Influenza vaccine (with adjuvant)
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Martin Nino [2]
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Overview
Influenza vaccine (with adjuvant) is an inactivated influenza vaccine that is FDA approved for the prevention of influenza disease caused by influenza virus subtypes A and type B in persons 65 years of age and older. Common adverse reactions include injection site pain (25%), tenderness (21%), myalgia (15%), headache (13%) and fatigue (13%).
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Indications
Influenza vaccine (with adjuvant) is an inactivated influenza vaccine indicated for active immunization against influenza disease caused by influenza virus subtypes A and type B contained in the vaccine. Influenza vaccine (with adjuvant) is approved for use in persons 65 years of age and older. Approval is based on the immune response elicited by Influenza vaccine (with adjuvant). Data demonstrating a decrease in influenza disease after vaccination with Influenza vaccine (with adjuvant) are not available.
Dosage
Administer Influenza vaccine (with adjuvant) as a single 0.5 mL intramuscular injection in adults 65 years of age and older.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Influenza vaccine (with adjuvant) in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Influenza vaccine (with adjuvant) in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
The safety and effectiveness of Influenza vaccine (with adjuvant) in the pediatric population have not been established.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Influenza vaccine (with adjuvant) in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Influenza vaccine (with adjuvant) in pediatric patients.
Contraindications
Do not administer Influenza vaccine (with adjuvant) to anyone with a history of severe allergic reaction (e.g. anaphylaxis) to any component of the vaccine, including egg protein, or to a previous influenza vaccine.
Warnings
If Guillain-Barré syndrome (GBS) has occurred within 6 weeks of receipt of prior influenza vaccine, the decision to give Influenza vaccine (with adjuvant) should be based on careful consideration of the potential benefits and risks. The 1976 swine influenza vaccine was associated with an elevated risk of GBS. Evidence for a causal relationship 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.
- Preventing and Managing Allergic Reactions
Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of the vaccine.
- Latex
The tip caps of the prefilled syringes contain natural rubber latex which may cause allergic reactions in latex sensitive individuals.
- Altered Immunocompetence
The immune response to Influenza vaccine (with adjuvant) in immunocompromised persons, including individuals receiving immunosuppressive therapy, may be lower than in immunocompetent individuals.
Syncope (fainting) may occur in association with administration of injectable vaccines including Influenza vaccine (with adjuvant). Ensure procedures are in place to avoid injury from falling associated with syncope.
- Limitations of Vaccine Effectiveness
Vaccination with Influenza vaccine (with adjuvant) may not protect all vaccine recipients against influenza disease.
Adverse Reactions
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, the 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 rates observed in clinical practice.
Solicited adverse reactions were assessed in a multicenter, observer-blind, randomized controlled study (Study 1) conducted in the United States, Colombia, Panama and the Philippines. The safety analysis set included 3545 Influenza vaccine (with adjuvant) recipients and 3537 AGRIFLU (Influenza Vaccine) recipients. The enrolled subject population in Study 1 was 65 to 97 years of age (mean 72 years) and 64% were female. Within each treatment group, 53% were Asian, 28% were Caucasian, 18% were Hispanic, 1% were Black, and fewer than 1% each were Native American/Alaskan, Pacific Islander/Hawaiian, or Other.
Solicited local (injection site) and systemic adverse reactions were collected from subjects in Study 1 who completed a symptom diary card for seven days following vaccination. The reported frequencies of solicited local and systemic adverse events from Study 1 are presented in TABLE 1.
- Table 1: Percentages of Subjects ≥ 65 Years of Age With Solicited Local and Systemic Adverse Reactions in Days 1-7 After Administration of Influenza vaccine (with adjuvant) or AGRIFLU (a U.S. Licensed Comparator) NCT01162122
FLUAD: Influenza vaccine (with adjuvant)'s Brand name
- Unsolicited Adverse Events (AEs): The clinical safety of Influenza vaccine (with adjuvant) was assessed in fifteen (15) randomized, controlled studies. The total safety population in these trials included 10,952 adults 65 years of age and older, comprising 5,754 who received Influenza vaccine (with adjuvant) and 5,198 who received other US licensed influenza vaccines. The percentage of subjects with an unsolicited AE within 30 days following vaccination was similar between vaccine groups (16.9% Influenza vaccine (with adjuvant) vs. 18.0% active comparator).
- Serious Adverse Events (SAEs) and Deaths: In Study 1, in which subjects were followed for SAEs and deaths for one year following vaccination (N=3,545 Influenza vaccine (with adjuvant), N=3,537 AGRIFLU), the percentages of subjects with an SAE were similar between vaccine groups (7% Influenza vaccine (with adjuvant) vs. 7% AGRIFLU). Four SAEs (1 Influenza vaccine (with adjuvant) and 3 AGRIFLU) were assessed as related to study vaccination over one year of observation and 2 of these occurred (1 Influenza vaccine (with adjuvant) and 1 AGRIFLU) within 21 days following study vaccination. There were 98 deaths (n=52 Influenza vaccine (with adjuvant), n=46 AGRIFLU) over one year of which none occurred within the first 21 days following vaccination.
In 14 additional randomized, controlled studies, SAEs were collected over a 3 to 4-week period in 4 studies, over a 8-week period in 1 study, and over a 6-month period in 9 studies (N= 2,209 Influenza vaccine (with adjuvant), N=1,661 US licensed influenza vaccines). The percentages of subjects with an SAE within 30 days (1.1% Influenza vaccine (with adjuvant) vs. 1.8% AGRIFLU) or within 6 months (4.3% Influenza vaccine (with adjuvant) vs. 5.9% AGRIFLU) were similar between vaccine groups. The percentages of deaths within 30 days (0.3% Influenza vaccine (with adjuvant) vs. 0.6% active comparator) or within 6 months (1.0% Influenza vaccine (with adjuvant) vs. 1.5% active comparator) were also similar.
- Adverse Events of Special Interest (AESIs): Rates of new onset neuroinflammatory and immune mediated diseases were assessed in a post hoc analysis of the 15 randomized controlled studies over the time periods specified above for SAEs. The percentage of subjects with an AESI at any time after vaccination was similar between vaccine groups (0.9% Influenza vaccine (with adjuvant) vs. 0.9% active comparator). There were no notable imbalances for specific AESIs.
- Safety of Annual Revaccination: In 5 of the randomized, controlled trials, subjects were followed for SAEs and deaths for 6 months following revaccination (N=492 Influenza vaccine (with adjuvant), N=330 US licensed and non-US licensed influenza vaccines). After the second annual vaccination, the percentages of subjects with an SAE were similar between vaccine groups (6.1% Influenza vaccine (with adjuvant) vs. 5.5% comparator influenza vaccines); 23 deaths (n=17 Influenza vaccine (with adjuvant), n=6 comparator influenza vaccines) were reported. Causes of death included cardiovascular events, malignancy, trauma, gastrointestinal disorders, and respiratory failure. Clinical characteristics of the deaths, including the variable causes, timing since vaccination, and underlying medical conditions, do not provide evidence for a causal relationship with Influenza vaccine (with adjuvant).
Postmarketing Experience
The following adverse events have been spontaneously reported during post-approval use of Influenza vaccine (with adjuvant) in Europe and other regions since 1997. 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 the vaccine.
- Blood and lymphatic system disorders: Thrombocytopenia (some cases were severe with platelet counts less than 5,000 per mm3), lymphadenopathy
- General disorders and administration site conditions: Extensive swelling of injected limb lasting more than one week, injection site cellulitis-like reactions (some cases of swelling, pain, and redness extending more than 10 cm and lasting more than 1 week)
- Immune system disorders: Allergic reactions including anaphylactic shock, anaphylaxis and angioedema
- Musculoskeletal and connective tissue disorders: Muscular weakness
- Skin and subcutaneous tissue disorders: Generalized skin reactions including erythema multiforme, urticaria, pruritis or non-specific rash
- Vascular disorders: Vasculitis with transient renal involvement
Drug Interactions
- Concomitant Use With Other Vaccines
There are no data to assess the concomitant administration of Influenza vaccine (with adjuvant) with other vaccines. If Influenza vaccine (with adjuvant) is given at the same time as other injectable vaccine(s), the vaccine(s) should be administered at different injection sites.
Do not mix Influenza vaccine (with adjuvant) with any other vaccine in the same syringe.
- Concurrent Use With Immunosuppressive Therapies
Immunosuppressive or corticosteroid therapies may reduce the immune response to Influenza vaccine (with adjuvant).
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA): B. A reproductive and developmental toxicity study has been performed in rabbits with a dose level that was approximately 15 times the human dose based on body weight. The study revealed no evidence of impaired female fertility or harm to the fetus due to Influenza vaccine (with adjuvant). 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 Influenza vaccine (with adjuvant) on embryo-fetal and post-natal development was evaluated in pregnant rabbits. Animals were administered Influenza vaccine (with adjuvant) 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 (45 mcg)/rabbit/occasion (approximately 15-fold excess relative to the adult human dose based on body weight). 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 teratogenesis.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Influenza vaccine (with adjuvant) in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Influenza vaccine (with adjuvant) during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Influenza vaccine (with adjuvant) in women who are nursing.
Pediatric Use
The safety and effectiveness of Influenza vaccine (with adjuvant) in the pediatric population have not been established.
Geriatic Use
Safety and immunogenicity of Influenza vaccine (with adjuvant) have been evaluated in adults 65 years of age and older.
Gender
There is no FDA guidance on the use of Influenza vaccine (with adjuvant) with respect to specific gender populations.
Race
There is no FDA guidance on the use of Influenza vaccine (with adjuvant) with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Influenza vaccine (with adjuvant) in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Influenza vaccine (with adjuvant) in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Influenza vaccine (with adjuvant) in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Influenza vaccine (with adjuvant) in patients who are immunocompromised.
Administration and Monitoring
Administration
- Gently shake each syringe. Influenza vaccine (with adjuvant) has a milky white appearance. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. If either condition exists, Influenza vaccine (with adjuvant) should not be administered.
- The vaccine should be administered by intramuscular injection, preferably in the region of the deltoid muscle of the upper arm. Do not inject the vaccine in the gluteal region or areas where there may be a major nerve trunk.
Monitoring
There is limited information regarding Influenza vaccine (with adjuvant) Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Influenza vaccine (with adjuvant) and IV administrations.
Overdosage
There is limited information regarding Influenza vaccine (with adjuvant) overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
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. Specific levels of hemagglutination inhibition (HI) antibody titers induced by vaccination with inactivated influenza virus vaccine have not been correlated with protection from influenza illness. In some human studies, HI antibody titers of 1:40 or greater have been associated with protection from influenza illness in up to 50% of subjects.
Antibody against one influenza virus type or subtype confers limited or no protection against another. Furthermore, antibody 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, inactivated trivalent influenza vaccines are standardized to contain the hemagglutinin of influenza virus strains (two subtypes A and one type B), representing the influenza viruses likely to be circulating in the United States in the upcoming winter.
Annual influenza vaccination is recommended because immunity declines during the year after vaccination, and because circulating strains of influenza virus change from year to year.
Structure
Influenza vaccine (with adjuvant), a sterile suspension for intramuscular injection, is a trivalent, inactivated influenza vaccine prepared from virus propagated in the allantoic cavity of embryonated hens' eggs inoculated with a specific type of influenza virus suspension.
Each 0.5 mL dose contains at least 15 mcg of hemagglutinin (HA) from each of the following three influenza strains recommended for the 2015/2016 influenza season: A/California/7/2009 NYMC X-181 (H1N1) (an A/California/7/2009 pdm09-like virus); A/Switzerland/9715293/2013 NIB-88 (H3N2) (an A/Switzerland/9715293/2013-like virus); and B/Brisbane/9/2014 (a B/Phuket/3073/2013-like virus). Influenza vaccine (with adjuvant) also contains MF59C.1 adjuvant (MF59®), a squalene based oil-in-water emulsion. Each of the strains is harvested and clarified separately by centrifugation and filtration prior to inactivation with formaldehyde. 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 cetyltrimethylammonium bromide (CTAB). The antigen preparation is further purified.
Influenza vaccine (with adjuvant) is prepared by combining the three virus antigens with the MF59C.1 adjuvant. After combining, Influenza vaccine (with adjuvant) is a sterile, milky-white suspension supplied in 0.5 mL single-dose pre-filled syringe. Each 0.5 mL dose contains 15 mcg of hemagglutinin (HA) from each of the three recommended influenza strains and MF59C.1 adjuvant (9.75 mg squalene, 1.175 mg of polysorbate 80, 1.175 mg of sorbitan trioleate, 0.66 mg of sodium citrate dihydrate and 0.04 mg of citric acid monohydrate) at pH 6.9-7.7.
Influenza vaccine (with adjuvant) may contain trace amounts of neomycin (≤ 0.02 mcg by calculation), kanamycin (≤ 0.03 mcg by calculation) and barium (˂ 0.5 mcg by calculation), which are used during the initial stages of manufacture, as well as residual egg proteins (˂ 0.4 mcg), formaldehyde (≤ 10 mcg), or CTAB (≤ 12 mcg).
Influenza vaccine (with adjuvant) does not contain a preservative.
The tip caps of the prefilled syringes contain natural rubber latex. The syringe and syringe plunger stopper are not made with natural rubber latex.
Pharmacodynamics
There is limited information regarding Influenza vaccine (with adjuvant) Pharmacodynamics in the drug label.
Pharmacokinetics
There is limited information regarding Influenza vaccine (with adjuvant) Pharmacokinetics in the drug label.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment of Fertility
Influenza vaccine (with adjuvant) has not been evaluated for carcinogenic or mutagenic potential, or for impairment of male fertility in animals. Influenza vaccine (with adjuvant) did not affect female fertility in a rabbit reproductive and developmental toxicity study.
Clinical Studies
Study 1 (NCT01162122) evaluated the safety and immunogenicity of Influenza vaccine (with adjuvant) in comparison to AGRIFLU. A total of 7,082 subjects were randomized and vaccinated with Influenza vaccine (with adjuvant) (N=3,541) or AGRIFLU (N=3,541). The primary immunogenicity analyses were conducted on all vaccinated subjects with a blood sample collected at Day 22 (N=3,225-3,227 [91%] and 3,256-3,259 [92%] in the Influenza vaccine (with adjuvant) and AGRIFLU groups, respectively). Non-inferiority of Influenza vaccine (with adjuvant) compared with AGRIFLU was demonstrated for all three vaccine strains based on pre-defined thresholds for seroconversion rate differences and GMT ratios (TABLE 2).
- Table 2: Immune Responses to Each Antigen 22 Days after Vaccination with Influenza vaccine (with adjuvant) or AGRIFLU in Adults 65 Years and Older(a)
FLUAD: Influenza vaccine (with adjuvant)'s Brand name
How Supplied
Influenza vaccine (with adjuvant) is supplied as a 0.5 mL pre-filled needleless syringe:
- package of 10 pre-filled syringes per carton (NDC number: 66521-000-01)
- pre-filled single syringe (NDC number: 66521-000-11)
The tip caps of prefilled syringes contain natural rubber latex. The syringe and syringe plunger stopper are not made with natural rubber latex.
Storage
Store Influenza vaccine (with adjuvant) refrigerated at 2°C to 8°C (36°F to 46°F). Protect from light. Do not freeze. Discard if the vaccine has been frozen. Do not use after expiration date.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
Inform vaccine recipients of the potential benefits and risks of immunization with Influenza vaccine (with adjuvant). Educate vaccine recipients regarding the potential side effects. Clinicians should emphasize that (1) Influenza vaccine (with adjuvant) contains non-infectious particles and cannot cause influenza and (2) Influenza vaccine (with adjuvant) is intended to help provide protection against illness due to influenza viruses only, and cannot provide protection against other respiratory illnesses.
Instruct vaccine recipients to report adverse reactions to their healthcare provider and/or to Vaccine Adverse Event Reporting System (VAERS) at 1-800-822-7967 and www.vaers.hhs.gov. Provide vaccine recipients with the Vaccine Information Statements which are required by the National Childhood Vaccine Injury Act of 1986. These materials are available free of charge at the Centers for Disease Control and Prevention (CDC) website (www.cdc.gov/vaccines). Inform vaccine recipients that annual vaccination is recommended.
Precautions with Alcohol
Alcohol-Influenza vaccine (with adjuvant) interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.
Brand Names
FLUAD™
Look-Alike Drug Names
There is limited information regarding Influenza vaccine (with adjuvant) Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.