[Protein Sciences Corporation]
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use Flublok® safely and effectively. See full prescribing information for Flublok.
Flublok (Influenza Vaccine) Sterile Solution for Intramuscular Injection 2013-2014 Formula
Initial U.S. Approval: 2013
INDICATIONS AND USAGE
Flublok is a vaccine indicated for active immunization against disease caused by influenza virus subtypes A and type B contained in the vaccine. Flublok is approved for use in persons 18 through 49 years of age. (1)
DOSAGE AND ADMINISTRATION
A single 0.5 mL dose for intramuscular injection. (2)
DOSAGE FORMS AND STRENGTHS
A sterile solution for injection supplied in 0.5mL single dose vials. (3)
Severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine. (4)
WARNINGS AND PRECAUTIONS
If Guillain-Barré syndrome has occurred within 6 weeks of receipt of a prior influenza vaccine, the decision to give Flublok should be based on careful consideration of potential benefits and risks. (5.1)
In adults 18 through 49 years of age, the most common (≥10%) injection-site reaction was pain (>37%); the most common (≥10%) solicited systemic adverse reactions were headache (>15%), fatigue (>15%) and myalgia (>11%). (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Protein Sciences Corporation at 1-888-855-7871 or VAERS at 1-800-822-7967 or www.vaers.hhs.gov
USE IN SPECIFIC POPULATIONS
See 17 for PATIENT COUNSELING INFORMATION.
FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
Flublok is a vaccine indicated for active immunization against disease caused by influenza virus subtypes A and type B contained in the vaccine. Flublok is approved for use in persons 18 through 49 years of age.
2 DOSAGE AND ADMINISTRATION
For intramuscular injection only.
Shake the single-dose vial gently before withdrawing the vaccine dose.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permits. If either of these conditions exists, the vaccine should not be administered.
The preferred site for injection is the deltoid muscle. Administration is by sterile needle and syringe.
Flublok should not be mixed with any other vaccine in the same syringe or vial.
Flublok is contraindicated in individuals with known severe allergic reactions (e.g., anaphylaxis), to any component of the vaccine (see Description ).
5 WARNINGS AND PRECAUTIONS
5.1 Guillain-Barré Syndrome
The 1976 swine influenza vaccine was associated with an increased frequency of 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 one additional case per 1 million persons vaccinated. If Guillain-Barré Syndrome (GBS) has occurred within 6 weeks of receipt of a prior influenza vaccine, the decision to give Flublok should be based on careful consideration of the potential benefits and risks.
5.2 Managing Allergic Reactions
Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of the vaccine.
5.3 Altered Immunocompetence
If Flublok is administered to immunocompromised individuals, including persons receiving immunosuppressive therapy, the immune response may be diminished.
6 ADVERSE REACTIONS
The most common (≥10%) injection-site reaction was pain (>37%); the most common (≥10%) solicited systemic adverse reactions were headache (>15%), fatigue (>15%) and myalgia (>11%).
6.1 Clinical Trials Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a vaccine cannot be directly compared to rates in the clinical studies of another vaccine and may not reflect the rates observed in clinical practice.
Flublok has been administered to and safety data collected from 2497 adults 18 through 49 years of age enrolled in two randomized, placebo-controlled clinical trials (1, 2). In both studies local (injection site) and systemic adverse reactions were solicited with the use of a memory aid for 7 days following vaccination. Unsolicited adverse reactions were collected for 28 days post-vaccination and Serious Adverse Events (SAEs) were collected for 6 months post-vaccination via clinic visit or telephone follow up on Day 28, telephone follow up on Day 180, or by spontaneous reporting.
In a clinical trial (Study 1, Table 1) that included 2,344 subjects randomized to receive Flublok and 2,304 subjects randomized to receive saline placebo, the mean age of participants was 32.5 years, 59% were female, and 67% were Caucasian (see Clinical Studies ).
|NOTE: Data based on the most severe response reported by subjects. Results >1% reported to nearest whole percent; results >0 but <1 reported as <1%.
‡ Fever defined as ≥99.8°F (37.7°C).
1 Total Vaccinated Cohort is defined as all randomized subjects who received study vaccine according to the treatment actually received and who provided data.
2 Study 1 is registered as NCT00539981 under the National Clinical Trials registry.
3 Denominators for Study 1: The total number of enrolled subjects was 2344 in the Flublok group and 2304 in the placebo group. For all categories except fever, the number of subjects with missing values was 72 in the Flublok group and 73 in the Placebo group so that these denominators are 2272 and 2231 respectively. For fever, 89 Flublok recipients and 104 Placebo recipients were missing data, making these denominators 2255 and 2200 respectively.
| Flublok |
|Local Adverse Reactions||%||%|
|Systemic Adverse Reactions||%||%|
Across trials, through 6 months post vaccination, two deaths were reported, one in a Flublok recipient and one in a placebo recipient. Both deaths occurred more than 28 days following vaccination and neither was considered vaccine-related. SAEs were reported by 32 Flublok recipients and 35 placebo recipients. One SAE in a Flublok recipient was assessed as possibly related to the vaccine: pleuropericarditis with effusions requiring hospitalization and drainage. No specific cause was identified. The patient recovered.
In Study 1, the most frequent unsolicited adverse events, occurring in 1%-2% of subjects, were nasopharyngitis, upper respiratory infection, headache, cough, nasal congestion, pharyngolaryngeal pain, and rhinorrhea.
7 DRUG INTERACTIONS
Data evaluating the concomitant administration of Flublok with other vaccines are not available.
8 USE IN SPECIFIC POPULATIONS
Pregnancy Category B
Reproduction studies have been performed in rats at a dose approximately 300 times the human dose (on a mg/kg basis) and have revealed no evidence of impaired fertility or harm to the fetus due to Flublok. 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. The effect of Flublok on embryo-fetal and pre-weaning development was evaluated in pregnant rats. Animals were administered Flublok by intramuscular injection twice prior to gestation and once during the period of organogenesis (gestation days 6), 0.5 ml/rat/occasion (approximately 300-fold excess relative to the projected human dose on a mg/kg basis). No adverse effects on mating, female fertility, pregnancy, parturition, lactation, embryo-fetal and pre-weaning development were observed. There were no vaccine-related fetal malformations or other evidence of teratogenesis.
8.3 Nursing Mothers
Flublok has not been evaluated in nursing mothers. It is not known whether Flublok is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Flublok is administered to a nursing woman.
8.4 Pediatric Use
Data from a randomized, controlled study demonstrated that children 6 months to less than 3 years of age had diminished hemagglutinin inhibition (HAI) responses to Flublok as compared to a U.S.-licensed influenza vaccine approved for use in this population, strongly suggesting that Flublok would not be effective in children younger than 3 years of age. Safety and effectiveness of Flublok in children 3 years to less than 18 years of age have not been established.
Flublok [Influenza Vaccine] is a sterile, clear, colorless solution of recombinant hemagglutinin (HA) proteins from three influenza viruses for intramuscular injection. It contains purified HA proteins produced in a continuous insect cell line (expresSF+®) that is derived from Sf9 cells of the fall armyworm, Spodoptera frugiperda, and grown in serum-free medium composed of chemically-defined lipids, vitamins, amino acids, and mineral salts. Each of the three HAs is expressed in this cell line using a baculovirus vector (Autographa californica nuclear polyhedrosis virus), extracted from the cells with Triton X-100 and further purified by column chromatography. The purified HAs are then blended and filled into single-dose vials.
Flublok is standardized according to United States Public Health Service (USPHS) requirements. For the 2013 - 2014 influenza season it is formulated to contain 135 mcg HA per 0.5 mL dose, with 45 mcg HA of each of the following 3 influenza virus strains: A/California/7/2009 (H1N1), A/Texas/50/2012 (H3N2; antigenically like the cell-propagated prototype virus A/Victoria/361/2011), and B/Massachusetts/2/2012.
A single 0.5 mL dose of Flublok contains sodium chloride (4.4 mg), monobasic sodium phosphate (0.195 mcg), dibasic sodium phosphate (1.3 mg), and polysorbate 20 (Tween®20) (27.5 mcg). Each 0.5 mL dose of Flublok may also contain residual amounts of baculovirus and host cell proteins (≤ 28.5 mcg), baculovirus and cellular DNA (≤ 10 ng), and Triton X-100 (≤ 100 mcg).
Flublok contains no egg proteins, antibiotics, or preservatives. The stoppers used for the single-dose vials are not made with natural rubber latex.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Flublok contains recombinant HA proteins of the three strains of influenza virus specified by health authorities for inclusion in the annual seasonal vaccine. These proteins function as antigens which induce a humoral immune response, measured by hemagglutinin inhibition antibody (HAI).
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 replacement of one or more influenza virus strains in each year's influenza vaccine. Therefore, influenza vaccines are standardized to contain the hemagglutinins of influenza virus strains (i.e., typically two type A and one type B), representing the influenza viruses likely to be circulating in the U.S. in the upcoming winter.
13 NONCLINICAL TOXICOLOGY
Flublok has not been evaluated for carcinogenic or mutagenic potential, or for impairment of male fertility in animals.
Reproduction studies performed in female rats revealed no evidence of impaired fertility due to Flublok (see Pregnancy [8.1]).
14 CLINICAL STUDIES
Efficacy Against Culture-Confirmed Influenza
The efficacy of Flublok was evaluated in a randomized, observer-blind, placebo-controlled multicenter trial conducted in the U.S. during the 2007-2008 influenza season (Study 1). The study enrolled and vaccinated 4648 healthy adults (mean age 32.5 years) randomized in a 1:1 ratio to receive a single dose of Flublok (n=2344) or saline placebo (n=2304). Among enrolled subjects, 59% were female, 67% were white, 19% African-American, 11% Latino/Hispanic, 2% Asian and < 1% other. The two groups were similar in demographics. Culture-confirmed influenza was assessed by active and passive surveillance for influenza-like illness (ILI) beginning 2 weeks post-vaccination until the end of the influenza season, approximately 7 months post- vaccination. ILI was defined as having at least 2 of 3 symptoms (no specified duration) in the following categories: 1) fever ≥ 100ºF; 2) respiratory symptoms (cough, sore throat, runny nose/stuffy nose); or 3) systemic symptoms (myalgias, arthralgias, headache, chills/sweats, tiredness/malaise). For subjects with an episode of ILI, nasal and throat swab samples were collected for viral culture.
The primary efficacy endpoint was Centers for Disease Control-defined influenza-like illness (CDC-ILI) with a positive culture for an influenza virus strain antigenically resembling a strain represented in Flublok. CDC-ILI is defined as fever of ≥100°F oral accompanied by cough, sore throat, or both on the same day or on consecutive days (1). Attack rates and vaccine efficacy (VE), defined as the relative reduction in the influenza rate for Flublok relative to placebo, were calculated for the total vaccinated cohort (n=4,648). The pre-defined success criterion for the primary efficacy analysis was that the lower bound of the 95% confidence interval (CI) of VE should be at least 40%. Vaccine efficacy against antigenically matched culture-confirmed CDC-ILI could not be determined reliably because 96% of the influenza isolates obtained from subjects in Study 1 were not antigenically matched to the strains represented in the vaccine. An exploratory analysis of VE of Flublok against all strains regardless of antigenic match isolated from any subject with an ILI, not necessarily CDC-defined ILI, demonstrated an efficacy estimate of 44.8% (95% CI 24.4, 60.0). See Table 2 for a presentation of VE by case definition and antigenic similarity.
|*In Study 1 (NCT00539981) vaccine efficacy analyses were conducted on the Total Vaccinated Cohort (all randomized subjects who received study vaccine according to the treatment actually received and who provided data). Vaccine efficacy (VE) = 1 minus the ratio of Flublok/placebo infection rates.
1 Determined under the assumption of Poisson event rates, according to Breslow and Day, 1987.
2 Meets CDC influenza-like illness (CDC-ILI) defined as fever of ≥100ºF oral accompanied by cough and/or sore throat, on the same day or on consecutive days.
3 Primary endpoint of study.
4 All culture-confirmed cases are considered, regardless of whether they qualified as CDC-ILI.
5 Secondary endpoint of study.
6 Exploratory (prespecified) endpoint of study.
|Cases, n||Rate, %||Cases, n||Rate, %|
|Positive culture with a strain represented in the vaccine|
|CDC-ILI, all matched strains2,3||1||0.04||4||0.2||75.4||(-148.0, 99.5)|
|Any ILI, all matched strains4,5||2||0.1||6||0.3||67.2||(-83.2, 96.8)|
|Positive culture with any strain, regardless of match to the vaccine|
|CDC-ILI, all strains2,6||44||1.9||78||3.4||44.6||(18.8, 62.6)|
|Sub-Type A||26||1.1||56||2.4||54.4||(26.1, 72.5)|
|Type B||18||0.8||23||1.0||23.1||(-49.0, 60.9)|
|Any ILI, all strains4||64||2.7||114||4.9||44.8||(24.4, 60.0)|
|Sub-Type A||41||1.7||79||3.4||49.0||(24.7, 65.9)|
|Type B||23||1.0||36||1.6||37.2||(-8.9, 64.5)|
1. Treanor JJ, El Sahly HM, King J, et al. Protective efficacy of a trivalent recombinant hemagglutinin protein vaccine (FluBlok) against influenza in healthy adults: a randomized, placebo-controlled trial. Vaccine, 2011, Vol. 13, 29, pp. 7733-7739.
2. Treanor JJ, Schiff GM, Hayden FG, et.al. Safety and immunogenicity of a baculovirus-expressed hemagglutinin influenza vaccine: a randomized controlled trial. JAMA. 2007, Vol. 297, pp. 1577-1582.
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
Flublok is supplied as a single-dose, 0.5 mL vial in a 10 vial carton:
|Presentation||Carton NDC Number||Components and NDC Number|
|Single-Dose Vial||42874-013-10||Ten 0.5 mL single-dose vials [NDC 42874-013-01]|
17 PATIENT COUNSELING INFORMATION
See FDA-approved patient labeling (Patient Information Sheet).
Inform the vaccine recipient of the potential benefits and risks of vaccination with Flublok.
Inform the vaccine recipient that:
- Flublok contains non-infectious proteins that cannot cause influenza.
- Flublok stimulates the immune system to produce antibodies that help protect against influenza viruses contained in the vaccine, but does not prevent other respiratory infections.
Instruct the vaccine recipient to report any adverse events to their healthcare provider and/or to the Vaccine Adverse Event Reporting System (VAERS).
Provide the vaccine recipient with the Vaccine Information Statements which are required by the National Childhood Vaccine Injury Act of 1986 to be given prior to vaccination. These materials are available free of charge at the Centers for Disease Control (CDC) website (www.cdc.gov/vaccines).
Inform the vaccine recipient that safety and efficacy have not been established in pregnant women. Register women who receive Flublok while pregnant in the pregnancy registry by calling 1-888-855-7871.
Instruct the vaccine recipient that annual vaccination to prevent influenza is recommended.
Manufactured by Protein Sciences Corporation (Meriden, CT)
US license 1795
Distributed by Protein Sciences Corporation
Flublok is a registered trademark of Protein Sciences Corporation.
Patient Information Sheet
Read this information sheet carefully before getting Flublok 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 Flublok vaccine?
- Flublok is a vaccine given by injection (shot) to prevent influenza illness (flu).
- Flublok vaccine is for people who are 18 - 49 years of age.
- Flublok vaccine may not protect all people who receive the vaccine.
Who should not get Flublok vaccine?
You should not get Flublok vaccine if you:
- Ever had a severe allergic reaction to any of the ingredients in Flublok vaccine (listed below)
- Are younger than 18 years of age or older than 49 years of age.
Tell your healthcare provider if you have or have had:
- Guillain Barré Syndrome (severe muscle weakness) after getting a flu shot
- Problems with your immune system as your immune response may be reduced
How is Flublok vaccine given?
Flublok vaccine is given as a single injection (shot) into a muscle in your arm.
What are the possible side effects of Flublok vaccine?
The most common side effects of Flublok vaccine are:
- pain, redness, bruising, and swelling where you get the shot
- muscle aches
These are not all of the possible side effects of Flublok vaccine. A list of other side effects is available from your healthcare professional.
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 Flublok vaccine?
Flublok vaccine contains three influenza proteins. Inactive ingredients include sodium chloride, sodium phosphate, and polysorbate 20. Flublok contains no preservatives, antibiotics, egg proteins, or latex.
Manufactured by Protein Sciences Corporation
(Meriden, CT) US License 1795
PACKAGE/LABEL PRINCIPAL DISPLAY PANEL – Carton
10 Vials, 1 dose each (0.5 mL)
For 18 to 49 years of age
For intramuscular injection only
Protein Sciences Corporation
Protein Sciences Corp.
Meriden, CT 06450
US License # 1795
influenza vaccine injection, solution
|Labeler - Protein Sciences Corporation (109124933)|