2.1. Preparation for Administration

Inspect Influenza A (H1N1) 2009 Monovalent Vaccine syringes and vials visually for particulate matter and/or discoloration prior to administration. If either of these conditions exist, the vaccine should not be administered.

Shake the syringe and single-dose vials well before administering the vaccine and shake the multi-dose vial each time before withdrawing a dose of vaccine.

2.2. Recommended Dose and Schedule

Clinical studies are ongoing with Influenza A (H1N1) 2009 Monovalent Vaccine to determine the optimal dosage, number of doses and schedule.

Available data show that children 9 years of age and younger are largely serologically naive to the pandemic (H1N1) 2009 virus. (1) Based upon these data Influenza A (H1N1) 2009 Monovalent Vaccine should be administered as follows:

5.1. Guillain-Barré Syndrome

Recurrence of Guillain-Barré syndrome (GBS) has been temporally associated with the administration of influenza vaccine. The decision to give Influenza A (H1N1) 2009 Monovalent Vaccine to individuals who have a prior history of Guillain-Barré syndrome should be based on careful consideration of the potential benefits and risks.

5.2. Altered Immunocompetence

If Influenza A (H1N1) 2009 Monovalent Vaccine is administered to immunocompromised persons, including those receiving immunosuppressive therapy, the immune response may be diminished.

5.3. Preventing and Managing Allergic Reaction

Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of the vaccine.

5.4. Limitations of Vaccine Effectiveness

Vaccination with Influenza A (H1N1) 2009 Monovalent Vaccine may not protect all recipients.

6.1. Clinical Trial Experience

Adverse event information from clinical trials provides the basis for identifying adverse events that appear to be related to vaccine use and for approximating the rates of these events. However, because clinical trials are conducted under widely varying conditions, adverse event rates observed in the clinical trials of a vaccine cannot be directly compared to rates in the clinical trial of another vaccine, and may not reflect the rates observed in practice.

6.2. Post-Marketing Experience

The following additional events have been reported during post-approval use of Fluzone vaccine. 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.

Blood and Lymphatic System Disorders: Thrombocytopenia, lymphadenopathy

Immune System Disorders: Anaphylaxis, other allergic/hypersensitivity reactions (including urticaria, angioedema)

Nervous System Disorders: GBS, 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, vasodilation/flushing

Respiratory, Thoracic and Mediastinal Disorders: Dyspnea, pharyngitis, rhinitis

Skin and Subcutaneous Tissue Disorders: Stevens-Johnson syndrome

General Disorders and Administration Site Conditions: Fever, pain, pruritis, asthenia/fatigue, pain in extremities, chest pain

6.3. Other Adverse Events Associated with Influenza Vaccines

Anaphylaxis has been reported after administration of influenza vaccines. Although Influenza A (H1N1) 2009 Monovalent Vaccine contains only a limited quantity of egg protein, this protein can induce immediate hypersensitivity reactions among persons who have severe egg allergy. Allergic reactions include hives, angioedema, allergic asthma, and systemic anaphylaxis. [See Contraindications (4)]

The 1976 swine influenza vaccine was associated with an increased frequency of Guillain-Barré syndrome (GBS). Evidence for a causal relation of GBS with subsequent vaccines prepared from other influenza viruses is unclear. If influenza vaccine does pose a risk, it is probably slightly more than 1 additional case/1 million persons vaccinated.

Neurological disorders temporally associated with influenza vaccination such as encephalopathy, optic neuritis/neuropathy, partial facial paralysis, and brachial plexus neuropathy have been reported.

Microscopic polyangitis (vasculitis) has been reported temporally associated with influenza vaccination.

7.1. Concomitant Administration with Other Vaccines

There are no data on the concomitant administration of Influenza A (H1N1) 2009 Monovalent Vaccine with seasonal trivalent influenza vaccines.

Influenza A (H1N1) 2009 Monovalent Vaccine should not be mixed with any other vaccine in the same syringe or vial.

If Influenza A (H1N1) 2009 Monovalent Vaccine is to be given at the same time as another injectable vaccine(s), the vaccine(s) should always be administered at different injection sites.

7.2. Immunosuppressive Therapies

If Influenza A (H1N1) 2009 Monovalent Vaccine is administered to immunosuppressed persons or persons receiving immunosuppressive therapy, immunologic response may be diminished.

8.1. Pregnancy

8.3. Nursing Mothers

It is not known whether Influenza A (H1N1) 2009 Monovalent Vaccine or Fluzone vaccine is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when this vaccine is administered to a nursing woman.

8.4. Pediatric Use

Safety and effectiveness in pediatric subjects below the age of 6 months have not been established. The immune response and safety of Fluzone vaccine was evaluated in 31 children between the ages of 6-26 months. [See Adverse Reactions (6.1), Clinical Studies (14)]

8.5. Geriatric Use

Immune response to Fluzone vaccine in subjects older than 61 years of age were lower when compared to immune responses in adults 19-59 years of age. [See Clinical Studies (14)]

12.1. 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 hemagglutinin 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 titer of ≥1:40 have been associated with protection from influenza illness in up to 50% of subjects. (4) (5)

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.

13.1. Carcinogenesis, Mutagenesis, Impairment of Fertility

Neither Fluzone vaccine nor Influenza A (H1N1) 2009 Monovalent Vaccine have been evaluated for carcinogenic or mutagenic potential, or for impairment of fertility.

14.1. Immunogenicity in the Adult and Geriatric Population

In an observational study of the immunogenicity of Fluzone vaccine in a geriatric population (median age: 72.0 range: 61 to 86 years of age) compared with younger adults (median age: 38.0 range: 19 to 59 years of age; racial distribution was 2 Asian, 11 Black, 106 Caucasian, and 2 other; no gender data were available), the following results were obtained using a single-dose of the year 1999–2000 formulation of Fluzone vaccine. (See Table 1.) Antibody levels were obtained on the day of and just prior to vaccination and approximately 21 days after vaccination. (4)

14.2. Immunogenicity in Children

In a study using 2 doses of Fluzone vaccine (2003-2004) in 31 healthy children 6–36 months of age (3 Black, 23 Caucasian, 2 Hispanic, and 3 other; 15 were male and 16 were female), the following immunogenicity results were obtained on day 0 before vaccination and approximately 14 days after dose number 2. (See Table 2.)

16.1. How Supplied

Single-dose prefilled syringe, without needle, 0.25 mL, package of 10 prefilled syringes per carton – Product No. NDC 49281-650-25.

Single-dose prefilled syringe, without needle, 0.25 mL, package of 25 prefilled syringes per carton – Product No. NDC 49281-650-70.

Single-dose prefilled syringe, without needle, 0.5 mL, package of 10 prefilled syringes per carton – Product No. NDC 49281-650-50.

Single-dose prefilled syringe, without needle, 0.5 mL, package of 25 prefilled syringes per carton – Product No. NDC 49281-650-90.

Single-dose vial, 0.5 mL, package of 10 vials per carton – Product No. NDC 49281-650-10.

Multi-dose vial, 5 mL, one vial per carton. The vial contains ten 0.5 mL doses – Product No. NDC 49281-640-15.

Vial stoppers and syringe plungers do not contain latex.

16.2. Storage and Handling

Store all Influenza A (H1N1) 2009 Monovalent Vaccine presentations refrigerated at 2° to 8°C (35° to 46°F). DO NOT FREEZE. Discard if vaccine has been frozen.

Between uses, return the multi-dose vial to the recommended storage conditions at 2º to 8ºC (35º to 46ºF).

Do not use after the expiration date shown on the label.