FLUZONE- influenza a virus a/california/7/2009 x-179a (h1n1) antigen (formaldehyde inactivated), influenza a virus a/switzerland/9715293/2013 nib-88 (h3n2) antigen (formaldehyde inactivated), and influenza b virus b/phuket/3073/2013 antigen (formaldehyde inactivated) injection, suspension
Sanofi Pasteur Inc.
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use Fluzone® safely and effectively. See full prescribing information for Fluzone.
Fluzone (Influenza Vaccine)
Suspension for Intramuscular Injection
Initial U.S. Approval 1980
INDICATIONS AND USAGE
DOSAGE AND ADMINISTRATION
DOSAGE FORMS AND STRENGTHS
Suspension for injection supplied in multi-dose vial, 5 mL. (3)
Severe allergic reaction to any component of the vaccine, including egg protein, or after previous dose of any influenza vaccine. (4)
WARNINGS AND PRECAUTIONS
To report SUSPECTED ADVERSE REACTIONS, contact Sanofi Pasteur Inc., Discovery Drive, Swiftwater, PA 18370 at 1-800-822-2463 (1-800-VACCINE) or VAERS at 1-800-822-7967 or www.vaers.hhs.gov.
USE IN SPECIFIC POPULATIONS
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
FULL PRESCRIBING INFORMATION: CONTENTS*
Fluzone® is a vaccine indicated for active immunization for the prevention of influenza disease caused by influenza A subtype viruses and type B virus contained in the vaccine.
Fluzone is approved for use in persons 6 months of age and older.
The dose and schedule for Fluzone are presented in Table 1.
|"-" Indicates information is not applicable|
|6 months through 35 months||One or two doses*, 0.25 mL each||If 2 doses, administer at least 1 month apart|
|36 months through 8 years||One or two doses*, 0.5 mL each||If 2 doses, administer at least 1 month apart|
|9 years and older||One dose, 0.5 mL||-|
Inspect Fluzone visually for particulate matter and/or discoloration prior to administration. If either of these conditions exist, the vaccine should not be administered.
Before administering a dose of vaccine, shake the prefilled syringe or multi-dose vial. Withdraw a single dose of vaccine using a sterile needle and syringe. Use a separate sterile needle and syringe for each dose withdrawn from the multi-dose vial.
The preferred sites for intramuscular injection are the anterolateral aspect of the thigh in infants 6 months through 11 months of age, the anterolateral aspect of the thigh (or the deltoid muscle if muscle mass is adequate) in persons ≥12 months through 35 months of age, or the deltoid muscle in persons ≥36 months of age. The vaccine should not be injected into the gluteal area or areas where there may be a major nerve trunk.
Do not administer this product intravenously or subcutaneously.
Fluzone should not be combined through reconstitution or mixed with any other vaccine.
Fluzone is a suspension for injection.
Fluzone is supplied in 1 presentation:
1) Multi-dose vial, 5 mL, for persons 6 months of age and older.
A severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine [see Description (11)], including egg protein, or to a previous dose of any influenza vaccine is a contraindication to administration of Fluzone.
The 1976 swine influenza vaccine was associated with an elevated risk of Guillain-Barré syndrome (GBS). Evidence for a causal relation 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. (1) If GBS has occurred within 6 weeks following previous influenza vaccination, the decision to give Fluzone should be based on careful consideration of the potential benefits and risks.
Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of the vaccine.
If Fluzone is administered to immunocompromised persons, including those receiving immunosuppressive therapy, the expected immune response may not be obtained.
Because clinical trials are conducted under widely varying conditions, adverse event rates observed in the clinical trial(s) of a vaccine cannot be directly compared to rates in the clinical trial(s) of another vaccine and may not reflect the rates observed in practice.
Children 6 Months through 8 Years of Age
In a multi-center study conducted in the US, children 6 months through 35 months of age received two 0.25 mL doses of Fluzone, and children 3 years through 8 years of age received two 0.5 mL doses of Fluzone, irrespective of previous influenza vaccination history. The two doses (2006-2007 formulation) were administered 26 to 30 days apart. The safety analysis set included 97 children 6 months through 35 months of age and 163 children 3 years through 8 years of age. Table 2 and Table 3 summarize solicited injection site reactions and systemic adverse events reported within 7 days post-vaccination via diary cards.
|Dose 1 (N*=90-92) |
|Dose 2 (N*=86-87)
|Dose 1 (N*=150-151) |
|Dose 2 (N*=144-145)
|"-" Indicates information was not collected|
During the period from the first vaccination through 6 months following the second vaccination, there were no serious adverse events considered to be caused by vaccination and no deaths reported in this study.
Adults 18 through 64 years of age received Fluzone (2008-2009 formulation) in a multi-center trial conducted in the US. The safety analysis set included 1421 Fluzone recipients. Table 4 summarizes solicited injection-site reactions and systemic adverse events reported within 7 days post-vaccination via diary cards.
|Any||Grade 2†||Grade 3‡|
Within 28 days and 6 months post-vaccination, a serious adverse event was reported by 5 (0.4%) and 20 (1.4%) Fluzone recipients, respectively. No serious adverse event was considered to be caused by vaccination. No deaths were reported during the 6 months post-vaccination.
Adults 65 years of age and older received Fluzone (2006-2007 formulation) in a multi-center, double-blind trial conducted in the US. The safety analysis set included 1260 Fluzone recipients.
Table 5 summarizes solicited injection-site reactions and systemic adverse events reported within 7 days post-vaccination via diary cards. Onset was usually within the first 3 days after vaccination and a majority of the reactions resolved within 3 days.
Within 6 months post-vaccination, 93 (7.4%) Fluzone recipients experienced a serious adverse event (N=1260). No deaths were reported within 28 days post-vaccination. A total of 7 deaths were reported during the period Day 29-180 post-vaccination: 7 (0.6%) among Fluzone recipients (N=1260). The majority of these participants had a medical history of cardiac, hepatic, neoplastic, renal, and/or respiratory diseases. No deaths were considered to be caused by vaccination.
The following events have been spontaneously reported during the post-approval use of Fluzone. 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 vaccine exposure. Adverse events were included based on one or more of the following factors: severity, frequency of reporting, or strength of evidence for a causal relationship to Fluzone.
Data evaluating the concomitant administration of Fluzone with other vaccines are not available.
It is not known whether Fluzone is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Fluzone is administered to a nursing woman.
Safety and effectiveness of Fluzone in children below the age of 6 months have not been established. Safety and immunogenicity of Fluzone were evaluated in children 6 months through 8 years of age. [See Adverse Reactions (6.1) and Clinical Studies (14.3).] Efficacy of Fluzone was evaluated in children 6 through 24 months of age. [See Clinical Studies (14.1).]
Fluzone (Influenza Vaccine) for intramuscular injection is an inactivated influenza vaccine, prepared from influenza viruses propagated in embryonated chicken eggs. The virus-containing allantoic fluid is harvested and inactivated with formaldehyde. Influenza virus is concentrated and purified in a linear sucrose density gradient solution using a continuous flow centrifuge. The virus is then chemically disrupted using a non-ionic surfactant, octylphenol ethoxylate (Triton® X-100), producing a "split virus". The split virus is further purified and then suspended in sodium phosphate-buffered isotonic sodium chloride solution.
Fluzone suspension for injection is clear and slightly opalescent in color.
Antibiotics are not used in the manufacture of Fluzone.
No presentation of Fluzone is made with natural rubber latex.
Fluzone is standardized according to United States Public Health Service requirements and is formulated to contain HA of each of the following three influenza strains recommended for the 2015-2016 influenza season: A/California/07/2009 X-179A (H1N1), A/Switzerland/9715293/2013 NIB-88 (H3N2), and B/Phuket/3073/2013 (B Yamagata lineage). The amounts of HA and other ingredients per dose of vaccine are listed in Table 6. The 0.5 mL single-dose, pre-filled syringe presentation is manufactured and formulated without thimerosal or any other preservative. The 5 mL multi-dose vial presentation contains thimerosal, a mercury derivative, added as a preservative. Each 0.5 mL dose from the multi-dose vial contains 25 mcg mercury. Each 0.25 mL dose from the multi-dose vial contains 12.5 mcg mercury.
0.25 mL Dose
0.5 mL Dose
|"-" Indicates information is not applicable|
|Active Substance: Split influenza virus, inactivated strains*:||22.5 mcg HA total||45 mcg HA total|
|A (H1N1)||7.5 mcg HA||15 mcg HA|
|A (H3N2)||7.5 mcg HA||15 mcg HA|
|B||7.5 mcg HA||15 mcg HA|
|Sodium phosphate-buffered isotonic sodium chloride solution||QS† to appropriate volume||QS† to appropriate volume|
|Formaldehyde||≤50 mcg||≤100 mcg|
|Octylphenol ethoxylate||≤75 mcg||≤150 mcg|
|Multi-dose presentation (thimerosal)||12.5 mcg mercury||25 mcg mercury|
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 titer post-vaccination with inactivated influenza virus vaccines have not been correlated with protection from influenza virus infection. In some human studies, antibody titers ≥1:40 have been associated with protection from influenza illness in up to 50% of participants. (2) (3)
Antibodies against one influenza virus type or subtype confer limited or no protection against another. Furthermore, antibodies 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, influenza vaccines are standardized to contain the hemagglutinins of influenza virus strains representing the influenza viruses likely to be circulating in the US during the influenza season.
Annual vaccination with the current vaccine is recommended because immunity during the year after vaccination declines and because circulating strains of influenza virus change from year to year.
A randomized, double-blind, placebo-controlled study was conducted at a single US center during the 1999-2000 (Year 1) and 2000-2001 (Year 2) influenza seasons. The intent-to-treat analysis set included a total of 786 children 6 through 24 months of age. Participants received two doses of either Fluzone (N = 525) or a placebo (N = 261). Among all randomized participants in both years, the mean age was 13.8 months; 52.5% were male, 50.8% were Caucasian, 42.0% were Black, and 7.2% were of other racial groups. Cases of influenza were identified through active and passive surveillance for influenza-like illness or acute otitis media and confirmed by culture. Influenza-like illness was defined as fever with signs or symptoms of an upper respiratory infection. Vaccine efficacy against all influenza viral types and subtypes was a secondary endpoint and is presented in Table 7.
|Fluzone†||Placebo‡||Fluzone vs. Placebo|
|Year||n§||N¶||Rate (n/N)#||(95% CI)||n§||N¶||Rate (n/N)#||(95% CI)||Relative Risk|
|Percent Relative ReductionÞ
|15||273||5.5||(3.1; 8.9)||22||138||15.9||(10.3; 23.1)||0.34 (0.18; 0.64)||66 (36; 82)|
|Year 2 à
|9||252||3.6||(1.6; 6.7)||4||123||3.3||(0.9; 8.1)||1.10 (0.34; 3.50)||-10 (-250; 66)|
A randomized, double-blind, placebo-controlled study was conducted in a single US center during the 2007-2008 influenza season. Participants received one dose of either Fluzone vaccine (N = 813), an active comparator (N = 814), or placebo (N = 325). The intent-to-treat analysis set included 1138 healthy adults who received Fluzone or placebo. Participants were 18 through 49 years of age (mean age was 23.3 years); 63.3% were female, 83.1% were Caucasian, and 16.9% were of other racial/ethnic groups. Cases of influenza were identified through active and passive surveillance and confirmed by cell culture and/or real-time polymerase chain reaction (PCR). Influenza-like illness was defined as an illness with at least 1 respiratory symptom (cough or nasal congestion) and at least 1 constitutional symptom (fever or feverishness, chills, or body aches). Vaccine efficacy of Fluzone against all influenza viral types and subtypes is presented in Table 8.
|Fluzone vs. Placebo|
|n¶||Rate (%)#||(95% CI)||n¶||Rate (%)#||(95% CI)||Relative Risk (95% CI)||Percent Relative ReductionÞ (95% CI)|
|Positive culture||21||2.6||(1.6; 3.9)||31||9.5||(6.6; 13.3)||0.27 (0.16; 0.46)||73 (54; 84)|
|Positive PCR||28||3.4||(2.3; 4.9)||35||10.8||(7.6; 14.7)||0.32 (0.20; 0.52)||68 (48; 80)|
|Positive culture, positive PCR, or both||28||3.4||(2.3; 4.9)||35||10.8||(7.6; 14.7)||0.32 (0.20; 0.52)||68 (48; 80)|
In a multi-center study conducted in the US, 68 children 6 months through 35 months of age given two 0.25 mL doses of Fluzone and 120 children 3 years through 8 years of age given two 0.5 mL doses of Fluzone were included in the per-protocol analysis set. The two doses (2006-2007 formulation) were administered 26 to 30 days apart. Females accounted for 42.6% of the participants in the 6 months through 35 months age group and 53.3% of the participants in the 3 years through 8 years age group. Most participants in the 6 months through 35 months and 3 years through 8 years age groups, respectively, were Caucasian (70.6% and 79.2%), followed by Hispanic (19.1% and 13.3%), and Black (7.4% and 4.2%).
The percentage of participants who received influenza vaccination during the previous influenza season was 54.4% for the 6 months through 35 months age group and 27.5% for the 3 years through 8 years age group. Table 9 shows seroconversion rates and the percentage of participants with an HI titer ≥1:40 pre-vaccination and one month following the second dose of Fluzone.
|Antigen||Age Group||Pre-Vaccination Titer ≥1:40|
% (95% CI)
|Post-Vaccination† Titer ≥1:40|
% (95% CI)
% (95% CI)
|N=68 (6 to 35 months); N=120 (3 through 8 years)|
|A (H1N1)||6 through 35 months||11.8 (5.2; 21.9)||92.6 (83.7; 97.6)||88.2 (78.1; 94.8)|
|3 through 8 years||40.0 (31.2; 49.3)||99.2 (95.4; 100.0)||78.3 (69.9; 85.3)|
|A (H3N2)||6 through 35 months||29.4 (19.0; 41.7)||100.0 (94.7; 100.0)||91.2 (81.8; 96.7)|
|3 through 8 years||80.0 (71.7; 86.7)||100.0 (97.0; 100.0)||61.7 (52.4; 70.4)|
|B||6 through 35 months||1.5 (0.0; 7.9)||20.6 (11.7; 32.1)||20.6 (11.7; 32.1)|
|3 through 8 years||3.3 (0.9; 8.3)||58.3 (49.0; 67.3)||53.3 (44.0; 62.5)|
Adults 18 through 64 years of age received Fluzone (2008-2009 formulation) in a multi-center trial conducted in the US. For immunogenicity analyses, there were 1287 participants who received Fluzone in the per-protocol analysis set. There were fewer males (35.8%) than females. The mean age was 42.6 years (ranged from 18.2 through 65.0 years). Most participants were Caucasian (80.0%), followed by Hispanic (11.0%), and Black (6.3%). Table 10 shows seroconversion rates at 28 days following vaccination and the percentage of participants with an HI titer ≥1:40 prior to vaccination and 28 days following vaccination.
|Antigen||Pre-Vaccination Titer ≥1:40||Post-Vaccination* Titer ≥1:40||Seroconversion†|
|% (95% CI) |
|% (95% CI) |
|% (95% CI)
|A (H1N1)||39.1 (36.4; 41.8)||91.7 (90.0; 93.1)||60.5 (57.7; 63.2)|
|A (H3N2)||33.6 (31.0; 36.2)||91.4 (89.8; 92.9)||74.8 (72.3; 77.1)|
|B||41.2 (38.5; 44.0)||89.3 (87.4; 90.9)||54.2 (51.4; 56.9)|
Adults 65 years of age and older received Fluzone (2006-2007 formulation) in a multi-center trial conducted in the US. For immunogenicity analyses, there were 1275 participants who received Fluzone in the immunogenicity analysis set. Females accounted for 54.7% of participants. The mean age was 72.9 years (ranged from 65 through 94 years of age); 36% of participants were 75 years of age or older. Most participants were Caucasian (92.9%), followed by Hispanic (3.7%), and Black (2.7%). Table 11 shows seroconversion rates at 28 days following vaccination and the percentage of participants with an HI titer ≥1:40 prior to vaccination and 28 days following vaccination.
|Antigen||Pre-Vaccination HI Titer ≥1:40||Post-Vaccination* Titer ≥1:40||Seroconversion†|
|% (95% CI) |
|% (95% CI) |
|% (95% CI)
|A (H1N1)||45.9 (43.2; 48.7)||76.8 (74.3; 79.1)||23.1 (20.8; 25.6)|
|A (H3N2)||68.6 (66.0; 71.2)||96.5 (95.3; 97.4)||50.7 (47.9; 53.5)|
|B||27.3 (24.9; 29.9)||67.6 (64.9; 70.2)||29.9 (27.4; 32.6)|
Multi-dose vial, 5 mL (NDC 49281-396-78) (not made with natural rubber latex). Supplied as package of one (NDC 49281-396-15). A maximum of ten doses can be withdrawn from the multi-dose vial.
Store all Fluzone presentations refrigerated at 2° to 8°C (35° to 46°F). DO NOT FREEZE. Discard if vaccine has been frozen.
Between uses, return the multi-dose vial to the recommended storage conditions at 2° to 8°C (35° to 46°F).
Do not use after the expiration date shown on the label.
See FDA-approved patient labeling (Patient Information).
Fluzone is a registered trademark of Sanofi Pasteur Inc.
Sanofi Pasteur Inc.
Swiftwater PA 18370 USA
Please read this information sheet before getting Fluzone vaccine. This summary is not intended to take the place of talking with your healthcare provider. If you have questions or would like more information, please talk with your healthcare provider.
What is Fluzone vaccine?
Fluzone is a vaccine that helps protect against influenza illness (flu).
Fluzone vaccine is for people who are 6 months of age and older.
Vaccination with Fluzone vaccine may not protect all people who receive the vaccine.
Who should not get Fluzone vaccine?
You should not get Fluzone vaccine if you:
Tell your healthcare provider if you or your child have or have had:
How is the Fluzone vaccine given?
Fluzone vaccine is a shot given into the muscle of the arm.
For infants, Fluzone vaccine is a shot given into the muscle of the thigh.
What are the possible side effects of Fluzone vaccine?
The most common side effects of Fluzone vaccine are:
These are not all of the possible side effects of Fluzone vaccine. You can ask your healthcare provider for a list of other side effects that is available to healthcare professionals.
Call your healthcare provider for advice about any side effects that concern you. You may report side effects to the Vaccine Adverse Event Reporting System (VAERS) at 1-800-822-7967 or http://vaers.hhs.gov.
What are the ingredients in Fluzone vaccine?
Fluzone vaccine contains 3 killed flu virus strains.
Inactive ingredients include formaldehyde, octylphenol ethoxylate, and gelatin. The preservative thimerosal is only in the multi-dose vial of Fluzone vaccine.
influenza a virus a/california/7/2009 x-179a (h1n1) antigen (formaldehyde inactivated), influenza a virus a/switzerland/9715293/2013 nib-88 (h3n2) antigen (formaldehyde inactivated), and influenza b virus b/phuket/3073/2013 antigen (formaldehyde inactivated) injection, suspension
|Labeler - Sanofi Pasteur Inc. (086723285)|
|Sanofi Pasteur Inc.||086723285||MANUFACTURE|