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.
• The vaccine should be administered by intramuscular injection, preferably in the region of the deltoid muscle of the upper arm. Do not inject the vaccine in the gluteal region or areas where there may be a major nerve trunk.

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. 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. [see References (1)]

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. Latex

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

5.4. Altered Immunocompetence

Theimmuneresponseto FLUADinimmunocompromisedpersons, including individuals receiving immunosuppressive therapy, may be lower than in immunocompetent individuals. [see Concurrent Use With Immunosuppressive Therapies (7.2)]

5.5. Syncope

Syncope (fainting) may occur in association with administration of injectable vaccines including FLUAD. Ensure procedures are in place to avoid injury from falling associated with syncope.

5.6. 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.

Solicited adverse reactions were assessed in a multicenter, observer-blind, randomized controlled study (Study 1) conducted in the United States, Colombia, Panama and the Philippines. The safety analysis set included 3545 FLUAD recipients and 3537 AGRIFLU (Influenza Vaccine) recipients. The enrolled subject population in Study 1 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 in Study 1 who completed a symptom diary card for seven days following vaccination. The reported frequencies of solicited local and systemic adverse events from Study 1 are presented in Table 1.

6.2. Postmarketing Experience

The following adverse events have been spontaneously reported during post-approval use of FLUAD in Europe and other regions since 1997. 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 the vaccine.

Blood and lymphatic system disorders:

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

General disorders and administration site conditions:

Extensive swelling of injected limb lasting more than one week, injection site cellulitis-like reactions (some cases of swelling, pain, and redness extending more than 10 cm and lasting more than 1 week)

Immune system disorders:

Allergic reactions including anaphylactic shock, anaphylaxis and angioedema

Musculoskeletal and connective tissue disorders:

Muscular weakness

Nervous system disorders:

Encephalomyelitis, Guillain-Barré Syndrome, convulsions, neuritis, neuralgia, paraesthesia, syncope, presyncope

Skin and subcutaneous tissue disorders:

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

Vascular disorders:

Vasculitis with transient renal involvement

7.1. Concomitant Use With Other Vaccines

There are no data to assess the concomitant administration of FLUAD with other vaccines. If FLUAD is given at the same time as other injectable vaccine(s), the vaccine(s) should be administered at different injection sites.

Do not mix FLUAD with any other vaccine in the same syringe.

7.2. Concurrent Use With Immunosuppressive Therapies

Immunosuppressive or corticosteroid therapies may reduce the immune response to FLUAD.

8.1. Pregnancy

Pregnancy Category B: A reproductive and developmental toxicity study has been performed in rabbits with a dose level that was approximately 15 times the human dose based on body weight. The study revealed no evidence of impaired female fertility or harm to the fetus due to FLUAD. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this vaccine should be used during pregnancy only if clearly needed.

In a reproductive and developmental toxicity study, the effect of FLUAD on embryo-fetal and post-natal development was evaluated in pregnant rabbits. Animals were administered FLUAD by intramuscular injection twice prior to gestation, during the period of organogenesis (gestation day 7) and later in pregnancy (gestation day 20), 0.5 mL (45 mcg)/rabbit/occasion (approximately 15-fold excess relative to the adult human dose based on body weight). No adverse effects on mating, female fertility, pregnancy, embryo-fetal development, or post-natal development were observed. There were no vaccine-related fetal malformations or other evidence of teratogenesis.

8.4. Pediatric Use

The safety and effectiveness of FLUAD in the pediatric population have not been established.

8.5. 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)]

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 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. Therefore, inactivated trivalent influenza vaccines are standardized to contain the hemagglutinin of influenza virus strains (two subtypes A and one type B), representing the influenza viruses likely to be circulating in the United States in the upcoming winter.

Annual influenza vaccination is recommended because immunity declines during the year after vaccination, and because circulating strains of influenza virus change from year to year.

13.1. Carcinogenesis, Mutagenesis, Impairment of Fertility

FLUAD has not been evaluated for carcinogenic or mutagenic potential, or for impairment of male fertility in animals. FLUAD did not affect female fertility in a rabbit reproductive and developmental toxicity study.