SIDE EFFECTS

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. As with any vaccine, there is the possibility that broad use of FLULAVAL could reveal adverse events not observed in clinical trials.

In the largest clinical trial, the most common ( ≥ 10%) solicited injection site reactions were pain (51%), redness (13%), and/or swelling (11%); the most common solicited systemic adverse events were fatigue (20%), headache (18%), and myalgia/arthralgia (18%).

Safety data has been obtained from 3 randomized, controlled trials, one of which was a placebo-controlled efficacy study. In these trials, 9,836 subjects were randomized to receive either FLULAVAL (5,114 subjects in the safety analysis), FLUZONE, a US-licensed trivalent, inactivated influenza virus vaccine, manufactured by Sanofi Pasteur SA (894 subjects in the safety analysis), or placebo (3,828 subjects in the safety analysis), intramuscularly. In these studies, solicited events were collected for 4 days (i.e., 30 minutes post-vaccination through the next 3 days) using diary cards. Unsolicited adverse events that occurred within 22 days of vaccination (day 0-21) were recorded based on spontaneous reports or in response to queries about changes in health status.

Study 1 (Immunogenicity)

Safety information was collected in a randomized, controlled US study. This study included 1,000 adults 18 to 64 years of age who were randomized to receive FLULAVAL (N = 721) or a US-licensed trivalent, inactivated influenza virus vaccine (N = 279). Among recipients of FLULAVAL, 57% were female; 91% of subjects were white and 9% were of other racial/ethnic groups. The mean age of subjects was 38 years; 80% were 18 to 49 years of age and 20% were 50 to 64 years of age.

Study 2 (Immunogenicity Non-Inferiority)

Safety information was collected in a randomized, double-blind, active-controlled US study. The study included 1,225 adults ≥ 50 years of age randomized to receive FLULAVAL (N = 610) or a US-licensed trivalent, inactivated influenza virus vaccine (N = 615). In the total population, 57% were female; 95% of subjects were white and 5% were of other racial/ethnic groups. The mean age of subjects was 66 years (46% were 50 to 64 years of age, 41% were 65 to 79 years of age, and 13% were ≥ 80 years of age).

Study 3 (Efficacy)

Safety information was collected in a double-blind, placebo-controlled US study. The study included 7,658 adults 18 to 49 years of age randomized to receive FLULAVAL (N = 3,807) or placebo (N = 3,851). In the total population, 61% were female; 84% of subjects were white, 10% black, 2% Asian, and 4% were of other racial/ethnic groups. The mean age of subjects was 33 years.

Solicited Adverse Events

Solicited local adverse reactions and systemic adverse events collected for 4 days (day of vaccination and the next 3 days) are presented in Table 1.

Table 1: Incidence of Solicited Local Adverse Reactions and Systemic Adverse Events in the First 4 Days After Administration of FLULAVAL, Comparator Influenza Vaccine^a, or Placebo (Total Vaccinated Cohort)

Unsolicited Adverse Events

The incidence of unsolicited adverse events in the 21 days post-vaccination was comparable for FLULAVAL and the active comparator in Study 1 (16% and 15%, respectively) and in Study 2 (18% and 21%, respectively). In Study 3, the incidence of unsolicited adverse events was comparable for the groups (21% for FLULAVAL and 19% for placebo).

Unsolicited adverse events defined as reported with FLULAVAL in > 1.0% of subjects are described as follows: Study 1: Cough, headache, and pharyngolaryngeal pain; Study 2: Diarrhea, headache, and nasopharyngitis; and Study 3: Pharyngolaryngeal pain, headache, fatigue, cough, injection site pain, upper respiratory tract infection, musculoskeletal pain, nasopharyngitis, injection site erythema and discomfort.

Serious Adverse Events (SAEs)

In Study 1, no SAEs were reported. In Study 2, 3% of subjects receiving FLULAVAL and 3% of subjects receiving the active comparator reported SAEs. In Study 3, 1% of subjects receiving FLULAVAL and 1% of subjects receiving placebo reported SAEs. In the 3 clinical trials, the rates of SAEs were comparable between groups and none of the SAEs were considered related to vaccination.

Postmarketing Experience

In addition to reports in clinical trials, the following adverse events have been identified during postapproval use of FLULAVAL. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their incidence rate or establish a causal relationship to the vaccine. Adverse events described here are included because: a) they represent reactions which are known to occur following immunizations generally or influenza immunizations specifically; b) they are potentially serious; or c) the frequency of reporting.

Blood and Lymphatic System Disorders: Lymphadenopathy.

Eye Disorders: Eye pain, photophobia.

Gastrointestinal Disorders: Dysphagia, vomiting.

General Disorders and Administration Site Conditions: Chest pain, injection site inflammation, asthenia, injection site rash, influenza-like symptoms, abnormal gait, injection site bruising, injection site sterile abscess.

Immune System Disorders: Allergic edema of the mouth, anaphylaxis, allergic edema of the throat.

Infections and Infestations: Rhinitis, laryngitis, cellulitis.

Musculoskeletal and Connective Tissue Disorders: Muscle weakness, arthritis.

Nervous System Disorders: Dizziness, paresthesia, hypoesthesia, hypokinesia, tremor, somnolence, syncope, Guillain-Barré syndrome, convulsions/seizures, facial or cranial nerve paralysis, encephalopathy, limb paralysis.

Psychiatric Disorders: Insomnia.

Respiratory, Thoracic, and Mediastinal Disorders: Dyspnea, dysphonia, bronchospasm, throat tightness.

Skin and Subcutaneous Tissue Disorders: Urticaria, localized or generalized rash, pruritus, sweating.

Vascular Disorders: Flushing, pallor.

Adverse Events Associated With Influenza Vaccines

Anaphylaxis has been reported after administration of FLULAVAL. Although FLULAVAL contains only a limited quantity of egg protein, this protein can induce immediate hypersensitivity reactions among persons who have severe egg allergy. Allergic reactions include hives, angioedema, allergic asthma, and systemic anaphylaxis [see CONTRAINDICATIONS].

The 1976 swine influenza vaccine was associated with an increased frequency of Guillain-Barré syndrome (GBS). Evidence for a causal relation of GBS with subsequent vaccines prepared from other influenza viruses is unclear. If influenza vaccine does pose a risk, it is probably slightly more than 1 additional case/1 million persons vaccinated.

Neurological disorders temporally associated with influenza vaccination such as encephalopathy, optic neuritis/neuropathy, partial facial paralysis, and brachial plexus neuropathy have been reported.

Microscopic polyangitis (vasculitis) has been reported temporally associated with influenza vaccination.

Read the entire FDA prescribing information for Flulaval (Influenza Virus Vaccine) »