Fluzone

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.

Study 1 (NCT00391053, see http://clinicaltrials.gov) was a multi-center, double-blind pre-licensure trial conducted in the US. In this study, adults 65 years of age and older were randomized 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 1 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.

Table 1: Study 1 : Frequency of Solicited Injection-Site Reactions and Systemic Adverse Events Within 7 Days After Vaccination with Fluzone High-Dose or Fluzone, Adults 65 Years of Age and Older

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 postvaccination. 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.

Study 2 (NCT01427309, see http://clinicaltrials.gov) was a multi-center, double-blind post-licensure efficacy trial conducted in the US and Canada over two influenza seasons. In this study, adults 65 years of age and older were randomized 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.

Post-Marketing Experience

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: Thrombocytopenia, lymphadenopathy
• Immune System Disorders: Anaphylaxis, other allergic/hypersensitivity reactions (including urticaria, angioedema)
• Eye Disorders: Ocular hyperemia
• Nervous System Disorders: Guillain-Barré syndrome (GBS), convulsions, febrile convulsions, myelitis (including encephalomyelitis and transverse myelitis), facial palsy (Bell's palsy), optic neuritis/neuropathy, brachial neuritis, syncope (shortly after vaccination), dizziness, paresthesia
• Vascular Disorders: Vasculitis, vasodilatation/flushing
• Respiratory, Thoracic and Mediastinal Disorders: Dyspnea, pharyngitis, rhinitis, cough, wheezing, throat tightness
• Skin and Subcutaneous Tissue Disorders: Stevens-Johnson syndrome
• General Disorders and Administration Site Conditions: Pruritus, asthenia/fatigue, pain in extremities, chest pain
• Gastrointestinal Disorders: Vomiting

• Gastrointestinal Disorders: Nausea, diarrhea
• General Disorders and Administration Site Conditions: Chills

The recommened dose for Fluzone is:

• 6 months through 8 years: One or two doses of Fluzone. If 2 doses are required, they will be given at least 1 month apart. (1 or 2 doses depends on vaccination history as per Advisory Committee on Immunization Practices annual recommendations on prevention and control of influenza with vaccines)
• 9 years and older: One dose of Fluzone

The injectable influenza virus vaccine (flu shot) is a "killed virus" vaccine. Influenza virus vaccine is also available in a nasal spray form, which is a "live virus" vaccine. This medication guide addresses only the injectable form of this vaccine.

You can still receive a vaccine if you have a minor cold. In the case of a more severe illness with a fever or any type of infection, wait until you get better before receiving this vaccine.

Keep track of any and all side effects you have after receiving this vaccine. If you ever need to receive influenza virus vaccine in the future, you will need to tell your doctor if the previous shot caused any side effects.

Like any vaccine, influenza virus vaccine may not provide protection from disease in every person. This vaccine will not prevent illness caused by avian flu ("bird flu").

Influenza virus injectable (killed virus) vaccine will not cause you to become ill with the flu virus that it contains. However, you may have flu-like symptoms at any time during flu season that may be caused by other strains of influenza virus.

Becoming infected with influenza is much more dangerous to your health than receiving this vaccine. However, like any medicine, this vaccine can cause side effects but the risk of serious side effects is extremely low.

You may not be able to receive this vaccine if you are allergic to eggs, or if you have:

• a history of severe allergic reaction to a flu vaccine; or
• a history of Guillian-Barre syndrome (within 6 weeks after receiving a flu vaccine).

To make sure influenza virus injectable vaccine is safe for you, tell your doctor if you have:

• a bleeding or blood clotting disorder such as hemophilia or easy bruising;
• a neurologic disorder or disease affecting the brain (or if this was a reaction to a previous vaccine);
• a history of seizures;
• a weak immune system caused by disease, bone marrow transplant, or by using certain medicines or receiving cancer treatments; or
• if you are allergic to latex rubber.

You can still receive a vaccine if you have a minor cold. In the case of a more severe illness with a fever or any type of infection, wait until you get better before receiving this vaccine.

Vaccines may be harmful to an unborn baby and generally should not be given to a pregnant woman. However, not vaccinating the mother could be more harmful to the baby if the mother becomes infected with a disease that this vaccine could prevent. Your doctor will decide whether you should receive this vaccine, especially if you have a high risk of infection with influenza.

It is not known whether influenza virus vaccine passes into breast milk or if it could harm a nursing baby. Do not receive this vaccine without telling your doctor if you are breast-feeding a baby.

This vaccine should not be given to a child younger than 6 months old.

• It is used to prevent the flu.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Sterile suspension for intramuscular injection is supplied in 5 presentations: 4 presentations of Fluzone (including 2 dosage strengths in pre-filled syringes) and 1 presentation of Fluzone High-Dose in a pre-filled syringe. Dosage strengths of the 3 different pre-filled syringes are distinguished by different colored plungers.

Fluzone

Sterile suspension for intramuscular injection supplied in 4 presentations:

1) Prefilled syringe, 0.25 mL, pediatric dose, for 6 through 35 months of age, distinguished by a pink syringe plunger rod.

2) Prefilled syringe, 0.5 mL, for 36 months of age and older, distinguished by a clear syringe plunger rod.

3) Single-dose vial, 0.5 mL, for 36 months of age and older.

4) Multi-dose vial, 5 mL, for 6 months of age and older, contains thimerosal as a preservative. [See Description (11).]

Each 0.25 mL dose of Fluzone contains influenza split virus antigens that are formulated to contain a total of 22.5 mcg of influenza virus hemagglutinin, 7.5 mcg each from the 3 influenza virus strains in the vaccine. Each 0.5 mL dose of Fluzone contains influenza split virus antigens formulated to contain a total of 45 mcg of influenza virus hemagglutinin, 15 mcg each from the 3 influenza virus strains in the vaccine. [See Description (11).]

Fluzone High-Dose

Sterile suspension for intramuscular injection supplied in prefilled syringes, 0.5 mL, for adults 65 years of age and older, distinguished by a gray syringe plunger rod.

Each 0.5 mL dose of Fluzone High-Dose contains influenza split virus antigens that are formulated to contain a total of 180 mcg of influenza virus hemagglutinin, 60 mcg each from the 3 influenza virus strains in the vaccine. [See Description (11).]

. Guillain-Barré Syndrome

If Guillain-Barré syndrome (GBS) has occurred within 6 weeks of previous influenza vaccination, the decision to give Fluzone or Fluzone High-Dose should be based on careful consideration of the potential benefits and risks.

. Altered Immunocompetence

If either Fluzone or Fluzone High-Dose are administered to immunocompromised persons, including those receiving immunosuppressive therapy, the immune response may be diminished.

. Preventing and Managing Allergic Reactions

Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of the vaccine. The tip caps of the Fluzone and Fluzone High-Dose prefilled syringes may contain natural rubber latex which may cause allergic reactions in latex sensitive individuals.

. Limitations of Vaccine Effectiveness

Vaccination with either Fluzone or Fluzone High-Dose may not protect all recipients.

. Mechanism of Action

Influenza illness and its complications follow infection with influenza viruses. Global surveillance of influenza identifies yearly antigenic variants. For example, since 1977, antigenic variants of influenza A (H1N1 and H3N2) viruses and influenza B viruses have been in global circulation. Specific levels of hemagglutination inhibition (HI) antibody titer post-vaccination with inactivated influenza virus vaccines have not been correlated with protection from influenza virus infection. In some human studies, antibody titers ≥1:40 have been associated with protection from influenza illness in up to 50% of subjects. (3) (4)

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 hemagglutinins of influenza virus strains (ie, typically two type A and one type B), representing the influenza viruses likely to be circulating in the US in the upcoming winter.

Annual vaccination with the current vaccine is recommended because immunity during the year after vaccination declines, and because circulating strains of influenza virus change from year to year. (1)

Inform the patient or guardian that Fluzone and Fluzone High-Dose contain killed viruses and cannot cause influenza. Fluzone and Fluzone High-Dose do not prevent other respiratory infections.

• Vaccine recipients and guardians should be instructed to report any severe or unusual adverse reactions to their health care provider and/or to VAERS (see Highlights, Adverse Reactions).

Fluzone is a registered trademark of Sanofi Pasteur Inc.

Product information
as of July 2010.

Manufactured by:
Sanofi Pasteur Inc.
Swiftwater PA 18370 USA

5959-5961

PRINCIPAL DISPLAY PANEL - 5 mL Vial Label

Flu

NDC 49281-386-15

Influenza
Virus
Vaccine
Fluzone®

5 mL

Rx only

PRINCIPAL DISPLAY PANEL - 5 mL Vial Carton

NDC 49281-386-15

Influenza
Virus Vaccine
Fluzone®

For 6 months and older

Flu

2010-2011 Formula

5 mL

Latex-free

Rx only

sanofi pasteur

PRINCIPAL DISPLAY PANEL - 0.25 mL Syringe Label

NDC 49281-010-25

0.25 mL Dose
Rx only
Flu

Influenza Virus Vaccine
Fluzone®
IM only

No Preservative: Pediatric Dose

2010-2011 Formula

Mfd by: Sanofi Pasteur Inc.

5882

[L]

[E]

PRINCIPAL DISPLAY PANEL - 0.25 mL Syringe Carton

No Preservative
Pediatric Dose

NDC 49281-010-25
Flu

2010 – 2011 Formula

Influenza
Virus Vaccine
Fluzone®

No Preservative:
PEDIATRIC DOSE
FOR 6 - 35 MONTHS OF AGE

Rx only

10 Prefilled
Syringes
0.25 mL each

sanofi pasteur

PRINCIPAL DISPLAY PANEL - 0.5 mL Syringe Label

NDC 49281-387-65

0.5 mL Dose
Rx only

Influenza Virus Vaccine
Fluzone® High-Dose
IM only

2010-2011 Formula

For 65 yrs of age and older

Mfd by: Sanofi Pasteur Inc.

5893

[L]

[E]

PRINCIPAL DISPLAY PANEL - 0.5 mL Syringe Carton

NDC 49281-387-65
2010-2011 Formula

No Preservative

10 Prefilled Syringes
0.5 mL each

65+

Influenza Virus Vaccine
Fluzone® High-Dose
For 65 years of age and older

Rx only

sanofi pasteur