Vaccine Information: FLUARIX QUADRIVALENT 2019/2020

FLUARIX QUADRIVALENT 2019/2020- influenza a virus a/brisbane/02/2018 ivr-190 (h1n1) antigen (formaldehyde inactivated), influenza a virus a/kansas/14/2017 x-327 (h3n2) antigen (formaldehyde inactivated), influenza b virus b/maryland/15/2016 bx-69a antigen (formaldehyde inactivated) and influenza b virus b/phuket/3073/2013 antigen (formaldehyde inactivated) suspension
GlaxoSmithKline Biologicals SA

1 INDICATIONS AND USAGE

FLUARIX QUADRIVALENT is indicated for active immunization for the prevention of disease caused by influenza A subtype viruses and type B viruses contained in the vaccine [see Description (11)]. FLUARIX QUADRIVALENT is approved for use in persons aged 6 months and older.

2 DOSAGE AND ADMINISTRATION

For intramuscular injection only.

2.1 Dosage and Schedule

The dose and schedule for FLUARIX QUADRIVALENT are presented in Table 1.

Table 1. FLUARIX QUADRIVALENT: Dosing
a One dose or 2 doses (0.5‑mL each) depending on vaccination history as per the annual Advisory Committee on Immunization Practices (ACIP) recommendation on prevention and control of influenza with vaccines. If 2 doses, administer each 0.5‑mL dose at least 4 weeks apart.

Age

Vaccination Status

Dose and Schedule

6 months through 8 years

Not previously vaccinated with influenza vaccine

Two doses (0.5‑mL each) at least 4 weeks apart

Vaccinated with influenza vaccine in a previous season

One or 2 dosesa (0.5‑mL each)

9 years and older

Not applicable

One 0.5‑mL dose

2.2 Administration Instructions

Shake well before administration. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If either of these conditions exists, the vaccine should not be administered.

Attach a sterile needle to the prefilled syringe and administer intramuscularly.

The preferred sites for intramuscular injection are the anterolateral thigh for children aged 6 through 11 months and the deltoid muscle of the upper arm for persons aged 12 months and older if muscle mass is adequate. Do not inject in the gluteal area or areas where there may be a major nerve trunk.

Do not administer this product intravenously, intradermally, or subcutaneously.

3 DOSAGE FORMS AND STRENGTHS

FLUARIX QUADRIVALENT is a suspension for injection. Each 0.5‑mL dose is supplied in single-dose prefilled TIP‑LOK syringes.

4 CONTRAINDICATIONS

Do not administer FLUARIX QUADRIVALENT to anyone with a history of severe allergic reactions (e.g., anaphylaxis) to any component of the vaccine, including egg protein, or following a previous administration of any influenza vaccine [see Description (11)].

5 WARNINGS AND PRECAUTIONS

5.1 Guillain-Barré Syndrome

If Guillain‑Barré syndrome (GBS) has occurred within 6 weeks of receipt of a prior influenza vaccine, the decision to give FLUARIX QUADRIVALENT should be based on careful consideration of the potential benefits and risks.

The 1976 swine influenza vaccine was associated with an increased frequency of GBS. Evidence for a causal relation of GBS with subsequent vaccines prepared from other influenza viruses is inconclusive. If influenza vaccine does pose a risk, it is probably slightly more than 1 additional case/1 million persons vaccinated.

5.2 Syncope

Syncope (fainting) can occur in association with administration of injectable vaccines, including FLUARIX 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.

5.3 Preventing and Managing Allergic Vaccine Reactions

Prior to administration, the healthcare provider should review the immunization history for possible vaccine sensitivity and previous vaccination‑related adverse reactions. Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of FLUARIX QUADRIVALENT.

5.4 Altered Immunocompetence

If FLUARIX QUADRIVALENT is administered to immunosuppressed persons, including individuals receiving immunosuppressive therapy, the immune response may be lower than in immunocompetent persons.

5.5 Limitations of Vaccine Effectiveness

Vaccination with FLUARIX QUADRIVALENT may not protect all susceptible individuals.

5.6 Persons at Risk of Bleeding

As with other intramuscular injections, FLUARIX QUADRIVALENT should be given with caution in individuals with bleeding disorders, such as hemophilia or on anticoagulant therapy, to avoid the risk of hematoma following the injection.

6 ADVERSE REACTIONS

The safety experience with FLUARIX (trivalent influenza vaccine) is relevant to FLUARIX QUADRIVALENT because both vaccines are manufactured using the same process and have overlapping compositions [see Description (11)].

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared with rates in the clinical trials of another vaccine and may not reflect the rates observed in practice. There is the possibility that broad use of FLUARIX QUADRIVALENT could reveal adverse reactions not observed in clinical trials.

In adults who received FLUARIX QUADRIVALENT, the most common (≥10%) solicited local adverse reaction was pain (36%). The most common (≥10%) systemic adverse reactions were muscle aches (16%), headache (16%), and fatigue (16%).

In children aged 6 through 35 months who received FLUARIX QUADRIVALENT, the most common (≥10%) solicited local adverse reactions were pain (17%) and redness (13%). The most common (≥10%) systemic adverse reactions were irritability (16%), loss of appetite (14%), and drowsiness (13%). In children aged 3 through 17 years who received FLUARIX QUADRIVALENT, solicited local adverse reactions were pain (44%), redness (23%), and swelling (19%). In children aged 3 through 5 years, the most common (≥10%) systemic adverse reactions were drowsiness (17%), irritability (17%), and loss of appetite (16%); in children aged 6 through 17 years, the most common systemic adverse reactions were fatigue (20%), muscle aches (18%), headache (16%), arthralgia (10%), and gastrointestinal symptoms (10%).

FLUARIX QUADRIVALENT in Adults

Trial 1 (NCT01204671) was a randomized, double-blind (2 arms) and open-label (one arm), active-controlled, safety, and immunogenicity trial. In this trial, subjects received FLUARIX QUADRIVALENT (n = 3,036) or one of 2 formulations of comparator trivalent influenza vaccine (FLUARIX; TIV-1, n = 1,010; or TIV-2, n = 610), each containing an influenza type B virus that corresponded to one of the 2 type B viruses in FLUARIX QUADRIVALENT (a type B virus of the Victoria lineage or a type B virus of the Yamagata lineage). The population was aged 18 years and older (mean age: 58 years) and 57% were female; 69% were white, 27% were Asian, and 4% were of other racial/ethnic groups. Solicited events were collected for 7 days (day of vaccination and the next 6 days). The frequencies of solicited adverse reactions are shown in Table 2.

Table 2. FLUARIX QUADRIVALENT: Incidence of Solicited Local Adverse Reactions and Systemic Adverse Reactions within 7 Daysa of Vaccination in Adultsb (Total Vaccinated Cohort)
Total vaccinated cohort for safety included all vaccinated subjects for whom safety data were available. n = Number of subjects with diary card completed.a Seven days included day of vaccination and the subsequent 6 days.b Trial 1: NCT01204671.c Contained the same composition as FLUARIX (trivalent formulation) manufactured for the 2010-2011 season and an additional influenza type B virus of Yamagata lineage.d Contained the same composition as FLUARIX manufactured for the 2010-2011 season (2 influenza A subtype viruses and an influenza type B virus of Victoria lineage).e Contained the same 2 influenza A subtype viruses as FLUARIX manufactured for the 2010-2011 season and an influenza type B virus of Yamagata lineage.f Grade 3 pain: Defined as significant pain at rest; prevented normal everyday activities. Grade 3 redness, swelling: Defined as >100 mm. Grade 3 muscle aches, headache, fatigue, arthralgia, gastrointestinal symptoms, shivering: Defined as prevented normal activity. Grade 3 fever: Defined as >102.2°F (39.0°C). g Gastrointestinal symptoms included nausea, vomiting, diarrhea, and/or abdominal pain.h Fever: Defined as ≥99.5°F (37.5°C).

Adverse Reaction

Trivalent Influenza Vaccine (TIV)

FLUARIX QUADRIVALENTc

n = 3,011-3,015

%

TIV-1

(B Victoria)d

n = 1,003

%

TIV-2

(B Yamagata)e

n = 607

%

Any

Grade 3f

Any

Grade 3f

Any

Grade 3f

Local

Pain

36.4

0.8

36.8

1.2

31.3

0.5

Redness

1.9

0

1.7

0

2.0

0

Swelling

2.1

0

2.1

0

1.3

0

Systemic

Muscle aches

16.4

0.5

19.4

0.8

16.1

0.5

Headache

15.9

0.9

16.4

0.8

13.2

0.7

Fatigue

15.8

0.7

18.4

0.6

14.8

0.5

Arthralgia

8.4

0.5

10.4

0.7

9.4

0.3

Gastrointestinal symptomsg

6.5

0.4

6.5

0.2

5.9

0.3

Shivering

4.2

0.4

5.0

0.3

4.3

0.2

Feverh

1.6

0

1.2

0

1.5

0

Unsolicited events occurring within 21 days of vaccination (Day 0 to 20) were reported in 13%, 14%, and 15% of subjects who received FLUARIX QUADRIVALENT, TIV-1, or TIV-2, respectively. The unsolicited adverse reactions that occurred most frequently (≥0.1% for FLUARIX QUADRIVALENT) included dizziness, injection site hematoma, injection site pruritus, and rash. Serious adverse events occurring within 21 days of vaccination were reported in 0.5%, 0.6%, and 0.2% of subjects who received FLUARIX QUADRIVALENT, TIV-1, or TIV-2, respectively.

FLUARIX QUADRIVALENT in Children

Trial 7 (NCT01439360) was a randomized, observer-blind, non-influenza vaccine-controlled trial evaluating the efficacy of FLUARIX QUADRIVALENT. In this trial, subjects aged 6 through 35 months received FLUARIX QUADRIVALENT (n = 6,006) or a control vaccine (n = 6,012). The comparator was pneumococcal 13-valent conjugate vaccine [Diphtheria CRM197 Protein] (Wyeth Pharmaceuticals, Inc.) in children younger than 12 months, HAVRIX (Hepatitis A Vaccine) in children 12 months and older with a history of influenza vaccination, or HAVRIX (Dose 1) and a varicella vaccine (U.S. Licensed Manufactured by Merck & Co., Inc. or Non-U.S. Licensed Manufactured by GlaxoSmithKline Biologicals) (Dose 2) in those with no history of influenza vaccination. Subjects were aged 6 through 35 months, and one child aged 43 months (mean age: 22 months); 51% were male; 27% were white, 45% were Asian, and 28% were of other racial/ethnic groups. Children aged 12 months and older with no history of influenza vaccination and children younger than 12 months received 2 doses of FLUARIX QUADRIVALENT or the control vaccine approximately 28 days apart. Children aged 12 months and older with a history of influenza vaccination received one dose. Solicited local adverse reactions and systemic adverse events were collected using diary cards for 7 days (day of vaccination and the next 6 days). The incidences of solicited adverse reactions are shown in Table 3.

Table 3. FLUARIX QUADRIVALENT: Incidence of Solicited Local Adverse Reactions and Systemic Adverse Reactions within 7 Daysa after First Vaccination in Children Aged 6 through 35 Monthsb (Total Vaccinated Cohort)
Total vaccinated cohort for safety included all vaccinated subjects for whom safety data were available.n = Number of subjects with diary card completed.a Seven days included day of vaccination and the subsequent 6 days.b Trial 7: NCT01439360.c Children younger than 12 months: pneumococcal 13-valent conjugate vaccine [Diphtheria CRM197 Protein] (Wyeth Pharmaceuticals, Inc.). d Children 12 months and older: HAVRIX (Hepatitis A Vaccine) for those with a history of influenza vaccination; or HAVRIX (Dose 1) and a varicella vaccine (U.S. Licensed Manufactured by Merck & Co., Inc. or Non-U.S. Licensed Manufactured by GlaxoSmithKline Biologicals) (Dose 2) for those with no history of influenza vaccination.e Grade 3 pain: Defined as cried when limb was moved/spontaneously painful. Grade 3 swelling, redness: Defined as >50 mm. Grade 3 irritability: Defined as crying that could not be comforted/prevented normal activity. Grade 3 loss of appetite: Defined as not eating at all. Grade 3 drowsiness: Defined as prevented normal activity. Grade 3 fever: Defined as >102.2°F (39.0°C). f Fever: Defined as ≥100.4°F (38.0°C).

Adverse Reaction

FLUARIX QUADRIVALENT

%

Non-Influenza Active Comparatorc,d

%

Any

Grade 3e

Any

Grade 3e

Local

n = 5,899

n = 5,896

Pain

17.2

0.4

17.8

0.5

Redness

13.1

0

14.1

0

Swelling

7.9

0

8.8

0

Systemic

n = 5,898

n = 5,896

Irritability

16.2

0.7

17.5

1.1

Loss of appetite

14.4

1.2

14.8

1.0

Drowsiness

12.5

0.7

14.1

0.9

Feverf

6.3

1.3

7.2

1.3

In children who received a second dose of FLUARIX QUADRIVALENT or the Non-Influenza Active Comparator vaccine, the incidences of solicited adverse reactions following the second dose were generally lower than those observed after the first dose.

Unsolicited adverse events occurring within 28 days of vaccination were reported in 44% and 45% of subjects who received FLUARIX QUADRIVALENT (n = 6,006) and the comparator vaccine (n = 6,012), respectively. Serious adverse events (SAEs) occurring during the study period (6 to 8 months) were reported in 3.6% of subjects who received FLUARIX QUADRIVALENT and in 3.3% of subjects who received the comparator vaccine.

Trial 2 (NCT01196988) was a randomized, double-blind, active-controlled, safety, and immunogenicity trial. In this trial, subjects received FLUARIX QUADRIVALENT (n = 915) or one of 2 formulations of comparator trivalent influenza vaccine (FLUARIX; TIV-1, n = 912; or TIV-2, n = 911), each containing an influenza type B virus that corresponded to one of the 2 type B viruses in FLUARIX QUADRIVALENT (a type B virus of the Victoria lineage or a type B virus of the Yamagata lineage). Subjects were aged 3 through 17 years and 52% were male; 56% were white, 29% were Asian, 12% were black, and 3% were of other racial/ethnic groups. Children aged 3 through 8 years with no history of influenza vaccination received 2 doses approximately 28 days apart. Children aged 3 through 8 years with a history of influenza vaccination and children aged 9 years and older received one dose. Solicited local adverse reactions and systemic adverse events were collected using diary cards for 7 days (day of vaccination and the next 6 days). The frequencies of solicited adverse reactions are shown in Table 4.

Table 4. FLUARIX QUADRIVALENT: Incidence of Solicited Local Adverse Reactions and Systemic Adverse Reactions within 7 Daysa after First Vaccination in Children Aged 3 through 17 Yearsb (Total Vaccinated Cohort)
Total vaccinated cohort for safety included all vaccinated subjects for whom safety data were available.n = Number of subjects with diary card completed.a Seven days included day of vaccination and the subsequent 6 days.b Trial 2: NCT01196988.c Contained the same composition as FLUARIX (trivalent formulation) manufactured for the 2010-2011 season and an additional influenza type B virus of Yamagata lineage.d Contained the same composition as FLUARIX manufactured for the 2010-2011 season (2 influenza A subtype viruses and an influenza type B virus of Victoria lineage).e Contained the same 2 influenza A subtype viruses as FLUARIX manufactured for the 2010-2011 season and an influenza type B virus of Yamagata lineage.f Grade 3 pain: Defined as cried when limb was moved/spontaneously painful (children ˂6 years), or significant pain at rest, prevented normal everyday activities (children ≥6 years). Grade 3 redness, swelling: Defined as >50 mm. Grade 3 drowsiness: Defined as prevented normal activity. Grade 3 irritability: Defined as crying that could not be comforted/prevented normal activity. Grade 3 loss of appetite: Defined as not eating at all. Grade 3 fever: Defined as >102.2°F (39.0°C). Grade 3 fatigue, muscle aches, headache, arthralgia, gastrointestinal symptoms, shivering: Defined as prevented normal activity. g Percentage of subjects with any pain by age subgroup: 39%, 38%, and 37% for FLUARIX QUADRIVALENT, TIV-1, and TIV-2, respectively, in children aged 3 through 8 years and 52%, 50%, and 46% for FLUARIX QUADRIVALENT, TIV-1, and TIV-2, respectively, in children aged 9 through 17 years.h Fever: Defined as ≥99.5°F (37.5°C).i Gastrointestinal symptoms included nausea, vomiting, diarrhea, and/or abdominal pain.

Trivalent Influenza Vaccine (TIV)

FLUARIX QUADRIVALENTc

%

TIV-1

(B Victoria)d

%

TIV-2

(B Yamagata)e

%

Any

Grade 3f

Any

Grade 3f

Any

Grade 3f

Adverse Reaction

Aged 3 through 17 Years

Local

n = 903

n = 901

n = 905

Paing

43.7

1.6

42.4

1.8

40.3

0.8

Redness

23.0

1.0

21.3

0.2

20.9

0.7

Swelling

18.5

0.8

17.2

1.1

14.9

0.2

Aged 3 through 5 Years

Systemic

n = 291

n = 314

n = 279

Drowsiness

17.2

1.0

12.4

0.3

13.6

0.7

Irritability

16.8

0.7

13.4

0.3

14.3

0.7

Loss of appetite

15.5

0.3

8.0

0

10.4

0.7

Feverh

8.9

0.3

8.9

0.3

8.2

1.1

Aged 6 through 17 Years

Systemic

n = 613

n = 588

n = 626

Fatigue

19.7

1.5

18.5

1.4

15.5

0.5

Muscle aches

17.5

0.7

16.0

1.4

15.8

0.5

Headache

16.3

1.3

19.2

0.7

15.2

0.6

Arthralgia

9.8

0.3

9.4

0.7

7.3

0.2

Gastrointestinal symptomsi

9.8

1.0

9.5

0.7

7.2

0.3

Shivering

6.4

0.5

4.4

0.5

5.0

0

Feverh

6.0

1.1

8.5

0.5

6.1

0.3

In children who received a second dose of FLUARIX QUADRIVALENT, TIV-1, or TIV-2, the incidences of adverse reactions following the second dose were generally lower than those observed after the first dose.

Unsolicited adverse events occurring within 28 days of any vaccination were reported in 31%, 33%, and 34% of subjects who received FLUARIX QUADRIVALENT, TIV-1, or TIV-2, respectively. The unsolicited adverse reactions that occurred most frequently (≥0.1% for FLUARIX QUADRIVALENT) included injection site pruritus and rash. Serious adverse events occurring within 28 days of any vaccination were reported in 0.1%, 0.1%, and 0.1% of subjects who received FLUARIX QUADRIVALENT, TIV-1, or TIV-2, respectively.

FLUARIX (Trivalent Formulation)

FLUARIX has been administered to 10,317 adults aged 18 through 64 years, 606 subjects aged 65 years and older, and 2,115 children aged 6 months through 17 years in clinical trials. The incidence of solicited adverse reactions in each age-group is shown in Tables 5 and 6.

Table 5. FLUARIX (Trivalent Formulation): Incidence of Solicited Local Adverse Reactions and Systemic Adverse Reactions within 4 Daysa of Vaccination in Adults (Total Vaccinated Cohort)
Total vaccinated cohort for safety included all vaccinated subjects for whom safety data were available. n = Number of subjects with diary card completed.a Four days included day of vaccination and the subsequent 3 days.b Trial 3 was a randomized, double-blind, placebo-controlled, safety, and immunogenicity trial (NCT00100399).c Trial 4 was a randomized, single-blind, active-controlled, safety, and immunogenicity trial (NCT00197288). The active control was FLUZONE, a U.S.-licensed trivalent, inactivated influenza vaccine (Sanofi Pasteur Inc.).d Grade 3 pain, muscle aches, fatigue, headache, arthralgia, shivering: Defined as prevented normal activity. Grade 3 redness, swelling: Defined as >50 mm. Grade 3 fever: Defined as >102.2°F (39.0°C). e Fever: Defined as ≥100.4°F (38.0°C) in Trial 3, and ≥99.5°F (37.5°C) in Trial 4.

Adverse Reaction

Trial 3b

Trial 4c

Aged 18 through 64 Years

Aged 65 Years and Older

FLUARIX

n = 760

%

Placebo

n = 192

%

FLUARIX

n = 601-602

%

Comparator

n = 596

%

Any

Grade 3d

Any

Grade 3d

Any

Grade 3d

Any

Grade 3d

Local

Pain

54.7

0.1

12.0

0

19.1

0

17.6

0

Redness

17.5

0

10.4

0

10.6

0.2

13.1

0.7

Swelling

9.3

0.1

5.7

0

6.0

0

8.9

0.7

Systemic

Muscle aches

23.0

0.4

12.0

0.5

7.0

0.3

6.5

0

Fatigue

19.7

0.4

17.7

1.0

9.0

0.3

9.6

0.7

Headache

19.3

0.1

21.4

1.0

7.5

0.3

7.9

0.3

Arthralgia

6.4

0.1

6.3

0.5

5.5

0.5

5.0

0.2

Shivering

3.3

0.1

2.6

0

1.7

0.2

2.2

0

Fevere

1.7

0

1.6

0

1.7

0

0.5

0

Table 6. FLUARIX (Trivalent Formulation): Incidence of Solicited Local Adverse Reactions and Systemic Adverse Reactions within 4 Daysa of First Vaccination in Children Aged 3 through 17 Yearsb (Total Vaccinated Cohort)
Total vaccinated cohort for safety included all vaccinated subjects for whom safety data were available.n = Number of subjects with diary card completed. a Four days included day of vaccination and the subsequent 3 days.b Trial 6 was a single-blind, active-controlled, safety, and immunogenicity U.S. trial (NCT00383123). The active control was FLUZONE, a U.S.-licensed trivalent, inactivated influenza vaccine (Sanofi Pasteur Inc.).c Grade 3 pain, irritability, loss of appetite, drowsiness, muscle aches, fatigue, headache, arthralgia, shivering: Defined as prevented normal activity. Grade 3 swelling, redness: Defined as >50 mm. Grade 3 fever: Defined as >102.2°F (39.0°C). d Fever: Defined as ≥99.5°F (37.5°C).

Adverse Reaction

Aged 3 through 4 Years

Aged 5 through 17 Years

FLUARIX

n = 350

%

Comparator

n = 341

%

FLUARIX

n = 1,348

%

Comparator

n = 451

%

Any

Grade 3c

Any

Grade 3c

Any

Grade 3c

Any

Grade 3c

Local

Pain

34.9

1.7

38.4

1.2

56.2

0.8

56.1

0.7

Redness

22.6

0.3

19.9

0

17.7

1.0

16.4

0.7

Swelling

13.7

0

13.2

0

13.9

1.5

13.3

0.7

Systemic

Irritability

20.9

0.9

22.0

0

Loss of appetite

13.4

0.9

15.0

0.9

Drowsiness

13.1

0.6

19.6

0.9

Feverd

6.6

1.4

7.6

1.5

4.2

0.3

3.3

0.2

Muscle aches

28.8

0.4

28.8

0.4

Fatigue

19.9

1.0

18.8

1.1

Headache

15.1

0.5

16.4

0.9

Arthralgia

5.6

0.1

6.2

0.2

Shivering

3.1

0.1

3.5

0.2

In children who received a second dose of FLUARIX or the comparator vaccine, the incidences of adverse reactions following the second dose were similar to those observed after the first dose.

Serious Adverse Reactions: In the 4 clinical trials in adults (N = 10,923), there was a single case of anaphylaxis within one day following administration of FLUARIX (<0.01%).

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