Consumer medicine information

Fluzone High-Dose Suspension for injection

Influenza virus vaccine, trivalent (inactivated)

BRAND INFORMATION

Brand name

Fluzone High-Dose

Active ingredient

Influenza virus vaccine, trivalent (inactivated)

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Fluzone High-Dose Suspension for injection.

What is in this leaflet

Read all of this leaflet carefully before you are 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. Do not pass it on to others.
  • If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

  • What Fluzone High-Dose is and what it is used for
  • Before you are given Fluzone High-Dose
  • How Fluzone High-Dose is given
  • Possible side effects
  • Storing Fluzone High-Dose
  • Further information

What Fluzone High-Dose is and what it is used for

Fluzone High-Dose is a vaccine. Vaccines are used to help protect you against infectious diseases.

Fluzone High-Dose is recommended to help protect you against influenza. Fluzone High-Dose may be administered to persons aged 65 years and older. Influenza (flu) is a disease caused by different strains of the influenza virus. The influenza virus can spread rapidly, especially in homes or institutions, where it can be very easy for someone to catch flu and spread the disease.

Your doctor will be able to recommend the best time for you to be vaccinated. Flu is present every year, even when epidemics or outbreaks are not reported.

Fluzone High-Dose will only help to prevent flu if it is caused by one of the three strains of virus contained in the vaccine, or other strains closely related to them. Fluzone High-Dose will not prevent flu if you are incubating the disease before vaccination or if it is caused by another virus.

You should also note that there are many germs which can cause influenza-like illness. The vaccine will not protect you against these.

Previous injections of flu vaccine are unlikely to give you protection against the current strains of flu virus most common this year, so you will need to receive a vaccine against flu every year especially if you are at risk.

How Fluzone High-Dose works

Fluzone High-Dose works by helping the body to make antibodies. These antibodies help the body to recognise the flu virus and help prevent the infection. It takes a few weeks for the body to produce these antibodies. The vaccine will protect you only against the influenza strains contained in the vaccine. It will not protect you from viruses that are unrelated to those contained in the vaccine.

Before you are given Fluzone High-Dose

When you must not be given it

Do not have Fluzone High-Dose:

  • If you have ever had a severe allergic reaction to:
    - Eggs or egg products
    - Any of the other ingredients of Fluzone High-Dose listed in the FURTHER INFORMATION section.
  • If you have ever had a severe allergic reaction after getting any flu vaccine.
  • Before speaking to your doctor, if you have an acute illness with or without high temperature.

Take special care with Fluzone High-Dose

  • Tell your doctor or pharmacist if you have or have had Guillain-Barré syndrome (severe muscle weakness) after getting a flu vaccine
  • Tell your doctor or pharmacist if you have or have had an immune response problem because the immune response to the vaccine may be diminished
  • Tell your doctor or pharmacist if you have bleeding problems or bruise easily
  • Tell your doctor or pharmacist if you are pregnant or breast feeding.

Your doctor will discuss the possible risks and benefits of having Fluzone High-Dose during pregnancy or breastfeeding.

Your doctor should make sure the benefits of vaccination outweigh the risks when recommending Fluzone High-Dose.

Taking other medicines

  • Tell your doctor or pharmacist if you are taking medicines that may reduce your immune response: such as corticosteroids (for example prednisone), medicines used to treat cancer (chemotherapy), radiotherapy or other medicines affecting the immune system.

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without prescription.

Having other vaccines

  • Your doctor will advise you if Fluzone High-Dose may be given with another vaccine.

How Fluzone High-Dose is given

Fluzone High-Dose is administered to you by a health care professional.

Dose and Schedule

Adults over 65 years: A single 0.5 mL injection

Method of Administration

Fluzone High-Dose is injected into the muscles of the upper arm (preferably).

The vaccines should not be injected directly into a blood vessel (intravascularly).

When is it given?

Fluzone High-Dose should be given annually

Possible side effects

Like all medicines, Fluzone High-Dose can cause side effects, although not everybody gets them.

The most common local side effects of Fluzone High-Dose include:

  • pain, redness (erythema) and swelling, at the injection site

Systemic side effects include:

  • muscle aches (myalgia)
  • feeling unwell (malaise)
  • headache
  • fever

These side effects usually clear up within a few days. If events continue or become severe, please tell your doctor or pharmacist.

Other side effects not listed above have been reported occasionally with Fluzone High-Dose and other flu vaccines:

  • inflammation of nerves leading to weakness, such as weakness of facial muscles (facial palsy), visual disturbances (optic neuritis/neuropathy) or shoulder and arm pain (brachial neuritis)
  • fainting (syncope), dizziness, tingling or numbness of hands or feet (paraesthesia)
  • Shortness of breath (dyspnoea), sore throat and discomfort when swallowing (pharyngitis), runny or blocked nose and sneezing (rhinitis)
  • Vomiting
  • temporary inflammation of nerves causing pain, paralysis and sensitivity disorders (Guillain-Barré syndrome [GBS])
  • fits (convulsions) with or without fever
  • unusual weakness (asthenia) or tiredness (fatigue), pain in extremities or chest pain
  • Redness of the eyes (ocular hyperaemia)
  • Skin disorders such as Stevens-Johnson syndrome
  • severe allergic reaction (anaphylaxis)
  • temporary reduction in the number of blood particles called platelets (thrombocytopenia), swollen glands in neck, armpit or groin (lymphadenopathy)

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 Fluzone High-Dose

Fluzone High-Dose is usually stored in the doctor’s surgery or clinic, or at the pharmacy. However, if you need to store Fluzone High-Dose:

  • Keep out of reach and sight of children.
  • Keep Fluzone High-Dose in the original packaging until it is time for it to be given.
  • Keep it in the refrigerator, store at 2C to 8C. Do not freeze Fluzone High-Dose.

Do not use Fluzone High-Dose after the expiry date which is stated on the carton after EXP.

Do not have Fluzone High-Dose if the packaging is torn or shows signs of tampering.

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

Further Information

What Fluzone High-Dose contains

Ingredients

Active Ingredients:

Fluzone High-Dose contains 3 killed influenza virus strains recommended for the 2019 influenza season:

  • A/Michigan/45/2015 (H1N1)pdm09-like virus (A/Michigan/45/2015 X-275)
  • A/Switzerland/8060/2017 (H3N2)- like virus (A/Brisbane/1/2018 X-311)
  • B/Phuket/3073/2013-like virus (B/Phuket/3073/2013)

The other ingredients include sodium chloride, dibasic sodium phosphate, monobasic sodium phosphate, octoxinol-9, water for injection, and traces of formaldehyde.

Fluzone High-Dose contains less than 1 microgram ovalbumin (egg protein) per dose.

Fluzone High-Dose does not contain any antibiotics or preservative.

Fluzone High-Dose syringes are not made with natural rubber latex.

What Fluzone High-Dose looks like and contents of the pack

Fluzone High Dose is supplied as:

  • Single-dose, 0.5mL pre-filled syringe (gray plunger rod) without needles.

Name and Address of Australian Sponsor

sanofi-aventis australia pty ltd
Talavera Corporate Centre - Building D
12-24 Talavera Road
Macquarie Park NSW 2113
Australia
Tel: 1800 818 806

Name and Address of New Zealand Sponsor

sanofi-aventis new zealand limited
Level 856 Cawley St
Ellerslie
Auckland
New Zealand
Tel: 0800 283 684

AUST R number

AUST R 285932

Date of preparation

10 December 2018

fluzonehd-ccdsv1-cmiv3-10dec18

Published by MIMS February 2019

BRAND INFORMATION

Brand name

Fluzone High-Dose

Active ingredient

Influenza virus vaccine, trivalent (inactivated)

Schedule

S4

 

1 Name of Medicine

Inactivated trivalent influenza vaccine, split virion (Influenza virus haemagglutinin).

2 Qualitative and Quantitative Composition

Fluzone High-Dose for intramuscular injection is an inactivated influenza virus vaccine. It contains 180 micrograms (microgram) haemagglutinin (HA) per 0.5 mL dose in the recommended ratio of 60 microgram HA of each of the three strains recommended for the 2019 influenza season:
A/Michigan/45/2015 (H1N1) pdm09-like virus (A/Michigan/45/2015 X-275);
A/Switzerland/8060/2017 (H3N2)- like virus (A/Brisbane/1/2018 X-311);
B/Phuket/3073/2013-like virus (B/Phuket/3073/2013; Yamagata lineage).
The type and amount of viral antigens contained in Fluzone High-Dose conform to the annual requirements of the Australian Influenza Vaccine Committee (AIVC) recommendations for the season.
Fluzone High-Dose is prepared from influenza viruses propagated in embryonated chicken eggs and inactivated with formaldehyde. The influenza virus is concentrated and purified, and is then chemically disrupted to produce a “split virus”. The split virus is further purified by ultrafiltration and diluted to appropriate concentration. Antigens from the three strains included in the vaccine are produced separately and then combined to make the trivalent formulation.
The ingredients per dose of vaccine are listed in Table 1.
For the full list of excipients, see Section 6.1 List of Excipients.
Fluzone High-Dose is presented in prefilled syringes that are not made with natural rubber latex.

3 Pharmaceutical Form

Fluzone High-Dose suspension for injection is clear and slightly opalescent in colour.

4 Clinical Particulars

4.1 Therapeutic Indications

Fluzone High-Dose is indicated for active immunisation against influenza disease caused by influenza virus types A and B contained in the vaccine for use in persons 65 years of age and older.

4.2 Dose and Method of Administration

Fluzone High-Dose should be given in accordance with the national recommendation as per the current Immunisation Handbook.
Fluzone High-Dose should be administered as a single 0.5 mL injection by the intramuscular route in adults 65 years of age and older.
Injections of Fluzone High-Dose should be administered intramuscularly, preferably in the deltoid muscle in the elderly. The vaccine should not be injected into the gluteal region, or into areas where there may be a major nerve trunk.
For needle size and length, refer to the national recommendations as per the current Immunisation Handbook.
Before administering a dose of vaccine, shake the prefilled syringe.
Inspect Fluzone High-Dose visually for particulate matter and/or discolouration prior to administration. If any of these defects or conditions exist, the vaccine should not be administered.
The syringe is for single use only and must not be reused. Discard any remaining unused contents.
Fluzone High-Dose should not be mixed with any other vaccine in the same syringe or vial.

4.3 Contraindications

Fluzone High-Dose should not be administered to anyone with a known systemic hypersensitivity reaction after previous administration of any influenza vaccine or to any component of the vaccine (e.g. egg or egg products) (see Section 2 Qualitative and Quantitative Composition).
Fluzone High-Dose should be given in accordance with national recommendations as per the current Immunisation Handbook.

4.4 Special Warnings and Precautions for Use

Do not administer intravenously.

Hypersensitivity.

Prior to any vaccine injection, all known precautions should be taken to prevent hypersensitivity reactions. This includes a review of the individual’s prior vaccination history with respect to possible hypersensitivity to the vaccine or similar vaccines. 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).
As each dose may contain traces of formaldehyde and octoxinol 9 which are used during vaccine production, caution should be exercised when the vaccine is administered to individuals with hypersensitivity to either one of these products.

Neurological disorders.

Recurrence of Guillain-Barre syndrome (GBS) has been temporally associated with the administration of influenza vaccine. Fluzone High-Dose should be administered to individuals who have a prior history of Guillain-Barre syndrome only based on careful consideration of the potential benefits and risks.
Immunisation should be delayed in a patient with an active neurological disorder, but should be considered when the disease process has stabilized.

Immunosuppressive treatments or conditions.

The immunogenicity of Fluzone High-Dose may be reduced by immunosuppressive treatment or in individuals with immune deficiency syndromes. In such cases it is recommended to postpone the vaccination until after the immunosuppressive treatment or resolution of the immunosuppressive condition, if feasible.

Febrile or acute disease.

Vaccination should be postponed in case of an acute or febrile disease, but a disease with low-grade fever is usually not a reason to postpone vaccination.

Protection.

As with any vaccine, vaccination with Fluzone High-Dose 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 disorder.

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

Use in the elderly.

Fluzone High-Dose is intended for adults 65 years of age and over (see Section 5.1 Pharmacodynamic Properties, Clinical trials).

Paediatric use.

Safety and effectiveness of Fluzone High-Dose in persons < 65 years of age have not been established.

Effects on laboratory tests.

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

4.5 Interactions with Other Medicines and Other Forms of Interactions

Fluzone High-Dose should not be mixed with any other vaccine in the same syringe or vial.
There are no data to assess the concomitant administration of Fluzone High-Dose with other vaccines.
If Fluzone High-Dose is to be given at the same time as another injectable vaccine, the vaccines should always be administered at different injection sites.
If the vaccine is used in individuals deficient in producing antibodies due to immunosuppressive therapy, the expected immune response may not be obtained.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Fluzone High-Dose has not been evaluated for possible effects on human fertility.
(Category C)
Animal reproduction studies have not been conducted with Fluzone High-Dose. It is also not known whether Fluzone High-Dose can cause foetal harm when administered to a pregnant woman or can affect reproduction capacity.
Fluzone High-Dose should not be given to a pregnant woman unless the potential benefits outweigh the risks.
 It is not known whether Fluzone High-Dose is excreted in human milk hence, caution should be used when administering the vaccine to breastfeeding women.

4.7 Effects on Ability to Drive and Use Machines

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

4.8 Adverse Effects (Undesirable Effects)

Clinical trials experience.

Because clinical trials are conducted under widely varying conditions, adverse event rates observed in the clinical trial(s) of a vaccine cannot be directly compared to rates in the clinical trial(s) of another vaccine and may not reflect the rates observed in practice.
Two clinical studies have evaluated the safety of Fluzone High-Dose.
FIM05 was a multi-centre, double-blind trial conducted in the US. In this study, adults 65 years of age and older were randomised to receive either Fluzone High-Dose or Fluzone (2006-2007 formulation). The study compared the safety and immunogenicity of Fluzone High-Dose to those of Fluzone. The safety analysis set included 2573 Fluzone High-Dose recipients and 1260 Fluzone recipients.
Table 2 summarizes solicited injection-site reactions and systemic adverse events reported within 7 days post-vaccination via diary cards. Onset was usually within the first 3 days after vaccination and a majority of the reactions resolved within 3 days. Solicited injection-site reactions and systemic adverse events were more frequent after vaccination with Fluzone High-Dose compared to Fluzone.
Within 6 months post-vaccination, 156 (6.1%) Fluzone High-Dose recipients and 93 (7.4%) Fluzone recipients experienced a serious adverse event (SAE). No deaths were reported within 28 days post-vaccination. A total of 23 deaths were reported during Days 29 - 180 post-vaccination: 16 (0.6%) among Fluzone High-Dose recipients and 7 (0.6%) among Fluzone recipients. The majority of these participants had a medical history of cardiac, hepatic, neoplastic, renal, and/or respiratory diseases. These data do not provide evidence for a causal relationship between deaths and vaccination with Fluzone High-Dose.
FIM12 was a multi-centre, double-blind efficacy trial conducted in the US and Canada over two influenza seasons. In this study, adults 65 years of age and older were randomised to receive either Fluzone High-Dose or Fluzone (2011-2012 and 2012-2013 formulations). The study compared the efficacy and safety of Fluzone High-Dose to those of Fluzone. The safety analysis set included 15,992 Fluzone High-Dose recipients and 15,991 Fluzone recipients.
Within the study surveillance period (approximately 6 to 8 months post-vaccination), 1323 (8.3%) Fluzone High-Dose recipients and 1442 (9.0%) Fluzone recipients experienced an SAE. Within 30 days post-vaccination, 204 (1.3%) Fluzone High-Dose recipients and 200 (1.3%) Fluzone recipients experienced an SAE. The majority of these participants had one or more chronic comorbid illnesses. A total of 167 deaths were reported within 6 to 8 months post-vaccination: 83 (0.5%) among Fluzone High-Dose recipients and 84 (0.5%) among Fluzone recipients. A total of 6 deaths were reported within 30 days post-vaccination: 6 (0.04%) among Fluzone High-Dose recipients and 0 (0%) among Fluzone recipients. These data do not provide evidence for a causal relationship between deaths and vaccination with Fluzone High-Dose.

Adverse reactions from post-marketing surveillance.

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

Blood and lymphatic system disorders.

Thrombocytopaenia, lymphadenopathy.

Immune system disorders.

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

Eye disorders.

Ocular hyperaemia.

Nervous system disorders.

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

Vascular disorders.

Vasculitis, vasodilatation/flushing.

Respiratory, thoracic and mediastinal disorders.

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

Skin and subcutaneous tissue disorders.

Stevens-Johnson syndrome.

General disorders and administration site conditions.

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

Gastrointestinal disorders.

Vomiting, diarrhoea.

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

For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia) or the National Poisons Centre, 0800 POISON or 0800 764 766 (New Zealand).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Influenza vaccine, ATC code: J07BB.

Mechanism of action.

Fluzone High-Dose provides active immunisation against three influenza virus strains (two A subtypes and one B strain) contained in the vaccine. Fluzone High-Dose induces humoral antibodies against the haemagglutinins. Specific levels of haemagglutination inhibition (HI) antibody titre post-vaccination with inactivated influenza virus vaccines have not been correlated with protection from influenza virus infection. In some human studies, HI antibody titres of ≥ 1:40 have been associated with protection from influenza illness in up to 50% of participants. Antibodies against one influenza virus type or subtype confer limited or no protection against another. Furthermore, antibodies to one antigenic variant of influenza virus might not protect against a new antigenic variant of the same type or subtype. Frequent development of antigenic variants through antigenic drift is the virologic basis for seasonal epidemics and the reason for the usual change of one or more new strains in each year's influenza vaccine. Therefore, influenza vaccines are standardized to contain the haemagglutinins of influenza virus strains representing the influenza viruses likely to be circulating in the Southern Hemisphere during the influenza season.

Clinical trials.

Two multi-centre, double-blind trials were conducted: one to determine safety and immunogenicity and one to evaluate efficacy in a total of 35 826 participants.

Immunogenicity of Fluzone High-Dose in adults 65 years of age and older.

FIM05 was a multi-center, double-blind trial conducted in the US in which adults 65 years of age and older were randomised to receive either Fluzone High-Dose or Fluzone1 (2006-2007 formulation). The study compared the safety and immunogenicity of Fluzone High-Dose to those of Fluzone. For immunogenicity analyses, 2576 participants were randomised to Fluzone High-Dose and 1275 participants were randomised to Fluzone. Females accounted for 51.3% of participants in the Fluzone High-Dose group and 54.7% of participants in the Fluzone group. In both groups, the mean age was 72.9 years (ranged from 65 through 97 years in the Fluzone High-Dose group and 65 through 94 years in the Fluzone group); 35% of participants in the Fluzone High-Dose group and 36% of participants in the Fluzone group were 75 years of age or older. Most participants in the Fluzone High-Dose and Fluzone groups, respectively, were White (91.7% and 92.9%), followed by Hispanic (4.8% and 3.7%), and Black (2.7% and 2.7%).
1 Fluzone is the US-licensed standard-dose TIV upon which manufacture of Fluzone High-Dose is based.
The primary endpoints of the study were HI geometric mean titres (GMTs) and seroconversion rates 28 days after vaccination. Pre-specified statistical superiority criteria required that the lower limit (LL) of the 2-sided 95% confidence interval (CI) of the GMT ratio (Fluzone High-Dose/Fluzone) be greater than 1.50 for at least two of the strains, and if one strain failed, non-inferiority of that strain must be demonstrated (LL > 0.67), and that the lower limit of the 2-sided 95% CI of the seroconversion rate difference (Fluzone High-Dose minus Fluzone) be greater than 10% for at least two of the strains, and if one strain failed, non-inferiority of that strain must be demonstrated (LL > -10%). As shown in Table 3, statistically superior HI GMTs and seroconversion rates after vaccination with Fluzone High-Dose compared to Fluzone were demonstrated for influenza A subtypes, A (H1N1) and A (H3N2), but not for influenza type B. For strain B, non-inferiority of Fluzone High-Dose compared to Fluzone was demonstrated for both the HI GMTs and seroconversion rates.

Secondary immunogenicity objective: seroprotection.

The secondary immunogenicity objective was to describe the seroprotection of Fluzone High-Dose (based on the pooled responses elicited by the three lots) compared to that of Fluzone vaccine, where seroprotection was defined as an anti-hemagglutinin antibody titer ≥ 1:40. The percentage of subjects who had a titer of ≥ 1:40 at baseline were comparable for both groups for all three strains.
For the A (H1N1) strain, seroprotection was achieved by 89.9% of subjects in the Fluzone High-Dose group compared with 76.8% of subjects in the Fluzone vaccine group (difference between groups of 13.14%); for A (H3N2), seroprotection was achieved by 99.3% compared with 96.5%, respectively (difference of 2.81%); and for B, the values were 79.3% compared with 67.6%, respectively (difference of 11.70%). See Tables 4 and 5.

Efficacy of Fluzone High-Dose in adults 65 years of age and older.

FIM12 was a multi-center, double-blind efficacy trial conducted in the US and Canada in which adults 65 years of age and older were randomised (1:1) to receive either Fluzone High-Dose or Fluzone. The study was conducted over two influenza seasons (2011-2012 and 2012-2013) with a total of 31,989 participants randomised and vaccinated; 53% of participants enrolled in the first year of the study were re-enrolled and re-randomised in the second year. The per-protocol analysis set for efficacy assessments included 15,892 Fluzone High-Dose recipients and 15,911 Fluzone recipients. The majority (67%) of participants in the per-protocol analysis set for efficacy had one or more high-risk chronic comorbid conditions.
In the per-protocol analysis set, females accounted for 57.2% of participants in the Fluzone High-Dose group and 56.1% of participants in the Fluzone group. In both groups, the median age was 72.2 years (range 65 through 100 years). Overall, most participants in the study were White (95%); approximately 4% of study participants were Black, and approximately 6% reported Hispanic ethnicity.
The primary endpoint of the study was the occurrence of laboratory-confirmed influenza (as determined by culture or polymerase chain reaction) caused by any influenza viral type/subtype in association with influenza-like illness (ILI), defined as the occurrence of at least one of the following respiratory symptoms: sore throat, cough, sputum production, wheezing, or difficulty breathing; concurrent with at least one of the following systemic signs or symptoms: temperature > 37.2°C, chills, tiredness, headaches or myalgia. Participants were monitored for the occurrence of a respiratory illness by both active and passive surveillance, starting 2 weeks post-vaccination for approximately 7 months. After an episode of respiratory illness, nasopharyngeal swab samples were collected for analysis; attack rates and vaccine efficacy were calculated (see Table 6).
A secondary endpoint of the study was the occurrence of culture-confirmed influenza caused by viral types/subtypes antigenically similar to those contained in the respective annual vaccine formulations in association with a modified CDC-defined ILI, defined as the occurrence of a temperature > 37.2°C with cough or sore throat. The efficacy of Fluzone High-Dose relative to Fluzone for this endpoint was 51.1% (95% CI: 16.8; 72.0).

5.2 Pharmacokinetic Properties

No pharmacokinetic studies have been performed.

5.3 Preclinical Safety Data

Fluzone High-Dose has not been evaluated in non-clinical studies.

Genotoxicity.

Fluzone High-Dose has not been tested for genotoxic potential.

Carcinogenicity.

Fluzone High-Dose has not been tested for carcinogenic potential.

6 Pharmaceutical Particulars

6.1 List of Excipients

Fluzone High-Dose contains sodium chloride, dibasic sodium phosphate, monobasic sodium phosphate, octoxinol-9 and water for injections as excipients.
Fluzone High-Dose may also contain traces of formaldehyde (≤ 100 microgram) and ovalbumin (< 1 microgram). Neither antibiotics nor preservative are used during manufacture.

6.2 Incompatibilities

Fluzone High-Dose should not be mixed with any other vaccine in the same syringe or vial.

6.3 Shelf Life

9 months.

6.4 Special Precautions for Storage

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

6.5 Nature and Contents of Container

Fluzone High-Dose is available as a 0.5 mL single-dose, pre-filled syringe without needle. Packs of 5 or 10 syringes*.
* Not all pack sizes are marketed.

6.6 Special Precautions for Disposal

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

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes