FLUARIX 2011/2012- influenza a virus a/california/7/2009 x-181 (h1n1) antigen (formaldehyde inactivated), influenza a virus a/victoria/210/2009 x-187 (h3n2) antigen (formaldehyde inactivated) and influenza b virus b/brisbane/60/2008 antigen (formaldehyde inactivated) suspension
FLUARIX 2012/2013- influenza a virus a/christchurch/16/2010 nib-74xp (h1n1) antigen (formaldehyde inactivated), influenza a virus a/victoria/361/2011 ivr-165 (h3n2) antigen (formaldehyde inactivated) and influenza b virus b/hubei-wujiagang/158/2009 bx-39 antigen (formaldehyde inactivated) suspension
GlaxoSmithKline Biologicals SA

1 INDICATIONS AND USAGE

FLUARIX^® is indicated for active immunization for the prevention of disease caused by influenza virus subtypes A and type B contained in the vaccine. FLUARIX is approved for use in persons 3 years of age and older.

2 DOSAGE AND ADMINISTRATION

2.1 Preparation for Administration

Shake well before administration. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If either of these conditions exists, the vaccine should not be administered.

Attach a sterile needle to the prefilled syringe and administer intramuscularly.

Do not administer this product intravenously, intradermally, or subcutaneously.

2.2 Recommended Dose and Schedule

FLUARIX should be administered as an intramuscular injection preferably in the region of the deltoid muscle of the upper arm. Do not inject in the gluteal area or areas where there may be a major nerve trunk.

Children: Children 3 years to <9 years of age previously unvaccinated or vaccinated for the first time last season with only one dose receive two 0.5-mL doses; each 0.5-mL dose is administered at least 4 weeks apart.

Children 3 years to <9 years of age who have been previously vaccinated with 2 doses of any influenza vaccine receive only one 0.5-mL dose.

Children 9 years of age and older receive only one 0.5-mL dose.

Adults: Administer as a single 0.5-mL dose.

3 DOSAGE FORMS AND STRENGTHS

FLUARIX is a suspension available in 0.5-mL single-dose prefilled TIP‑LOK^® syringes.

4 CONTRAINDICATIONS

Do not administer FLUARIX to anyone with known severe allergic reactions (e.g., anaphylaxis) to egg proteins (a vaccine component) or a life-threatening reaction to previous administration of any influenza vaccine [see Description (11)].

5 WARNINGS AND PRECAUTIONS

5.1 Guillain-Barré Syndrome

If Guillain‑Barré syndrome has occurred within 6 weeks of receipt of a prior influenza vaccine, the decision to give FLUARIX should be based on careful consideration of the potential benefits and risks.

5.2 Latex

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

​ 5.3 Syncope

​ Syncope (fainting) can occur in association with administration of ​ injectable ​ vaccines, including FLUARIX. Syncope can be accompanied by transient neurological signs such as visual disturbance, ​ paresthesia ​ , and tonic- ​ clonic ​ limb movements. Procedures should be in place to avoid falling injury and to restore cerebral perfusion following syncope.

5.4 Altered Immunocompetence

If FLUARIX is administered to immunosuppressed persons, including individuals receiving immunosuppressive therapy, the immune response may be lower than in immunocompetent persons.

5.5 Preventing and Managing Allergic Vaccine Reactions

Prior to administration, the healthcare provider should review the immunization history for possible vaccine sensitivity and previous vaccination‑related adverse reactions. Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of FLUARIX.

5.6 Limitations of Vaccine Effectiveness

Vaccination with FLUARIX may not protect all susceptible individuals.

5.7 Persons at Risk of Bleeding

As with other intramuscular injections, FLUARIX should be given with caution in individuals with bleeding disorders such as hemophilia or on anticoagulant therapy, to avoid the risk of hematoma following the injection.

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, 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 the rates observed in practice. There is the possibility that broad use of FLUARIX could reveal adverse reactions not observed in clinical trials.

Adults: In adults, the most common (≥10%) local adverse reactions and general adverse events observed with FLUARIX were pain and redness at the injection site, muscle aches, fatigue, and headache.

FLUARIX has been administered to 10,317 adults 18 to 64 years of age and 606 subjects ≥65 years of age in 4 clinical trials.

One of the 4 clinical trials was a randomized, double-blind, placebo-controlled study that evaluated a total of 952 subjects: FLUARIX (N = 760) and placebo (N = 192). The population was 18 to 64 years of age (mean 39.1), 54% were female and 80% were white. Solicited events were collected for 4 days (day of vaccination and the next 3 days) (Table 1). Unsolicited events that occurred within 21 days of vaccination (day 0-20) were recorded using diary cards supplemented by spontaneous reports and a medical history as reported by subjects.

Total vaccinated cohort for safety included all vaccinated subjects for whom safety data were available.

^a 4 days included day of vaccination and the subsequent 3 days.

Unsolicited adverse events that occurred in ≥1% of recipients of FLUARIX and at a rate greater than placebo included upper respiratory tract infection (3.9% versus 2.6%), nasopharyngitis (2.5% versus 1.6%), nasal congestion (2.2% versus 2.1%), diarrhea (1.6% versus 0%), influenza-like illness (1.6% versus 0.5%), vomiting (1.4% versus 0%), and dysmenorrhea (1.3% versus 1.0%).

A randomized, single-blind, active-controlled US study evaluated subjects randomized to receive FLUARIX (N = 917) or FLUZONE (N = 910), a US‑licensed trivalent, inactivated influenza virus vaccine (Sanofi Pasteur SA) stratified by age: 18 to 64 years and ≥65 years of age. In the overall population, 59% of subjects were female and 91% were white. Solicited events were collected using diary cards for 4 days (day of vaccination and the next 3 days) (Table 2). Unsolicited events that occurred within 21 days of vaccination (day 0-20) were recorded using diary cards.

Total vaccinated cohort for safety included all vaccinated subjects for whom safety data were available.

^a 4 days included day of vaccination and the subsequent 3 days.

Unsolicited adverse events that occurred in ≥1% of all recipients of FLUARIX or the comparator influenza vaccine in the 21-day post-vaccination period included headache (2.8% versus 2.3%), back pain (1.5% versus 0.4%), pain in extremity (1.2% versus 0.7%), pharyngolaryngeal pain (1.2% versus 0.9%), cough (1.1% versus 0.9%), fatigue (1.1% versus 0.7%), nasopharyngitis (1.0% versus 1.3%), nausea (0.4% versus 1.0%), arthralgia (0.3% versus 1.0%), and injection site pruritus (0.2% versus 1.0%).

A double-blind, placebo-controlled study in subjects 18 to 64 years of age randomized (2:1) to receive FLUARIX (N = 5,103) or placebo (N = 2,549) was conducted to evaluate the efficacy of FLUARIX. In the total population, 60% were female and 99.9% were white. In a subset (FLUARIX [N = 305] and placebo [N = 155]), unsolicited events that occurred within 21 days of vaccination (day 0-20) were recorded on diary cards. The percentage of subjects reporting at least one unsolicited event was similar among the groups (24.3% for FLUARIX and 22.6% for placebo). Unsolicited adverse events that occurred in ≥1% of recipients of FLUARIX and at a rate greater than placebo included injection site pain (5.2% versus 1.3%), dysmenorrhea (1.3% versus 0.6%), and migraine (1.0% versus 0.0%).

Incidence of Adverse Events Reported in ≥1% of Subjects in Non-US Clinical Trials: The following additional adverse events have been observed in adults in non-US clinical trials with FLUARIX. No adverse events were observed at an incidence of >10%.

General Disorders and Administration Site Conditions: Injection site ecchymosis, injection site induration, malaise.

Infections and Infestations: Rhinitis.

Musculoskeletal and Connective Tissue Disorders: Musculoskeletal pain, neck pain.

Skin and Subcutaneous Tissue Disorders: Sweating.

Serious Adverse Events: In the 4 clinical trials in adults (N = 10,923), there was a single case of anaphylaxis reported with FLUARIX (<0.01%).

Children: In children 5 years to <18 years of age, the most common (≥10%) local and general adverse events were similar to those in adults but also included swelling at the injection site. In children 3 years to <5 years of age, the most common (≥10%) local and general adverse events included pain, redness, and swelling at the injection site, irritability, loss of appetite, and drowsiness.

A single-blind, active-controlled US study evaluated subjects 6 months to <18 years of age who received FLUARIX (N = 2,081) or FLUZONE (N = 1,173), a US‑licensed trivalent, inactivated influenza virus vaccine (Sanofi Pasteur SA) (Study 005). Children 6 months to <9 years of age with no history of influenza vaccination received 2 doses approximately 28 days apart. Children 6 months to <9 years of age with a history of influenza vaccination and children 9 years of age and older received 1 dose. Children 6 months to <3 years of age received 0.25 mL of FLUARIX or comparator influenza vaccine, and children 3 years of age and older received 0.5 mL of FLUARIX or comparator influenza vaccine.

Study subjects were 6 months to <18 years of age and 49% were female; 68% were white, 18% were black, 3% were Asian, and 11% were of other racial/ethnic groups.

Solicited local and general adverse events were collected using diary cards for 4 days (day of vaccination and the next 3 days). Unsolicited adverse events that occurred within 28 days of vaccination (day 0-27) after the first vaccination in all subjects and 21 days (day 0-20) after the second vaccination in unprimed subjects were recorded using diary cards.

The frequencies of solicited adverse events for children 3 years to <5 years of age and for children 5 years to <18 years of age were similar for FLUARIX and the comparator vaccine (Table 3).

^a 4 days included day of vaccination and the subsequent 3 days.

In children who received a second dose of FLUARIX or the comparator vaccine, the incidences of adverse events following the second dose were similar to those observed after the first dose.

Unsolicited adverse events that occurred in ≥1% of recipients of FLUARIX 6 months to <18 years of age included upper respiratory tract infection (5.5%), pyrexia (4.8%), cough (4.7%), vomiting (3.2%), headache (2.8%), rhinorrhea (2.7%), diarrhea (2.5%), pharyngolaryngeal pain (2.4%), nasopharyngitis (2.3%), otitis media (2.0%), nasal congestion (1.8%), upper abdominal pain (1.4%), and upper respiratory tract congestion (1.0%). The incidences of these events were similar in recipients of the comparator vaccine.