Fluquadri

Quadrivalent influenza vaccine 2020 Southern Hemisphere strains.

FluQuadri 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 FluQuadri 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.
FluQuadri suspension for injection is clear and slightly opalescent in color.
Neither antibiotics nor preservative are used in the manufacture of FluQuadri.
The FluQuadri prefilled syringe presentations are not made with natural rubber latex.
FluQuadri is standardized according to United States Public Health Service requirements and is formulated to contain 60 micrograms (mcg) HA per 0.5 mL dose in the recommended ratio of 15 mcg HA of each of the following four influenza strains recommended for the 2020 Southern Hemisphere influenza season: A/Michigan/45/2015 X-275 (H1N1), A/Brisbane/1/2018 X-311 (an A/Switzerland/8060/2017 (H3N2)-like strain), B/Phuket/3073/2013 (B Yamagata lineage), and B/Maryland/15/2016 BX-69A (a B/Colorado/6/2017-like virus, B Victoria lineage). The amounts of HA and other ingredients per dose of vaccine are listed in Table 1. See Table 1.

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Pharmacology: Pharmacodynamics: Mechanism of Action: 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. 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.
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 next 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.
Clinical Studies: Immunogenicity of FluQuadri in Children 6 Months through 8 Years of Age: In a multi-center study conducted in the US, 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 received one or two 0.25 mL doses or one or two 0.5 mL doses, respectively of FluQuadri, TIV-1, or TIV-2. For participants who received two doses, the doses were administered approximately 4 weeks apart.
HI antibody geometric mean titers (GMTs) and seroconversion rates 28 days following vaccination with FluQuadri were non-inferior to those following each TIV for all four strains, based on prespecified criteria (the lower limit of the 2-sided 95% CI of the ratio of GMTs [FluQuadri divided by pooled TIV for the A strains, or the TIV containing the corresponding B strain] was >0.66 and the lower limit of the 2-sided 95% CI of the difference in seroconversion rates [FluQuadri minus pooled TIV for the A strains, or the TIV containing the corresponding B strain] was >-10%). For strain A (H1N1), the GMT ratio was 1.03 (95% CI: 0.93; 1.14) and the difference of seroconversion rates was 0.9% (95% CI: -0.9%; 3.0%). For strain A (H3N2), the GMT ratio was 0.99 (95% CI: 0.91; 1.08) and the difference of seroconversion rates was 3.8% (95% CI: 1.4%; 6.3%). For strain B/Brisbane/60/2008 (B Victoria), the GMT ratio was 1.34 (95% CI: 1.20; 1.50) and the difference of seroconversion rates was 10.7% (95% CI: 6.4%; 15.1%). For strain B/Florida/04/2006 (B Yamagata), the GMT ratio was 1.06 (95% CI: 0.94; 1.18) and the difference of seroconversion rates was 2.0% (95% CI: -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 FluQuadri 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 [FluQuadri divided by TIV] >1.5 for each B strain in FluQuadri 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 [FluQuadri minus TIV] >10% for each B strain in FluQuadri compared with the corresponding B strain not contained in each TIV).
Immunogenicity of FluQuadri in Adults ≥18 Years of Age: In a multi-center study conducted in the US, 565 adults 18 years of age and older who had received one dose of FluQuadri, TIV-1, or TIV-2 were included in the per-protocol immunogenicity analysis.
HI antibody GMTs 21 days following vaccination with FluQuadri were non-inferior to those following each TIV for all four strains, based on pre-specified criteria (the lower limit of the 2-sided 95% CI of the ratio of GMTs [FluQuadri divided by pooled TIV for the A strains, or the TIV containing the corresponding B strain] was >2/3). For strain A (H1N1), the GMT ratio was 1.06 (95% CI: 0.87; 1.31), for strain A (H3N2), the GMT ratio was 0.90 (95% CI: 0.70; 1.15), for strain B/Brisbane/60/2008 (B Victoria), the GMT ratio was 0.89 (95% CI: 0.70; 1.12), and for strain B/Florida/04/2006 (B Yamagata), the GMT ratio was 1.15 (95% CI: 0.93; 1.42).
Immunogenicity of FluQuadri in Geriatric Adults ≥65 Years of Age: In a multi-center study conducted in the US, 660 adults 65 years of age and older were included in the per-protocol immunogenicity analysis.
HI antibody GMTs 21 days following vaccination with FluQuadri were non-inferior to those following TIV for all four strains, based on pre-specified criteria (the lower limit of the 2-sided 95% CI of the ratio of GMTs [FluQuadri divided by pooled TIV for the A strains, or the TIV containing the corresponding B strain] was >0.66). For strain A (H1N1), the GMT ratio was 0.85 (95% CI: 0.67; 1.09), for strain A (H3N2), the GMT ratio was 1.55 (95% CI: 1.25; 1.92), for strain B/Brisbane/60/2008 (B Victoria), the GMT ratio was 1.27 (95% CI: 1.05; 1.55), and for strain B/Florida/04/2006 (B Yamagata), the GMT ratio was 1.11 (95% CI: 0.90; 1.37). Seroconversion rates 21 days following FluQuadri were non-inferior to those following TIV for H3N2, B/Brisbane, and B/Florida, but not for H1N1, based on pre-specified criteria (the lower limit of the 2-sided 95% CI of the difference in seroconversion rates [FluQuadri minus pooled TIV for the A strains, or the TIV containing the corresponding B strain] was >-10%). For strain A (H1N1), the difference of seroconversion rates was -3.86% (95% CI: -11.50%; 3.56%), for strain A (H3N2), the difference of seroconversion rates was 9.77% (95% CI: 1.96%; 17.20%), for strain B/Brisbane/60/2008 (B Victoria), the difference of seroconversion rates was 9.91% (95% CI: 1.96%; 17.70%), and for strain B/Florida/04/2006 (B Yamagata), the difference of seroconversion rates was 1.96% (95% CI: -6.73%; 10.60%).
The HI antibody GMT following FluQuadri 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 [FluQuadri divided by TIV] >1.5 for each B strain in FluQuadri compared with the corresponding B strain not contained in each TIV). The GMT ratio for B/Brisbane was 1.75 (95% CI: 1.43; 2.14). Seroconversion rates following FluQuadri 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 [FluQuadri minus TIV] >10% for each B strain in FluQuadri compared with the corresponding B strain not contained in each TIV).
Toxicology: Non-clinical Toxicology: Carcinogenesis, Mutagenesis, Impairment of Fertility: FluQuadri has not been evaluated for carcinogenic or mutagenic potential or for impairment of fertility.

FluQuadri (Quadrivalent Influenza Vaccine) is an inactivated quadrivalent influenza vaccine indicated for the prevention of influenza disease caused by influenza types A and B viruses contained in the vaccine.
FluQuadri is approved for use in persons 6 months of age and older.

For intramuscular use only.
Dose and Schedule: The dose and schedule for FluQuadri is presented in Table 2 (see Table 2).

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Administration: Inspect FluQuadri 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. Withdraw the vaccine using a sterile needle and sterile syringe.
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.
FluQuadri vaccine should not be combined through reconstitution or mixed with any other vaccine.

A severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine (see Description), including egg protein, or to a previous dose of any influenza vaccine is a contraindication to administration of FluQuadri.

Guillain-Barré Syndrome: Recurrence of Guillain-Barré syndrome (GBS) has been temporally associated with administration of influenza vaccine. If GBS has occurred within 6 weeks of previous influenza vaccination, the decision to give FluQuadri should be based on careful consideration of the potential benefits and risks.
Preventing and Managing Allergic Reactions: Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of the vaccine.
Altered Immunocompetence: If FluQuadri is administered to immunocompromised persons, including those receiving immunosuppressive therapy, the expected immune response may not be obtained.
Limitations of Vaccine Effectiveness: Vaccination with FluQuadri may not protect all recipients.
Pediatric Use: Safety and effectiveness of FluQuadri in children below the age of 6 months have not been established. Safety and immunogenicity of FluQuadri was evaluated in children 6 months through 8 years of age. (See Adverse Reactions and Pharmacology: Pharmacodynamics: Clinical Studies under Actions.)
Geriatric Use: Safety and immunogenicity of FluQuadri was evaluated in adults 65 years of age and older. (See Adverse Reactions and Pharmacology: Pharmacodynamics: Clinical Studies under Actions.)
Antibody responses to FluQuadri are lower in persons ≥65 years of age than in younger adults.

Pregnancy: Animal reproduction studies have not been conducted with FluQuadri. It is also not known whether FluQuadri can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. FluQuadri should be given to a pregnant woman only if clearly needed.
Nursing Mothers: It is not known whether FluQuadri is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when FluQuadri is administered to a nursing woman.

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 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 one or two 0.25 mL doses of either FluQuadri or one of two formulations of a comparator trivalent influenza vaccine (TIV-1 or TIV-2), and children 3 years through 8 years of age received one or two 0.5 mL doses of either FluQuadri, TIV-1, or TIV-2. Each of the trivalent formulations contained an influenza type B virus that corresponded to one of the two type B viruses in FluQuadri (a type B virus of the Victoria lineage or a type B virus of the Yamagata lineage). For participants who received two doses, the doses were administered approximately 4 weeks apart. The safety analysis set included 1841 children 6 months through 35 months of age and 2506 children 3 years through 8 years of age.
In children 6 months through 35 months of age, the most common (≥10%) injection-site reactions were pain (57.0%)^a or tenderness (54.1%)^b, erythema (37.3%), and swelling (21.6%); the most common solicited systemic adverse reactions were irritability (54.0%)^b, abnormal crying (41.2%)^b, malaise (38.1%)^a, drowsiness (37.7%)^b, appetite loss (32.3%)^b, myalgia (26.7%)^a, vomiting (14.8%)^b, and fever (14.3%). In children 3 years through 8 years of age, the most common (≥10%) injection-site reactions were pain (66.6%), erythema (34.1%), and swelling (24.8%); the most common solicited systemic adverse reactions were myalgia (38.6%), malaise (31.9%), and headache (23.1%).
^a Assessed in children 24 months through 35 months of age.
^b Assessed in children 6 months through 23 months of age.
During the 28 days following vaccination, a total of 16 (0.6%) recipients in the FluQuadri group, 4 (0.5%) recipients in the TIV-1 group, and 4 (0.6%) recipients in the TIV-2 group, experienced at least one SAE; no deaths occurred. Throughout the study period, a total of 41 (1.4%) recipients in the FluQuadri group, 7 (1.0%) recipients in the TIV-1 group, and 14 (1.9%) recipients in the TIV-2 group, experienced at least one SAE. Three SAEs were considered to be possibly related to vaccination: croup in a FluQuadri recipient and 2 episodes of febrile seizure, 1 each in a TIV-1 recipient and a TIV-2 recipient. One death occurred in the TIV-1 group (a drowning 43 days postvaccination).
Adults: In a multi-center trial conducted in the US, adults 18 years of age and older received one dose of either FluQuadri or one of two formulations of comparator trivalent influenza vaccine (TIV-1 or TIV-2). Each of the trivalent formulations contained an influenza type B virus that corresponded to one of the two type B viruses in FluQuadri (a type B virus of the Victoria lineage or a type B virus of the Yamagata lineage). The safety analysis set included 570 recipients, half aged 18-60 years and half aged 61 years or older.
In adults 18 years and older, the most common (≥10%) injection-site reaction was pain (47.4%); the most common solicited systemic adverse reactions were myalgia (23.7%), headache (15.8%), and malaise (10.5%).
In the follow-up period, there were two SAEs, 1 (0.5%) in the FluQuadri group and 1 (0.5%) in the TIV-2 group. No deaths were reported during the trial period.
Geriatric Adults: In a multi-center trial conducted in the US, adults 65 years of age and older received one dose of either FluQuadri, or one of two formulations of comparator trivalent influenza vaccine (TIV-1 or TIV-2). Each of the trivalent formulations contained an influenza type B virus that corresponded to one of the two type B viruses in FluQuadri (a type B virus of the Victoria lineage or a type B virus of the Yamagata lineage). The safety analysis set included 675 recipients.
In adults 65 years of age and older, the most common (³10%) injection-site reaction was pain (32.6%); the most common solicited systemic adverse reactions were myalgia (18.3%), headache (13.4%), and malaise (10.7%).
Three SAEs were reported during the follow-up period, 2 (0.9%) in the TIV-1 group and 1 (0.4%) in the TIV-2 group. No deaths were reported during the trial period.
Reporting adverse reactions: Persons who receive the vaccine and their guardians should be instructed to report any adverse or unusual reaction to their healthcare provider.
Post-Marketing Experience: Currently, there are no post-marketing data available for FluQuadri vaccine.
The following events have been spontaneously reported during the post-approval use of the trivalent formulation 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.
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, vasodilation/flushing.
Respiratory, Thoracic and Mediastinal Disorders: Dyspnea, pharyngitis, rhinitis, cough, wheezing, throat tightness.
Skin and Subcutaneous Tissue Disorders: Stevens-Johnson syndrome.
General Disorders and Administration Site Conditions: Pruritus, asthenia/fatigue, pain in extremities, chest pain.
Gastrointestinal Disorders: Vomiting.

Data evaluating the concomitant administration of FluQuadri with other vaccines are not available.

Store all FluQuadri presentations refrigerated at 2° to 8°C (35° to 46°F). Do not freeze. Discard if vaccine has been frozen.

Vaccines, Antisera & Immunologicals

J07BB02 - influenza, inactivated, split virus or surface antigen ; Belongs to the class of influenza viral vaccines.

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