2.1 Dose and Schedule

Fluzone Intradermal Quadrivalent 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 Quadrivalent 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. Note: A potential way to make vaccination more efficient is to have the patient place the hand of the arm being immunized on his/her hip, so the arm bends at the elbow. This can help create a more accessible angle to the skin in the deltoid region.

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

1.

Gently shake the device and remove needle cap
To prepare for vaccination, gently shake the device and remove needle cap before administering the vaccine.

2.

Position the device in your hand between the thumb and middle finger, keeping the index finger free
Hold the device by placing the thumb and middle finger on the finger pads above device window. Keep the index finger free.

3.

Gently pierce the skin over the deltoid region
Using light pressure, gently pierce the skin perpendicular to the deltoid region.

4.

Press the plunger to inject the vaccine
Using index finger, gently press the plunger to inject the vaccine. Do not aspirate. When the plunger stops, vaccination is complete. Note: Excessive pressure on the plunger may prematurely activate the needle shield on the patient's arm. Because the vaccine is injected into the skin, a wheal (superficial bump) and/or redness may be visible at the injection site.

5.

Activate the needle shield and dispose
Remove the needle from the skin. Direct the needle away from you and others. 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. Dispose the device in an appropriate container.

5.1 Guillain-Barré Syndrome

If Guillain-Barré syndrome (GBS) has occurred within 6 weeks following previous influenza vaccination, the decision to give Fluzone Intradermal Quadrivalent should be based on careful consideration of the potential benefits and risks. The 1976 swine influenza vaccine was associated with an elevated risk of 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 (See references 1 and 2).

5.2 Preventing and Managing Allergic Reactions

Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of Fluzone Intradermal Quadrivalent.

5.3 Altered Immunocompetence

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

5.4 Limitations of Vaccine Effectiveness

Vaccination with Fluzone Intradermal Quadrivalent 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 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.

6.2 Post-Marketing Experience

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

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

• 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, vasodilation/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

8.3 Nursing Mothers

It is not known whether Fluzone Intradermal Quadrivalent is excreted in human milk. Because many drugs are excreted in human milk, the decision to give Fluzone Intradermal Quadrivalent to a nursing woman should be based on careful consideration of the potential benefits and risks.

8.4 Pediatric Use

Safety and effectiveness of Fluzone Intradermal Quadrivalent 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 the trivalent formulation 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 Quadrivalent 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. Since 1977, antigenic variants of influenza A (H1N1 and H3N2) viruses and influenza B viruses have been in global circulation. Since 2001, two distinct lineages of influenza B (Victoria and Yamagata lineages) have co-circulated worldwide. Protection from influenza virus infection has not been correlated with a specific level of hemagglutination inhibition (HAI) antibody titer post-vaccination. However, in some human studies, antibody titers ≥1:40 have been associated with protection from influenza illness in up to 50% of subjects (See references 3 and 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, representing the influenza viruses likely to be circulating in the US during the influenza season.

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.

14.1 Immunogenicity of Fluzone Intradermal Quadrivalent in Adults 18 through 64 Years of Age

In Study 1 (NCT01712984), study participants were randomized to receive one dose of Fluzone Intradermal Quadrivalent, TIV-ID1, or TIV-ID2. Of the 2249 participants randomized to provide blood samples for immunogenicity analyses, 2113 adults 18 through 64 years of age were included in the per-protocol analysis set. The distribution of demographics was similar to that of the safety analysis set [see Clinical Trials Experience (6.1)].

HAI antibody geometric mean titers (GMTs) and seroconversion rates 28 days following vaccination with Fluzone Intradermal Quadrivalent were non-inferior to those following each TIV-ID for all four strains, based on pre-specified criteria (see Table 4 and Table 5).

16.1 How Supplied

Single-dose prefilled microinjection system, 0.1 mL (NDC 49281-708-48) (not made with natural rubber latex). Supplied as package of 10 (NDC 49281-708-40).

16.2 Storage and Handling

Store Fluzone Intradermal Quadrivalent 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.