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These highlights do not include all the information needed to use • History of severe allergic reactions (e.g., anaphylaxis) to egg proteins, or any
FLUVIRIN® (Influenza Virus Vaccine) safely and effectively. See full component of FLUVIRIN®, or life-threatening reactions to previous influenza
prescribing information for FLUVIRIN®. vaccinations. (4.1, 11)
FLUVIRIN® (Influenza Virus Vaccine)
Suspension for Intramuscular Injection ---------------------- WARNINGS AND PRECAUTIONS ------------------------------
2017-2018 Formula • If Guillain-Barré syndrome has occurred within 6 weeks of receipt of prior
Initial US Approval: 1988 influenza vaccine, the decision to give FLUVIRIN® should be based on
-------------------------- INDICATIONS AND USAGE ---------------------------------- careful consideration of the potential benefits and risks. (5.1)
• FLUVIRIN® is an inactivated influenza virus vaccine indicated for active • Immunocompromised persons may have a reduced immune response to
immunization of persons 4 years of age and older against influenza disease FLUVIRIN®. (5.2)
caused by influenza virus subtypes A and type B contained in the vaccine (1). • The tip caps of the FLUVIRIN® prefilled syringes may contain natural rubber
• FLUVIRIN® is not indicated for children less than 4 years of age because latex which may cause allergic reactions in latex sensitive individuals.
there is evidence of diminished immune response in this age group (8.4).
----------------------------- ADVERSE REACTIONS -------------------------------------
--------------------- DOSAGE AND ADMINISTRATION ----------------------------- The most frequently reported adverse reactions are mild hypersensitivity
• For intramuscular use only. reactions (such as rash), local reactions at the injection site, and influenza-like
symptoms. (6)
Age Dose Schedule
To report SUSPECTED ADVERSE REACTIONS contact Seqirus at 1-855-
4 years through 8 One or two doses a, 0.5 If 2 doses, administer at least 1 358-8966 or VAERS at 1-800-822-7967 and www.vaers.hhs.gov.
years mL each month apart
9 years and older One dose, 0.5 mL - ----------------------------- DRUG INTERACTIONS -------------------------------------
a
1 or 2 doses depends on vaccination history as per Advisory Committee on • Do not mix with any other vaccine in the same syringe or vial. (7.1)
Immunization Practices annual recommendations on prevention and control of • Immunosuppressive therapies may reduce immune response to FLUVIRIN®.
influenza with vaccines. (2) (7.2)
“-” indicates information is not applicable (2) ---------------------- USE IN SPECIFIC POPULATIONS ------------------------------
-------------------- DOSAGE FORMS AND STRENGTHS ---------------------------- • Safety and effectiveness of FLUVIRIN® have not been established in pregnant
FLUVIRIN®, a sterile suspension for intramuscular injection, is supplied in two women, nursing mothers or children less than 4 years of age. (8.1, 8.3, 8.4)
presentations: • Antibody responses were lower in the geriatric population than in younger
subjects. (8.5)
• 0.5 mL single-dose prefilled syringe (3, 11)
• 5.0 mL multi-dose vial containing 10 doses (each dose is 0.5 mL) (3,11) See 17 for PATIENT COUNSELING INFORMATION.
Revised: 3/2017
FULL PRESCRIBING INFORMATION: CONTENTS* 7.2 Concurrent Use with Immunosuppressive Therapies
1 INDICATIONS AND USAGE 8 USE IN SPECIFIC POPULATIONS
1 INDICATIONS AND USAGE 8.1 Pregnancy
2 DOSAGE AND ADMINISTRATION 8.3 Nursing Mothers
2.1 Preparation for Administration 8.4 Pediatric Use
2.2 Recommended Dose and Schedule 8.5 Geriatric Use
3 DOSAGE FORMS AND STRENGTHS 11 DESCRIPTION
4 CONTRAINDICATIONS 12 CLINICAL PHARMACOLOGY
4.1 Hypersensitivity 12.1 Mechanism of Action
5 WARNINGS AND PRECAUTIONS 13 NONCLINICAL TOXICOLOGY
5.1 Guillain-Barré Syndrome 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
5.2 Altered Immunocompetence 14 CLINICAL STUDIES
5.3 Preventing and Managing Allergic Reactions 14.1 Immunogenicity in Adults (18 to 64 years of age)
5.4 Limitations of Vaccine Effectiveness 14.2 Immunogenicity in Geriatric Subjects (65 years of age
5.5 Syncope and older)
6 ADVERSE REACTIONS 14.3 Immunogenicity in Pediatric Subjects
6.1 Overall Adverse Reaction Profile 15 REFERENCES
6.2 Clinical Trial Experience 16 HOW SUPPLIED/STORAGE AND HANDLING
6.3 Postmarketing Experience 16.1 How Supplied
6.4 Other Adverse Reactions Associated with Influenza 16.2 Storage and Handling
Vaccination 17 PATIENT COUNSELING INFORMATION
7 DRUG INTERACTIONS *Sections or subsections omitted from the full prescribing
7.1 Concomitant Administration with Other Vaccines information are not listed.
4 CONTRAINDICATIONS
4.1 Hypersensitivity
Do not administer FLUVIRIN® to anyone with known history of severe allergic reactions (e.g., anaphylaxis) to egg proteins (eggs or
egg products), or to any component of FLUVIRIN®, or who has had a life-threatening reaction to previous influenza vaccinations.
5 WARNINGS AND PRECAUTIONS
5.5 Syncope
Syncope (fainting) can occur in association with administration of injectable vaccines, including Fluvirin. Syncope can be
accompanied by transient neurological signs such as visual disturbance, paresthesia, and tonic-clonic limb movements. Procedures
should be in place to avoid falling injury and to restore cerebral perfusion following syncope by maintaining a supine or
Trendelenburg position.
6 ADVERSE REACTIONS
TABLE 2 Solicited Adverse Events in the First 72-96 Hours After Administration of FLUVIRIN® in Adult (18-64 years of age)
and Geriatric (≥65 years of age) Subjects.
TABLE 3 Solicited Adverse Events in the First 72 Hours After Administration of FLUVIRIN® in Adult Subjects (18-49 years
of age).
TABLE 4 Adverse Events Reported by at least 5% of Subjects in Clinical Trials since 1998
7 DRUG INTERACTIONS
8.1 Pregnancy
Pregnancy Category B: A reproductive and developmental toxicity study has been performed in rabbits at a dose level that was
approximately 15 times the human dose based on body weight. The study revealed no evidence of impaired fertility or harm to the
fetus due to FLUVIRIN®. There are, however, no adequate and well-controlled studies in pregnant women. Because animal
reproduction studies are not always predictive of human response, this vaccine should be used during pregnancy only if clearly
needed.
In a reproductive and developmental toxicity study, the effect of FLUVIRIN® on embryo-fetal and post-natal development was
evaluated in pregnant rabbits. Animals were administered FLUVIRIN® by intramuscular injection twice prior to gestation, during the
period of organogenesis (gestation day 7) and later in pregnancy (gestation day 20), 0.5 mL/rabbit/occasion (approximately 15-fold
excess relative to the projected human dose on a body weight basis). No adverse effects on mating, female fertility, pregnancy,
embryo-fetal development, or post-natal development were observed. There were no vaccine related fetal malformations or other
evidence of teratogenicity.
11 DESCRIPTION
FLUVIRIN® is a trivalent, sub-unit (purified surface antigen) influenza virus vaccine prepared from virus propagated in the allantoic
cavity of embryonated hens' eggs inoculated with a specific type of influenza virus suspension containing neomycin and polymyxin.
Each of the influenza virus strains is harvested and clarified separately by centrifugation and filtration prior to inactivation with
betapropiolactone. The inactivated virus is concentrated and purified by zonal centrifugation. The surface antigens, hemagglutinin and
neuraminidase, are obtained from the influenza virus particle by further centrifugation in the presence of nonylphenol ethoxylate, a
process which removes most of the internal proteins. The nonylphenol ethoxylate is removed from the surface antigen preparation.
FLUVIRIN® is a homogenized, sterile, slightly opalescent suspension in a phosphate buffered saline. FLUVIRIN® has been
standardized according to USPHS requirements for the 2017/2018 influenza season and is formulated to contain 45 mcg
hemagglutinin (HA) per 0.5-mL dose in the recommended ratio of 15 mcg HA of each of the following 3 viruses:
A/Singapore/GP1908/2015,IVR-180 (an A/Michigan/45/2015 (H1N1)pdm09- like virus;
A/Hong Kong/4801/2014, NYMC X-263B (H3N2) (an A/Hong Kong/4801/2014- like virus);
and B/Brisbane/60/2008, wild type (a B/Brisbane/60/2008-like virus).
The 0.5-mL prefilled syringe presentation is formulated without preservative. However, thimerosal, a mercury derivative used during
manufacturing, is removed by subsequent purification steps to a trace amount (≤ 1 mcg mercury per 0.5-mL dose).
The 5-mL multidose vial formulation contains thimerosal, a mercury derivative, added as a preservative. Each 0.5-mL dose from the
multidose vial contains 25 mcg mercury.
Each dose from the multidose vial or from the prefilled syringe may also contain residual amounts of egg proteins (≤ 1 mcg
ovalbumin), polymyxin (≤ 3.75 mcg), neomycin (≤ 2.5 mcg), betapropiolactone (not more than 0.5 mcg) and nonylphenol ethoxylate
(not more than 0.015% w/v).
The tip caps of the FLUVIRIN® prefilled syringes may contain natural rubber latex. The multidose vial stopper and the syringe
stopper/plunger do not contain latex.
12 CLINICAL PHARMACOLOGY
13 NONCLINICAL TOXICOLOGY
14 CLINICAL STUDIES
Between 1982 and 1991, twelve clinical studies were conducted in healthy adult and geriatric subjects and one in children between 4
and 12 years of age who were considered to be ‘at risk'. Since 1991 an annual clinical study has been conducted in the UK in healthy
adults aged 18 years or older. FLUVIRIN® was also used as a control in a US clinical trial in adults (18-49 years of age). In all the
trials, blood samples were taken prior to vaccination and approximately three weeks after vaccination to assess the immunogenic
response to vaccination by measurement of anti-HA antibodies. Three clinical studies were carried out between 1995 and 2004 in a
total of 520 pediatric subjects (age range 6-47 months). Of these, 285 healthy subjects plus 41 ‘at risk' pediatric subjects received
FLUVIRIN®. FLUVIRIN® should only be used for the immunization of persons aged 4 years and over.
TABLE 5 Summary of the Seroconversion and Proportion of Subjects Achieving an HI titer ≥1:40 for Adult Subjects
TABLE 6 Summary of the Geometric Mean Hemagglutination Inhibition Antibody Titers, Pre- and Post-Immunization, for
Adult Subjects
TABLE 7 Summary of the Seroconversion and Proportion of Subjects Achieving an HI titer ≥1:40 for Geriatric Subjects
TABLE 8 Summary of the Geometric Mean Hemagglutination Inhibition Antibody Titers, Pre- and Post-Immunization, for
Geriatric Subjects
15 REFERENCES
15.1 Hannoun C, Megas F, Piercy J. Immunogenicity and protective efficacy of influenza vaccination. Virus Res 2004; 103:133-138.
15.2 Hobson D, Curry RL, Beare A, et. al. The role of serum hemagglutinin- inhibiting antibody in protection against challenge
infection with influenza A2 and B viruses. J Hyg Camb 1972; 767-777.
15.3 Centers for Disease Control and Prevention. Prevention and Control of Influenza with Vaccines. Recommendations of the
Advisory Committee on Immunization Practices (ACIP). MMWR 2011; 60(33):1128-1132.
Seqirus Inc.