Consumer medicine information

VAXIGRIP TETRA

Influenza virus vaccine, split virion, quadrivalent (inactivated)

BRAND INFORMATION

Brand name

Vaxigrip Tetra

Active ingredient

Influenza virus vaccine, split virion, quadrivalent (inactivated)

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using VAXIGRIP TETRA.

SUMMARY CMI

Vaxigrip Tetra

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 or pharmacist.

1. Why am I using Vaxigrip Tetra?

Vaxigrip Tetra is a vaccine. This vaccine helps to protect you or your child against influenza (flu). Vaxigrip Tetra is used to prevent flu in persons of 6 months of age and older. If you are pregnant, one dose of vaccine given to you during pregnancy may protect your baby from birth to less than 6 months of age.

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

2. What should I know before I am given Vaxigrip Tetra?

Do not use if you have ever had an allergic reaction to Vaxigrip Tetra 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 I am given Vaxigrip Tetra? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Vaxigrip Tetra 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 Vaxigrip Tetra given?

Vaxigrip Tetra is given by your doctor, nurse or pharmacist.

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

5. What should I know about after being given Vaxigrip Tetra?

Things you should doCall your doctor straight away if:
you notice signs 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.
Looking after your medicineVaxigrip Tetra is usually stored in the surgery or clinic, or at the pharmacy. However, if you need to store Vaxigrip Tetra:
  • keep in the fridge between 2-8°C. Do not freeze.

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

6. Are there any side effects?

Serious side effects can include severe allergic reactions, pain situated on the nerve route, fits, neurological disorders that may result in stiff neck, confusion, numbness, pain and weakness of the limbs, loss of balance, loss of reflexes, paralysis of part or all of the body and blood vessel inflammation which may result in skin rashes and in very rare cases temporary kidney problems. 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 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

Vaxigrip Tetra

Active ingredient(s): Influenza virus haemagglutinin


Consumer Medicine Information (CMI)

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

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

1. Why am I using Vaxigrip Tetra?

Vaxigrip Tetra contains the active ingredient influenza virus haemagglutinin.

Vaxigrip Tetra is a vaccine for persons 6 months of age and older. This vaccine helps to protect you or your child against influenza (flu). If you are pregnant, one dose of vaccine given to you during pregnancy may protect your baby from birth to less than 6 months of age.

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 flu.

Flu is a disease that can spread rapidly and is caused by different types of strains that can change every year. This is why you 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 flu until then. Your doctor will be able to recommend the best time to be vaccinated.

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

2. What should I know before I am given Vaxigrip Tetra?

Warnings

Do not use Vaxigrip Tetra:

  • 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 Vaxigrip Tetra.
    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 Vaxigrip Tetra during pregnancy or breastfeeding.

Vaxigrip Tetra can be used in all stages of pregnancy.

Vaxigrip Tetra may be used during breast-feeding.

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 Vaxigrip Tetra.

3. What if I am taking other medicines?

Some medicines may interfere with Vaxigrip Tetra 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 Vaxigrip Tetra is to be given with another vaccine.

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

4. How is Vaxigrip Tetra given?

How much is given

Vaxigrip Tetra 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 less than 9 years old, 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 after being given Vaxigrip Tetra?

Things you should do

Call your doctor straight away if:

You notice signs 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.

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

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

  • keep it where young children cannot reach it.
  • keep Vaxigrip Tetra 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 Vaxigrip Tetra.

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

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

Getting rid of any 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 effectsWhat to do
  • pain, tenderness, redness, swelling, bruising and hardness at the injection site
  • feeling unwell
  • headache
  • dizziness
  • muscle aches
  • joint pain
  • fever
  • shivering
  • diarrhoea
  • nausea
  • excessive sweating
  • hot flush (in elderly)
  • chest tightness (in adults)
  • irritability, abnormal crying, drowsiness, appetite loss, vomiting (in children)
  • temporary reduction in the number of blood particles called platelets (thrombocytopenia), swollen glands in neck, armpit or groin (lymphadenopathy)
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
  • pain situated on the nerve route (neuralgia), fits (convulsion), neurological disorders that may result in stiff neck
  • tingling or numbness of the hands or feet (paraesthesia)
  • confusion, numbness, pain and weakness of the limbs, loss of balance, loss of reflexes, paralysis of part or all of the body (encephalomyelitis, neuritis, Guillain-Barre syndrome)
  • blood vessel inflammation (vasculitis) which may result in skin rashes and in very rare cases temporary kidney problems
  • severe allergic reaction (anaphylaxis)
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. By reporting side effects, you can help provide more information on the safety of this medicine.

7. Product details

What Vaxigrip Tetra contains

Active ingredient
(main ingredient)
Influenza virus haemagglutinin of the following strains
  • A/Victoria/2570/2019 (H1N1)pdm09 - like strain (A/Victoria/2570/2019, IVR-215)
  • A/Darwin/9/2021 (H3N2)-like strain (A/Darwin/9/2021, IVR-228)
  • 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, potassium chloride, dibasic sodium phosphate dihydrate, monobasic potassium phosphate, water for injections, and traces of ovalbumin (egg protein), neomycin, octoxinol-9 and formaldehyde.
Potential allergensVaxigrip Tetra may contain less than 0.05 microgram ovalbumin (egg protein) per dose.

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

Vaxigrip Tetra syringes are not made with natural rubber latex.

What Vaxigrip Tetra looks like

Vaxigrip Tetra suspension for injection is clear and slightly opalescent in colour.

Vaxigrip Tetra is available in packs of 1 or 10 single dose (0.5 mL) pre-filled syringes with attached needle or with one separate needle or no needle provided per syringe.

AUST R 315082 – prefilled syringe with attached needle*

AUST R 299922 – prefilled syringe needle free *

*Not all pack sizes may be marketed.

Who distributes Vaxigrip Tetra

Name and Address of Australian sponsor

sanofi-aventis australia pty ltd
12-24 Talavera Road
Macquarie Park NSW 2113
Telephone: 1800 818 806

This leaflet was prepared in November 2021.

vaxi-tet-ccdsv7-cmiv8-03dec21

Published by MIMS February 2022

BRAND INFORMATION

Brand name

Vaxigrip Tetra

Active ingredient

Influenza virus vaccine, split virion, quadrivalent (inactivated)

Schedule

S4

 

1 Name of Medicine

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

2 Qualitative and Quantitative Composition

Vaxigrip Tetra is formulated to contain the following four influenza strains* (see Table 1):
The type and amount of viral antigens contained in Vaxigrip Tetra conform to the annual requirements of the Australian Influenza Vaccine Committee (AIVC) and the World Health Organisation (WHO) recommendations for the 2022 season.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Suspension for injection in pre-filled syringe.
The vaccine, after shaking gently, is a colourless opalescent liquid.

4 Clinical Particulars

4.1 Therapeutic Indications

Vaxigrip Tetra is indicated for the prevention of influenza disease caused by the two influenza A virus subtypes and the two influenza B virus types contained in the vaccine for:
active immunisation of adults, including pregnant women, and children from 6 months of age and older;
passive protection of infant(s) from birth to less than 6 months of age following vaccination of pregnant women (see Section 4.2 Dose and Method of Administration; Section 4.4 Special Warnings and Precautions for Use; Section 4.6 Fertility, Pregnancy and Lactation; Section 5.1 Pharmacodynamic Properties, Clinical trials).

4.2 Dose and Method of Administration

Vaxigrip Tetra should be given in accordance with the national recommendation as per the current immunisation handbook.
Given the antigenic variation in circulating influenza viruses and the duration of immunity provided by the vaccine, it is recommended to perform vaccination against influenza every year at the beginning of the risk period.

Individuals from 9 years of age.

One injection of 0.5 mL dose.

Children from 6 months to 8 years of age.

If the child has not previously been vaccinated: two 0.5 mL injections at least one month apart.
If the child has been previously vaccinated: a single 0.5 mL injection.

Infants younger than 6 months of age.

No data are available regarding the safety and efficacy of Vaxigrip Tetra administration (active immunisation) in infants younger than 6 months of age.
Regarding passive protection, one 0.5 mL dose given to pregnant women may protect infants from birth to less than 6 months of age; however not all these infants will be protected (see Section 5.1 Pharmacodynamic Properties, Clinical trials).

Method of administration.

The vaccine should be given by intramuscular or deep subcutaneous injection.
The preferred site of administration is into the deltoid muscle in adults and children ≥ 12 months of age. The preferred site for infants (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.
Shake before use to distribute uniformly the suspension before administration.
Parenteral drug products should be inspected visually for particulate matter and/or discolouration prior to administration whenever solution and container permit. If either of these conditions exists, the vaccine should not be administered.
The syringe is for single use only in one patient and must not be reused. Discard any remaining unused contents.

4.3 Contraindications

Vaxigrip Tetra should not be given to individuals with a history of severe allergic reaction to any component of the vaccine (see Section 2 Qualitative and Quantitative Composition; Section 6.1 List of Excipients). Vaxigrip Tetra should not be given to individuals with a history of severe allergic reaction after previous administration of Vaxigrip Tetra or a vaccine containing the same components.
See Section 4.4 Special Warnings and Precautions for Use for influenza vaccination for individuals with a known egg allergy.
Vaccination should be postponed in case of moderate or severe febrile or acute disease.

4.4 Special Warnings and Precautions for Use

Vaxigrip Tetra should under no circumstances be administered 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. Adrenaline (epinephrine) injection (1:1000) and other appropriate agents used for the control of immediate allergic reactions must be available to treat unexpected reactions (e.g. anaphylaxis).
Individuals with egg allergy, including a history of anaphylaxis, can be safely vaccinated with influenza vaccines. Refer to the current immunisation handbook for guidance on the use of influenza vaccines in individuals with egg allergy.
Vaxigrip Tetra 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 each dose may contain undetectable traces of neomycin, which is used during vaccine production, caution should be exercised when the vaccine is administered to individuals with hypersensitivity to this antibiotic (and other antibiotics of the same class).

Neurological disorders.

Patients with a history of Guillain-Barre 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 Vaxigrip Tetra should be based on careful consideration of the potential benefits and risks.

Immunosuppressive treatments or conditions.

If Vaxigirip Tetra is administered to immunocompromised individuals, whether due to genetic defect, immunodeficiency disease, or immunosuppressive therapy, they may have a reduced immune response to vaccination. For current recommendation, refer to the current immunisation handbook.

Protection.

As with any vaccine, vaccination with Vaxigrip Tetra may not protect 100% of recipients.
Regarding passive protection, not all infants younger than 6 months of age born to women vaccinated during pregnancy will be protected (see Section 5.1 Pharmacodynamic Properties, Clinical trials).
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.

Bleeding disorders.

As with other vaccines administered intramuscularly, the vaccine should be administered with caution to individuals with thrombocytopenia or a bleeding disorder since bleeding may occur following an intramuscular administration to these individuals.

Syncope.

Syncope (fainting) can occur following, or even before, any vaccination as a psychogenic response to the needle injection. Procedures should be in place to prevent injury from fainting and manage syncopal reactions.

Use in the elderly.

Annual influenza vaccination is recommended for individuals 65 years of age and over.

Paediatric use.

Infants younger than 6 months of age.

No data are available regarding the safety and efficacy of Vaxigrip Tetra administration (active immunisation) in infants younger than 6 months of age. Regarding passive protection, one 0.5 mL dose given to pregnant women may protect infants from birth to less than 6 months of age; however not all these infants will be protected (see Section 4.2 Dose and Method of Administration; Section 5.1 Pharmacodynamic Properties, Clinical trials).

Effects on laboratory tests.

Interference of Vaxigrip Tetra 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. The Western Blot technique can be used to disprove these results. The transient false positive reactions could be due to IgM response by the vaccine.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No studies regarding the simultaneous administration of Vaxigrip Tetra and other vaccines have been conducted.
Nevertheless, clinical data showing that Vaxigrip (Inactivated Trivalent Influenza Vaccine (Split Virion)) can be administered concomitantly with other vaccines are available for the following vaccines: 23-valent pneumococcal polysaccharide vaccine in elderly, dTpa-IPV (diphtheria-tetanus-acellular pertussis-inactivated poliovirus vaccine) in adults aged ≥ 60 years, and zoster vaccine in adults aged 50 and older.
Vaxigrip Tetra can be given at the same time as other vaccines.
Separate injection sites and separate syringes should be used in case of concomitant administration.
Individuals deficient in producing antibodies due to immunosuppressive therapy may have a reduced immune response to vaccination.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There are no fertility data available in humans. One animal study with Vaxigrip Tetra did not indicate harmful effects on female fertility in rabbits.
(Category A)
One development and reproductive study conducted in rabbits with Vaxigrip Tetra did not indicate direct or indirect harmful effects with respect to pregnancy, embryo-fetal development or early post-natal development.
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.
Data from four clinical studies conducted with Vaxigrip (trivalent influenza vaccine, TIV) administered to pregnant women during the second and third trimesters (more than 5,000 exposed pregnancies and more than 5,000 live births, followed up to approximately 6 months postpartum) did not indicate any adverse fetal, newborn, infant, or maternal outcomes attributable to the vaccine.
In three of these clinical studies conducted in South Africa and Nepal, there were no significant differences between the Vaxigrip (TIV) and placebo groups with regards to fetal, newborn, infant, or maternal outcomes (including miscarriage, stillbirth, premature birth, low birth weight).
In the fourth study conducted in Mali, there were no significant differences between the Vaxigrip (TIV) and control vaccine (quadrivalent meningococcal conjugate vaccine) groups with regards to prematurity rate, stillbirth rate, or rate of low birth weight/small for gestational age.
Data from a clinical study conducted in Finland with Vaxigrip Tetra administered in pregnant women during the second or third trimester (230 exposed pregnancies and 231 live births) did not indicate any adverse fetal or maternal outcomes attributable to the vaccine.
Vaxigrip Tetra can be administered in all stages of pregnancy based on the safety data from clinical studies and post-marketing experience. Larger datasets on safety of inactivated influenza vaccines are available for the second and third trimesters than for the first trimester. Data from worldwide use of inactivated influenza vaccines, including Vaxigrip Tetra and Vaxigrip (trivalent inactivated influenza vaccine), do not indicate any adverse fetal and maternal outcomes attributable to the vaccine. Because of the known adverse consequences of influenza infection in pregnant women, health authorities recommend vaccination of pregnant women.
There are no data on the effect of the vaccine in breastfed newborns/infants of women vaccinated with Vaxigrip Tetra during breastfeeding period. Based on experience with inactivated influenza vaccines, Vaxigrip Tetra may be used during breastfeeding.

4.7 Effects on Ability to Drive and Use Machines

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

4.8 Adverse Effects (Undesirable Effects)

Within each system organ class, the adverse events are ranked under headings of frequency, using the following convention: Very common ≥ 1/10 (≥ 10%); common ≥ 1/100 and < 1/10 (≥ 1% and < 10%); uncommon ≥ 1/1000 and < 1/100 (≥ 0.1% and < 1%); rare ≥ 1/10,000 and < 1/1000 (≥ 0.01% and < 0.1%); very rare < 1/10,000 (< 0.01%). Not known: cannot be estimated from available data.
Adverse event information is derived from clinical trials with Vaxigrip Tetra and from worldwide post-marketing experience with Vaxigrip Tetra and Vaxigrip.

Clinical trial data.

The safety of Vaxigrip Tetra was assessed in six randomised controlled clinical trials in which 3040 adults from 18 to 60 years of age, 1392 elderly over 60 years of age and 429 children from 9 to 17 years of age received one dose of Vaxigrip Tetra and 884 children from 3 to 8 years of age received one or two doses of Vaxigrip Tetra depending on their influenza vaccination history and 1614 children from 6 to 35 months of age received two doses (0.5 mL) of Vaxigrip Tetra.
Most reactions usually occurred within the first 3 days following vaccination and resolved spontaneously within 1 to 3 days after onset. The intensity of these reactions was mild.
The most frequently reported adverse reaction after vaccination, in all populations including the whole group of children from 6 to 35 months of age, was injection site pain (between 52.8% and 56.5% in children from 3 to 17 years of age and in adults, 26.8% in children from 6 to 35 months of age and 25.8% in elderly). In subpopulation of children less than 24 months of age, irritability (32.3%) was the most frequently reported adverse reaction.
In subpopulation children from 24 to 35 months of age, malaise (26.8%) is the most frequently reported adverse reaction.
The other most frequently reported adverse reactions after vaccination were:
In adults: headache (27.8%), myalgia (23%) and malaise (19.2%);
In elderly: headache (15.6%) and myalgia (13.9%);
In children from 9 to 17 years of age: myalgia (29.1%), headache (24.7%), malaise (20.3%) and injection site swelling (10.7%);
In children from 3 to 8 years of age: malaise (30.7%), myalgia (28.5%), headache (25.7%), injection site swelling (20.5%), injection site erythema (20.4%), injection site induration (16.4%), shivering (11.2%);
In all children from 6 to 35 months of age: fever (20.4%) and injection site erythema (17.2%);
In children less than 24 months of age: appetite lost (28.9%), crying abnormal (27.1%), vomiting (16.1%) and drowsiness (13.9%);
In children from 24 to 35 months of age: headache (11.9%) and myalgia (11.6%).
Overall, adverse reactions were generally less frequent in the elderly than in adults and children.

Adults and elderly.

The safety profile presented in Table 2 is based on data from 3,040 adults from 18 to 60 years of age and 1,392 elderly over 60 years of age.

Paediatric population.

The safety profile presented in Table 3 is based on data from 429 children from 9 to 17 years of age who received one dose of Vaxigrip Tetra and from 884 children from 3 to 8 years of age who received one or two doses of Vaxigrip Tetra depending on their influenza vaccination history.
The safety profile presented in Table 4 is based on data from 1,614 children from 6 to 35 months of age who received two doses of Vaxigrip Tetra.
In children from 6 months to 8 years of age, the safety profile of Vaxigrip Tetra was similar after the first and the second injections with a trend of lower incidence of adverse reactions after the second injection compared to the first one in children from 6 to 35 months.

Other special populations.

The safety profile of Vaxigrip Tetra observed in a limited number of subjects with co-morbidities enrolled in the clinical studies does not differ from the one observed in the overall population. In addition, studies conducted with Vaxigrip in renal transplant patients, and asthmatic patients showed no major differences in terms of safety profile of Vaxigrip in these populations.

Pregnant women.

In clinical studies conducted in pregnant women in South Africa and Mali with Vaxigrip (TIV) (see Section 4.6 Fertility, Pregnancy and Lactation; Section 5.1 Pharmacodynamic Properties, Clinical trials), frequencies of local and systemic solicited reactions reported within 7 days following administration of Vaxigrip, were generally consistent with those reported for the adult population during clinical studies conducted with Vaxigrip; In the study conducted in South Africa, local reactions were more frequent in the Vaxigrip group than in the placebo group in both HIV-negative and HIV-positive cohorts.
There were no other significant differences in solicited reactions between Vaxigrip and placebo groups in both cohorts.
In one clinical study conducted in pregnant women in Finland with Vaxigrip Tetra (see Section 4.6 Fertility, Pregnancy and Lactation; Section 5.1 Pharmacodynamic Properties, Immunogenicity of Vaxigrip Tetra), frequencies of local and systemic solicited reactions reported within 7 days following administration of Vaxigrip Tetra were consistent with those reported for the non-pregnant adult population during clinical studies conducted with Vaxigrip Tetra even though higher for some adverse reactions (injection site pain, malaise, shivering, headache, myalgia). When higher frequencies were observed, this increase was also seen with Vaxigrip (TIV), used as comparator, suggesting a clinical study effect in this pregnant women population.

Post marketing experience.

Immune system disorders.

Not known: allergic including anaphylactic reactions.
The following adverse events were reported following commercial use of Vaxigrip. A causal relationship with Vaxigrip Tetra has not been established.

Blood and lymphatic system disorders.

Transient thrombocytopenia*, lymphadenopathy*.

Nervous system disorders.

Paraesthesia*, Guillain-Barre syndrome (GBS), neuritis, neuralgia, convulsions, encephalomyelitis.

Vascular disorders.

Vasculitis, such as Henoch-Schonlein purpura, with transient renal involvement in certain cases.
* These adverse events were reported during clinical trials only in some age groups (see Section 4.8 Adverse Effects (Undesirable Effects), Clinical trial data).

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

Cases of administration of more than the recommended dose (overdose) have been reported with Vaxigrip Tetra. When adverse reactions were reported, the information was consistent with the known safety profile of Vaxigrip Tetra described in Adverse Effects (Undesirable Effects).
For information on the management of overdose, contact the Poisons Information Centre, on 13 11 26.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Influenza vaccine, ATC code: J07BB02.

Mechanism of action.

Vaxigrip Tetra provides active immunisation against four influenza virus strains (two A subtypes and two B types) contained in the vaccine.
Vaxigrip Tetra induces humoral antibodies against the haemagglutinins within 2 to 3 weeks. These antibodies neutralise influenza viruses.
Specific levels of haemagglutination-inhibition (HAI) antibody titre post-vaccination with inactivated influenza virus vaccines have not been correlated with protection from influenza illness but the HAI antibody titres have been used as a measure of vaccine activity. In some human challenge studies, HAI antibody titres of ≥ 1:40 have been associated with protection from influenza illness in up to 50% of subjects.
Since influenza viruses constantly evolve, the virus strains selected in the vaccine are reviewed annually by the WHO.
Annual revaccination with Vaxigrip Tetra has not been studied. However, based on clinical experience with TIV, annual influenza vaccination is recommended given the duration of immunity provided by the vaccine and because circulating strains of influenza virus change from year to year.

Clinical trials.

Efficacy of Vaxigrip Tetra.

Children aged from 6 to 35 months (active immunisation).

A randomised placebo controlled study was conducted in 4 regions (Africa, Asia, Latina America and Europe) over 4 influenza seasons, in more than 5400 children from 6 to 35 months of age who received two doses (0.5 mL) of Vaxigrip Tetra (N = 2722), or placebo (NaCl 0.9%, N = 2717) 28 days apart to assess Vaxigrip Tetra efficacy for the prevention of laboratory confirmed influenza illness caused by any strain A and/or B and caused by vaccine similar strains (as determined by sequencing).
Laboratory-confirmed influenza illness was defined as influenza like-illness (ILI) [occurrence of fever ≥ 38°C (that lasts at least 24 hours) concurrently with at least one of the following symptoms: cough, nasal congestion, rhinorrhoea, pharyngitis, otitis, vomiting, or diarrhoea] laboratory-confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) and/or viral culture. See Table 5.
In addition, a predefined complementary analysis showed Vaxigrip Tetra prevented 56.6% (95% CI: 37.0; 70.5) of severe laboratory-confirmed influenza illnesses due to any strain, and 71.7% (95% CI: 43.7; 86.9) of severe laboratory-confirmed influenza illnesses due to vaccine-similar strains. Furthermore, subjects receiving Vaxigrip Tetra were 59.2% (95% CI: 44.4; 70.4) less likely to experience a medically attended influenza illness than subjects receiving placebo.
Severe laboratory-confirmed influenza illnesses were defined as ILI laboratory-confirmed by RT-PCR and/or viral culture with at least one of the following items:
fever > 39.5°C for subjects aged < 24 months or ≥ 39.0°C for subjects aged ≥ 24 months;
and/or at least one significant ILI symptom which prevents daily activity (cough, nasal congestion, rhinorrhoea, pharyngitis, otitis, vomiting, diarrhoea);
and/or one of the following events: acute otitis media, acute lower respiratory infection (pneumonia, bronchiolitis, bronchitis, croup), inpatient hospitalisation.

Children from 3 to 8 years of age (active immunisation).

Based on immune responses observed in children 3 to 8 years of age, the efficacy of Vaxigrip Tetra in this population is expected to be at least similar to the efficacy observed in children from 6 to 35 months (see Children aged from 6 to 35 months (active immunisation) above, Immunogenicity of Vaxigrip Tetra below).

Pregnant women.

There are no clinical efficacy data describing use of Vaxigrip Tetra in pregnant women. However, data are available on Vaxigrip (TIV) and cited below, and can be extrapolated to Vaxigrip Tetra.
In the randomised, controlled, phase IV, clinical studies conducted in Mali, Nepal, and South Africa, approximately 5,000 pregnant women received Vaxigrip (TIV) and approximately 5,000 pregnant women received placebo or control vaccine (quadrivalent meningococcal conjugate vaccine) during the second or third trimester of pregnancy. Vaccine efficacy against laboratory-confirmed influenza in pregnant women was evaluated as a secondary endpoint in all three studies.
The studies conducted in Mali and South Africa demonstrated the efficacy of Vaxigrip for the prevention of influenza in pregnant women (during pregnancy and for approximately 6 months post-delivery), following vaccination during these trimesters of pregnancy. See Table 6.
In the study conducted in Nepal, the efficacy of Vaxigrip (TIV) for the prevention of influenza in pregnant women following vaccination during these trimesters of pregnancy was not demonstrated.

Infants younger than 6 months of age born to vaccinated pregnant women (passive protection).

Infants younger than 6 months of age are at high risk of influenza, resulting in high rates of hospitalization; however, influenza vaccines are not indicated for use in this age group.
There are no clinical efficacy data in infants born to women vaccinated with Vaxigrip Tetra during pregnancy; however, efficacy in infants younger than 6 months of age whose mothers received a single 0.5 mL dose of Vaxigrip (TIV) during the second or third trimester has been demonstrated in clinical trials in Nepal, Mali and South Africa and can be extrapolated to Vaxigrip Tetra. Efficacy of Vaxigrip (TIV) in infants younger than 6 months of age whose mothers were vaccinated during the first trimester has not been studied in these trials. Nevertheless, influenza vaccination during the first trimester should not be postponed (see Section 4.6 Fertility, Pregnancy and Lactation). See Table 7.
The efficacy data indicate a waning of protection in infants born to vaccinated mothers over time after birth.
In the trial conducted in South Africa, vaccine efficacy was highest among infants 8 weeks of age or younger (85.8% [95% CI, 38.3 to 98.4]) and decreased over time; vaccine efficacy was 25.5% (95% CI, -67.9 to 67.8) for infants > 8 to 16 weeks of age and 30.4% (95% CI, -154.9 to 82.6) for infants > 16 to 24 weeks of age.
In the trial conducted in Mali, there is also a trend of higher efficacy of the trivalent inactivated influenza vaccine in infants during the first 4 months after birth (70.2% [95% CI, 35.7 to 87.6]), with lower efficacy within the fifth month of surveillance (60.7% [95% CI, 33.8 to 77.5]) and a marked fall within the sixth month (37.3% [95% CI, 7.6 to 57.8]).
The prevention of influenza disease can only be expected if the infant(s) are exposed to strains included in the vaccine administered to the mother.

Immunogenicity of Vaxigrip Tetra.

Clinical studies performed in adults from 18 to 60 years of age, in elderly over 60 years of age, in children from 3 to 8 years of age and from 6 to 35 months of age assessed the non-inferiority of Vaxigirip Tetra versus Vaxigrip for HAI (hemagglutinin inhibition) Geometric Mean antibody Titre (GMT) at day 21 (for adults) and at day 28 (for children), HAI seroconversion rate (4-fold rise in reciprocal titre or change from undetectable [< 10] to a reciprocal titre of ≥ 40), and HAI GMTR (post-/pre-vaccination titres).
One clinical study performed in adults from 18 to 60 years of age and in children from 9 to 17 years of age described the immune response of Vaxigrip Tetra versus Vaxigrip for HAI GMT at day 21. Another clinical study performed in children from 9 to 17 years of age described only the immune response of Vaxigrip Tetra.
One clinical study performed in pregnant women described the immune response of Vaxigrip Tetra versus Vaxigrip (TIV) for HAI GMT at Day 21, HAI seroconversion rate, and HAI GMTR after one dose administered during the second or third trimester of pregnancy. In this study, the transplacental transfer was evaluated using HAI GMTs of maternal blood, of cord blood and of ratio cord blood/maternal blood, at delivery.
Vaxigrip Tetra induced a significant immune response to the 4 influenza strains contained in the vaccine.
In children from 3 years of age, in adults including pregnant women and the elderly, Vaxigrip Tetra was as immunogenic as Vaxigrip for the strains in common.
Vaxigrip Tetra elicited a superior immune response against the additional B strain included in Vaxigrip Tetra compared to Vaxigrip.

Adults and elderly.

A randomised, active controlled non-inferiority study was conducted to assess the immunogenicity of Vaxigrip Tetra compared to Vaxigrip. A total of 1114 adults from 18 to 60 years of age and 1111 elderly over 60 years of age were randomised to receive either one dose of Vaxigrip Tetra or one dose of Vaxigrip (one of two formulations of comparator vaccine (TIV), each containing a B strain that corresponds to one of the two B strains in Vaxigirip Tetra (a B strain of the Yamagata lineage and a B strain of the Victoria lineage).
The immunogenicity of Vaxigrip Tetra was assessed 21 days after injection by HAI method in all subjects (832 adults from 18 to 60 years of age and 831 elderly over 60 years of age) and by seroneutralisation (SN) method in subsets of subjects (150 adults from 18 to 60 years of age and 150 elderly over 60 years of age).
Immunogenicity results in adults from 18 to 60 years of age and in elderly over 60 years of age for Vaxigrip Tetra are presented in Table 8 and Table 9, respectively.
The same trend as that described using HAI method was observed using SN method for both adult and elderly population.

Pregnant women and transplacental transfer.

In a randomised, controlled clinical study conducted in Finland, a total of 230 pregnant women received Vaxigrip Tetra and 116 pregnant women received Vaxigrip (TIV) during the second or third trimester of pregnancy (from 20 to 32 weeks of pregnancy).
Immunogenicity results by HAI method, in pregnant women 21 days after vaccination with Vaxigrip Tetra or Vaxigrip (TIV) are presented in Table 10.
Immunogenicity descriptive assessment by HAI method, at delivery, in blood sample of mother (BL03M), in cord blood sample (BL03B) and of the transplacental transfer (BL03B/ BL03M) are presented in Table 10.
At delivery, the level of antibodies in the cord sample compared to the mother sample was almost doubled for the A/H1N1 strain and increased between 1.5 and 1.7 times for the A/H3N2, B/Brisbane, and B/Phuket strains, supporting that there is transplacental antibody transfer from mother to the newborn, following vaccination of women with Vaxigrip Tetra or Vaxigrip (TIV) during the second or third trimester of pregnancy.
These data are consistent with the passive protection demonstrated in infants from birth to approximately 6 months of age following vaccination of women during the second or third trimester of pregnancy with Vaxigrip (TIV) in studies conducted in Mali, Nepal, and South Africa.

Children from 3 to 8 years of age.

A randomised, active controlled study was conducted to assess the immunogenicity of Vaxigrip Tetra compared to Vaxigrip. A total of 1242 children 3 to 8 years of age were randomised to receive either one or two doses of Vaxigrip Tetra or of Vaxigrip (control vaccine) depending on their previous influenza vaccination history.
The immunogenicity of Vaxigrip Tetra was assessed 28 days after receipt of the last injection of Vaxigrip Tetra by HAI method in all subjects and by SN method in subsets of subjects.
Children who received a one-or two-dose schedule of Vaxigrip Tetra presented a similar immune response following the last dose of the respective schedule. See Table 11.

Children from 9 to 17 years of age.

In a total of 429 children from 9 to 17 years of age who received one dose of Vaxigrip Tetra the immune response against the 4 strains contained in the vaccine was similar to the immune response induced in adults 18 to 60 years of age.

Children from 6 months to 35 months of age.

In addition to the Vaxigrip Tetra efficacy, the immunogenicity of two 0.5 mL of doses of Vaxigrip Tetra (N = 341) compared to two 0.5 mL of doses of Vaxigrip (N = 369) was assessed 28 days after receipt of the last injection of Vaxigrip Tetra by HAI method in children 6 to 35 months of age and by SN method in subsets of subjects. See Table 12.
These immunogenicity data provide supportive information in addition to vaccine efficacy data available in this population.

5.2 Pharmacokinetic Properties

No pharmacokinetic studies have been performed.

5.3 Preclinical Safety Data

Genotoxicity.

Vaxigrip Tetra has not been tested for genotoxic potential.

Carcinogenicity.

Vaxigrip Tetra has not been tested for carcinogenic potential.

6 Pharmaceutical Particulars

6.1 List of Excipients

Buffer solution: sodium chloride; potassium chloride; dibasic sodium phosphate dihydrate; monobasic potassium phosphate; water for injections.
No adjuvant and no preservative are added.
Vaxigrip Tetra may contain traces of ovalbumin (≤ 0.05 micrograms), neomycin (≤ 10.1 picograms), formaldehyde (≤ 30 micrograms) and octoxinol-9 (≤ 222.5 micrograms), which are used during the manufacturing process (see Section 4.4 Special Warnings and Precautions for Use).

6.2 Incompatibilities

This vaccine must not be mixed with other vaccines or medicinal products.

6.3 Shelf Life

Vaxigrip Tetra has a shelf life of 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. In the absence of photostability studies, this vaccine should be protected from light.

6.5 Nature and Contents of Container

0.5 mL of suspension in pre-filled syringe with attached needle or with one separate needle or no needle provided per syringe - pack size of 1 or 10*.
Vaxigrip Tetra pre-filled syringe is not made with natural rubber latex.
* Not all pack sizes or presentations may be marketed.

6.6 Special Precautions for Disposal

After use, any remaining vaccine and container must be disposed of safely, preferably by heat inactivation or incineration, according to locally agreed procedures.

6.7 Physicochemical Properties

Chemical structure and CAS number.

Not applicable/defined for vaccines.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes