2.1 Dosage and Schedule

Administer FLUAD as a single 0.5 mL intramuscular injection in adults 65 years of age and older.

2.2 Administration

• Gently shake each syringe. FLUAD has a milky-white appearance. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit [see Description (11)]. If either condition exists, FLUAD should not be administered.
• To use a pre-filled syringe fitted with a Luer Lok system, remove the tip cap by unscrewing it in a counter-clockwise direction. Once the tip cap is removed, attach a needle to the syringe by screwing it on in a clockwise direction until it locks. Once the needle is locked in place, remove the needle protector and administer the vaccine.

5.1 Guillain-Barré Syndrome

If Guillain-Barré syndrome (GBS) has occurred within 6 weeks of receipt of prior influenza vaccine, the decision to give FLUAD 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. [see References (1)] Evidence for a causal relationship 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.

5.2 Preventing and Managing Allergic Reactions

Appropriate medical treatment must be immediately available to manage potential anaphylactic reactions following administration of FLUAD.

5.3 Altered Immunocompetence

The immune response to FLUAD in immunocompromised persons, including individuals receiving immunosuppressive therapy, may be lower than in immunocompetent individuals.

5.4 Syncope

Syncope (fainting) may occur in association with administration of injectable vaccines including FLUAD. Procedures should be in place to avoid injury from fainting.

5.5 Limitations of Vaccine Effectiveness

Vaccination with FLUAD may not protect all vaccine recipients against influenza disease.

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared to rates in the clinical trials of another vaccine and may not reflect rates observed in clinical practice.

The safety of FLUAD and FLUAD QUADRIVALENT was evaluated in 17 clinical studies in 10,911 adults 65 years of age and older. Data for FLUAD QUADRIVALENT are relevant to FLUAD because both vaccines are manufactured using the same process and have overlapping compositions.

Study 1 (NCT01162122) was a multicenter, observer-blind, randomized controlled study conducted in the United States, Colombia, Panama and the Philippines during the 2010-2011 Northern Hemisphere influenza season. The safety analysis set included 3545 FLUAD recipients and 3537 AGRIFLU (Influenza Vaccine) recipients. The enrolled subject population was 65 to 97 years of age (mean 72 years) and 64% were female. Within each treatment group, 53% were Asian, 28% were Caucasian, 18% were Hispanic, 1% were Black, and fewer than 1% each were Native American/Alaskan, Pacific Islander/Hawaiian, or Other.

Solicited local (injection site) and systemic adverse reactions were collected from subjects who completed a symptom diary card for seven days following vaccination. The reported frequencies of solicited local adverse reactions are presented in Table 1a and systemic adverse reactions are presented in Table 1b.

6.2 Postmarketing Experience

In addition to the adverse reactions observed during clinical trials, the following adverse events were reported from postmarketing surveillance in individuals 65 years of age and older for FLUAD or FLUAD QUADRIVALENT. Data for FLUAD QUADRIVALENT are relevant to FLUAD because both vaccines are manufactured using the same process and have overlapping compositions. Because these events were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or to establish, for all events, a causal relationship to vaccine exposure.

Blood and lymphatic system disorders:

Thrombocytopenia (some cases were severe with platelet counts less than 5,000 per mm3), lymphadenopathy

Immune system disorders:

Allergic reactions including anaphylactic shock (in rare cases), anaphylaxis

Nervous system disorders:

Encephalomyelitis, Guillain-Barré Syndrome, convulsions, neuritis, neuralgia, paresthesia, syncope, presyncope, dizziness

Vascular disorders:

Vasculitis which may be associated with transient renal involvement

Skin and subcutaneous tissue disorders:

Generalized skin reactions including erythema multiforme, urticaria, pruritis or non-specific rash, erythema, angioedema

Musculoskeletal and connective tissue disorders:

Muscular weakness, pain in extremity

General disorders and administration site conditions:

Extensive swelling of injected limb, injection site cellulitis-like reaction, injection site swelling, peripheral swelling, asthenia, malaise, pyrexia

8.1 Pregnancy

8.2 Lactation

8.3 Pediatric Use

Safety and effectiveness of FLUAD and FLUAD QUADRIVALENT were evaluated in clinical trials conducted in children 6 months to <72 months of age. Data for FLUAD QUADRIVALENT are relevant to FLUAD because both vaccines are manufactured using the same process and have overlapping compositions. Data from these trials are inconclusive to demonstrate the safety and effectiveness of FLUAD in children 6 months to <72 months of age. The safety and effectiveness of FLUAD in infants less than 6 months of age and in children older than 72 months of age have not been evaluated.

8.4 Geriatric Use

Safety and immunogenicity of FLUAD have been evaluated in adults 65 years of age and older. [See Adverse Reactions (6.1) and Clinical Studies (14)]

Mechanism of Action

Specific levels of hemagglutination inhibition (HI) antibody titers induced by vaccination with inactivated influenza virus vaccine have not been correlated with protection from influenza illness. In some human studies, HI antibody titers of 1:40 or greater have been associated with protection from influenza illness in up to 50% of subjects. [see References (2,3)]

Antibody against one influenza virus type or subtype confers limited or no protection against another. Furthermore, antibody 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.

Carcinogenesis, Mutagenesis, Impairment of Fertility

FLUAD has not been evaluated for carcinogenic or mutagenic potential, or for impairment of male fertility in animals.