation of nerves leading to weakness, fainting, dizziness, tingling or numbness of hands or feet, temporary inflammation of nerves, fits, temporary reduction in the number of platelets, swollen glands in neck, armpit or groin. See your doctor immediately if you notice this.

Common side effects include pain, tenderness, redness, swelling, bruising and hardness at the injection site, headache, muscle aches, feeling unwell, fever and shivering. In children, other common side effects include irritability, abnormal crying, drowsiness, appetite loss, cough, runny nose and vomiting.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

FULL CMI

FluQuadri™

Active ingredient(s): Influenza virus haemagglutinin

Consumer Medicine Information (CMI)

This leaflet provides important information about using FluQuadri. You should also speak to your doctor, nurse or pharmacist if you would like further information or if you have any concerns or questions about using FluQuadri.

This vaccine can be given to adults and children so you may be reading this leaflet for you or for your child.

Where to find information in this leaflet:

1. Why am I using FluQuadri?
2. What should I know before being given FluQuadri?
3. What if I am taking other medicines?
4. How is FluQuadri given?
5. What should I know about being given FluQuadri?
6. Are there any side effects?
7. Product details

1. Why am I using FluQuadri?

FluQuadri contains the active ingredient influenza virus haemagglutinin.

FluQuadri is a vaccine for persons 6 months of age and older. This vaccine helps to protect you against influenza (flu).

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.

Flu is a disease that can spread rapidly and is caused by different types of strains that can change every year. Therefore, this is why you might need to be vaccinated every year. The greatest risk of catching flu is during the cold months between June and September. If you were not vaccinated in the autumn, it is still sensible to be vaccinated up until the spring since you run the risk of catching influenza until then. Your doctor will be able to recommend the best time to be vaccinated.

As with all vaccines, FluQuadri may not fully protect all persons who are vaccinated.

2. What should I know before being given FluQuadri?

Warnings

Do not use FluQuadri:

if you are allergic to the active ingredients or any of the ingredients listed at the end of this leaflet. Symptoms of allergic reaction may include difficulty breathing, shortness of breath, swelling of the face, lips, throat or tongue, cold, clammy skin, palpitations, dizziness, weakness, fainting, rash or itching. If you are not sure if you are allergic, talk to your doctor, nurse or pharmacist before you receive FluQuadri.
Always check the ingredients to make sure you can receive this vaccine.

Tell your doctor, nurse or pharmacist:

if you have an acute illness with or without high temperature.
if you have or have had an immune response problem because the immune response to the vaccine may be diminished.
if you have a bleeding problem or bruise easily.
if you have ever fainted from an injection. Fainting, sometimes with falling, can occur during, following, or even before, any injection with a needle.
if you have or have had Guillain-Barré syndrome (severe muscle weakness) after getting a flu vaccine.
if you have a known allergy to egg protein.

After vaccination, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Your doctor will discuss the possible risks and benefits of having FluQuadri during pregnancy or breastfeeding. Due to the known adverse consequences of influenza infection in pregnant women, health authorities recommend vaccination for pregnant women.

Your doctor should make sure the benefits of vaccination outweigh the risks when recommending FluQuadri.

3. What if I am taking other medicines?

Some medicines may interfere with FluQuadri and affect how it works. Tell your doctor, nurse or pharmacist if

you are taking, have recently taken or might take any other vaccines or medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Your doctor will advise you if FluQuadri is to be given with another vaccine.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect FluQuadri.

4. How is FluQuadri given?

How much is given

FluQuadri is given by your doctor, nurse or pharmacist as a 0.5 mL injection in the muscle in the upper arm (preferably). For infants, the injection is normally given into the muscle of the thigh.

Children who have not been vaccinated against influenza before, require a second injection a month later. Doses of influenza vaccine for infants and young children are decided by your doctor based on the official national recommendations.

5. What should I know about being given FluQuadri?

Things you should do

Call your doctor straight away if:

You notice signs of allergic reaction which may include difficulty breathing, shortness of breath, swelling of the face, lips, throat or tongue, cold, clammy skin, palpitations, dizziness, weakness, fainting, rash or itching.

Driving or using machines

Do not drive or use machines if you are feeling unwell after vaccination. Wait until any effects of the vaccine have worn off before you drive or use machines.

Looking after your medicine

FluQuadri is usually stored in the doctor's surgery or clinic, or at the pharmacy. However, if you need to store FluQuadri:

keep it where young children cannot reach it.
keep FluQuadri in the original pack until it is time for it to be given.
keep it in the refrigerator, store at 2°C to 8°C. Do not freeze FluQuadri.

Do not use FluQuadri after the expiry date which is stated on the carton after EXP.

Do not use FluQuadri if the packaging is torn or shows signs of tampering.

Getting rid of unwanted Medicine

Medicines including vaccines should not be disposed of via wastewater or household waste. Ask your doctor, nurse or pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor, nurse or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effects	What to do
pain, tenderness, redness, swelling, bruising and hardness at the injection site feeling unwell headache muscle aches fever shivering irritability, abnormal crying, drowsiness, appetite loss, cough, runny nose, vomiting (in children)	Speak to your doctor, nurse or pharmacist if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effects

What to do

inflammation of nerves leading to weakness, such as weakness of facial muscles (facial palsy) or visual disturbance (optic neuritis/neuropathy)
fainting (syncope), dizziness, tingling or numbness of hands or feet (paraesthesia)
temporary inflammation of nerves causing pain, paralysis and sensitivity disorders (Guillain Barre syndrome [GBS])
fits (convulsions) with or without fever
severe allergic reaction (anaphylaxis)
temporary reduction in the number of blood particles called platelets (thrombocytopenia), swollen glands in neck, armpit or groin (lymphadenopathy)

Call your doctor straight away or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor, nurse or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems in Australia or in New Zealand at nzphvc.otago.ac.nz/reporting. By reporting side effects, you can help provide more information on the safety of this medicine.

7. Product details

What FluQuadri contains

Active ingredient (main ingredient)	Influenza virus haemagglutinin of the following strains A/Victoria/4897/2022 (H1N1)pdm09-like strain (A/Victoria/4897/2022, IVR-238) A/Thailand/8/2022 (H3N2)-like strain (A/California/122/2022, SAN-022) B/Austria/1359417/2021-like strain (B/Michigan/01/2021, wild type) B/Phuket/3073/2013 - like strain (B/Phuket/3073/2013, wild type)
Other ingredients (inactive ingredients)	Sodium chloride, dibasic sodium phosphate, monobasic sodium phosphate, water for injection, and traces of ovalbumin (egg protein), octoxinol-9 and formaldehyde.
Potential allergens	FluQuadri contains less than 1 microgram ovalbumin (egg protein) per dose.

Do not receive this vaccine if you are allergic to any of these ingredients.

FluQuadri does not contain any antibiotics or preservative.

FluQuadri syringes are not made with natural rubber latex.

What FluQuadri looks like

FluQuadri suspension for injection is clear and slightly opalescent in colour.

FluQuadri is available in packs of 5 single dose (0.5 mL) pre-filled syringes with or without separate needles. Not all packs may be marketed.

Who distributes FluQuadri

Distributed in Australia by:

sanofi-aventis australia pty ltd
12-24 Talavera Road
Macquarie Park NSW 2113
Freecall: 1800 818 806
Email: [email protected]

Distributed in New Zealand by:

Pharmacy Retailing (NZ) Ltd t/a Healthcare Logistics
PO Box 62027
Sylvia Park Auckland 1644
Freecall: 0800 283 684
Email: [email protected]

This leaflet was prepared in November 2023.

fluq-ccdsv2-cmiv11-13nov23

Published by MIMS December 2023

BRAND INFORMATION

Brand name

FluQuadri

Active ingredient

Influenza virus vaccine, split virion, quadrivalent (inactivated)

Schedule

1 Name of Medicine

Inactivated quadrivalent influenza vaccine, split virion (influenza virus haemagglutinin).

2 Qualitative and Quantitative Composition

FluQuadri for intramuscular injection is an inactivated influenza virus vaccine, prepared from influenza viruses propagated in embryonated chicken eggs. The virus-containing allantoic fluid is harvested and inactivated with formaldehyde. Influenza virus is concentrated and purified in a linear sucrose density gradient solution using a continuous flow centrifuge. The virus is then chemically disrupted using a non-ionic surfactant, octoxinol-9 (Triton X-100), producing a "split virus". The split virus is further purified and then suspended in sodium phosphate-buffered isotonic sodium chloride solution. Antigens from the four strains included in the vaccine are produced separately and then combined to make the quadrivalent formulation.
It is formulated to contain the following four influenza strains* recommended for the 2024 influenza season. See Table 1.
* Propagated in fertilised hens' eggs from healthy chicken flocks.
FluQuadri contains 60 microgram haemagglutinin (HA) per 0.5 mL dose in the recommended ratio of 15 microgram HA of each of the four strains.
The type and amount of viral antigens contained in FluQuadri conform to the annual requirements of the Australian Influenza Vaccine Committee (AIVC) and the World Health Organization (WHO) recommendations for the season.
Neither antibiotics nor preservative are used during manufacture.
FluQuadri is presented in prefilled syringes that are not made with natural rubber latex.

3 Pharmaceutical Form

Sterile aqueous suspension for injection.
FluQuadri suspension for injection is clear and slightly opalescent in colour.

4 Clinical Particulars

4.1 Therapeutic Indications

FluQuadri is indicated for active immunisation of influenza disease caused by influenza A subtype viruses and type B viruses contained in the vaccine.
FluQuadri is indicated for use in adults and children 6 months and older.

4.2 Dose and Method of Administration

FluQuadri should be given in accordance with the national recommendation as per the current Immunisation Handbook.
Inspect FluQuadri visually for particulate matter and/or discolouration prior to administration. If any of these defects or conditions exist, the vaccine should not be administered.
Before administering a dose of vaccine, shake the prefilled syringe.
The syringe is for single use only and must not be reused. Discard any remaining unused contents.
For needle size and length, refer to the national recommendations as per the current Immunisation Handbook.
FluQuadri should not be mixed with any other vaccine in the same syringe or vial.
Administration should be carried out by the intramuscular route. The dose and schedule are as follows:
Adults and children 6 months of age and older: 0.5 mL dose.
For children who have not been adequately primed based on influenza vaccination history, a second dose should be administered approximately 4 weeks apart. Refer to the current Immunisation Handbook for the recommended doses of influenza vaccine for young children at different ages.
The preferred site of administration is into the deltoid muscle in adults and children ≥ 12 months of age. The preferred site for infants and young children (6 months to < 12 months of age) is the anterolateral aspect of the thigh. The vaccine should be administered into healthy well developed muscle and should not be injected into the gluteal region where there may be a risk of local neural, vascular and tissue injury.

4.3 Contraindications

FluQuadri should not be administered to anyone with a known systemic hypersensitivity reaction, such as anaphylaxis, after previous administration of any influenza vaccine or to any component of the vaccine (see Section 2 Qualitative and Quantitative Composition; Section 6.1 List of Excipients).
Vaccination should be postponed in case of moderate or severe acute or febrile disease with or without fever but a mild disease with low-grade fever is usually not a reason to postpone vaccination.

4.4 Special Warnings and Precautions for Use

Do not administer intravenously.

Hypersensitivity.

Prior to any vaccine injection, all known precautions should be taken to prevent hypersensitivity reactions. This includes a review of the individual's prior vaccination history with respect to possible hypersensitivity to the vaccine or similar vaccines.
As each dose may contain traces of formaldehyde and octoxinol-9 which are used during vaccine production, caution should be exercised when the vaccine is administered to individuals with hypersensitivity to either one of these products.
As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic event following administration of the vaccine especially for individuals who have a known allergy to egg protein.

Neurological disorders.

Patients with a history of Guillain-Barré syndrome (GBS) with an onset related in time to influenza vaccination may be at increased risk of again developing GBS, but whether vaccination specifically might increase the risk for recurrence is unknown. Because patients with a history of GBS have an increased likelihood of again developing the syndrome, the chance of them coincidentally developing the syndrome following influenza vaccination may be higher than in individuals with no history of GBS. If GBS has occurred within 6 weeks following previous influenza vaccination, the decision to give FluQuadri should be based on careful consideration of the potential benefits and risks. Refer to the current Immunisation Handbook for further details.

Immunosuppressive treatments or conditions.

The immunogenicity of FluQuadri may be reduced by immunosuppressive treatment or in individuals with immune deficiency syndromes. Vaccination of individuals with chronic immunodeficiencies is recommended even though the antibody response may be limited.

Protection.

Influenza virus is remarkably unpredictable in that significant antigenic changes may occur from time to time. It is known that influenza vaccines, as now constituted, are not effective against all possible strains of influenza virus. Protection is limited to those strains of virus from which the vaccine is prepared or to closely related strains.
As with any vaccine, vaccination with FluQuadri may not protect 100% of susceptible individuals.

Bleeding disorder.

Because any intramuscular injection can cause an injection site haematoma in individuals with any bleeding disorder, such as haemophilia or thrombocytopenia, or in individuals on anticoagulant therapy, intramuscular injections with FluQuadri should not be administered to such individuals unless the potential benefits outweigh the risk of administration. If the decision is made to administer any product by intramuscular injection to such individuals, it should be given with caution, with steps taken to avoid the risk of haematoma formation following injection.

Syncope.

Syncope (fainting) has been reported following vaccination with FluQuadri. Procedures should be in place to prevent falling injury and manage syncopal reactions.

Use in the elderly.

Safety and immunogenicity of FluQuadri were evaluated in adults 65 years of age and older (see Section 5.1 Pharmacodynamic Properties, Clinical trials). Antibody responses to FluQuadri are lower in individuals ≥ 65 years of age than in younger adults.
Adults aged ≥ 65 years are strongly recommended to receive either high-dose or adjuvanted influenza vaccine every year. Refer to the current Immunisation Handbook.

Paediatric use.

Safety and effectiveness of FluQuadri in children below the age of 6 months have not been established. Children in Study GRC88 aged between 6 and < 12 months were required to be born at full term of pregnancy (≥ 37 weeks) and/or with a birth weight ≥ 2.5 kg.
Preterm infants (< 37 weeks gestation) are strongly recommended to receive influenza vaccine each year, starting at ≥ 6 months of age. Refer to the current Immunisation Handbook.

Effects on laboratory tests.

Interference of FluQuadri with laboratory and/or diagnostic tests has not been studied.
Following influenza vaccination, false positive results in serology tests using the ELISA method to detect antibodies against HIV1, hepatitis C, and especially HTLV1 have been observed. An appropriate Western blot test should be used to confirm or disprove the results of the ELISA test. The transient false-positive reactions could be due to a non-specific IgM response induced by the vaccine.

4.5 Interactions with Other Medicines and Other Forms of Interactions

FluQuadri should not be mixed with any other vaccine in the same syringe or vial.
Data evaluating the concomitant administration of FluQuadri with other vaccines are not available.
If FluQuadri is to be given at the same time as another injectable vaccine(s), the vaccine(s) should always be administered at different injection sites. Refer to the current Immunisation Handbook for further details.
Although inhibition of hepatic clearance of phenytoin, theophylline and warfarin has been reported after influenza vaccination, subsequent studies have not shown any evidence of undesirable effects related to this phenomenon.
If the vaccine is used in individuals deficient in producing antibodies due to immunosuppressive therapy, the expected immune response may not be obtained.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

FluQuadri has not been evaluated for the possible effects on human fertility. A reproductive toxicity study in which female rabbits were administered FluQuadri 24 and 10 days before insemination showed no effects on female fertility (see Use in pregnancy).
(Category A)
A developmental and reproductive toxicity study has been performed in female rabbits at a dose approximately 20 times the human dose (on a mg/kg basis) and has revealed no evidence of impaired female fertility or harm to the foetus due to FluQuadri. There are, however, no adequate and well-controlled studies in pregnant women.
In the developmental and reproductive toxicity study, female rabbits were administered FluQuadri or control saline (each 0.5 mL/dose) by intramuscular injection 24 and 10 days before insemination, and on days 6, 12, and 27 of gestation. The administration of FluQuadri did not result in systemic maternal toxicity (no adverse clinical signs and no change in body weight or food consumption). In addition, no adverse effects on pregnancy, parturition, lactation, or embryo-foetal or pre-weaning development were observed. There were no vaccine-related foetal malformations or other evidence of teratogenesis noted in this study.
Data from studies involving large numbers of women (> 80,000) vaccinated during pregnancy with inactivated influenza vaccines do not indicate any adverse fetal and maternal outcomes attributable to the vaccine. FluQuadri should be given to a pregnant woman following an assessment of the risks and benefits. Because of the known adverse consequences of influenza infection in pregnant women, health authorities recommend vaccination of pregnant women.
It is not known whether FluQuadri is excreted in human milk, hence, caution should be used when administering vaccine to breastfeeding women.

4.7 Effects on Ability to Drive and Use Machines

No studies on the effects on the ability to drive or use machines have been performed.

4.8 Adverse Effects (Undesirable Effects)

Clinical trials experience.

Because clinical trials are conducted under widely varying conditions, adverse event rates observed in the clinical trials of a vaccine cannot be directly compared to rates in the clinical trial of another vaccine, and may not reflect the rates observed in practice.
The safety of FluQuadri was evaluated in 3,307 trial participants in 3 clinical trials in the United States (1,223 children 6 to 35 months of age, 1,669 children 3 to 8 years of age, 190 adults ≥ 18 years of age, and 225 adults ≥ 65 years of age). For children requiring a second dose, the doses were administered approximately 4 weeks apart. The most common injection site reaction in children and adults was pain. The most frequent systemic reaction in infants and toddlers (6 to 35 months receiving 0.25 mL) was irritability, while myalgia was the most frequent systemic reaction reported in children (3 to 8 years) and adults.
In children, the most commonly reported unsolicited non-serious adverse events were cough, vomiting, and pyrexia. In adults, oropharyngeal pain, rhinorrhoea, injection site induration, and headache were the most commonly reported unsolicited adverse events.
Across the 3 trials, one serious adverse event was thought to be caused by vaccination with FluQuadri: a 13-month old who experienced croup 3 days post-first vaccination; the participant recovered within 18 days without sequelae and continued in the trial. In clinical trial QIV04 other serious adverse events considered to be possibly related to vaccination were: in the US-licensed comparator 2010-2011 TIV group a 4-year old who experienced a febrile convulsion one day post-first vaccination, and in the unlicensed investigational TIV group an 11-month old who experienced a febrile convulsion on the day of second vaccination.
The frequency of the solicited injection site and systemic reactions reported in the trials are shown in Table 2 and Table 3.

A 0.5-mL dose of FluQuadri in children 6 months through 35 months of age.

GRC88 was an observer-blind multi-centre study conducted in the US, including healthy children age between 6 and 35 months. Infants less than 12 months of age were of gestational age ≥ 37 weeks and/or birth weight ≥ 2.5 kg. Participants were randomly assigned to receive a FluQuadri dose of 0.25 mL (Group 1) or 0.5 mL (Group 2). For children requiring a second dose, the same dose was administered 4 weeks after the first. Participants who received at least one dose of study vaccine were included in the safety analysis set: Group 1 n = 949; Group 2 n = 992.
The primary objective was to assess difference in fever rate ≥ 38°C (Group 2 minus Group 1). The difference, 0.84% (95% CI: -2.13%; 3.80%), met the prespecified non-inferiority criterion (upper limit of the 2-sided 95% CI of the difference in fever rates < 5%).
The frequencies of solicited injection-site reactions occurring within 7 days after vaccination (Group 1 vs. Group 2) were: tenderness (47% vs. 50%), erythema (23% vs. 24%), and swelling (13% vs. 15%).
The frequency of systemic adverse reactions occurring within 7 days after vaccination (Group 1 vs. Group 2) were: irritability (47% vs. 49%), abnormal crying (33% vs. 34%), drowsiness (32% vs. 31%), appetite loss (27% vs. 28%), fever of ≥ 38°C (11% vs. 12%), and vomiting (10% vs. 10%).
The frequency of solicited systemic reactions tended to be higher in the subgroup aged 6 to < 24 months than the subgroup aged 24 to > 36 months. Group 1 (n = 533) vs. Group 2 (n = 561): fever 12% vs. 16%, vomiting 12% vs. 14%, abnormal crying 38% vs. 39%, drowsiness 34% vs. 35%, loss of appetite 27% vs. 31% and irritability 49% vs. 54%.
Participants were monitored for unsolicited adverse events for the 28 days following vaccination. Non-serious adverse events were reported in 44% of Group 1 and 40% of Group 2, the most commonly reported in both groups being cough and rhinorrhoea. Five serious adverse events were reported in each group, one event of chronic urticaria occurring in Group 1 was considered vaccine related and an event of special interest. There were no deaths reported during the trial period.

Adverse reactions from post-marketing surveillance.

Currently, there are limited post-marketing data available for FluQuadri.
The following events have been spontaneously reported during the post-approval use of Fluzone (TIV)¹. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccine exposure. Adverse events were included based on one or more of the following factors: severity, frequency of reporting, or strength of evidence for a causal relationship to Fluzone.

Blood and lymphatic system disorders.

Thrombocytopenia, lymphadenopathy.

Immune system disorders.

Anaphylaxis, other allergic/ hypersensitivity reactions (including urticaria, angioedema).

Eye disorders.

Ocular hyperemia.

Nervous system disorders.

Guillain-Barré syndrome (GBS), convulsions, febrile convulsions, myelitis (including encephalomyelitis and transverse myelitis), facial palsy (Bell's palsy), optic neuritis/ neuropathy, brachial neuritis, syncope (shortly after vaccination), dizziness, paresthesia.

Vascular disorders.

Vasculitis, vasodilation/ flushing.

Respiratory, thoracic and mediastinal disorders.

Dyspnea, pharyngitis, rhinitis, cough, wheezing, throat tightness.

Skin and subcutaneous tissue disorders.

Stevens-Johnson syndrome.

General disorders and administration site conditions.

Pruritus, asthenia/ fatigue, pain in extremities, chest pain.

Gastrointestinal disorders.

Vomiting.
¹ Fluzone is the US-licensed TIV upon which manufacture of FluQuadri is based.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.9 Overdose

For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Influenza vaccine, ATC code: J07BB.

Mechanism of action.

FluQuadri provides active immunisation against the four influenza virus strains (two A subtypes and two B strains) contained in the vaccine. FluQuadri induces humoral antibodies against the haemagglutinins. Specific levels of haemagglutination-inhibition (HI) antibody titre post-vaccination with inactivated influenza virus vaccines have not been correlated with protection from influenza illness, but HI antibody titres have been used as a measure of vaccine activity. In some human challenge studies, HI antibody titres of ≥ 1:40 have been associated with protection from influenza illness in up to 50% of participants. HI antibody titres ≥ 1:40 are generally obtained within 3 to 4 weeks. Annual influenza vaccination is recommended as immunity declines during the year after vaccination and because circulating strains of influenza virus may change from year to year.

Clinical trials.

Immunogenicity of FluQuadri in children 6 months to 8 years of age.

QIV04 (NCT01240746, see http://clinicaltrials.gov) was a phase III, randomised, observer-blinded, active-controlled, 3-arm, multi-centre trial of children aged 6 months to 8 years stratified into 2 age groups: 6 to 35 months of age and 3 to 8 years of age. The trial was conducted in the United States during November 2010-January 2012.
The aim was to compare the immunogenicity and safety of FluQuadri containing A/California, A/Victoria, B/Brisbane (Victoria lineage), and B/Florida (Yamagata lineage) with the 2010-2011 seasonal trivalent inactivated influenza vaccine (TIV) containing B/Brisbane, and an investigational TIV containing B/Florida. Each TIV contained the same A strains as FluQuadri. The manufacturing process was the same for each vaccine and was based on the production process for the US-licensed TIV (Fluzone).
Participants were randomised to receive one of three vaccines (FluQuadri, 2010-2011 TIV, or investigational TIV). Children 6 to 35 months of age were administered 0.25 mL of assigned vaccine containing 7.5 microgram of HA per strain. Children 3 to 8 years were administered 0.5 mL of assigned vaccine containing 15 microgram of HA per strain. As per recommendations of the United States Advisory Committee on Immunization Practices, children who were considered adequately primed based on influenza vaccination history received one dose; all other children received two doses with a four-week interval between vaccinations.
The primary objective was to demonstrate non-inferiority of antibody responses to each of the four virus strains in FluQuadri compared with each TIV within each age group and overall.
Non-inferiority was demonstrated if the lower limit of the two-sided 95% confidence interval (CI) of the post-vaccination geometric mean titre (GMT) ratio (FluQuadri/TIV) was > 0.66 for each of the four virus strains separately.
Non-inferiority in terms of seroconversion rates was demonstrated if the lower limit of the two-sided 95% CI of the difference in rates (FluQuadri - TIV) was > -10% for each of the four virus strains separately.
The secondary objective was to demonstrate superiority of antibody responses to each B strain in FluQuadri compared with responses to the TIV not containing the corresponding B strain, as assessed by GMT ratios and seroconversion rates.
Superiority by GMT ratios was demonstrated if the lower limit of the two-sided 95% CI of post-vaccination GMT ratios (FluQuadri/TIV) was > 1.5 for each B strain in FluQuadri compared with the corresponding B strain not contained in each TIV.
Superiority by seroconversion rates was demonstrated if the lower limit of the two-sided 95% CI of the difference in post-vaccination seroconversion rates (FluQuadri - TIV) was > 10% for each B strain in FluQuadri compared with the corresponding B strain not contained in each TIV.
Description of seroprotection rates, defined as the percentages of participants with serum HI antibody titre ≥ 1:40, was an observational objective.
A total of 4348 participants were vaccinated: 2893 in the FluQuadri group, 734 in the 2010-2011 TIV group, and 721 in the investigational TIV group. Demographic characteristics for vaccine recipients were similar among vaccine groups; mean ages were 49.6-49.9 months, females accounted for approximately half of each vaccine group, and the majority of participants were Caucasian (range: 57.8%-58.9%). The per protocol analysis set, which was used for the immunogenicity analyses, included the following numbers (% of randomised): 2339 (80.6%) children in the FluQuadri group, 582 (79.1%) in the 2010-2011 TIV group, and 599 (82.6%) in the investigational TIV group.
All non-inferiority criteria were met. GMT ratios and seroconversion rates 28 days following vaccination with FluQuadri were non-inferior to those following TIV for all four strains overall and for each age group (Table 4). In addition, HI antibody GMTs and seroconversion rates following FluQuadri were superior to those following TIV for the B strain not contained in each respective TIV based on pre-specified criteria (Table 5).

Twenty-eight days following vaccination with a dose of 0.25 mL, the percentages of FluQuadri recipients with serum HI antibody titre ≥ 1:40 were:
Age 6 to 35 months: 97.7% (95% CI: 96.5; 98.5) for H1N1, 99.9% (95% CI: 99.4; 100.0) for H3N2, 75.5% (95% CI: 72.7; 78.2) for B/Brisbane, and 58.0% (95% CI: 54.8; 61.2) for B/Florida.
Age 3 to 8 years: 99.3% (95% CI: 98.7; 99.7) for H1N1, 99.5% (95% CI: 99.0; 99.8) for H3N2, 80.7% (95% CI: 78.5; 82.8) for B/Brisbane, and 80.9% (95% CI: 78.7; 82.9) for B/Florida.

Immunogenicity of a 0.5 mL dose of FluQuadri in children 6 months to 35 months.

GRC88 (NCT02915302, see http://clinicaltrials.gov) was a randomised, observer-blind, multi-centre study including healthy children age between 6 and 35 months, randomly assigned to receive a FluQuadri dose of 0.25 mL (Group 1) or 0.5 mL (Group 2). For children requiring a second dose, the same dose was administered 4 weeks after the first. The per-protocol immunogenicity set included 715 participants in Group 1 and 745 in Group 2. Immunogenicity was assessed 28 - 35 days after the final vaccination. (Also see Section 4.8 Adverse Effects (Undesirable Effects).)
HI antibody GMTs following the 0.5 mL dose of FluQuadri were non-inferior to those following a 0.25 mL dose for all four strains, based on pre-specified criteria of lower limit of the 2-sided 95% CI of the ratio of GMTs (GMT 0.5 mL/GMT 0.25 mL) > 0.667.
A/H1N1 strain: GMT ratio = 1.42 (95% CI: 1.16; 1.74).
A/H3N2 GMT ratio: = 1.48 (95% CI: 1.21; 1.82).
B Victoria lineage strain GMT ratio: = 1.33 (95% CI: 1.09; 1.62).
B Yamagata lineage strain GMT ratio: = 1.41 (95% CI: 1.17; 1.70).
Seroconversion rates 28 days following final vaccination with a 0.5 mL dose of FluQuadri were non-inferior to those following a 0.25 mL dose for all four strains, based on pre-specified criteria of lower limit of the 2-sided 95% CI of the difference in seroconversion rates > -10% (GMT 0.5 mL minus GMT 0.25 mL) > -10%).
A/H1N1 strain: difference in SC rates = 4.6% (95% CI: 0.4%; 9.6%).
A/H3N2 strain: difference in SC rates = 5.1% (95% CI: 0.4%; 9.8%).
B Victoria lineage strain: difference in SC rates = 1.3% (95% CI: -2.9%; 5.6%).
For the B Yamagata lineage strain: difference in SC rates = 2.6% (95% CI: -1.4%; 6.5%).

Immunogenicity of FluQuadri in adults ≥ 18 years of age.

GRC43 (NCT00988143, see http://clinicaltrials.gov) was a phase II, open-label, active-controlled, 3-arm, multi-centre trial of adults ≥ 18 years of age conducted in the United States during October 2009-December 2009.
The aim was to compare the immunogenicity and safety of FluQuadri containing A/Brisbane, A/Uruguay, B/Brisbane (Victoria lineage), and B/Florida (Yamagata lineage) with the 2009-2010 seasonal TIV (containing B/Brisbane) and the 2008-2009 seasonal TIV (containing B/Florida). Each TIV contained the same A strains as FluQuadri. The manufacturing process was the same for each vaccine and was based on the production process for the US-licensed TIV (Fluzone).
Participants were randomised to receive one of three vaccines (FluQuadri, 2009-2010 TIV, or 2008-2009 TIV) and were administered one 0.5 mL dose of assigned vaccine, which contained 15 microgram of HA per strain.
The primary objective was to demonstrate non-inferiority of B-strain antibody responses induced by FluQuadri compared with the 2009-2010 TIV and the 2008-2009 TIV in terms of GMT ratios. Non-inferiority was shown if the lower limit of the two-sided 95% CI for the ratio of GMT FluQuadri/GMT TIV was > 2/3 for each A and B strain separately.
Description of seroprotection rates, defined as the percentages of participants with serum HI antibody titre ≥ 1:40, was an observational objective.
A total of 570 participants were vaccinated: 190 in each vaccine group. Demographic characteristics for vaccine recipients were similar among vaccine groups; mean ages were 54.9-56.7 years, females accounted for approximately two-thirds of each vaccine group, and the majority of participants were Caucasian (range: 86.8%-91.1%). The per-protocol analysis set included the following numbers (% of randomised): 190 (100%) adults in the FluQuadri group, 187 (98.4%) in the 2009-2010 TIV group, and 188 (98.9%) in the 2008-2009 TIV group.
HI antibody GMTs 21 days following vaccination with FluQuadri were non-inferior to those following TIV for all four strains (Table 6).

At 21 days following vaccination, the percentages of FluQuadri recipients with serum HI antibody titre ≥ 1:40 were 92.6% (95% CI: 87.9; 95.9) for H1N1, 94.7% (95% CI: 90.5; 97.4) for H3N2, 85.3% (95% CI: 79.4; 90.0) for B/Brisbane, and 92.1% (95% CI: 87.3; 95.5) for B/Florida.

Immunogenicity of FluQuadri in adults ≥ 65 years of age.

QIV03 (NCT01218646, see http://clinicaltrials.gov) was a phase III, randomised, double-blind, active-controlled, 4-arm, multi-centre trial of adults ≥ 65 years of age. The trial was conducted in the United States during October 2010-December 2010.
The aim was to compare the immunogenicity and safety of FluQuadri containing A/California, A/Victoria, B/Brisbane (Victoria lineage) and B/Florida (Yamagata lineage) with the 2010-2011 seasonal TIV containing B/Brisbane, and an investigational TIV containing B/Florida. Each TIV contained the same A strains as FluQuadri. The manufacturing process was the same for each vaccine and was based on the production process for the US-licensed TIV (Fluzone).
Participants were randomised to one of three vaccine groups (FluQuadri, 2010-2011 TIV, or investigational TIV) and were administered one 0.5 mL dose of assigned vaccine, which contained 15 microgram of HA per strain.
The primary objective was to demonstrate non-inferiority of GMT antibody responses to each of the four virus strains in FluQuadri compared with each TIV.
Non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the post-vaccination GMT ratio (FluQuadri/TIV) was > 0.66 for each of the four virus strains separately.
Observational objectives were to:
Demonstrate non-inferiority of antibody responses induced by FluQuadri compared with each TIV as assessed by seroconversion rates. Non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the difference in rates (FluQuadri - TIV) was > -10%.
Demonstrate superiority of antibody responses to each B strain in FluQuadri compared with responses to the TIV not containing the corresponding B strain, as assessed by GMT ratios and seroconversion rates.
Superiority by GMT ratios was demonstrated if the lower limit of the two-sided 95% CI of post-vaccination GMT ratios (FluQuadri/TIV) was > 1.5 for each B strain in QIV compared with the corresponding B strain not contained in each TIV.
Superiority by seroconversion rates was demonstrated if the lower limit of the two-sided 95% CI of the difference in post-vaccination seroconversion rates (FluQuadri - TIV) was > 10% for each B strain in QIV compared with the corresponding B strain not contained in each TIV.
Describe seroprotection rates, defined as the percentages of participants with serum HI antibody titre ≥ 1:40.
A total of 675 participants were vaccinated: 225 in each vaccine group. Demographic characteristics for vaccine recipients were similar among vaccine groups; mean ages were 72.4-72.8 years, females accounted for slightly more than half of each vaccine group, and the majority of participants were Caucasian (range: 87.6%-91.1%). The per-protocol analysis set included the following numbers (% of randomised): 220 (97.8%) participants in the FluQuadri group, 219 (97.3%) in the 2010-2011 TIV group, and 221 (98.2%) in the investigational TIV group.
HI antibody GMTs 21 days following vaccination with FluQuadri were non-inferior to those following TIV for all four strains, based on pre-specified criteria (Table 7). Seroconversion rates 21 days following FluQuadri were non-inferior to those following TIV for H3N2, B/Brisbane, and B/Florida, but not for H1N1 (Table 7). The HI antibody GMT following FluQuadri was superior to that following 2010-2011 TIV for B/Florida but not superior to that following investigational TIV for B/Brisbane; based on pre-specified criteria. Seroconversion rates following FluQuadri were superior to those following TIV for the B strain not contained in each respective TIV, based on pre-specified criteria.

Results for the observational objective, the percentages of FluQuadri recipients with serum HI antibody titre ≥ 1:40 at 21 days post-vaccination were: 91.4% (95% CI: 86.8; 94.7) for H1N1, 100% (95% CI: 98.3; 100) for H3N2, 77.7% (95% CI: 71.6; 83.0) for B/Brisbane, and 73.2% (95% CI: 66.8; 78.9) for B/Florida. See Table 8.

5.2 Pharmacokinetic Properties

No pharmacokinetic studies have been performed.

5.3 Preclinical Safety Data

FluQuadri has not been evaluated in non-clinical studies.

Genotoxicity.

FluQuadri has not been evaluated for genotoxic potential.

Carcinogenicity.

FluQuadri has not been evaluated for carcinogenic potential.

6 Pharmaceutical Particulars

6.1 List of Excipients

Buffer solution: sodium chloride, dibasic sodium phosphate, monobasic sodium phosphate, water for injections.
FluQuadri may also contain traces of octoxinol-9 (≤ 250 microgram), formaldehyde (≤ 100 microgram) and ovalbumin (≤ 1 microgram).

6.2 Incompatibilities

FluQuadri should not be mixed with any other vaccine in the same syringe or vial.

6.3 Shelf Life

12 months when stored at 2°C to 8°C.

6.4 Special Precautions for Storage

Store at 2°C to 8°C (Refrigerate, do not freeze). Discard if vaccine has been frozen.

6.5 Nature and Contents of Container

Prefilled syringe (clear syringe plunger rod), 0.5 mL with or without separate needle. Packs of 5 syringes.
Not all packs may be marketed.

6.6 Special Precautions for Disposal

After use, any remaining vaccine and container must be disposed of safely, according to locally acceptable procedures.

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FluQuadri

Influenza virus vaccine, split virion, quadrivalent (inactivated)

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