Vaccine Information: Flucelvax Quadrivalent
FLUCELVAX QUADRIVALENT- influenza a virus a/delaware/55/2019 cvr-45 (h1n1) antigen (mdck cell derived, propiolactone inactivated), influenza a virus a/darwin/11/2021 (h3n2) antigen (mdck cell derived, propiolactone inactivated), influenza b virus b/singapore/wuh4618/2021 antigen (mdck cell derived, propiolactone inactivated) and influenza b virus b/singapore/inftt-16-0610/2016 antigen (mdck cell derived, propiolactone inactivated) injection, suspension
Seqirus Inc.
1 INDICATIONS AND USAGE
FLUCELVAX QUADRIVALENT is an inactivated vaccine indicated for active immunization for the prevention of influenza disease caused by influenza virus subtypes A and types B contained in the vaccine. FLUCELVAX QUADRIVALENT is approved for use in persons 6 months of age and older. [see Clinical Studies (14)]
2 DOSAGE AND ADMINISTRATION
For intramuscular injection only.
2.1 Dosage and Schedule
Administer FLUCELVAX QUADRIVALENT as a single 0.5 mL intramuscular injection.
| 1 1 or 2 doses depends on vaccination history as per Advisory Committee on Immunization Practices annual recommendations on prevention and control of influenza with vaccines. | ||
| Age | Dose | Schedule |
| 6 months through 8 years of age | One or two doses1 , 0.5 mL each | If 2 doses, administer at least 4 weeks apart |
| 9 years of age and older | One dose, 0.5 mL | Not Applicable |
2.2 Administration
Shake the syringe vigorously before administering and shake the multi-dose vial preparation each time before withdrawing a dose of vaccine. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. [see Description (11)] If either condition exists, do not administer the vaccine. Between uses, return the multi-dose vial to the recommended storage conditions between 2º and 8ºC (36º and 46ºF). Do not freeze. Discard if the vaccine has been frozen.
Administer intramuscularly only, preferably in the region of the deltoid muscle of the upper arm. Younger children with insufficient deltoid mass should be vaccinated in the anterolateral aspect of the thigh.
3 DOSAGE FORMS AND STRENGTHS
FLUCELVAX QUADRIVALENT is a suspension for injection supplied in two presentations:
- a 0.5 mL single-dose pre-filled Luer Lock syringe
- a 5 mL multi-dose vial containing 10 doses (each dose is 0.5 mL)
4 CONTRAINDICATIONS
Do not administer FLUCELVAX QUADRIVALENT to anyone with a history of severe allergic reaction (e.g. anaphylaxis) to any component of the vaccine [see Description (11)].
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.1 If GBS has occurred after receipt of a prior influenza vaccine, the decision to give FLUCELVAX 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 the vaccine.
5.3 Syncope
Syncope (fainting) can occur in association with administration of injectable vaccines, including FLUCELVAX QUADRIVALENT. 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.
5.4 Altered Immunocompetence
After vaccination with FLUCELVAX QUADRIVALENT, immunocompromised individuals, including those receiving immunosuppressive therapy, may have a reduced immune response.
5.5 Limitations of Vaccine Effectiveness
Vaccination with FLUCELVAX QUADRIVALENT may not protect all vaccine recipients against influenza disease.
6 ADVERSE REACTIONS
In children 6 months through 3 years of age who received FLUCELVAX QUADRIVALENT, the most commonly reported injection-site adverse reactions were tenderness (27.9%), erythema (25.8%), induration (17.3%) and ecchymosis (10.7%). The most common systemic adverse reactions were irritability (27.9%), sleepiness (26.9%), diarrhea (17.9%) and change of eating habits (17.4%).
In children 2 through 8 years of age who received FLUCELVAX QUADRIVALENT, the most commonly reported injection-site adverse reactions were tenderness (28.7%), pain (27.9%) and erythema (21.3%), induration (14.9%) and ecchymosis (10.0%). The most common systemic adverse reactions were sleepiness (14.9%), headache (13.8%), fatigue (13.8%), irritability (13.8%) and loss of appetite (10.6%).
In children and adolescents 9 through 17 years of age who received FLUCELVAX QUADRIVALENT, the most commonly reported injection-site adverse reactions were injection site pain (21.7%), erythema (17.2%) and induration (10.5%). The most common systemic adverse reactions were headache (18.1%) and fatigue (17.0%).
In adults 18 through 64 years of age who received FLUCELVAX QUADRIVALENT, the most commonly reported (≥ 10%) injection-site adverse reactions were pain (45.4%), erythema (13.4%) and induration (11.6%). The most common systemic adverse reactions were headache (18.7%), fatigue (17.8%) and myalgia (15.4%).
In adults ≥65 years of age who received FLUCELVAX QUADRIVALENT, the most commonly reported injection-site adverse reactions were pain (21.6%) and erythema (11.9%).
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 clinical studies of another vaccine and may not reflect rates observed in clinical practice.
Children and Adolescents 6 months through 17 years of age:
The safety of FLUCELVAX QUADRIVALENT was evaluated in children and adolescents in two clinical studies: Study 1 and 2.
Study 1 was a randomized, observer-blind, multicenter study in children 6 months through 3 years of age. The safety population included a total of 2402 children 6 months through 3 years of age who received FLUCELVAX QUADRIVALENT (N=1597) or a US-licensed quadrivalent influenza vaccine comparator, AFLURIA QUADRIVALENT (N=805). In the safety population, 894 subjects (37.2%) were 6 months through 23 months of age, and 1508 subjects (62.8%) were 24 months through 47 months of age. The solicited safety set consisted of 2348 subjects who received FLUCELVAX QUADRIVALENT (N=1564) or a US-licensed quadrivalent influenza vaccine comparator (N=784). Study subjects received one or two doses (separated by 4 weeks) of FLUCELVAX QUADRIVALENT or the comparator vaccine depending on the subject’s prior influenza vaccination history.
In this study, solicited local injection site and systemic adverse reactions were collected on a symptom diary card for 7 days following vaccination.
In children 6 months through 3 years of age, the incidence of local and systemic solicited adverse reactions reported by children who received FLUCELVAX QUADRIVALENT and comparator are summarized in Table 2.
| Percentage (%) 2 of participants Reporting a Reaction | ||||||||
|---|---|---|---|---|---|---|---|---|
| Participants 6 through 23 months | Participants 24 through 47 months | |||||||
| FLUCELVAX QUADRIVALENTN=581 | Comparator 3 N=292 | FLUCELVAX QUADRIVALENTN=983 | Comparator 3 N=492 | |||||
| Any | Gr 3 | Any | Gr 3 | Any | Gr 3 | Any | Gr 3 | |
| Abbreviations: Gr 3, Grade 3. | ||||||||
| N = number of participants in the Safety Population for each study vaccine group. | ||||||||
| 1 Solicited Safety Population: participants who were vaccinated and provided any solicited local or systemic adverse reaction safety data on subject diary cards from Day 1 through Day 7 after vaccination. | ||||||||
| 2 Proportion of participants reporting each solicited local adverse reaction or systemic adverse event by study vaccine group based on the number of participants contributing any follow up safety information for at least one data value of an individual sign/symptom | ||||||||
| 3 Comparator: US-Licensed Quadrivalent Influenza vaccine | ||||||||
| 4 Local adverse reactions: Grade 3 tenderness defined as, “Cried when limb was moved/spontaneously painful” in subjects 6 through 23 months, and “Prevents daily activity” in subjects 24 months and older; Erythema, induration and ecchymosis: any = ≥1mm diameter, Grade 3 => 50 mm diameter. | ||||||||
| 5 Systemic adverse reactions: Fever: any = ≥ 100.4°F , Grade 3 = ≥ 104.0°F (either rectal, oral, axillary, or tympanic membrane); Grade 3 change of eating habits: Missed more than 2 feeds/meals; Grade 3 sleepiness: Sleeps most of the time and is hard to arouse him/her; Grade 3 vomiting: 6 or more times in 24 hours or requires intravenous hydration; Grade 3 diarrhea: 6 or more loose stools in 24 hours or requires intravenous hydration; Grade 3 irritability: unable to console. Grade 3 for all other adverse reactions is that which prevents daily activity. | ||||||||
| The rates of antipyretic or analgesic use reported on the diary card for prophylaxis or treatment of high temperature or pain were as follows: 6 through 23 months of age FLUCELVAX QUADRIVALENT 20.3%, Comparator 23.6%; 24 through 47 months of age FLUCELVAX QUADRIVALENT 12.4%, Comparator 13.6%. | ||||||||
| Study 1: NCT 04074928 | ||||||||
| Local Adverse Reactions 4 | ||||||||
| Tenderness | 25.5 | 2.1 | 23.3 | 1.4 | 29.3 | 2.2 | 33.9 | 1.4 |
| Erythema | 25.3 | 0 | 18.2 | 0 | 26.0 | 0.7 | 28.5 | 0 |
| Induration | 16.5 | 0.5 | 12.0 | 0 | 17.7 | 0.3 | 18.3 | 0 |
| Ecchymosis | 11.2 | 0.2 | 7.5 | 0 | 10.5 | 0.1 | 12.8 | 0 |
| Systemic Adverse Reactions 5 | ||||||||
| Irritability | 35.1 | 5.2 | 35.6 | 2.1 | 23.6 | 1.8 | 26.0 | 3.0 |
| Sleepiness | 35.5 | 2.4 | 30.5 | 1.7 | 21.8 | 1.9 | 22.6 | 1.2 |
| Diarrhea | 23.2 | 2.4 | 20.2 | 0.7 | 14.8 | 1.1 | 14.0 | 1.2 |
| Change of eating habits | 21.0 | 1.7 | 21.9 | 2.4 | 15.3 | 1.4 | 15.0 | 1.2 |
| Fever | 9.3 | 0.7 | 10.3 | 0 | 5.4 | 0.6 | 4.8 | 0.2 |
| Vomiting | 10.5 | 0.7 | 6.8 | 0.7 | 4.6 | 0.5 | 5.9 | 0.4 |
| Shivering | 3.1 | 0.2 | 3.1 | 0 | 3.3 | 0.2 | 3.7 | 0 |
In children who received two doses, the rates of solicited local and systemic adverse reactions were generally similar or lower after the second dose compared to the first dose.
All unsolicited adverse events were collected for 28 days after last vaccination. In children 6 months through 3 years of age, unsolicited adverse events were reported in 26.2% of subjects who received FLUCELVAX QUADRIVALENT and 25.7% of subjects who received the US-licensed quadrivalent influenza vaccine comparator within 28 days after last vaccination.
In children 6 months through 3 years of age, serious adverse events (SAEs) were collected throughout the study duration (until 6 months after last vaccination) and were reported by 0.9% of the subjects who received FLUCELVAX QUADRIVALENT and 0.9% of subjects who received the US-licensed quadrivalent influenza vaccine comparator. None of the SAEs were assessed as being related to study vaccine.
Study 2 was a multi-season, multi-national (Australia, Estonia, Finland, Lithuania, Philippines, Poland, Spain, Thailand), randomized, observer-blind study in children and adolescents 2 through 17 years of age. The solicited safety population included a total of 4509 children and adolescents 2 through 17 years of age who received FLUCELVAX QUADRIVALENT(N=2255) or a non-influenza (meningococcal (Groups A, C, Y, and W-135) oligosaccharide diphtheria CRM197 conjugate) comparator vaccine (N=2254).
Children 2 through 8 years of age received one or two doses (separated by 4 weeks) of FLUCELVAX QUADRIVALENT or comparator vaccine depending on the subject’s prior influenza vaccination history. Children in the 2-dose comparator group received non-influenza comparator as the first dose and saline placebo as the second dose. Children and adolescents 9 through 17 years of age received a single dose of FLUCELVAX QUADRIVALENT or non-influenza comparator vaccine.
In this study, solicited local injection site and systemic adverse reactions were collected on a symptom diary card for 7 days following vaccination.
In children 2 through 8 and children and adolescents 9 through 17 years of age, the incidence of local and systemic solicited adverse reactions reported by children and adolescents who received FLUCELVAX QUADRIVALENT and comparator are summarized in Table 3.
| Percentage (%) 2 of participants in each Age Cohort Reporting a Reaction | ||||||||
|---|---|---|---|---|---|---|---|---|
| Participants 2 through 8 years | Participants 9 through 17 years | |||||||
| FLUCELVAX QUADRIVALENT N=559-1143 | Comparator 3 N=562-1142 | FLUCELVAX Q UADRIVALENT N=1096-1109 | Comparator 3 N=1100-1108 | |||||
| Abbreviations: Gr 3, Grade 3. | ||||||||
| N = number of participants in the Safety Population for each study vaccine group. | ||||||||
| 1 Solicited Safety Population: participants who were vaccinated and provided any solicited local or systemic adverse reaction safety data on subject diary cards from Day 1 through Day 7 after vaccination. | ||||||||
| 2 Proportion of participants reporting each solicited local adverse reaction or systemic adverse event by study vaccine group based on the number of participants contributing any follow up safety information for at least one data value of an individual sign/symptom | ||||||||
| 3 Non-influenza vaccine comparator: MENVEO, meningococcal (Groups A, C, Y, and W-135) oligosaccharide diphtheria CRM197 conjugate vaccine (GlaxoSmithKline Biologicals SA); children assigned to 2 doses received saline placebo as the second dose. | ||||||||
| 4 Local adverse reactions: Grade 3 pain is that which prevents daily activity; Erythema, induration and ecchymosis: any = ≥ 1mm diameter, Grade 3 = > 50 mm diameter for 2 through 5 years and > 100 mm diameter for 6 through 17 years. | ||||||||
| 5 Tenderness, change in eating habits, sleepiness, and irritability were collected for participants 2 through 6 years of age only. | ||||||||
| 6 Systemic adverse reactions: Fever: any = ≥ 100.4°F (Oral), Grade 3 = ≥ 104.0°F (Oral); Grade 3 change of eating habits: Missed more than 2 feeds/meals; Grade 3 sleepiness: Sleeps most of the time and is hard to arouse him/her; Grade 3 vomiting: 6 or more times in 24 hours or requires intravenous hydration; Grade 3 diarrhea: 6 or more loose stools in 24 hours or requires intravenous hydration; Grade 3 irritability: unable to console. Grade 3 for all other adverse events is that which prevents daily activity. | ||||||||
| The rates of antipyretic or analgesic use reported on the diary card for prophylaxis or treatment of high temperature or pain were as follows: 2 through 8 years of age FLUCELVAX QUADRIVALENT 11.0%, Comparator 7.7%; 9 through 18 years of age FLUCELVAX QUADRIVALENT 6.7%, Comparator 7.1%. | ||||||||
| Study 2: NCT03165617 | ||||||||
| Any | Gr 3 | Any | Gr 3 | Any | Gr 3 | Any | Gr 3 | |
| Local Adverse Reactions 4 | ||||||||
| Tenderness5 | 28.7 | 1.0 | 25.4 | 1.4 | – | – | – | – |
| Pain | 27.9 | 1.2 | 20.3 | 1.6 | 21.7 | 0.5 | 18.3 | 1.0 |
| Erythema | 21.3 | 0.4 | 23.7 | 1.1 | 17.2 | 0 | 18.7 | 0.5 |
| Induration | 14.9 | 0.2 | 15.2 | 0.4 | 10.5 | 0.1 | 11.0 | 0.2 |
| Ecchymosis | 10.0 | 0 | 7.5 | 0.1 | 5.0 | 0 | 5.2 | 0 |
| Systemic Adverse Reactions 6 | ||||||||
| Sleepiness5 | 14.9 | 0.9 | 17.6 | 1.8 | – | – | – | – |
| Headache | 13.8 | 0.4 | 11.8 | 0.5 | 18.1 | 1.4 | 17.4 | 0.6 |
| Fatigue | 13.8 | 0.9 | 12.7 | 0.7 | 17.0 | 1.1 | 18.2 | 1.2 |
| Irritability5 | 13.8 | 0.2 | 10.8 | 0.5 | – | – | – | – |
| Loss of Appetite | 10.6 | 0.5 | 8.0 | 0.5 | 8.5 | 0.5 | 7.5 | 0.5 |
| Change of eating habits5 | 9.9 | 1.0 | 10.1 | 0.7 | – | – | – | – |
| Fever | 7.6 | 0.5 | 6.1 | 0.2 | 2.8 | 0.1 | 3.0 | 0.3 |
| Diarrhea | 6.5 | 0.4 | 6.8 | 0.6 | 7.4 | 0.5 | 8.1 | 0.3 |
| Arthralgia | 5.2 | 0.4 | 6.2 | 0.3 | 7.1 | 0.4 | 8.4 | 0.5 |
| Nausea | 5.2 | 0 | 4.5 | 0.7 | 6.0 | 0.2 | 6.1 | 0.6 |
| Vomiting | 4.9 | 0.6 | 4.1 | 0.6 | 3.0 | 0.3 | 3.0 | 0.4 |
| Shivering/Chills | 4.7 | 0.7 | 3.9 | 0.4 | 7.6 | 0.4 | 7.6 | 0.3 |
| Myalgia | 2.9 | 0.2 | 4.0 | 0.3 | 6.1 | 0.5 | 5.5 | 0.5 |
In children who received a second dose (N=762) of FLUCELVAX QUADRIVALENT, the rates of solicited local and systemic adverse reactions were generally lower after the second dose compared to the first dose.
Serious adverse events (SAEs) were collected throughout the study duration (until 6 months after last vaccination) and were reported by 1.1% of the children and adolescents who received FLUCELVAX QUADRIVALENT. None of the SAEs were assessed as being related to study vaccine.
Adults 18 years of age and older:
The safety of FLUCELVAX QUADRIVALENT in adults was evaluated in a randomized, double-blind, controlled study conducted in the US (Study 3). The safety population included a total of 2680 adults 18 years of age and older; 1340 adults 18 through 64 years of age and 1340 adults 65 years of age and older.
In this study, adults received FLUCELVAX QUADRIVALENT or one of the two formulations of comparator trivalent influenza vaccine (TIV1c and TIV2c) (FLUCELVAX QUADRIVALENT (N=1335), TIV1c, N=676 or TIV2c, N= 669). The mean age of adults who received FLUCELVAX QUADRIVALENT was 57.4 years of age; 54.8% of adults were female and 75.6% were Caucasian, 13.4% were Black, 9.1% were Hispanics, 0.7% were American Indian and 0.3%, 0.1% and 0.7% were Asian, Native Hawaiian and others, respectively.
In this study, solicited local injection site and systemic adverse reactions were collected from adults who completed a symptom diary card for 7 days following vaccination.
Solicited adverse reactions for FLUCELVAX QUADRIVALENT and comparator are summarized in Table 4.
| Percentage (%) 2 of participants in each Age Cohort Reporting a Reaction | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Participants 18 through 64 years | Participants ≥ 65 years | |||||||||||
| FLUCELVAX Quadrivalent N=663 | TIV1c N=330 | TIV2c N=327 | FLUCELVAX Quadrivalent N=656 | TIV1c N=340 | TIV2c N=336 | |||||||
| Abbreviations: Gr 3, Grade 3. | ||||||||||||
| N = number of participants in the Safety Population for each study vaccine group. | ||||||||||||
| 1 Safety population: all participants in the exposed population who provided post-vaccination safety data | ||||||||||||
| 2 Proportion of participants reporting each solicited local adverse reaction or systemic adverse reaction by study vaccine group based on the number of participants contributing any follow up safety information for at least one data value of an individual sign/symptom | ||||||||||||
| 3 Local Adverse reactions: Grade 3 pain is that which prevents daily activity; Erythema, induration and ecchymosis: any = ≥ 1 mm diameter, Grade 3 = > 100 mm diameter. | ||||||||||||
| 4 Systemic adverse reactions: Fever: any = ≥ 100.4°F (Oral), Grade 3 = ≥ 104.0°F (Oral); Grade 3 vomiting: requires outpatient hydration; Grade 3 diarrhea: 6 or more stools or requires outpatient IV hydration; Grade 3 for all other adverse reactions is that which prevents daily activity. | ||||||||||||
| Study 3: NCT01992094 | ||||||||||||
| Any | Gr 3 | Any | Gr 3 | Any | Gr 3 | Any | Gr 3 | Any | Gr 3 | Any | Gr 3 | |
| Local Adverse Reactions 3 | ||||||||||||
| Pain | 45.4 | 0.5 | 37.0 | 0.3 | 40.7 | 0 | 21.6 | 0 | 18.8 | 0 | 18.5 | 0 |
| Erythema | 13.4 | 0 | 13.3 | 0 | 10.1 | 0 | 11.9 | 0 | 10.6 | 0 | 10.4 | 0 |
| Induration | 11.6 | 0 | 9.7 | 0.3 | 10.4 | 0 | 8.7 | 0 | 6.8 | 0 | 7.7 | 0 |
| Ecchymosis | 3.8 | 0 | 3.3 | 0.3 | 5.2 | 0 | 4.7 | 0 | 4.4 | 0 | 5.4 | 0 |
| Systemic Adverse Reactions 4 | ||||||||||||
| Headache | 18.7 | 0.9 | 18.5 | 0.9 | 18.7 | 0.6 | 9.3 | 0.3 | 8.5 | 0.6 | 8.3 | 0.6 |
| Fatigue | 17.8 | 0.6 | 22.1 | 0.3 | 15.6 | 1.5 | 9.1 | 0.8 | 10.6 | 0.3 | 8.9 | 0.6 |
| Myalgia | 15.4 | 0.8 | 14.5 | 0.9 | 15.0 | 1.2 | 8.2 | 0.2 | 9.4 | 0.3 | 8.3 | 0.6 |
| Nausea | 9.7 | 0.3 | 7.3 | 0.9 | 8.9 | 1.2 | 3.8 | 0.2 | 4.1 | 0 | 4.2 | 0.3 |
| Loss of appetite | 8.3 | 0.3 | 8.5 | 0.3 | 8.3 | 0.9 | 4.0 | 0.2 | 5.0 | 0 | 3.6 | 0.3 |
| Arthralgia | 8.1 | 0.5 | 8.2 | 0 | 9.5 | 0.9 | 5.5 | 0.5 | 5.0 | 0.3 | 6.8 | 0.9 |
| Diarrhea | 7.4 | 0.6 | 7.6 | 0 | 7.6 | 0.6 | 4.3 | 0.5 | 5.0 | 0.9 | 5.1 | 0.3 |
| Chills | 6.2 | 0.2 | 6.4 | 0.6 | 6.4 | 0 | 4.4 | 0.3 | 4.1 | 0.3 | 4.5 | 0.6 |
| Vomiting | 2.6 | 0 | 1.5 | 0.3 | 0.9 | 0 | 0.9 | 0.2 | 0.3 | 0 | 0.6 | 0 |
| Fever | 0.8 | 0 | 0.6 | 0 | 0.3 | 0 | 0.3 | 0 | 0.9 | 0 | 0.6 | 0 |
Unsolicited adverse events were collected for 21 days after vaccination. In adults 18 years of age and older, unsolicited adverse events were reported in 16.1% of adults who received FLUCELVAX QUADRIVALENT, within 21 days after vaccination.
In adults 18 years of age and older, serious adverse events (SAEs) were collected throughout the study duration (until 6 months after vaccination) and were reported by 3.9% of the adults who received FLUCELVAX QUADRIVALENT. None of the SAEs were assessed as being related to study vaccine.
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