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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 Vaccinea, or Placebo (Total Vaccinated Cohort)
|Percentage of Subjects Reporting Eventb|
|Study 1 (18 to 64 years of age)||Study 2c (50 years of age and older)||Study 3c (18 to 49 years of age)|
N = 721
N = 279
N = 610
N = 615
N = 3,783
N = 3,828
|Fever ( ≥ 99.5° F)||11||10||1||1||3||1|
|a US-licensed trivalent, inactivated
influenza virus vaccine (manufactured by Sanofi Pasteur SA).
b Total vaccinated cohort for safety included all vaccinated subjects for whom safety data were available.
c Study 2: NCT00232947; Study 3: NCT00216242.
d For Study 2 and Study 3, includes myalgia and arthralgia.
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.
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.
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.
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.
Read the Flulaval (influenza virus vaccine) Side Effects Center for a complete guide to possible side effects »
Concomitant Administration With Other Vaccines
There are no data to assess the concomitant administration of FLULAVAL with other vaccines. If FLULAVAL is to be given at the same time as another injectable vaccine(s), the vaccines should always be administered at different injection sites. FLULAVAL should not be mixed with any other vaccine in the same syringe or vial.
Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs, and corticosteroids (used in greater than physiologic doses), may reduce the immune response to FLULAVAL.
Last reviewed on RxList: 1/10/2012
This monograph has been modified to include the generic and brand name in many instances.
Additional Flulaval Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
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