Consumer medicine information

Flucelvax Quad

Influenza virus vaccine, surface antigen, quadrivalent (inactivated)

BRAND INFORMATION

Brand name

Flucelvax Quad

Active ingredient

Influenza virus vaccine, surface antigen, quadrivalent (inactivated)

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Flucelvax Quad.

SUMMARY CMI

Flucelvax® Quad

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 being given Flucelvax® Quad?

Flucelvax® Quad contains the active ingredient influenza virus haemagglutinin. Flucelvax® Quad is a vaccine used to help prevent certain types of influenza or “flu”. It is for use in people aged 6 months and older.

For more information, see Section 1. Why am I being given Flucelvax® Quad? in the full CMI.

2. What should I know before being given Flucelvax® Quad?

Tell your doctor, nurse or pharmacist if you or your child have ever had an allergic reaction to any influenza vaccine or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you or your child 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 Flucelvax® Quad? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Flucelvax® Quad and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How is Flucelvax® Quad given?

  • Flucelvax® Quad is given as an injection, usually into your upper arm muscle by a doctor, nurse or pharmacist.
  • In young children, the injection may be given in the thigh muscle of the leg.
  • Flucelvax® Quad is given once every year, as follows:
    - Adults and children 9 years and older: one injection of 0.5 mL.
    - Children 6 months to less than 9 years of age: One or two 0.5 mL doses. Children less than 9 years of age who have not been previously vaccinated against influenza, should receive a second dose (at least 4 weeks after the first dose).

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

5. What should I know about being given Flucelvax® Quad?

Things you should doCall your doctor straight away if you or your child do not feel well after having Flucelvax® Quad.
Keep an updated record of you and your child's vaccinations.
Keep any follow-up appointments with your doctor or clinic.

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

6. Are there any side effects?

Common side effects may include local reaction around injection site, headache, tiredness, muscle ache and nausea. Mostly these are mild and short lived. Serious side effects are rare.

Sudden signs of allergy may be a serious side effect. If you or your child experience this, tell your doctor immediately. Typical symptoms include rash, itching or hives on the skin, swelling of the face, lips, tongue or other parts of the body.

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



FULL CMI

Flucelvax® Quad

Active ingredient(s): influenza virus haemagglutinin


Consumer Medicine Information (CMI)

This leaflet provides important information about using Flucelvax® Quad. 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 Flucelvax® Quad.

Where to find information in this leaflet:

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

1. Why am I being given Flucelvax® Quad?

Flucelvax® Quad contains the active ingredient influenza virus haemagglutinin.

Flucelvax® Quad is a cell derived vaccine used to help prevent certain types of influenza or “flu”. It is for use in people aged 6 months and older.

Influenza is a sudden respiratory infection caused by the ‘flu’ virus. It is very contagious. It is usually spread from one person to another by small droplets from coughs and sneezes. The virus enters the nose or throat and may spread to the lungs. Influenza infection can lead to serious illness.

Vaccination with Flucelvax® Quad helps prevent infection with influenza and to control the spread of the disease. Influenza strains can change every year therefore previous influenza vaccinations are unlikely to give you protection against the current strains most common this year. You will therefore need to receive a vaccine against flu every year to lower the chance of catching the ‘flu’, especially if you are at risk.

Flucelvax® Quad works by causing your body to produce its own protection against the four types of influenza virus from which it is made. It does this by making substances called antibodies in the blood that fight the influenza virus. Your body usually takes 2-3 weeks after vaccination to develop protection against influenza. Most people will produce enough antibodies against the influenza virus. However, as with all vaccines, 100% protection cannot be guaranteed.

An influenza vaccine will only protect you against the types of influenza virus used to make it. It will not protect you from other types of influenza virus or from infections with other agents causing flu-like symptoms (such as the common cold).

The virus in Flucelvax® Quad has been killed therefore the vaccine cannot ‘give’ you the flu.

2. What should I know before being given Flucelvax® Quad?

Warnings

Do not use Flucelvax® Quad if:

  • Your child is under 6 months of age. Flucelvax® Quad is for use in people aged 6 months and older only.
  • You or your child have been severely allergic to any of the ingredients listed at the end of this leaflet or any previous influenza vaccines.
  • Symptoms of a severe allergic reaction may include shortness of breath, wheezing or difficulty breathing, swelling of the face, lips, tongue or other parts of the body, skin rash, itching or hives.
  • Always check the ingredients to make sure you can use this medicine.

Tell your doctor if you or your child:

  • have reacted to previous vaccination with any of the following:
    - severe allergic reaction (anaphylaxis),
    - difficulty breathing,
    - swelling of the throat,
    - fainting or collapse,
    - fits or convulsions,
    - high temperature (greater than 38°C),
    - severe skin reaction at the injection site, including severe bruising,
  • have or have had any other medical conditions especially the following:
    - Guillain-Barre Syndrome (an illness affecting the nerves resulting in weakness of muscles),
    - lowered immunity due to diseases such as some blood disorders, malaria, kidney disease requiring dialysis, HIV/AIDS or cancer,
    - lowered immunity due to treatment with medicines such as corticosteroids, cyclosporin or other medicines used to treat cancer (including radiation therapy),
    - take any medicines for any other condition,
    - have/has allergy to
    -- any other medicines,
    -- or any other substances, such as latex food, preservatives or dyes.

Your doctor, nurse or pharmacist will decide if you can receive Flucelvax® Quad. A minor illness such as a cold should not be a problem but talk to your doctor about it if being vaccinated.

After vaccination, you or your child 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. Influenza vaccination is recommended for pregnant women during any stage of pregnancy.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Your doctor will discuss the potential risks and benefits of being given Flucelvax® Quad while you are breast-feeding.

3. What if I am taking other medicines?

Tell your doctor, nurse or pharmacist if you or your child are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with Flucelvax® Quad and affect how it works.

These include medicines which lower the immune system, such as corticosteroids, cyclosporin or other medicines used to treat cancer (including radiation therapy).
Your doctor will consider whether an adjustment of medication is necessary.

Tell your doctor if you or your child have had any vaccines in the last 4 weeks. Flucelvax® Quad can be given at the same time as other vaccines.

Check with your doctor, nurse or pharmacist if you are not sure about what medicines, vitamins or supplements you or your child are taking and if these affect Flucelvax® Quad.

4. How is Flucelvax® Quad given?

How much is given

Flucelvax® Quad is given, as follows:

  • Adults and children 9 years and over: one injection of 0.5 mL
    Children 6 months to less than 9 years of age: One or two 0.5 mL doses. Children less than 9 years of age who have not been previously vaccinated against influenza, should receive a second dose (at least 4 weeks after the first dose).

When is Flucelvax® Quad given

  • Flucelvax® Quad is usually given before the start of the influenza season or when recommended by your doctor, nurse or pharmacist.
  • Vaccination for influenza should be repeated every year as new types of influenza virus can appear each year.

How is Flucelvax® Quad given

  • It is given as an injection, usually into your upper arm muscle by a doctor, nurse or pharmacist.
  • In young children, it may be given in the thigh muscle of the leg.

5. What should I know about being given Flucelvax® Quad?

Things you should do

Call your doctor straight away if you or your child do not feel well after having Flucelvax® Quad.

Keep an updated record of you and your child's vaccinations.

Keep any follow-up appointments with your doctor or clinic.

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

Flucelvax® Quad is usually stored in the doctor's surgery or clinic, or at the pharmacy.

However, if you need to store Flucelvax® Quad:

  • Keep it where young children cannot reach it.
  • Keep Flucelvax® Quad in the original pack until it is time for it to be given.
  • Keep it in the refrigerator, between 2°C and 8°C. Do not freeze Flucelvax® Quad. Protect from light. Discard if the vaccine has been frozen. Freezing destroys the vaccine.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal. A doctor, nurse or pharmacist will dispose of any unused vaccine.

Do not use Flucelvax® Quad after the expiry date.

6. Are there any side effects?

All vaccines can have side effects. If you or your child 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 effectsWhat to do
  • local reaction around the injection site such as pain or tenderness, redness, swelling or the formation of hard lumps and bruising
  • muscle aches or joint pain (not caused by exercise)
  • flu-like symptoms, such as headache, tiredness or sleepiness, fever, sore throat, runny nose, blocked nose, sneezing, cough, chills or shivering
  • nausea, vomiting, diarrhoea
  • loss of appetite, change in eating habits, (children less than 6 years of age)
  • irritability (children less than 6 years of age)
  • fainting, collapse or feeling faint just before, during or after vaccination
Speak to your doctor if you or your child have any of these less serious side effects and they worry you.
Mostly these are mild and short lived.

Serious side effects

Serious side effectsWhat to do
  • tingling of the hands or feet, or sudden numbness or weakness in the legs or arms
  • extensive swelling of the injected limb
  • generalised skin reactions including itching, bumps on the skin or non-specific rash
  • sudden signs of allergy such as rash, itching or hives on the skin, swelling of the face, lips, tongue or other parts of the body, (anaphylaxis)
  • shortness of breath, wheezing or trouble breathing
  • feeling weak or paralysed, or generally feeling sore or tender
  • rapid, shallow breathing, cold, clammy skin, a rapid, weak pulse, dizziness, weakness and fainting (shock)
  • very rarely, a serious disorder called Guillain-Barré syndrome (GBS) may occur. GBS is an autoimmune syndrome caused by your body's own immune system. GBS may make you feel weak; you may have difficulty moving around or you may experience numbness and tingling in your limbs.
  • fits, convulsions or seizures associated with fever
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you or your child notice any of these serious side effects.
All of these side effects are rare.

Tell your doctor, nurse or pharmacist if you notice anything else that may be making you or your child 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 or your child experienced, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this vaccine.

7. Product details

Flucelvax® Quad is only available with a doctor's prescription.

What Flucelvax® Quad contains

Active ingredient
(main ingredient)
Influenza virus haemagglutinin
Each 0.5 mL contains 15 micrograms of influenza virus fragments from each of the following types of influenza virus:
  • A/Wisconsin/67/2022 (H1N1)pdm09-like virus
  • A/Massachusetts/18/2022 (H3N2)-like strain
  • B/Austria/1359417/2021-like strain
  • B/Phuket/3073/2013-like strain
These strains have been recommended by the Australian Influenza Vaccine Committee for the 2024 Southern Hemisphere winter.
Other ingredients
(inactive ingredients)
Sodium chloride, Potassium chloride, Magnesium chloride hexahydrate, Dibasic sodium phosphate dihydrate, Monobasic potassium phosphate, Water for injections.
May also contain traces of beta-propiolactone, cetyltrimethylammonium bromide, and polysorbate 80, as residues of the manufacturing process.

Tell your doctor if you or your child have/has allergy to any of the above ingredients. Your doctor will decide if you can receive Flucelvax® Quad.

Flucelvax® Quad does not contain lactose, gluten, tartrazine, any other azo dyes, antibiotics or preservative.

What Flucelvax® Quad looks like

Flucelvax® Quad is a clear to slightly milky-white liquid in a pre-filled syringe with or without a needle for single use only (AUST R 319093 and AUST R 341450).

Who distributes Flucelvax® Quad

Seqirus Pty Ltd
ABN 26 160 735 035
63 Poplar Road
Parkville VIC 3052
AUSTRALIA

This leaflet was prepared in July 2023.

Flucelvax® Quad is a trademark of Seqirus UK Limited or its affiliates.

Published by MIMS March 2024

BRAND INFORMATION

Brand name

Flucelvax Quad

Active ingredient

Influenza virus vaccine, surface antigen, quadrivalent (inactivated)

Schedule

S4

 

1 Name of Medicine

Quadrivalent influenza vaccine (surface antigen, inactivated, prepared in cell cultures), suspension for injection containing Influenza virus haemagglutinin as active ingredient.

2 Qualitative and Quantitative Composition

This is a purified, inactivated, subunit influenza vaccine. Each 0.5 mL dose contains influenza virus surface antigens (haemagglutinin and neuraminidase)*, for the 2024 influenza season representative of the following types:
A/Wisconsin/67/2022 (H1N1)pdm09-like virus (A/Georgia/12/2022 CVR-167) 15 micrograms HA**;
A/Massachusetts/18/2022 (H3N2)-like virus (A/Sydney/1304/2022) 15 micrograms HA**;
B/Austria/1359417/2021-like virus (B/Singapore/WUH4618/2021) 15 micrograms HA**;
B/Phuket/3073/2013-like virus (B/Singapore/INFTT-16-0610/2016) 15 micrograms HA**;
per 0.5 mL dose.
* Propagated in Madin Darby Canine Kidney (MDCK) cells.
** Haemagglutinin.
Flucelvax Quad is prepared in MDCK cells, adapted to grow freely in suspension in culture medium. The virus is inactivated with β-propiolactone, disrupted by the detergent cetyltrimethylammonium bromide and purified through several process steps. Therefore Flucelvax Quad may contain traces of propiolactone, cetyltrimethylammonium bromide, and polysorbate 80 (see Section 4.3 Contraindications). Eggs are not used in the manufacturing process, therefore, Flucelvax Quad does not contain egg proteins. For the full list of excipients, see Section 6.1 List of Excipients.
The vaccine complies with the World Health Organization (WHO) recommendation and Australian Influenza Vaccine Committee (AIVC) for the 2024 Southern Hemisphere Influenza season. The strains chosen for vaccine manufacture are endorsed by the AIVC as being antigenically equivalent to the reference virus.

3 Pharmaceutical Form

Flucelvax Quad is a clear to slightly opalescent suspension for injection.

4 Clinical Particulars

4.1 Therapeutic Indications

For the prevention of influenza caused by Influenza Virus, Types A and B contained in the vaccine. The vaccine is indicated for use in adults and children 6 months of age and older.
For full details regarding recommendations for influenza vaccination, please refer to the relevant national immunisation guidelines.

4.2 Dose and Method of Administration

Dose.

See Table 1.

Method of administration.

Flucelvax Quad should be administered by intramuscular injection only. The vaccine must not be injected intravascularly, subcutaneously or intradermally.
The preferred site for intramuscular injection is the deltoid muscle of the upper arm.
Younger children with insufficient deltoid mass should be vaccinated in the anterolateral aspect of the thigh.
Flucelvax Quad must not be mixed with other vaccines in the same syringe.
Shake before use. After shaking, the vaccine should appear as a clear to slightly opalescent suspension.
Visually inspect the contents of each pre-filled syringe for particulate matter and/or variation in appearance prior to administration. If either condition is observed, do not administer the vaccine.
Flucelvax Quad does not contain preservative or antibiotics. Each pre-filled syringe is for use in one patient on one occasion only. Discard any residue.

4.3 Contraindications

The vaccine is contraindicated in individuals with known severe allergic reactions (e.g. anaphylaxis) to:
any component of the vaccine (see Section 2 Qualitative and Quantitative Composition; Section 6.1 List of Excipients); or
a previous dose of any influenza vaccine.

4.4 Special Warnings and Precautions for Use

As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic event following the administration of the vaccine.
Immunisation should be postponed in patients with febrile illness until the fever is resolved.
In immunocompromised patients the antibody response may be lower.
A protective immune response may not be elicited in all vaccine recipients.
If Guillain-Barré syndrome has occurred within 6 weeks of previous influenza vaccination, the decision to give Flucelvax Quad vaccine should be based on careful consideration of the potential benefits and risks.
The syringe and all associated syringe components for Flucelvax Quad AUST R 319093 pre-filled syringe needle-free do not contain natural rubber latex.
Flucelvax Quad AUST R 341450 pre-filled syringe with attached needle cannot be considered to be latex-free as the sheath covering the needle may contain natural rubber latex. See Section 6.5 Nature and Contents of Container for further information.

Use in the elderly.

Of the total number of subjects who received one dose of Flucelvax Quad in clinical studies and included in the safety population (2493), 26.47% (660) were 65 years of age and older and 7.7% (194) were 75 years of age or older.
Antibody responses to Flucelvax Quad were lower in the geriatric (adults 65 years and older) population than in younger subjects.

Paediatric use.

Flucelvax Quad is not indicated in children less than 6 months of age.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

There are no data available on co-administration of Flucelvax Quad with other vaccines. Based on clinical experience with cell-based trivalent influenza vaccine (TIVc), Flucelvax Quad can be given at the same time as other vaccines. If Flucelvax Quad is to be given at the same time as another injectable vaccine(s), the vaccine(s) should always be administered to separate limbs. It should be noted that adverse reactions may be intensified.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There are no reproductive and developmental toxicity studies with Flucelvax Quad.
A reproductive and developmental toxicity study in which female rabbits were administered cell-based TIVc, 45 microgram HA/dose, 3 times prior to mating and twice during gestation, showed no adverse effects on the mating performance or female fertility. Male fertility has not been assessed in animals.
(Category A)
The safety of Flucelvax Quad in pregnancy has not been assessed in randomised clinical trials. A prospective Pregnancy Exposure Registry was conducted in the United States (US) and data were collected from 665 women vaccinated with Flucelvax Quad during 3 Northern Hemisphere influenza seasons (2017-18 to 2019-20), of whom 28% were exposed during their first trimester. Based on pregnancy outcomes and predefined infant safety outcomes, there was no evidence of adverse foetal, newborn or pregnancy outcomes attributable to the vaccine during any stage of pregnancy.
There are no reproductive and developmental toxicity studies with Flucelvax Quad. Reproductive and developmental toxicity data from TIVc do not predict an increased risk of developmental abnormalities. In a reproductive and developmental toxicity study with TIVc, the effect of cell culture-derived antigens on embryo-foetal development was evaluated in pregnant rabbits. Anti-influenza antibodies were detected in treated rabbits and their offspring. No adverse effects on pregnancy or embryo-foetal development were observed.
Influenza vaccination is recommended for pregnant women during any stage of pregnancy. This recommendation is based on the known adverse consequences of influenza infection during pregnancy and the large body of data showing that large numbers of women have been vaccinated during pregnancy with inactivated influenza vaccines with no increased risk of adverse foetal or maternal outcomes attributable to the vaccine. Flucelvax Quad vaccine should be given to a pregnant woman following an assessment of the risks and benefits.
Flucelvax Quad has not been evaluated in nursing mothers. No data are available on the use of Flucelvax Quad during lactation.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Clinical trials.

Because clinical trials are conducted under very specific conditions, the adverse event rates observed in the clinical trials may not reflect the rates observed in the clinical studies of another vaccine and may not reflect the rates of events observed in clinical practice.

Adults 18 years of age and older.

The safety of Flucelvax Quad in adults 18 years and older was evaluated in a randomised, double-blind, controlled study conducted in the US (NCT01992094, see http://clinicaltrials.gov) (Study V130_01). The safety population included a total of 2680 adults 18 years of age and older; 1340 adults 18 to < 65 years of age and 1340 adults 65 years of age and older. In this study, subjects received Flucelvax Quad or one of the two formulations of comparator trivalent influenza vaccine (TIVc) (Flucelvax Quad N=1334, TIV1c N=677 or TIV2c N=669).
In this study, solicited local injection site and systemic adverse events were collected from subjects who completed a symptom diary card for 7 days following vaccination.
Unsolicited adverse events were collected for 21 days after vaccination. Serious adverse events (SAEs) were collected throughout the study duration (until 6 months after vaccination). All adverse events are presented regardless of any treatment causality assigned by study investigators.
Solicited adverse events in the safety population of adults 18 to < 65 years of age and 65 years of age and older are shown in Table 2.
The most commonly reported unsolicited adverse events (reported by ≥ 3% of subjects administered Flucelvax Quad) in adults 18 to < 65 years, and with a similar frequency to the trivalent influenza vaccine comparators, were upper respiratory tract infection (3.5%; TIV1c 2.7%; TIV2c 4.6%) and nasopharyngitis (3.0%; TIV1c 2.4%; TIV2c 2.7%). In adults ≥ 65 years, the most commonly reported unsolicited adverse events (reported by ≥ 3% of subjects administered Flucelvax Quad) were nasopharyngitis (4.4%; TIV1c 4.1%; TIV2c 3.3%) and upper respiratory tract infection (3.3%; TIV1c 3.5%; TIV2c 3.3%).
There were no serious adverse events assessed as being related to study vaccines.

Children and adolescents 6 months to less than 18 years of age.

Flucelvax Quad is indicated for use in adults and children 6 months of age and older (see Section 4.1 Therapeutic Indications).
The safety of Flucelvax Quad in children 6 months to less than 18 years of age has been evaluated in studies V130_03, V130_12 and V130_10.
Study V130_03 was a randomised, double-blind, controlled study in children 4 to less than 18 years of age conducted in the US (NCT01992107, see http://clinicaltrials.gov). The safety population included a total of 2332 children 4 to less than 18 years of age; 1161 children 4 to less than 9 years of age and 1171 children 9 to less than 18 years of age.
In this study, subjects received Flucelvax Quad or one of the two formulations of comparator trivalent influenza vaccine (Flucelvax Quad N=1159, TIV1c N=593 or TIV2c N=580).
Study V130_12 was a multinational, randomised, observer-blind study in children 2 to less than 18 years of age (NCT03165617, see http://clinicaltrials.gov). The safety population included a total of 4509 children 2 to less than 18 years of age who received Flucelvax Quad (N=2255) or a non-influenza comparator vaccine (N=2254).
In these studies, children 9 to less than 18 years of age received a single dose of Flucelvax Quad or comparator vaccine. Children less than 9 years of age received one or two doses (separated by 4 weeks) of Flucelvax Quad or comparator vaccine depending on the subject's prior influenza vaccination history. In Study V130_12, children in the 2-dose comparator group received a non-influenza comparator vaccine as the first dose and saline placebo as the second dose.
Study V130_10 was a randomised, observer-blind, multicentre safety and immunogenicity study in children 6 months to less than 4 years of age conducted in the US (NCT04074928, see http://clinicaltrials.gov). The safety population included a total of 2402 children 6 months to less than 4 years of age who received Flucelvax Quad (N=1597) or a quadrivalent influenza comparator (N=805). Study subjects received one or two doses (separated by 4 weeks) of Flucelvax Quad or the comparator vaccine depending on the subject's prior influenza vaccination history.
In the paediatric studies, solicited local injection site and systemic adverse events were collected from subjects who completed a symptom diary card for 7 days following vaccination. Unsolicited adverse events were collected for 28 days for Study V130_10 and 21 days after each vaccination for studies V130_03 and V130_12. Serious adverse events (SAEs) were collected throughout the study duration (until 6 months after last vaccination or end of the influenza season, whichever was longer). All adverse events are presented regardless of any treatment causality assigned by study investigators.
Solicited adverse events in the safety population of children 4 years to less than 18 years of age in Study V130_03 are shown in Table 3 (4 to less than 6 years of age) and Table 4 (6 to less than 18 years), children 2 to less than 18 years of age in Study V130_12 are shown in Table 5 and for children 6 months to less than 4 years of age in Study V130_10 are shown in Table 6.
The incidence of local and systemic solicited adverse events in children 2 to less than 18 years of age who received Flucelvax Quad or the non-influenza comparator vaccine in Study V130_12 are presented in Table 5.
The incidence of local and systemic solicited adverse events in children 6 months to less than 4 years of age who received Flucelvax Quad or influenza comparator vaccine in Study V130_10 are presented in Table 6.
In Study V130_03, the most commonly reported unsolicited adverse event (reported by ≥ 3% of subjects administered Flucelvax Quad) in children 4 to less than 18 years of age (regardless of treatment causality), was cough (3.0%), with a similar frequency reported for the trivalent influenza vaccine comparators (TIV1c 4.0%; TIV2c 3.0%).
In Study V130_12, the most commonly reported unsolicited adverse events (reported by ≥ 3% of subjects administered Flucelvax Quad) in children 2 to less than 18 years of age (regardless of causality), and with a similar frequency to the non-influenza comparator vaccine were influenza-like illness (9.4%; comparator 8.9%), upper respiratory tract infection (4.5%; comparator 4.1%), cough (3.4%; comparator 3.2%) and rhinitis (3.4%; comparator 3.8%).
In Study V130_10, the most commonly reported unsolicited adverse events (reported by ≥ 3% of subjects administered Flucelvax Quad) in children 6 months to less than 4 years of age (regardless of causality), were upper respiratory tract infection (3.7%; Comparator 5.5%) and pyrexia (2.9%; Comparator 3.1%).
In children who received two doses, the rates of solicited local and systemic adverse events was generally similar or lower after the second dose compared to the first dose.
In children 6 months to less than 18 years of age, there were no serious adverse events assessed as being related to the study vaccines in either Study V130_03, Study V130_12 or Study V130_10.

Post-marketing adverse reactions.

The following events have been identified during post-approval use of Flucelvax Quad:

General disorders and administration site conditions.

Extensive swelling of injected limb.

Immune system disorders.

Allergic or immediate hypersensitivity reactions, including anaphylactic shock.

Nervous system disorders.

Paraesthesia, syncope, presyncope, Guillain-Barré syndrome, febrile convulsions.

Skin and subcutaneous tissue disorders.

Generalised skin reactions including pruritus, urticaria, or non-specific rash.

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 (Australia) or https://nzphvc.otago.ac.nz/reporting/ (New Zealand).

4.9 Overdose

There is no experience of overdose with Flucelvax Quad.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia) or the New Zealand Poisons Centre on 0800 POISON or 0800 767 4766 (New Zealand).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Influenza illness and its complications follow infection with influenza viruses. Global surveillance and analysis of influenza virus isolates permits identification of yearly antigenic variants. Specific levels of haemagglutination inhibition (HI) antibody titres post-vaccination with inactivated influenza vaccine have not been correlated with protection from influenza virus. In some human studies, antibody titres of 1:40 or greater have been associated with protection from influenza illness in up to 50% of subjects.
Antibody against one influenza virus type or subtype confers limited or no protection against another. Furthermore, antibody to one antigenic variant of influenza virus might not protect against a new antigenic variant of the same type or subtype.
Annual revaccination with current influenza vaccines is recommended because immunity declines during the year after vaccination and circulating strains of influenza virus may change from year to year.

Clinical trials.

Immunogenicity of Flucelvax Quad.

Adult studies. V130_01.

Immunogenicity of Flucelvax Quad was evaluated in adults 18 years of age and older in a randomised, double-blind, controlled study conducted in the US (NCT01992094, see http://clinicaltrials.gov). In this study, subjects received Flucelvax Quad or one of the two formulations of comparator trivalent influenza vaccine (Flucelvax Quad N=1334, TIV1c N=677 or TIV2c N=669). In the per protocol set, the mean age of subjects who received Flucelvax Quad was 57.5 years; 55.1% of subjects were female and 76.1% of subjects were Caucasian, 13% were Black and 9% were Hispanic. The immune response to each of the vaccine antigens was assessed, 21 days after vaccination.
The immune response of Flucelvax Quad was non-inferior to TIVc for all 4 influenza strains (geometric mean titre (GMT) ratio and differences in vaccine group seroconversion rates). The antibody response to influenza B strains contained in Flucelvax Quad was superior to the antibody response after vaccination with TIVc containing an influenza B strain from the alternate lineage. There was no evidence that the addition of the second influenza B strain resulted in immune interference to other strains included in the vaccine.
Non-inferiority criteria were also met for all 4 influenza strains in age subgroup analyses for subjects 18 to less than 65 years of age and 65 years of age and above.
The non-inferiority data observed are summarised in Table 7.

Paediatric studies. Study V130_03.

Immunogenicity of Flucelvax Quad was evaluated in children 4 to less than 18 years of age in a randomised, double-blind, controlled study conducted in the US (NCT01992107, see http://clinicaltrials.gov). In this study, subjects received Flucelvax Quad or one of the two formulations of comparator trivalent influenza vaccine (Flucelvax Quad N=1159, TIV1c N=593 or TIV2c N=580). In the per protocol set, the mean age of subjects who received Flucelvax Quad was 9.8 years; 47% of subjects were female and 54% of subjects were Caucasian, 22% were Black and 19% were Hispanic. The immune response to each of the vaccine antigens was assessed, 21 days after vaccination.
The immune response of Flucelvax Quad was non-inferior to TIVc for all 4 influenza strains (GMT ratio and differences in vaccine group seroconversion rates). The antibody response to influenza B strains contained in Flucelvax Quad was superior to the antibody response after vaccination with TIVc containing an influenza B strain from the alternate lineage. There was no evidence that the addition of the second influenza B strain resulted in immune interference to other strains included in the vaccine.
The non-inferiority data observed are summarised in Table 8 in children and adolescents aged 4 to less than 18 years.

Study V130_10.

Immunogenicity of Flucelvax Quad was evaluated in children 6 months to less than 4 years of age in a randomised, observer-blind, multicentre study conducted in the US (NCT04074928, see http://clinicaltrials.gov). In this study, subjects received Flucelvax Quad or a comparator quadrivalent influenza vaccine (Flucelvax Quad N=1597, Comparator QIV N=805). In the per protocol set, the mean age of subjects was 29 months; 49% of subjects were female and 67% of subjects were Caucasian, 27% were Black and < 1% were Asian, Hawaiian or other Pacific Islander and American Indian or Alaska Native. 26% of subjects were of Hispanic origin. The immune response to each of the vaccine antigens was assessed 28 days after last vaccination.
The immunogenicity endpoints were GMTs and percentage of subjects who achieved seroconversion, defined as a pre-vaccination HI or microneutralization (MN) titre of < 1:10 with a post-vaccination titre ≥ 1:40 or with a pre-vaccination HI or MN titre ≥ 1:10 and a minimum 4-fold increase in serum antibody titre. GMTs and seroconversion rates were measured by HI assay for A/H1N1, B/Yamagata and B/Victoria strains and by MN assay for the A/H3N2 strain.
Flucelvax Quad was non-inferior to the comparator QIV. Noninferiority was established for all 4 influenza strains as assessed by ratios of GMTs and the differences in the percentages of subjects achieving seroconversion at 4 weeks following vaccination.
The non-inferiority data observed are summarised in Table 9.
Efficacy of Flucelvax Quad in children (2 to less than 18 years of age).

V130_12.

Efficacy of Flucelvax Quad was evaluated in children 2 to less than 18 years of age in Study V130_12 (NCT03165617, see http://clinicaltrials.gov). This was a multinational, randomised, non-influenza vaccine comparator-controlled efficacy study conducted in 8 countries. The study enrolled 4513 subjects who received either Flucelvax Quad (N=2258) or a non-influenza vaccine comparator, Menveo Meningococcal ACWY Conjugate Vaccine (N=2255). The full analysis set (FAS) for efficacy consisted of 4509 subjects.
Children 2 to less than 9 years of age received one or two doses (separated by 4 weeks) of Flucelvax Quad or comparator vaccine depending on the subject's prior influenza vaccination history. Children 9 to less than 18 years of age received a single dose of Flucelvax Quad or comparator vaccine. Children in the 2-dose comparator group received non-influenza comparator vaccine as the first dose and saline placebo as the second dose. Among all enrolled subjects, the mean age was 8.8 years, 49% were female, 51% were 2 to less than 9 years of age, 50% were Caucasian and 49% were Asian. There were no notable differences in the distribution of demographic and baseline characteristics between the two treatment groups.
Flucelvax Quad efficacy was assessed by the number of confirmed influenza illness caused by any influenza Type A or B strain in the vaccine groups. Influenza cases were identified by active and passive surveillance of influenza-like illness (ILI) and confirmed by cell culture or real-time polymerase chain reaction (RT-PCR). ILI was defined as a fever (oral temperature ≥ 100.0°F / 37.8°C) along with any of the following: cough, sore throat, nasal congestion, or rhinorrhea. Overall vaccine efficacy was determined for influenza caused by any Type A or B strain (Table 10).
Efficacy of trivalent influenza vaccine. The efficacy experience with trivalent influenza vaccine (TIVc) is relevant to Flucelvax Quad because both vaccines are manufactured using the same process and have overlapping compositions.

Efficacy against culture-confirmed influenza. Study V58P13.

A multinational (US, Finland and Poland), randomised, observer-blinded, placebo-controlled trial was performed to assess clinical efficacy and safety of TIVc during the 2007-2008 influenza season in adults aged 18 to 49 years (NCT00630331, see http://clinicaltrials.gov). A total of 11,404 subjects were enrolled to receive TIVc (N=3828), Agrippal (N=3676) or placebo (N=3900) in a 1:1:1 ratio. Among the overall study population enrolled, the mean age was 33 years, 55% were female, 84% were Caucasian, 7% were Black, 7% were Hispanic, and 2% were of other ethnic origin.
TIVc efficacy was defined as the prevention of culture-confirmed symptomatic influenza illness caused by viruses antigenically matched to those in the vaccine compared to placebo. Influenza cases were identified by active and passive surveillance of influenza-like illness (ILI). ILI was defined according to Centers for Disease Control and Prevention (CDC) case definition, i.e. a fever (oral temperature ≥ 100.0°F / 38°C) and cough or sore throat. After an episode of ILI, nose and throat swab samples were collected for analysis. Vaccine efficacies against vaccine-matched influenza viral strains, against all influenza viral strains, and against individual influenza viral subtypes were calculated (Table 11).

5.2 Pharmacokinetic Properties

Not applicable.

5.3 Preclinical Safety Data

Genotoxicity.

Flucelvax Quad has not been evaluated for genotoxic potential.

Carcinogenicity.

Flucelvax Quad has not been evaluated for carcinogenic potential.

6 Pharmaceutical Particulars

6.1 List of Excipients

Each 0.5 mL dose of Flucelvax Quad contains the following excipients, see Table 12.
Flucelvax Quad does not contain preservative or antibiotics.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store at +2°C to +8°C. (Refrigerate. Do not freeze.) Discard if the vaccine has been frozen. Protect from light.

6.5 Nature and Contents of Container

Not all presentations or pack sizes may be marketed.

AUST R 319093.

Flucelvax Quad (Influenza virus haemagglutinin) Suspension for Injection needle-free (AUST R 319093) is a 0.5 mL suspension for injection in a needle-free pre-filled Type 1 glass syringe. The syringe and all associated syringe components do not contain natural rubber latex.
Pack sizes: 1's, 10's.

AUST R 341450.

Flucelvax Quad (Influenza virus haemagglutinin) Suspension for Injection (AUST R 341450) is a 0.5 mL suspension for injection pre-filled Type 1 glass syringe with attached needle. The sheath covering the needle may contain natural rubber latex (see Section 4.4 Special Warnings and Precautions for Use).
Pack sizes: 1's, 10's.

6.6 Special Precautions for Disposal

Any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Not applicable.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine (S4).

Summary Table of Changes