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Clinical Trials Experience
In adults who received FLULAVAL, the most common ( ≥ 10%) solicited local adverse reactions were pain (51%), redness (13%), and swelling (11%); the most common ( ≥ 10%) solicited systemic adverse events were fatigue (20%), headache (18%), and muscle aches/arthralgia (18%).
In children 3 through 17 years of age who received FLULAVAL, the most common ( ≥ 10%) solicited local adverse reaction was pain (56%). In children 3 through 4 years of age, the most common ( ≥ 10%) solicited systemic adverse events were irritability (25%), drowsiness (19%), and loss of appetite (16%). In children 5 through 17 years of age, the most common ( ≥ 10%) systemic adverse events were muscle aches (24%), headache (17%), and fatigue (17%).
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 FLULAVAL could reveal adverse reactions not observed in clinical trials.
FLULAVAL in Adults
Safety data was 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 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 postvaccination through the next 3 days). 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 through 64 years of age who were randomized to receive FLULAVAL (N = 721) or a US-licensed trivalent, inactivated influenza 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 through 49 years of age and 20% were 50 through 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 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 through 64 years of age, 41% were 65 through 79 years of age, and 13% were ≥ 80 years of age.
Study 3 (Efficacy)
Safety information was collected in a double-blind, placebocontrolled US study. The study included 7,658 adults 18 through 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 2.
Table 2: FLULAVAL: Incidence of Solicited Local
Adverse Reactions and Systemic Adverse Events Within 4 Daysa of
Vaccination in Adults (Total Vaccinated Cohort)
|Percentage of Subjects Reporting Event|
|Study 1b 18 Through 64 Years of Age||Study 2b 50 Years of Age and Older||Study 3b 18 Through 49 Years of Age|
N = 721
N = 279
N = 610
N = 615
N = 3,783
N = 3,828
|Local Adverse Reactions|
|Systemic Adverse Events|
|Fever ≥ 99.5°F (37.5°C)||11||10||1||1||3||1|
|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.
b Study 1: NCT01389479; Study 2: NCT00232947; Study 3: NCT00216242.
c US-licensed trivalent, inactivated influenza vaccine (manufactured by Sanofi Pasteur SA).
d For Study 2 and Study 3, includes muscle aches 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.
FLULAVAL in Children
Study 4 (Immunogenicity Non-Inferiority)
An observerblind, active-controlled US study evaluated subjects 3 through 17 years of age who received FLULAVAL (N = 1,055) or FLUZONE (N = 1,061), a US-licensed trivalent, inactivated influenza vaccine, manufactured by Sanofi Pasteur SA. In the overall population, 53% were male; 78% of subjects were white, 12% were black, 2% were Asian, and 8% were of other racial/ethnic groups. The mean age of subjects was 8 years. Children 3 through 8 years of age with no history of influenza vaccination received 2 doses approximately 28 days apart. Children 3 through 8 years of age with a history of influenza vaccination and children 9 years of age and older received one dose. Solicited local adverse reactions and systemic adverse events were collected for 4 days (day of vaccination and the next 3 days) (Table 3).
Table 3: FLULAVAL: Incidence of Solicited Local
Adverse Reactions and Systemic Adverse Events Within 4 Daysa of First
Vaccination in Children 3 Through 17 Years of Total vaccinated cohort
for safety included all vaccinated subjects for whom safety data were available.
|FLULAVAL %||Active Comparatorc %|
|3 Through 17 Years of Age|
|Local Adverse Reactions||N = 1,042||N = 1,026|
|3 Through 4 Years of Age|
|Systemic Adverse Events||N = 293||N = 279|
|Loss of appetite||16||13|
|Fever ≥ 100.4°F (38.0°C)||5||3|
|5 Through 17 Years of Age|
|Systemic Adverse Events||N = 750||N = 747|
|Fever ≥ 100.4°F (38.0°C)||5||4|
|a 4 days included day of vaccination and the
subsequent 3 days.
b Study 4: NCT00980005.
c US-licensed trivalent, inactivated influenza vaccine (manufactured by Sanofi Pasteur SA).
In children who received a second dose of FLULAVAL or the comparator vaccine, the incidences of adverse events following the second dose were generally lower than those observed after the first dose.
The incidence of unsolicited adverse events that occurred within 28 days (day 0-27) of any vaccination reported in subjects who received FLULAVAL (N = 1,055) or FLUZONE (N = 1,061) was 40% and 37%, respectively. The unsolicited adverse events that occurred most frequently ( > 0.1% of subjects for FLULAVAL) and considered possibly related to vaccination included diarrhea, influenza-like illness, injection site hematoma, injection site rash, injection site warmth, rash, upper abdominal pain, and vomiting. The rates of SAEs were comparable between groups (0.9% and 0.6% for FLULAVAL and the comparator, respectively); 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.
Musculoskeletal and Connective Tissue Disorders: Muscle weakness, arthritis.
Nervous System Disorders: Dizziness, paresthesia, hypoesthesia, hypokinesia, tremor, somnolence, syncope, Guillain-Barre syndrome, convulsions/seizures, facial or cranial nerve paralysis, encephalopathy, limb paralysis.
Psychiatric Disorders: Insomnia.
Vascular Disorders: Flushing, pallor.
Read the Flulaval (influenza virus vaccine) Side Effects Center for a complete guide to possible side effects
Concomitant Administration With Other Vaccines
FLULAVAL should not be mixed with any other vaccine in the same syringe or vial.
There are insufficient data to assess the concomitant administration of FLULAVAL with other vaccines. When concomitant administration of other vaccines is required, the vaccines should be administered at different injection sites.
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: 9/8/2014
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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