2.1 Dose and Schedule

Fluzone Intradermal should be administered as a single 0.1 mL injection by the intradermal route in adults 18 through 64 years of age.

2.2 Administration

Inspect Fluzone Intradermal microinjection system visually for particulate matter and/or discoloration prior to administration. If either of these conditions exist, the vaccine should not be administered.

The preferred site of injection is the skin in the region of the deltoid.

Fluzone Intradermal vaccine should not be combined through reconstitution or mixed with any other vaccine.

Gently shake the microinjection system before administering the vaccine.

1. Remove Needle Cap

Remove the needle cap from the microinjection system.

2. Hold Microinjection System Between Thumb and Middle Finger

Hold the system by placing the thumb and middle finger only on the finger pads, the index finger remains free. Do not place fingers on the windows.

3. Insert Needle Rapidly and Perpendicular to the Skin

Insert the needle perpendicular to the skin, in the region of the deltoid, in a short, quick movement.

4. Inject Using the Index Finger

Once the needle has been inserted, maintain light pressure on the surface of the skin and inject using the index finger to push on the plunger. Do not aspirate. Once the intradermal vaccine has been administered, a wheal may be visible at the injection site.

5. Remove Needle from Skin and Activate Needle Shield by Pushing Firmly on Plunger

Remove the needle from the skin. Direct the needle away from you and others. With the same hand, push very firmly with the thumb on the plunger to activate the needle shield. You will hear a click when the shield extends to cover the needle.

5.1 Guillain-Barré Syndrome

The 1976 swine influenza vaccine was associated with an elevated risk of Guillain-Barré syndrome (GBS). Evidence for a causal relation of GBS with other influenza vaccines is inconclusive; if an excess risk exists, it is probably slightly more than 1 additional case per 1 million persons vaccinated. (1) If GBS has occurred within 6 weeks of previous influenza vaccination, the decision to give Fluzone Intradermal should be based on careful consideration of the potential benefits and risks.

5.2 Preventing and Managing Allergic Reactions

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

5.3 Altered Immunocompetence

If Fluzone Intradermal is administered to an immunocompromised person, including those receiving immunosuppressive therapy, the expected immune response may not be obtained.

5.4 Limitations of Vaccine Effectiveness

Vaccination with Fluzone Intradermal may not protect all recipients.

6.1 Clinical Trials Experience

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.

Adults 18 through 64 years of age were randomized to receive Fluzone Intradermal or Fluzone (year 2008-2009 formulation) in a multi-center trial conducted in the US. The trial was open-label for administration route. The safety analysis set included 2855 Fluzone Intradermal recipients and 1421 Fluzone recipients. Table 1 summarizes solicited injection-site reactions and systemic adverse events reported within 7 days post-vaccination via diary cards. With the exception of pain, solicited injection-site reactions were more frequent after vaccination with Fluzone Intradermal compared to Fluzone. Nine percent of Fluzone recipients and 49% of Fluzone Intradermal recipients had an injection-site reaction present beyond Day 3 post-vaccination. Approximately 20% of subjects in both groups had a solicited systemic adverse event present beyond Day 3 post-vaccination.

Within 28 days post-vaccination, a serious adverse event was reported by 10 (0.4%) Fluzone Intradermal recipients and 5 (0.4%) Fluzone recipients. Within 6 months post-vaccination, a serious adverse event was reported by 47 (1.6%) Fluzone Intradermal recipients and 20 (1.4%) Fluzone recipients. No deaths were reported during the 6 months post-vaccination. Throughout the study, one reported serious adverse event was considered to be caused by vaccination: a pruritic rash on the extremities and torso that began 48 hours after receipt of Fluzone Intradermal and resulted in hospitalization and treatment with an antihistamine and steroids.

6.2 Post-Marketing Experience

Currently, there are no post-marketing data available for Fluzone Intradermal vaccine.

The following events have been spontaneously reported during the post-approval use of Fluzone. 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.

Events Reported During Post-Approval Use of Fluzone.

• 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

8.1 Pregnancy

Pregnancy Category B: A developmental and reproductive toxicity study has been performed in female rabbits at a dose approximately 20 times the human dose (on a mg/kg basis) and has revealed no evidence of impaired female fertility or harm to the fetus due to Fluzone Intradermal. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Fluzone Intradermal should be used during pregnancy only if clearly needed.

Healthcare providers are encouraged to register women who receive Fluzone Intradermal during pregnancy in Sanofi Pasteur Inc.'s vaccination pregnancy registry by calling 1-800-822-2463.

8.3 Nursing Mothers

It is not known whether Fluzone Intradermal is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Fluzone Intradermal is administered to a nursing woman.

8.4 Pediatric Use

Safety and effectiveness of Fluzone Intradermal in persons <18 years of age have not been established. In a clinical trial, 97 infants and toddlers 6 months through 35 months of age and 160 children 3 years through 8 years of age were enrolled to receive two injections of Fluzone Intradermal. Infants and children in a control group received two injections of Fluzone. Fluzone Intradermal was associated with increased local reactogenicity relative to Fluzone. The size of the study was not adequate to reliably evaluate serious adverse events or the immune response elicited by Fluzone Intradermal relative to Fluzone.

8.5 Geriatric Use

Safety and effectiveness of Fluzone Intradermal in persons 65 years of age and older have not been established.

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 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. (2) (3)

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.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Fluzone Intradermal has not been evaluated for carcinogenic or mutagenic potential, or for impairment of fertility.

14.1 Immunogenicity of Fluzone Intradermal in Adults

Adults 18 through 64 years of age were randomized to receive Fluzone Intradermal or Fluzone (year 2008-2009 formulation) in a multi-center trial conducted in the US. The trial was open-label for administration route. For immunogenicity analyses, there were 2581 participants who received Fluzone Intradermal and 1287 participants who received Fluzone in the per protocol analysis set. There were fewer males than females (36.1% and 35.8% males in the Fluzone Intradermal and Fluzone groups, respectively). In the Fluzone Intradermal group, the mean age was 42.7 years (ranged from 18.1 through 65.0 years), and in the Fluzone group, the mean age was 42.6 years (ranged from 18.2 through 65.0 years). Most participants in the Fluzone Intradermal and Fluzone groups, respectively, were Caucasian (79.6% and 80.0%), followed by Hispanic (10.2% and 11.0%), and Black (7.7% and 6.3%). HI antibody geometric mean titers (GMTs) following Fluzone Intradermal were non-inferior to those following Fluzone for all three strains. (See Table 3) Seroconversion rates following Fluzone Intradermal were non-inferior to those following Fluzone for strains A (H1N1) and A (H3N2), but not for strain B. (See Table 4) At 28 days following vaccination with either Fluzone or Fluzone Intradermal, the percentages of subjects with a serum HI antibody titer of at least 1:40 ranged from 87% to 92%, depending on the influenza strain.

16.1 How Supplied

Fluzone Intradermal microinjection system does not contain latex.

Single-dose prefilled microinjection system, 0.1 mL, package of 10 – NDC 49281-705-55.

16.2 Storage and Handling

Store Fluzone Intradermal refrigerated at 2° to 8°C (35° to 46°F). DO NOT FREEZE. Discard if vaccine has been frozen.

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