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.

What is in this leaflet

Read all of this leaflet carefully before you or your child is vaccinated.

  • Keep this leaflet. You may need to read it again.
  • If you have any further questions, ask your doctor or pharmacist.
  • This vaccine has been prescribed for you or your child. Do not pass it on to others.
  • If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

  • What VAXIGRIP/VAXIGRIP Junior are and what they are used for
  • Before you or your child is given VAXIGRIP / VAXIGRIP Junior
  • How VAXIGRIP/VAXIGRIP Junior is given
  • Possible side effects
  • Storing VAXIGRIP/VAXIGRIP Junior
  • Further Information

What VAXIGRIP/VAXIGRIP Junior are and what they are used for

VAXIGRIP and VAXIGRIP Junior are vaccines.

These vaccines help to protect you or your child against influenza (flu), particularly if you or your child runs a high risk of associated complications. VAXIGRIP/VAXIGRIP Junior should be used according to official recommendations.

When a person is given VAXIGRIP/VAXIGRIP Junior, the immune system (the body’s natural defence system) will produce its own protection (antibodies) against the disease. 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 virus strains that can change every year. This is why you or your child may need to be vaccinated every year. The greatest risk of catching flu is during the cold months. If you or your child was not vaccinated in the autumn, it is still possible to do it until spring since you or your child runs the risk of catching flu until then. Your doctor will be able to recommend the best time to be vaccinated.

VAXIGRIP/VAXIGRIP Junior will protect you or your child against the three strains of virus contained in the vaccine after about 2 to 3 weeks following the injection.

The incubation period for flu is a few days, so if you or your child is exposed to flu immediately before or after your vaccination, you or your child could still develop the illness.

The vaccine will not protect you or your child against the common cold, even though some of the symptoms are similar to flu.

Before you or your child is given VAXIGRIP/VAXIGRIP Junior

When You or Your Child Must Not Be Given It

Do not have VAXIGRIP/VAXIGRIP Junior:

  • If you or your child is allergic (hypersensitive) to:
    - The active substances or
    - Any of the other ingredients of VAXIGRIP/VAXIGRIP Junior, see "Further information" or
    - Any component that may be present in very small amounts such as eggs (egg proteins or chicken proteins), neomycin, formaldehyde or octoxinol-9.
  • If you or your child has an illness with a high or moderate temperature or acute infection, the vaccination should be postponed until after you or your child has recovered.

Take special care with VAXIGRIP/VAXIGRIP Junior

  • You should tell your doctor before vaccination if you or your child has or has had Guillain-Barré Syndrome (severe muscle weakness) after getting a flu vaccine.
  • You should tell your doctor before vaccination if you or your child has a poor immune response (immunodeficiency or taking medicines affecting the immune system).
  • You should tell your doctor before vaccination if you or your child has bleeding problems or bruise easily.

Your doctor will decide if you or your child should receive the vaccine.

If, for any reason, you or your child has to have a blood test within the days following the flu vaccination, please tell your doctor. This is because false positive blood test results have been observed in a few patients who had recently been vaccinated.

As with all vaccines, VAXIGRIP/VAXIGRIP Junior may not fully protect all persons who are vaccinated.

Pregnancy and breast-feeding

Tell your doctor or pharmacist if you are pregnant or think you may be pregnant.

Flu vaccines can be used in all stages of pregnancy. Larger datasets on safety are available for the second and third trimester, compared with the first trimester; however, data from worldwide use of inactivated influenza vaccines do not indicate any adverse fetal and maternal outcomes attributable to the vaccine.

VAXIGRIP may be used during breast-feeding.

Your doctor or pharmacist will be able to decide if you should receive VAXIGRIP.

Taking Other Medicines

Please tell your doctor or pharmacist if you or your child is taking or has recently taken any other vaccines or any other medicines, including medicines obtained without a prescription.

VAXIGRIP/VAXIGRIP Junior can be given at the same time as other vaccines by using separate limbs. In this case, the side effects may be intensified.

The immunological response may decrease in case of immunosuppressant treatment, such as corticosteroids, cytotoxic drugs or radiotherapy.

Having Other Vaccines

VAXIGRIP/VAXIGRIP Junior may be given at the same time as pneumococcal vaccine and all of the vaccines scheduled for use in children.

How VAXIGRIP/VAXIGRIP Junior is given

VAXIGRIP/VAXIGRIP Junior is given as an injection, usually into muscle or tissue below the skin of upper arm (adults and children) or leg (infants and young children).

VAXIGRIP / VAXIGRIP Junior should not be injected directly into the veins.

How Much Is Given

  • Adults and children over 35 months: A single injection (0.5 mL)
  • Children 6 to 35 months: A single injection (0.25 mL)

Some children require a second injection a month later.

Please ask your doctor if this includes your child.

When It Is Given

VAXIGRIP/VAXIGRIP Junior should be given annually.

Possible Side effects

Like all medicines, VAXIGRIP/VAXIGRIP Junior can cause side effects, although not everybody gets them.

Allergic reactions

See a doctor IMMEDIATELY if you or your child experiences:

− Severe allergic reactions:

  • That may lead to medical emergency with low blood pressure, rapid, shallow breathing, rapid heart rate and weak pulse, cold, clammy skin, dizziness, that may lead to collapse (shock)
  • Swelling most often situated on the head and neck, including the face, lips, tongue, throat or any other part of the body and which may cause difficulty in swallowing or breathing (angioedema)

− Allergic reactions such as skin reactions that may spread throughout the body including itching, hives, rash, redness (erythema).

These side effects are rare (may affect up to 1 in 1,000 people) except urticaria which is uncommon (may affect up to 1 in 100 people) in children aged 3 years to 8 years

Other side effects reported

Very common (may affect more than 1 in 10 people) in adults and elderly

  • Headache (1)
  • Muscle pain (1)
  • Malaise (1) (2), unusual tiredness or weakness (1) (2)
  • Injection site reactions (1): pain, redness, swelling, hardening, itchiness (2)

Very common (may affect more than 1 in 10 people) in paediatric* population

  • Headache (1) (5) (6), unusual crying (1) (4), irritability (1) (4), drowsiness (1) (4)
  • Muscle pain (1) (5) (6)
  • Diarrhoea (1) (4)
  • Decrease or loss of appetite (1) (4)
  • Malaise (1) (5) (6), fever (1) (4), shivering (1) (6)
  • Injection site reactions (1): pain, redness, swelling, hardening (4) (5)

Common (may affect up to 1 in 10 people) in adults and elderly

  • Joint pain (1)
  • Increased sweating (1)
  • Injection site reactions: bruising (1), itchiness (3)
  • Shivering (1), fever (1), malaise (3), unusual tiredness or weakness (3)

Common (may affect up to 1 in 10 people) in paediatric* population

  • Dizziness (6)
  • Insomnia (1) (4)
  • Vomiting (1) (4)
  • Fever (5) (6), shivering (5)
  • Injection site reactions: bruising (1), itchiness, discomfort (6), hardening (6), warmth (6)

Uncommon (may affect up to 1 in 100 people) in adults and elderly

  • Swelling of the glands in the neck, armpit or groin (2)
  • Sleepiness (3), dizziness (3)
  • Nausea (2), diarrhoea (1)
  • Flu-like syndrome (2)
  • Injection site reactions (2): discomfort, warmth

Uncommon (may affect up to 1 in 100 people) in paediatric* population

  • Swelling of the glands in the neck, armpit or groin (5)
  • Diarrhoea (5)
  • Injection site reactions (5): haemorrhage, warmth

* Children/adolescents aged 6 months to 17 years

Rare (may affect up to 1 in 1000 people) in adults and elderly

  • Numbness or pins and needles sensation (paraesthesia), decrease of sensitivity (hypoesthesia) (2), numbness, pain and weakness of the arm (brachial radiculitis) (3), pain situated on the nerve route (neuralgia) (3)
  • Swelling of the glands in the neck, armpit or groin (3)

Not known frequency (frequency cannot be estimated from the available data)

  • Swelling of the glands in the neck, armpit or groin (4) (6)
  • Numbness or pins and needles sensation (paraesthesia) (7)
  • Pain situated on the nerve route (neuralgia) (5) (6)
  • Convulsions
  • 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 the body (encephalomyelitis, neuritis (2) (3) (5) (6), Guillain-Barré Syndrome (2) (3) (5) (6))
  • Blood vessel inflammation (vasculitis) which may result in skin rashes and in very rare cases in temporary kidney problems
  • Temporary reduction in the number of certain blood elements called platelets; a low number of these can result in excessive bruising or bleeding (transient thrombocytopenia).

(1) These side effects usually occurred within the 3 days following vaccination and disappeared within 1 to 3 days without treatment. Most of these side effects were of mild to moderate intensity.

(2) In adults

(3) In the elderly

(4) 6 to 35 months old

(5) 3 to 8 years old

(6) 9 to 17 years old

(7) 6 months to 17 years old

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Storing VAXIGRIP/VAXIGRIP Junior

VAXIGRIP/VAXIGRIP Junior is usually stored in the doctor’s surgery or clinic, or at the pharmacy. However, if you need to store VAXIGRIP/VAXIGRIP Junior:

  • Keep it where children cannot reach.
  • Keep it 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. Protect from light.

Freezing destroys the vaccine.

Further Information

What it looks like

VAXIGRIP is 0.5 mL of liquid vaccine in a single dose syringe.

VAXIGRIP Junior is 0.25 mL of liquid vaccine in a single dose syringe.

Ingredients

Active ingredients:

VAXIGRIP /VAXIGRIP Junior has been prepared on eggs and is made from inactivated parts of the following influenza virus strains:

  • A/California/7/2009 NYMC X-179A (A/California/7/2009 [H1N1]pdm09 - like),
  • A/South Australia/55/2014 IVR-175 (A/Switzerland/9715293/2013 [H3N2]-like),
  • B/Phuket/3073/2013

Other ingredients:

Buffered saline solution composed of:

  • Sodium chloride
  • Potassium chloride
  • Sodium phosphate (dibasic dihydrate)
  • Potassium phosphate (monobasic)
  • Water for injection

VAXIGRIP/VAXIGRIP Junior may also contain traces of egg proteins, formaldehyde, octoxinol 9 and neomycin.

VAXIGRIP/VAXIGRIP Junior does not contain lactose, gluten, tartrazine or any other azo dyes.

Name and Address of Australian Sponsor

Australia:

sanofi-aventis australia pty ltd
Talavera Corporate Centre – Building D
12 – 24 Talavera Road
Macquarie Park
NSW 2113
Australia
Tel: 1800 829 468

Aust R Number

Aust R 80198 (VAXIGRIP)

Aust R 97971 (VAXIGRIP Junior)

Date of Preparation

20 November 2015

vax-vax-jr-ccdsv8-cmiv3-20nov15

Published by MIMS March 2020

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 2020 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 active immunisation of adults and children from 6 months of age and older 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.

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.

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-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 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.
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.

Children less than 6 months of age: the safety and efficacy of Vaxigrip Tetra in children less than 6 months of age have not been established.

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. Vaxigrip Tetra 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.
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.
In all of the trials, the comparator vaccine was Vaxigrip. In addition, a placebo was also used as comparator in the 6 to 35 months population. The overall safety profile of Vaxigirip Tetra was comparable to Vaxigrip.
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. In subpopulation of children less than 24 months of age, the most frequently reported adverse reaction was irritability and in subpopulation of children from 24 to 35 months of age, it was malaise.
Overall, adverse reactions were generally less frequent in the elderly than in adults and children.

Adults and elderly.

In 3 randomised active controlled studies, 3040 adults from 18 to 60 years of age received one dose (0.5 mL) of Vaxigrip Tetra and 557 received one dose (0.5 mL) of Vaxigirip. The most frequently reported reactions following Vaxigrip Tetra administration were injection site pain, headache, myalgia and malaise.
In 2 randomised, active controlled studies, 1392 elderly over 60 years of age received one dose (0.5 mL) of Vaxigrip Tetra and 502 received one dose (0.5 mL) of Vaxigrip. The most frequently reported reactions following Vaxigrip Tetra administration were injection site pain, headache and myalgia.
Table 2 and Table 3 summarise the frequencies of solicited and unsolicited adverse reactions, respectively, that were recorded following vaccination with Vaxigrip Tetra in adults (18 to 60 years of age) and elderly (over 60 years of age).

Children from 9 to 17 years and 3 to 8 years.

In a randomised, active controlled study and an uncontrolled study, 429 children and adolescents from 9 to 17 years of age received one dose (0.5 mL) of Vaxigrip Tetra and 55 received one dose (0.5 mL) of Vaxigirip. The most frequently reported reactions following Vaxigrip Tetra administration were injection site pain, myalgia, headache, malaise and injection site swelling.
In a randomised active controlled study 884 children from 3 to 8 years of age received one or two doses (0.5 mL) of Vaxigrip Tetra and 354 received one or two doses (0.5 mL) of Vaxigrip.
The safety profile of Vaxigrip Tetra was similar after the first and the second injections.
The most frequently reported reactions following Vaxigrip Tetra administration were injection site pain malaise, myalgia, headache, injection site swelling, injection site erythema, injection site induration and shivering.
Table 4 and Table 5 summarise the frequencies of the solicited and unsolicited adverse reactions, respectively, that were recorded following vaccination with Vaxigrip Tetra in children from 9 to 17 years of age and from 3 to 8 years of age.

Children from 6 to 35 months.

In one study, 1614 children from 6 to 35 months of age received 2 doses (0.5 mL) of Vaxigrip Tetra, 1612 received 2 doses (0.5 mL) of placebo (NaCl 0.9%) and 367 received 2 doses (0.5 mL) of Vaxigirip.
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.
The most frequently reported reactions following Vaxigrip Tetra, administration were:
For all children from 6 to 35 months of age: injection site pain/tenderness, fever and injection site erythema;
In subpopulation of children less than 24 months of age: irritability, appetite lost, crying abnormal, vomiting and drowsiness;
In subpopulation of children from 24 months to 35 months of age: malaise, headache and myalgia. See Table 6 and Table 7.

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.
In the South Africa and Mali studies conducted in pregnant women with Vaxigrip (thiomersal free) (see Section 4.6 Fertility, Pregnancy and Lactation), 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; when higher frequencies were noted, the differences were limited and may be explained by the pregnant status of the study subjects. In the South Africa study, local reactions were more frequent in the Vaxigrip group than in the placebo group in both HIV-uninfected and HIV-infected cohorts. There were no other significant differences in solicited reactions between Vaxigrip and placebo groups in both cohorts.

Post marketing experience.

Immune system disorders.

Frequency not known: allergic reactions 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-Barré Syndrome (GBS), neuritis, neuralgia, convulsions, encephalomyelitis.

Vascular disorders.

Vasculitis, such as Henoch-Schönlein 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)).

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, see Section 4.8 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.

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 8.
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.

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 above, Immunogenicity of Vaxigrip Tetra below).

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.
Vaxigrip Tetra induced a significant immune response to the 4 influenza strains contained in the vaccine.
In children from 3 years of age and in adults and 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 9 and Table 10, respectively.
The same trend as that described using HAI method was observed using SN method for both adult and elderly population.

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 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 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 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

No data available.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes