Drug Detail:Fluzone quadrivalent (Influenza virus vaccine (injection) [ in-floo-en-za-vye-rus-vak-seen ])
Drug Class: Viral vaccines
Highlights of Prescribing Information
Fluzone Quadrivalent (Influenza Vaccine)
Suspension for Intramuscular Injection
2023-2024 Formula
Initial U.S. Approval (Fluzone Quadrivalent): 2013
Indications and Usage for Fluzone Quadrivalent
Fluzone Quadrivalent is a vaccine indicated for active immunization for the prevention of influenza disease caused by influenza A subtype viruses and type B viruses contained in the vaccine. (1)
Fluzone Quadrivalent is approved for use in persons 6 months of age and older. (1)
Fluzone Quadrivalent Dosage and Administration
- For intramuscular use only (2)
| Age | Vaccination Status | Dose | Schedule |
|---|---|---|---|
| "-" Indicates information is not applicable | |||
|
|||
| 6 months through 35 months | Not previously vaccinated with influenza vaccine or unknown vaccination history | Two doses, either 0.25 mL or 0.5 mL* | Administer at least 4 weeks apart |
| Previously vaccinated with influenza vaccine | One or two doses†, either 0.25 mL or 0.5 mL* | If two doses, administer at least 4 weeks apart | |
| 36 months through 8 years | Not previously vaccinated with influenza vaccine or unknown vaccination history | Two 0.5 mL doses | Administer at least 4 weeks apart |
| Previously vaccinated with influenza vaccine | One or two 0.5 mL doses† | If two doses, administer at least 4 weeks apart | |
| 9 years and older | - | One 0.5 mL dose | - |
Dosage Forms and Strengths
Suspension for injection supplied in 2 presentations: prefilled single-dose syringe (clear plunger rod), 0.5 mL and multi-dose vial, 5 mL. (3)
Contraindications
Severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine, including egg protein, or after previous dose of any influenza vaccine. (4)
Warnings and Precautions
- If Guillain-Barré syndrome (GBS) has occurred within 6 weeks following previous influenza vaccination, the decision to give Fluzone Quadrivalent should be based on careful consideration of the potential benefits and risks. (5.1)
Adverse Reactions/Side Effects
- In children 6 months through 35 months of age, the most common (≥10%) injection-site reactions were pain (57%) or tenderness (47%–54%), erythema (23%–37%), and swelling (13%–22%); the most common solicited systemic adverse reactions were irritability (47%–54%), abnormal crying (33%–41%), malaise (38%), drowsiness (31%–38%), appetite loss (27%–32%), myalgia (27%), vomiting (10%–15%), and fever (11%–14%). (6.1)
- In children 3 years through 8 years of age, the most common (≥10%) injection-site reactions were pain (67%), erythema (34%), and swelling (25%); the most common solicited systemic adverse reactions were myalgia (39%), malaise (32%), and headache (23%). (6.1)
- In adults 18 years and older, the most common (≥10%) injection-site reaction was pain (47%); the most common solicited systemic adverse reactions were myalgia (24%), headache (16%), and malaise (11%). (6.1)
- In adults 65 years of age and older, the most common (≥10%) injection-site reaction was pain (33%); the most common solicited systemic adverse reactions were myalgia (18%), headache (13%), and malaise (11%). (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Sanofi Pasteur Inc., at 1-800-822-2463 (1-800-VACCINE) or VAERS at 1-800-822-7967 or www.vaers.hhs.gov.
Use In Specific Populations
- Pregnancy: Pregnancy exposure registry available. Call Sanofi Pasteur Inc. at 1-800-822-2463.
- Antibody responses to Fluzone Quadrivalent are lower in persons ≥65 years of age than in younger adults. (8.5)
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
Revised: 7/2023
Full Prescribing Information
1. Indications and Usage for Fluzone Quadrivalent
Fluzone® Quadrivalent is a vaccine indicated for active immunization for the prevention of influenza disease caused by influenza A subtype viruses and type B viruses contained in the vaccine.
Fluzone Quadrivalent is approved for use in persons 6 months of age and older.
2. Fluzone Quadrivalent Dosage and Administration
For intramuscular use only
2.1 Dose and Schedule
The dose and schedule for Fluzone Quadrivalent are presented in Table 1.
Prior to vaccination, always refer to the current Advisory Committee on Immunization Practices annual recommendations on prevention and control of influenza vaccines.
| Age | Vaccination Status | Dose | Schedule |
|---|---|---|---|
| "-" Indicates information is not applicable | |||
|
|||
| 6 months through 35 months | Not previously vaccinated with influenza vaccine or unknown vaccination history | Two doses, either 0.25 mL or 0.5 mL* | Administer at least 4 weeks apart |
| Previously vaccinated with influenza vaccine | One or two doses†, either 0.25 mL or 0.5 mL* | If two doses, administer at least 4 weeks apart | |
| 36 months through 8 years | Not previously vaccinated with influenza vaccine or unknown vaccination history | Two 0.5 mL doses | Administer at least 4 weeks apart |
| Previously vaccinated with influenza vaccine | One or two 0.5 mL doses† | If two doses, administer at least 4 weeks apart | |
| 9 years and older | - | One 0.5 mL dose | - |
2.2 Administration
Parenteral drug products should be inspected visually for particulate matter and/or discoloration prior to administration, whenever solution and container permit. If any of these defects or conditions exist, Fluzone Quadrivalent should not be administered.
Before administering a dose of vaccine, shake the prefilled syringe or vial. Use a separate sterile needle and syringe for each dose withdrawn from the multi-dose vial. A maximum of ten doses can be 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, intradermally, or subcutaneously.
Fluzone Quadrivalent should not be combined through reconstitution or mixed with any other vaccine.
3. Dosage Forms and Strengths
Fluzone Quadrivalent is a suspension for injection.
Fluzone Quadrivalent is supplied in 3 presentations:
1) Prefilled single-dose syringe (clear syringe plunger rod), 0.5 mL, for persons 6 months of age and older.
2) Multi-dose vial, 5 mL, for persons 6 months of age and older.
4. Contraindications
Do not administer Fluzone Quadrivalent to anyone with a history of 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.
5. Warnings and Precautions
5.1 Guillain Barré Syndrome
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. (See ref. 1) If GBS has occurred within 6 weeks following previous influenza vaccination, the decision to give Fluzone Quadrivalent should be based on careful consideration of the potential benefits and risks.
5.2 Preventing and Managing Allergic Reactions
Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of Fluzone Quadrivalent.
5.3 Altered Immunocompetence
If Fluzone Quadrivalent is administered to immunocompromised persons, including those receiving immunosuppressive therapy, the expected immune response may not be obtained.
6. Adverse Reactions/Side Effects
In children 6 months through 35 months of age receiving a 0.25 mL dose of Fluzone Quadrivalent in Study 1 (NCT01240746), the most common (≥10%) injection-site reactions were pain (57%)1 or tenderness (54%)2, erythema (37%), and swelling (22%); the most common solicited systemic adverse reactions were irritability (54%)2, abnormal crying (41%)2, malaise (38%)1, drowsiness (38%)2, appetite loss (32%)2, myalgia (27%)1, vomiting (15%)2, and fever (14%). In children 3 years through 8 years of age, the most common (≥10%) injection-site reactions were pain (67%), erythema (34%), and swelling (25%); the most common solicited systemic adverse reactions were myalgia (39%), malaise (32%), and headache (23%). In adults 18 years and older, the most common (≥10%) injection-site reaction was pain (47%); the most common solicited systemic adverse reactions were myalgia (24%), headache (16%), and malaise (11%). In adults 65 years of age and older, the most common (≥10%) injection-site reaction was pain (33%); the most common solicited systemic adverse reactions were myalgia (18%), headache (13%), and malaise (11%).
- 1
- Assessed in children 24 months through 35 months of age
- 2
- Assessed in children 6 months through 23 months of age
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse event rates observed in the clinical trials 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.
6.2 Post-Marketing Experience
The following events have been spontaneously reported during the post-approval use of Fluzone (trivalent) or Fluzone Quadrivalent. 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 (trivalent) or Fluzone Quadrivalent.
- Blood and Lymphatic System Disorders: Thrombocytopenia, lymphadenopathy
- Immune System Disorders: Anaphylaxis, other allergic/hypersensitivity reactions (including urticaria, angioedema)
- Eye Disorders: Ocular hyperemia
- Nervous System Disorders: Guillain Barré syndrome (GBS), convulsions, febrile convulsions, myelitis (including encephalomyelitis and transverse myelitis), facial palsy (Bell's palsy), optic neuritis/neuropathy, brachial neuritis, syncope (shortly after vaccination), dizziness, paresthesia
- Vascular Disorders: Vasculitis, vasodilatation/flushing
- Respiratory, Thoracic and Mediastinal Disorders: Dyspnea, cough, wheezing, throat tightness, oropharyngeal pain, rhinorrhea
- Skin and Subcutaneous Tissue Disorders: Rash, pruritus, and Stevens-Johnson syndrome
- General Disorders and Administration Site Conditions: Asthenia/fatigue, pain in extremities, chest pain
- Gastrointestinal Disorders: Vomiting
8. Use In Specific Populations
8.1 Pregnancy
Data
Animal Data: In a developmental and reproductive toxicity study female rabbits were administered a 0.5 mL/dose of Fluzone Quadrivalent by intramuscular injection 24 and 10 days before insemination, and on Days 6, 12, and 27 of gestation (a single human dose is 0.5 mL). There were no adverse effects on pre-weaning development or vaccine-related fetal malformations noted in this study.
11. Fluzone Quadrivalent Description
Fluzone Quadrivalent (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. The Fluzone Quadrivalent process uses an additional concentration factor after the ultrafiltration step in order to obtain a higher hemagglutinin (HA) antigen concentration. Antigens from the four strains included in the vaccine are produced separately and then combined to make the quadrivalent formulation.
Fluzone Quadrivalent suspension for injection is clear and slightly opalescent in color.
Antibiotics are not used in the manufacture of Fluzone Quadrivalent.
The Fluzone Quadrivalent prefilled syringe and vial presentations are not made with natural rubber latex.
Fluzone Quadrivalent is standardized according to United States Public Health Service requirements and is formulated to contain HA of each of the following four influenza strains recommended for the 2023-2024 influenza season: A/Victoria/4897/2022 IVR-238 (H1N1), A/Darwin/9/2021 SAN-010 (H3N2), B/Phuket/3073/2013 (B Yamagata lineage), and B/Michigan/01/2021 (a B/Austria/1359417/2021-like virus, B Victoria lineage).
The amounts of HA and other ingredients per dose of vaccine are listed in Table 7. The single-dose, pre-filled syringe (0.5 mL) 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.
| Ingredient | Quantity (per dose) | |
|---|---|---|
| Fluzone Quadrivalent 0.25 mL Dose | Fluzone Quadrivalent 0.5 mL Dose |
|
| "-" Indicates information is not applicable | ||
|
||
| Active Substance: Split influenza virus, inactivated strains*: | 30 mcg HA total | 60 mcg HA total |
| A (H1N1) | 7.5 mcg HA | 15 mcg HA |
| A (H3N2) | 7.5 mcg HA | 15 mcg HA |
| B/(Victoria lineage) | 7.5 mcg HA | 15 mcg HA |
| B/(Yamagata lineage) | 7.5 mcg HA | 15 mcg HA |
| Other: | ||
| Sodium phosphate-buffered isotonic sodium chloride solution | QS† to appropriate volume | QS† to appropriate volume |
| Formaldehyde | ≤50 mcg | ≤100 mcg |
| Octylphenol ethoxylate | ≤125 mcg | ≤250 mcg |
| Preservative | ||
| Single-dose presentations | - | - |
| Multi-dose presentation (thimerosal) | 12.5 mcg mercury | 25 mcg mercury |
12. Fluzone Quadrivalent - Clinical Pharmacology
12.1 Mechanism of Action
Influenza illness and its complications follow infection with influenza viruses. Global surveillance of influenza identifies yearly antigenic variants. Since 1977, antigenic variants of influenza A (H1N1 and H3N2) viruses and influenza B viruses have been in global circulation. Since 2001, two distinct lineages of influenza B (Victoria and Yamagata lineages) have co-circulated worldwide. Protection from influenza virus infection has not been correlated with a specific level of hemagglutination inhibition (HI) antibody titer post-vaccination. However, in some human studies, antibody titers ≥1:40 have been associated with protection from influenza illness in up to 50% of subjects. (See ref. 2) (See ref. 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 influenza vaccine is recommended because immunity during the year after vaccination declines and because circulating strains of influenza virus change from year to year.
13. Nonclinical Toxicology
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Fluzone Quadrivalent has not been evaluated for carcinogenic or mutagenic potential, or for impairment of male fertility in animals. Vaccination of female rabbits with Fluzone Quadrivalent revealed no evidence of impaired female fertility [see Animal Data (8.1)].
14. Clinical Studies
The effectiveness of Fluzone Quadrivalent was demonstrated based on clinical endpoint efficacy data for Fluzone (trivalent influenza vaccine) and on an evaluation of serum HI antibody responses to Fluzone Quadrivalent. Fluzone Quadrivalent, an inactivated influenza vaccine that contains the hemagglutinins of two influenza A subtype viruses and two influenza type B viruses, is manufactured according to the same process as Fluzone.
14.1 Efficacy of Fluzone (Trivalent Influenza Vaccine) in Children 6 through 24 Months of Age
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 0.25 mL 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 8.
| Fluzone† | Placebo‡ | Fluzone vs. Placebo | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Year | n§ | N¶ | Rate (n/N)# | (95% CI) | n§ | N¶ | Rate (n/N)# | (95% CI) | Relative Risk (95% CI) | Percent Relative ReductionÞ
(95% CI) |
|
||||||||||
| Year 1ß
(1999-2000) | 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 2à
(2000-2001) | 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) |
14.2 Efficacy of Fluzone (Trivalent Influenza Vaccine) in Adults
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 9.
| Laboratory-Confirmed Symptomatic Influenza | Fluzone‡
(N=813)§ | Placebo¶
(N=325)§ | Fluzone vs. Placebo | |||||
|---|---|---|---|---|---|---|---|---|
| n# | Rate (%)Þ | (95% CI) | n# | Rate (%)Þ | (95% CI) | Relative Risk (95% CI) | Percent Relative Reductionß
(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) |
14.3 Immunogenicity of Fluzone Quadrivalent in Children 6 Months through 8 Years of Age
In Study 1 (NCT01240746) [see Adverse Reactions (6.1)], 1419 children 6 months through 35 months of age and 2101 children 3 years through 8 years of age were included in the per-protocol immunogenicity analysis. Participants 6 months through 35 months of age received one or two 0.25 mL doses and participants 3 years through 8 years of age received one or two 0.5 mL doses of Fluzone Quadrivalent, TIV-1, or TIV-2. For participants who received two doses, the doses were administered approximately 4 weeks apart. The distribution of demographic characteristics was similar to that of the safety analysis set [see Adverse Reactions (6.1)].
HI antibody geometric mean titers (GMTs) and seroconversion rates 28 days following vaccination with Fluzone Quadrivalent were non-inferior to those following each TIV for all four strains, based on pre-specified criteria (see Table 10 and Table 11).
|
||||
| Antigen Strain | Fluzone Quadrivalent§
N¶=2339 | Pooled TIV# N¶=1181 | GMT Ratio (95% CI)Þ |
|
| GMT | GMT | |||
| A (H1N1) | 1124 | 1096 | 1.03 (0.93; 1.14) | |
| A (H3N2) | 822 | 828 | 0.99 (0.91; 1.08) | |
| Fluzone Quadrivalent§
N¶=2339 | TIV-1ß
(B Victoria) N¶=582 | TIV-2à
(B Yamagata) N¶=599 | GMT Ratio (95% CI)Þ |
|
| GMT | GMT | GMT | ||
| B/Brisbane/60/2008 (B Victoria) | 86.1 | 64.3 | (19.5)è | 1.34 (1.20; 1.50) |
| B/Florida/04/2006 (B Yamagata) | 61.5 | (16.3)ð | 58.3 | 1.06 (0.94; 1.18) |
|
||||
| Antigen Strain | Fluzone Quadrivalent§
N¶=2339 | Pooled TIV#
N¶=1181 | Difference of Seroconversion Rates (95% CI)Þ |
|
| Seroconversionß (%) | ||||
| A (H1N1) | 92.4 | 91.4 | 0.9 (-0.9; 3.0) | |
| A (H3N2) | 88.0 | 84.2 | 3.8 (1.4; 6.3) | |
| Fluzone Quadrivalent§
N¶=2339 | TIV-1à
(B Victoria) N¶=582 | TIV-2è
(B Yamagata) N¶=599 | Difference of Seroconversion Rates (95% CI)Þ |
|
| Seroconversionß (%) | ||||
| B/Brisbane/60/2008 (B Victoria) | 71.8 | 61.1 | (20.0)ð | 10.7 (6.4; 15.1) |
| B/Florida/04/2006 (B Yamagata) | 66.1 | (17.9)ø | 64.0 | 2.0 (-2.2; 6.4) |
Non-inferiority immunogenicity criteria based on HI antibody GMTs and seroconversion rates were also met when age subgroups (6 months to <36 months and 3 years to <9 years) were examined. In addition, HI antibody GMTs and seroconversion rates following Fluzone Quadrivalent were higher than those following TIV for the B strain not contained in each respective TIV based on pre-specified criteria (the lower limit of the 2-sided 95% CI of the ratio of the GMTs [Fluzone Quadrivalent divided by TIV] >1.5 for each B strain in Fluzone Quadrivalent compared with the corresponding B strain not contained in each TIV and the lower limit of the two 2-sided 95% CI of the difference of the seroconversion rates [Fluzone Quadrivalent minus TIV] >10% for each B strain in Fluzone Quadrivalent compared with the corresponding B strain not contained in each TIV).
14.4 Immunogenicity of the 0.5 mL Dose of Fluzone Quadrivalent in Children 6 Months through 35 Months of Age
In Study 2 (NCT02915302) [see Adverse Reactions (6.1)], 1027 children, 6 months through 35 months of age, were included in the per-protocol immunogenicity analysis. The distribution of demographic characteristics was similar to that of the safety analysis set [see Adverse Reactions (6.1)].
In this study, children 6 months through 35 months of age received one or two doses of either 0.25 mL or 0.5 mL of Fluzone Quadrivalent. Non-inferiority of the 0.5 mL dose(s) relative to the 0.25 mL dose(s) of Fluzone Quadrivalent was demonstrated for all four strains based on pre-specified criteria (lower limit of the 2-sided 95% CI of the ratio of GMTs between groups > 0.667; lower limit of the 2-sided 95% CI of the difference in seroconversion rates >-10%). GMT ratios (GMT0.5-mL dose divided by GMT0.25-mL dose) for the A/H1N1, A/H3N2, B Victoria lineage, and B Yamagata lineage strains were 1.42 (95% CI: 1.16; 1.74), 1.48 (95% CI: 1.21; 1.82), 1.33 (95% CI: 1.09; 1.62), and 1.41 (95% CI: 1.17; 1.70), respectively. Seroconversion rate (SCR) differences (SCR0.5-mL dose minus SCR0.25-mL dose) for the A/H1N1, A/H3N2, B Victoria lineage, and B Yamagata lineage strains were 4.6% (95% CI: -0.4%; 9.6%), 5.1% (95% CI: 0.4%; 9.8%), 1.3% (95% CI: -2.9%; 5.6%), and 2.6% (95% CI: -1.4%; 6.5%).
14.5 Immunogenicity of Fluzone Quadrivalent in Adults ≥18 Years of Age
In Study 3 (NCT00988143) [see Adverse Reactions (6.1)], 565 adults 18 years of age and older who had received one dose of Fluzone Quadrivalent, TIV-1, or TIV-2 were included in the per-protocol immunogenicity analysis. The distribution of demographic characteristics was similar to that of the safety analysis set [see Adverse Reactions (6.1)].
HI antibody GMTs 21 days following vaccination with Fluzone Quadrivalent were non-inferior to those following each TIV for all four strains, based on pre-specified criteria (see Table 12).
|
||||
| Antigen Strain | Fluzone Quadrivalent‡
N§=190 | Pooled TIV¶
N§=375 | GMT Ratio (95% CI)# |
|
| GMT | GMT | |||
| A (H1N1) | 161 | 151 | 1.06 (0.87; 1.31) | |
| A (H3N2) | 304 | 339 | 0.90 (0.70; 1.15) | |
| Fluzone Quadrivalent‡
N§=190 | TIV-1Þ
(B Victoria) N§=187 | TIV-2ß
(B Yamagata) N§=188 | GMT Ratio (95% CI)# |
|
| GMT | GMT | GMT | ||
| B/Brisbane/60/2008 (B Victoria) | 101 | 114 | (44.0)à | 0.89 (0.70; 1.12) |
| B/Florida/04/2006 (B Yamagata) | 155 | (78.1)è | 135 | 1.15 (0.93; 1.42) |
14.6 Immunogenicity of Fluzone Quadrivalent in Geriatric Adults ≥65 Years of Age
In Study 4 (NCT01218646) [see Adverse Reactions (6.1)], 660 adults 65 years of age and older were included in the per-protocol immunogenicity analysis. The distribution of demographic characteristics was similar to that of the safety analysis set [see Adverse Reactions (6.1)].
HI antibody GMTs 21 days following vaccination with Fluzone Quadrivalent were non-inferior to those following TIV for all four strains, based on pre-specified criteria (see Table 13). Seroconversion rates 21 days following Fluzone Quadrivalent were non-inferior to those following TIV for H3N2, B/Brisbane, and B/Florida, but not for H1N1 (see Table 14). The HI antibody GMT following Fluzone Quadrivalent was higher than that following TIV-1 for B/Florida but not higher than that following TIV-2 for B/Brisbane, based on pre-specified criteria (the lower limit of the 2-sided 95% CI of the ratio of the GMTs [Fluzone Quadrivalent divided by TIV] >1.5 for each B strain in Fluzone Quadrivalent compared with the corresponding B strain not contained in each TIV). Seroconversion rates following Fluzone Quadrivalent were higher than those following TIV for the B strain not contained in each respective TIV, based on pre-specified criteria (the lower limit of the two 2-sided 95% CI of the difference of the seroconversion rates [Fluzone Quadrivalent minus TIV] >10% for each B strain in Fluzone Quadrivalent compared with the corresponding B strain not contained in each TIV).
|
||||
| Antigen Strain | Fluzone Quadrivalent‡
N§=220 | Pooled TIV¶
N§=440 | GMT Ratio (95% CI)# |
|
| GMT | GMT | |||
| A (H1N1) | 231 | 270 | 0.85 (0.67; 1.09) | |
| A (H3N2) | 501 | 324 | 1.55 (1.25; 1.92) | |
| Fluzone Quadrivalent‡
N§=220 | TIV-1Þ
(B Victoria) N§=219 | TIV-2ß
(B Yamagata) N§=221 | GMT Ratio (95% CI)# |
|
| GMT | GMT | GMT | ||
| B/Brisbane/60/2008 (B Victoria) | 73.8 | 57.9 | (42.2)à | 1.27 (1.05; 1.55) |
| B/Florida/04/2006 (B Yamagata) | 61.1 | (28.5)è | 54.8 | 1.11 (0.90; 1.37) |
|
||||
| Antigen Strain | Fluzone Quadrivalent‡
N§=220 | Pooled TIV¶
N§=440 | Difference of Seroconversion Rates (95% CI)# |
|
| SeroconversionÞ(%) | ||||
| A (H1N1) | 65.91 | 69.77 | -3.86 (-11.50; 3.56) | |
| A (H3N2) | 69.09 | 59.32 | 9.77 (1.96; 17.20) | |
| Fluzone Quadrivalent‡
N§=220 | TIV-1ß
(B Victoria) N§=219 | TIV-2à
(B Yamagata) N§=221 | Difference of Seroconversion Rates (95% CI)# |
|
| SeroconversionÞ(%) | ||||
| B/Brisbane/60/2008 (B Victoria) | 28.64 | 18.72 | (8.60)è | 9.91 (1.96; 17.70) |
| B/Florida/04/2006 (B Yamagata) | 33.18 | (9.13)ð | 31.22 | 1.96 (-6.73; 10.60) |
15. References
- 1
- Lasky T, Terracciano GJ, Magder L, et al. The Guillain-Barré syndrome and the 1992-1993 and 1993-1994 influenza vaccines. N Engl J Med 1998;339:1797-802.
- 2
- Hannoun C, Megas F, Piercy J. Immunogenicity and protective efficacy of influenza vaccination. Virus Res 2004;103:133-138.
- 3
- Hobson D, Curry RL, Beare AS, Ward-Gardner A. The role of serum haemagglutination-inhibiting antibody in protection against challenge infection with influenza A2 and B viruses. J Hyg Camb 1972;70:767-777.
16. How is Fluzone Quadrivalent supplied
16.1 How Supplied
Single-dose, prefilled syringe (clear plunger rod), without needle, 0.5 mL (NDC 49281-423-88) (not made with natural rubber latex). Supplied as package of 10 (NDC 49281-423-50).
Multi-dose vial, 5 mL (NDC 49281-639-78) (not made with natural rubber latex). Supplied as package of 1 (NDC 49281-639-15). A maximum of ten doses can be withdrawn from the multi-dose vial.
17. Patient Counseling Information
See FDA-approved patient labeling (Patient Information). Inform the vaccine recipient or guardian:
- Fluzone Quadrivalent contains killed viruses and cannot cause influenza.
- Fluzone Quadrivalent stimulates the immune system to protect against influenza, but does not prevent other respiratory infections.
- Annual influenza vaccination is recommended.
- Report adverse reactions to their healthcare provider and/or to the Vaccine Adverse Event Reporting System (VAERS) at 1-800-822-7967.
- Sanofi Pasteur Inc. is maintaining a prospective pregnancy exposure registry to collect data on pregnancy outcomes and newborn health status following vaccination with Fluzone Quadrivalent during pregnancy. Women who receive Fluzone Quadrivalent during pregnancy are encouraged to contact Sanofi Pasteur Inc. directly or have their healthcare provider contact Sanofi Pasteur Inc. at 1-800-822-2463.
Vaccine Information Statements must be provided to vaccine recipients or their guardians, as required by the National Childhood Vaccine Injury Act of 1986 prior to immunization. These materials are available free of charge at the Centers for Disease Control and Prevention (CDC) website (www.cdc.gov/vaccines).
Fluzone is a registered trademark of Sanofi Pasteur Inc.
Patient Information Sheet
Fluzone® Quadrivalent
Influenza Vaccine
Please read this information sheet before getting Fluzone Quadrivalent. 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 Quadrivalent?
Fluzone Quadrivalent is a vaccine that helps protect against influenza illness (flu).
Fluzone Quadrivalent is for people who are 6 months of age and older.
Vaccination with Fluzone Quadrivalent may not protect all people who receive the vaccine.
Who should not get Fluzone Quadrivalent?
You should not get Fluzone Quadrivalent if you:
- ever had a severe allergic reaction to eggs or egg products.
- ever had a severe allergic reaction after getting any flu vaccine.
- are younger than 6 months of age.
Tell your healthcare provider if you or your child have or have had:
- Guillain-Barré syndrome (severe muscle weakness) after getting a flu vaccine.
- problems with your immune system as the immune response may be diminished.
How is the Fluzone Quadrivalent given?
Fluzone Quadrivalent is a shot given into the muscle of the arm.
For infants, Fluzone Quadrivalent is a shot given into the muscle of the thigh.
What are the possible side effects of Fluzone Quadrivalent?
The most common side effects of Fluzone Quadrivalent are:
- pain, redness, and swelling where you got the shot
- muscle aches
- tiredness
- headache
- fever
These are not all of the possible side effects of Fluzone Quadrivalent. 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. Sanofi Pasteur Inc. is collecting information on pregnancy outcomes and the health of newborns following vaccination with Fluzone Quadrivalent during pregnancy. Women who receive Fluzone Quadrivalent during pregnancy are encouraged to contact Sanofi Pasteur Inc. directly or have their healthcare provider contact Sanofi Pasteur Inc. at 1-800-822-2463.
What are the ingredients in Fluzone Quadrivalent?
Fluzone Quadrivalent contains 4 killed flu virus strains.
Inactive ingredients include formaldehyde and octylphenol ethoxylate. The preservative thimerosal is only in the multi-dose vial of Fluzone Quadrivalent.
Manufactured by:
Sanofi Pasteur Inc.
Swiftwater, PA 18370 USA
| FLUZONE QUADRIVALENT NORTHERN HEMISPHERE
influenza a virus a/victoria/2570/2019 ivr-215 (h1n1) antigen (formaldehyde inactivated), influenza a virus a/darwin/9/2021 san-010 (h3n2) antigen (formaldehyde inactivated), influenza b virus b/phuket/3073/2013 antigen (formaldehyde inactivated), and influenza b virus b/michigan/01/2021 antigen (formaldehyde inactivated) injection, suspension |
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| FLUZONE QUADRIVALENT NORTHERN HEMISPHERE
influenza a virus a/victoria/2570/2019 ivr-215 (h1n1) antigen (formaldehyde inactivated), influenza a virus a/darwin/9/2021 san-010 (h3n2) antigen (formaldehyde inactivated), influenza b virus b/phuket/3073/2013 antigen (formaldehyde inactivated), and influenza b virus b/michigan/01/2021 antigen (formaldehyde inactivated) injection, suspension |
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| FLUZONE QUADRIVALENT NORTHERN HEMISPHERE
influenza a virus a/guangdong-maonan/swl1536/2019 cnic-1909 (h1n1) antigen (formaldehyde inactivated), influenza a virus a/hong kong/2671/2019 ivr-208 (h3n2) antigen (formaldehyde inactivated), influenza b virus b/phuket/3073/2013 antigen (formaldehyde inactivated), influenza b virus b/washington/02/2019 antigen (formaldehyde inactivated) injection, suspension |
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| FLUZONE QUADRIVALENT NORTHERN HEMISPHERE
influenza a virus a/michigan/45/2015 x-275 (h1n1) hemagglutinin antigen (formaldehyde inactivated), influenza a virus a/singapore/infimh-16-0019/2016 ivr-186 (h3n2) hemagglutinin antigen (formaldehyde inactivated), influenza b virus b/phuket/3073/2013 hemagglutinin antigen (formaldehyde inactivated), influenza b virus b/maryland/15/2016 bx-69a antigen (formaldehyde inactivated) injection, suspension |
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| FLUZONE QUADRIVALENT NORTHERN HEMISPHERE
influenza a virus a/michigan/45/2015 x-275 (h1n1) hemagglutinin antigen (formaldehyde inactivated), influenza a virus a/singapore/infimh-16-0019/2016 ivr-186 (h3n2) hemagglutinin antigen (formaldehyde inactivated), influenza b virus b/phuket/3073/2013 hemagglutinin antigen (formaldehyde inactivated), influenza b virus b/maryland/15/2016 bx-69a antigen (formaldehyde inactivated) injection, suspension |
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| FLUZONE QUADRIVALENT NORTHERN HEMISPHERE
influenza a virus a/guangdong-maonan/swl1536/2019 cnic-1909 (h1n1) antigen (formaldehyde inactivated), influenza a virus a/hong kong/2671/2019 ivr-208 (h3n2) antigen (formaldehyde inactivated), influenza b virus b/phuket/3073/2013 antigen (formaldehyde inactivated), influenza b virus b/washington/02/2019 antigen (formaldehyde inactivated) injection, suspension |
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| FLUZONE QUADRIVALENT NORTHERN HEMISPHERE
influenza a virus a/brisbane/02/2018 ivr-190 (h1n1) antigen (formaldehyde inactivated), influenza a virus a/kansas/14/2017 x-327 (h3n2) antigen (formaldehyde inactivated), influenza b virus b/phuket/3073/2013 antigen (formaldehyde inactivated), influenza b virus b/maryland/15/2016 bx-69a antigen (formaldehyde inactivated) injection, suspension |
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| FLUZONE QUADRIVALENT NORTHERN HEMISPHERE
influenza a virus a/brisbane/02/2018 ivr-190 (h1n1) antigen (formaldehyde inactivated), influenza a virus a/kansas/14/2017 x-327 (h3n2) antigen (formaldehyde inactivated), influenza b virus b/phuket/3073/2013 antigen (formaldehyde inactivated), influenza b virus b/maryland/15/2016 bx-69a antigen (formaldehyde inactivated) injection, suspension |
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| FLUZONE QUADRIVALENT NORTHERN HEMISPHERE
influenza a virus a/victoria/2570/2019 ivr-215 (h1n1) antigen (formaldehyde inactivated), influenza a virus a/tasmania/503/2020 ivr-221 (h3n2) antigen (formaldehyde inactivated), influenza b virus b/phuket/3073/2013 antigen (formaldehyde inactivated), influenza b virus b/washington/02/2019 antigen (formaldehyde inactivated) injection, suspension |
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| FLUZONE QUADRIVALENT NORTHERN HEMISPHERE
influenza a virus a/victoria/2570/2019 ivr-215 (h1n1) antigen (formaldehyde inactivated), influenza a virus a/tasmania/503/2020 ivr-221 (h3n2) antigen (formaldehyde inactivated), influenza b virus b/phuket/3073/2013 antigen (formaldehyde inactivated), influenza b virus b/washington/02/2019 antigen (formaldehyde inactivated) injection, suspension |
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| FLUZONE QUADRIVALENT NORTHERN HEMISPHERE
influenza a virus a/victoria/4897/2022 ivr-238 (h1n1) antigen (formaldehyde inactivated), influenza a virus a/darwin/9/2021 san-010 (h3n2) antigen (formaldehyde inactivated), influenza b virus b/phuket/3073/2013 antigen (formaldehyde inactivated), and influenza b virus b/michigan/01/2021 antigen (formaldehyde inactivated) injection, suspension |
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| FLUZONE QUADRIVALENT NORTHERN HEMISPHERE
influenza a virus a/victoria/4897/2022 ivr-238 (h1n1) antigen (formaldehyde inactivated), influenza a virus a/darwin/9/2021 san-010 (h3n2) antigen (formaldehyde inactivated), influenza b virus b/phuket/3073/2013 antigen (formaldehyde inactivated), and influenza b virus b/michigan/01/2021 antigen (formaldehyde inactivated) injection, suspension |
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| Labeler - Sanofi Pasteur Inc. (086723285) |
| Establishment | |||
| Name | Address | ID/FEI | Business Operations |
|---|---|---|---|
| Sanofi Pasteur Inc. | 086723285 | MANUFACTURE(49281-418, 49281-420, 49281-421, 49281-422, 49281-423, 49281-519, 49281-629, 49281-631, 49281-633, 49281-635, 49281-637, 49281-639) | |
