Fluarix

• Glaxo SmithKline Pharmaceuticals

Tell your doctor about all the medications you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take or have received:

• Other vaccines. If you have received  or will receive other vaccines, the vaccines should be given in different sites.
• Immunosuppressive therapies as these may reduce the effectiveness of the vaccine. Immunosuppressive therapies include:
  • Irradiation/radiation therapy
  • Antimetabolites (eg. Fluorouuracil, Capecitabine, Hydroxyurea)
  • Alkylating agents (eg. Cyclophosphamide, Carboplatin, Cisplatin)
  • Cytotoxic drugs (eg. Methotrexate, Azathioprine, Cyclophosphamide)
  • Corticosteroids ( eg. prednisone greater than 20 mg per day)

This is not a complete list of Fluarix drug interactions. Ask your doctor or pharmacist for more information.

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.

Preparation for Administration

Shake well before administration. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If either of these conditions exists, the vaccine should not be administered.

Recommended Dose and Schedule

Fluarix should be administered as an intramuscular injection preferably in the region of the deltoid muscle of the upper arm.

Children: Children 3 years to <9 years of age previously unvaccinated or vaccinated for the first time last season with only one dose receive two 0.5 mL doses; each 0.5 mL dose is administered at least 4 weeks apart.

Children 3 years to <9 years of age who have been previously vaccinated with 2 doses of any influenza vaccine receive only one 0.5 mL dose.

Children 9 years of age and older receive only one 0.5 mL dose.

Adults: Administer as a single 0.5 mL dose.

  Do not administer this product intravenously, intradermally, or subcutaneously.

Do not inject in the gluteal area or areas where there may be a major nerve trunk.

Guillain-Barré Syndrome

  If Guillain-Barré syndrome has occurred within 6 weeks of receipt of a prior influenza vaccine, the decision to give Fluarix should be based on careful consideration of the potential benefits and risks.

Latex

The tip caps of the prefilled syringes may contain natural rubber latex which may cause allergic reactions in latex sensitive individuals [see Description (11)].

Altered Immunocompetence

If Fluarix is administered to immunosuppressed persons, including individuals receiving immunosuppressive therapy, the immune response may be lower than in immunocompetent persons.

Preventing and Managing Allergic Vaccine Reactions

Prior to administration, the healthcare provider should review the patient's immunization history for possible vaccine sensitivity and previous vaccination-related adverse reactions. Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of Fluarix.

Limitations of Vaccine Effectiveness

Vaccination with Fluarix may not protect all susceptible individuals.

Persons at Risk of Bleeding

  As with other intramuscular injections, Fluarix should be given with caution in individuals with bleeding disorders such as hemophilia or on anticoagulant therapy, to avoid the risk of hematoma following the injection.

Efficacy Against Culture-Confirmed Influenza

The efficacy of Fluarix was evaluated in a randomized, double-blind, placebo-controlled study conducted in 2 European countries during the 2006-2007 influenza season. Efficacy of Fluarix, containing A/New Caledonia/20/1999 (H1N1), A/Wisconsin/67/2005 (H3N2), and B/Malaysia/2506/2004 influenza strains, was defined as the prevention of culture-confirmed influenza A and/or B cases, for vaccine antigenically matched strains, compared with placebo. Healthy subjects 18 to 64 years of age (mean 39.9 years) were randomized (2:1) to receive Fluarix (N = 5,103) or placebo (N = 2,549) and monitored for influenza-like illnesses (ILI) starting 2 weeks post vaccination and lasting for approximately 7 months. In the overall population, 60% of subjects were female and 99.9% were white. Culture-confirmed influenza was assessed by active and passive surveillance of ILI. Influenza-like illness was defined as at least one general symptom (fever ≥100°F and/or myalgia) and at least one respiratory symptom (cough and/or sore throat). After an episode of ILI, nose and throat swab samples were collected for analysis; attack rates and vaccine efficacy were calculated (Table 4).

Table 4. Attack Rates and Vaccine Efficacy Against Culture-Confirmed Influenza A and/or B in Adults 18 to 64 Years of Age (Total Vaccinated Cohort)

aThere were no vaccine matched culture-confirmed cases of A/New Caledonia/20/1999 (H1N1) or B/Malaysia/2506/2004 influenza strains with Fluarix or placebo.

b Vaccine efficacy for Fluarix exceeded a pre-defined threshold of 35% for the lower limit of the 2-sided 95% CI.

c Of the 22 additional cases, 18 were unmatched and 4 were untyped; 15 of the 22 cases were A (H3N2) (11 cases with Fluarix and 4 cases with placebo).

In a post-hoc, exploratory analysis by age, vaccine efficacy (against culture-confirmed influenza A and/or B cases, for vaccine antigenically matched strains) in subjects 18 to 49 years of age was 73.4% (95% CI: 59.3, 82.8) [number of influenza cases: Fluarix (n = 35/3,602) and placebo (n = 66/1,810)]. In subjects 50 to 64 years of age, vaccine efficacy was 13.8% (95% CI: -137.0, 66.3) [number of influenza cases: Fluarix (n = 14/1,501) and placebo (n = 8/739)]. As the study lacked statistical power to evaluate efficacy within age subgroups, the clinical significance of these results is unknown.

Immunological Evaluation

Adults: In a randomized, double-blind, placebo-controlled study conducted in healthy subjects 18 to 64 years of age (mean 39.1 years) in the United States, the immune responses to each of the antigens contained in Fluarix were evaluated in sera obtained 21 days after administration of Fluarix (N = 745) and were compared to those following administration of a placebo vaccine (N = 190). In the overall population, 54% of subjects were female and 80% were white. For each of the influenza antigens, the percentage of subjects who achieved seroconversion, defined as at least a 4-fold increase in serum hemagglutination-inhibition (HI) titer over baseline to ≥1:40 following vaccination, and the percentage of subjects who achieved HI titers of ≥1:40 are presented in Table 5. The lower limit of the 2-sided 95% CI for the percentage of subjects who achieved seroconversion or an HI titer of ≥1:40 exceeded the pre-defined lower limits of 40% and 70%, respectively.

Table 5. Rates With HI Titers ≥1:40 and Rates of Seroconversion to Each Antigen Following Fluarix or Placebo (21 Days After Vaccination) in Adults 18 to 64 Years of Age (ATP Cohort)

HI = hemagglutination-inhibition; ATP = according-to-protocol; CI = Confidence Interval.

ATP cohort for immunogenicity included subjects for whom assay results were available after vaccination for at least one study vaccine antigen.

a Results obtained following vaccination with Fluarix manufactured for the 2004-2005 season.

bSeroconversion defined as at least a 4-fold increase in serum titers of HI antibodies to ≥1:40.

Non-Inferiority Study: In a randomized, single-blind, active-controlled US study, immunological non-inferiority of Fluarix (N = 923) was compared with FLUZONE (N = 922), a US-licensed trivalent, inactivated influenza virus vaccine (Sanofi Pasteur SA). Subjects 18 to 64 years and ≥65 years of age were evaluated for immune responses to each of the vaccine antigens 21 days following vaccination [see Use in Specific Populations (8.5)]. In the overall population, 59% of subjects were female and 91% were white. The co-primary immunogenicity endpoints were geometric mean titers (GMTs) of serum HI antibodies and the percentage of subjects who achieved seroconversion, defined as at least a 4-fold increase in serum HI titer over baseline to ≥1:40, following vaccination. The primary immunogenicity analyses were performed on the According-to-Protocol (ATP) cohort which included all eligible and evaluable subjects with results of at least one serological assay. For each of the influenza antigens, the GMTs and the percentage of subjects who achieved seroconversion are presented in Table 6. Fluarix was non-inferior to the comparator influenza vaccine based on antibody GMTs (upper limit of the 2-sided 95% CI for the GMT ratio [comparator influenza vaccine/Fluarix] ≤1.5) and seroconversion rates (upper limit of the 2-sided 95% CI on difference of the comparator influenza vaccine minus Fluarix ≤10%).

Table 6. Immune Responses 21 Days After Vaccination With Fluarix Compared With Comparator Influenza Vaccine in Adults ≥18 Years of Age (ATP Cohort)

Comparator influenza vaccine manufactured by Sanofi Pasteur SA.

ATP = according-to-protocol; GMT = geometric mean antibody titer; CI = Confidence Interval; H1 = A/New Caledonia/20/99 (H1N1); H3 = A/New York/55/2004 (H3N2) for Fluarix and A/California/7/2004 (H3N2) for comparator influenza vaccine; B = B/Jiangsu/10/2003.

ATP cohort included all eligible and evaluable subjects with results of at least one serological assay.

a Seroconversion defined as at least a 4-fold increase in serum titers of HI antibodies to ≥1:40.

Children: The immune response of Fluarix was compared to FLUZONE, a US-licensed trivalent, inactivated influenza virus vaccine (Sanofi Pasteur SA), in a single-blind, randomized study in a subset of children 6 months to <5 years of age (Study 005). The immune responses to each of the antigens contained in Fluarix formulated for the 2006-2007 season were evaluated in sera obtained after 1 or 2 doses of Fluarix (N = 426) and were compared to those following administration of the comparator influenza vaccine (N = 445). Further details on the clinical study design and demographic information have been previously described [see Adverse Reactions (6.1)].

Non-inferiority of the immune response for Fluarix to comparator influenza vaccine for subjects 6 months to <5 years of age was not demonstrated mainly due to lower antibody response to Fluarix compared to the comparator influenza vaccine in subjects 6 months to <3 years of age. In subjects 3 years to <5 years of age, Fluarix met at least one of the pre-specified criteria for demonstration of non-inferiority (GMT and seroconversion rate) for the influenza A strains but not for the influenza B strain. Seroconversion rates and the percentage of subjects with HI titers ≥1:40 were analyzed as secondary endpoints. In subjects 3 years to <5 years of age, the lower limit of the 95% Confidence Interval of the seroconversion rate for Fluarix or the comparator influenza vaccine exceeded 40% for all 3 strains; also in this age group, the lower limit of the 95% Confidence Interval of the rate with HI titer ≥1:40 for Fluarix or the comparator influenza vaccine exceeded 70% for both A strains (Table 7).

Table 7. Rates With HI Titers ≥1:40 and Rates of Seroconversion to Each Antigen Following Fluarix or Comparator Influenza Vaccine in Children 3 Years to <5 Years of Age (ATP Cohort)

HI = hemagglutination inhibition; ATP = according to protocol; CI = Confidence Interval.

a Results obtained following vaccination with Fluarix manufactured for the 2006–2007 season.

b US-licensed trivalent, inactivated influenza virus vaccine (Sanofi Pasteur SA) without preservative manufactured for the 2006-2007 season.

c Seroconversion defined as at least a 4-fold increase in serum titers of HI antibodies to ≥1:40.

The vaccine recipient or guardian should be:

• informed of the potential benefits and risks of immunization with Fluarix.
• educated regarding potential side effects, emphasizing that: (1) Fluarix contains non-infectious killed viruses and cannot cause influenza and (2) Fluarix is intended to provide protection against illness due to influenza viruses only, and cannot provide protection against all respiratory illness.
• instructed to report any adverse events to their healthcare provider.
• given the Vaccine Information Statements, which are required by the National Childhood Vaccine Injury Act of 1986 to be given prior to immunization. These materials are available free of charge at the Centers for Disease Control and Prevention (CDC) website (www.cdc.gov/vaccines).
• instructed that annual revaccination is recommended.

Fluarix and TIP-LOK are registered trademarks of GlaxoSmithKline. FLUZONE is a registered trademark of Sanofi Pasteur Limited. TRITON is a registered trademark of Union Carbide Chemicals & Plastics Technology Corp.

Manufactured by GlaxoSmithKline Biologicals, Dresden, Germany,

a branch of SmithKline Beecham Pharma GmbH & Co. KG, Munich, Germany

Licensed by GlaxoSmithKline Biologicals, Rixensart, Belgium, US License 1617

Distributed by GlaxoSmithKline, Research Triangle Park, NC 27709

©2010, GlaxoSmithKline. All rights reserved.

July 2010

FLX:12PI

Principal Display Panel

Principal Display Panel

NDC 58160-877-46

Fluarix®

Influenza Virus Vaccine

2010/2011 Formula

Rx only

5 Disposable Prefilled Tip-Lok® Syringes each containing one 0.5 mL dose

Tip-Lok® Syringes are compatible with Luer-Lok® Needles

NEEDLES NOT INCLUDED

FOR INTRAMUSCULAR ADMINISTRATION ONLY

For 3 Years of Age and Older

GlaxoSmithKline

You may not be able to receive Fluarix 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 Guillain-Barre syndrome (within 6 weeks after receiving a flu vaccine).

• if you are allergic to eggs.

To make sure you can safely receive Fluarix, tell your doctor if you have any of these other conditions:

• 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 Fluarix.

The Centers for Disease Control and Prevention recommends that pregnant women get a flu shot during any trimester of pregnancy to protect themselves and their newborn babies from flu. The nasal spray form of influenza vaccine is not recommended for use in pregnant women.

It is not known whether influenza virus vaccine passes into breast milk or if it could harm a nursing baby. Do not receive Fluarix without telling your doctor if you are breast-feeding a baby. Fluarix should not be given to a child younger than 6 months old.

Since flu shots are usually given only one time per year, you will most likely not be on a dosing schedule. Call your doctor if you forget to receive your yearly flu shot in October or November.

If your child misses a booster dose of Fluarix, call your doctor for instructions.

Fluarix 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.

You should not receive a booster vaccine if you had a life-threatening allergic reaction after the first shot. Keep track of any and all side effects you have after receiving Fluarix. If you ever need to receive Fluarix in the future, you will need to tell your doctor if the previous shot caused any side effects. Get emergency medical help if you have any signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have a serious side effect such as:

• severe weakness or unusual feeling in your arms and legs (may occur 2 to 4 weeks after you receive the vaccine);

• a light-headed feeling, like you might pass out;

• high fever;

• seizure (convulsions); or

• unusual bleeding.

Less serious Fluarix side effects may include:

• low fever, chills;

• mild fussiness or crying;

• redness, bruising, pain, swelling, or a lump where the vaccine was injected;

• headache, tired feeling; or

• joint or muscle pain.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report vaccine side effects to the US Department of Health and Human Services at 1-800-822-7967.