Vaccine Information: Flulaval Quadrivalent 2019/2020

FLULAVAL QUADRIVALENT 2019/2020- influenza a virus a/brisbane/02/2018 ivr-190 (h1n1) antigen (uv, formaldehyde inactivated), influenza a virus a/kansas/14/2017 x-327 (h3n2) antigen (uv, formaldehyde inactivated), influenza b virus b/phuket/3073/2013 antigen (uv, formaldehyde inactivated) and influenza b virus b/maryland/15/2016 bx-69a antigen (uv, formaldehyde inactivated) suspension
ID Biomedical Corporation of Quebec

1 INDICATIONS AND USAGE

FLULAVAL 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. FLULAVAL 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 FLULAVAL QUADRIVALENT are presented in Table 1.

Table . FLULAVAL 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.

For the multi-dose vial, use a sterile needle and sterile syringe to withdraw the 0.5‑mL dose from the multi-dose vial and administer intramuscularly. A sterile syringe with a needle bore no larger than 23 gauge is recommended for administration. It is recommended that small syringes (0.5ºmL or 1ºmL) be used to minimize any product loss. Use a separate sterile needle and syringe for each dose withdrawn from the multi-dose vial.

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. Once entered, a multi-dose vial, and any residual contents should be discarded after 28 days.

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. 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

FLULAVAL QUADRIVALENT is a suspension for injection available in 0.5-mL prefilled TIP‑LOK syringes and 5‑mL multi-dose vials containing 10 doses (each dose is 0.5ºL).

4 CONTRAINDICATIONS

Do not administer FLULAVAL 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 dose 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 FLULAVAL QUADRIVALENT 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 relation of GBS with other influenza vaccines is inconclusive; if an excess risk exists, 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 FLULAVAL 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 FLULAVAL QUADRIVALENT.

5.4 Altered Immunocompetence

If FLULAVAL 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 FLULAVAL QUADRIVALENT may not protect all susceptible individuals.

5.6 Persons at Risk of Bleeding

As with other intramuscular injections, FLULAVAL 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

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 FLULAVAL QUADRIVALENT could reveal adverse reactions not observed in clinical trials.

In adults who received FLULAVAL QUADRIVALENT, the most common (≥10%) solicited local adverse reaction was pain (60%); the most common (≥10%) solicited systemic adverse events were muscle aches (26%), headache (22%), fatigue (22%), and arthralgia (15%).

In children aged 6 through 35 months who received FLULAVAL QUADRIVALENT, the most common (≥10%) solicited local adverse reaction was pain (40%); the most common (≥10%) solicited systemic adverse events were irritability (49%), drowsiness (37%), and loss of appetite (29%).

In children aged 3 through 17 years who received FLULAVAL QUADRIVALENT, the most common (≥10%) solicited local adverse reaction was pain (65%). In children aged 3 through 4 years, the most common (≥10%) solicited systemic adverse events were irritability (26%), drowsiness (21%), and loss of appetite (17%). In children aged 5 through 17 years, the most common (≥10%) systemic adverse events were muscle aches (29%), fatigue (22%), headache (22%), arthralgia (13%), and gastrointestinal symptoms (10%).

FLULAVAL QUADRIVALENT has been administered in 8 clinical trials to 1,384 adults aged 18 years and older, 1,965 children aged 6 through 35 months, and 3,516 children aged 3 through 17 years.

FLULAVAL QUADRIVALENT in Adults

Trial 1 (NCT01196975) was a randomized, double-blind, active-controlled, safety and immunogenicity trial. In this trial, subjects received FLULAVAL QUADRIVALENT (n = 1,272), or one of 2 formulations of a comparator trivalent influenza vaccine (FLULAVAL, TIV-1, n = 213 or TIV-2, n = 218), each containing an influenza type B virus that corresponded to one of the 2 B viruses in FLULAVAL 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: 50 years) and 61% were female; 61% of subjects were white, 3% were black, 1% were Asian, and 35% were of other racial/ethnic groups. Solicited adverse events were collected for 7 days (day of vaccination and the next 6 days). The incidence of local adverse reactions and systemic adverse events occurring within 7 days of vaccination in adults are shown in Table 2.

Table . FLULAVAL QUADRIVALENT: Incidence of Solicited Local Adverse Reactions and Systemic Adverse Events within 7 Daysa of Vaccination in Adults Aged 18 Years and Olderb (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 7 days included day of vaccination and the subsequent 6 days.b Trial 1: NCT01196975.c Contained 2 A strains and 2 B strains, one of Victoria lineage and one of Yamagata lineage.d Contained the same 2 A strains as FLULAVAL QUADRIVALENT and a B strain of Victoria lineage.e Contained the same 2 A strains as FLULAVAL QUADRIVALENT and a B strain of Yamagata lineage.f Grade 3 pain: Defined as significant pain at rest; prevented normal everyday activities. Grade 3 swelling, redness: Defined as >100 mm. Grade 3 muscle aches, headache, fatigue, arthralgia, gastrointestinal symptoms, shivering: Defined as prevented normal activity. Grade 3 (or higher) fever: Defined as ≥102.2°F (39.0°C).g Gastrointestinal symptoms included nausea, vomiting, diarrhea, and/or abdominal pain.h Fever: Defined as ≥100.4°F (38.0°C)

Adverse Reaction/Adverse Event

Trivalent Influenza Vaccine (TIV)

FLULAVAL

TIV-1

TIV-2

QUADRIVALENTc

(B Victoria)d

(B Yamagata)e

n = 1,260

n = 208

n = 216

%

%

%

Any

Grade 3f

Any

Grade 3f

Any

Grade 3f

Local Adverse Reactions

Pain

59.5

1.7

44.7

1.0

41.2

1.4

Swelling

2.5

0.0

1.4

0.0

3.7

0.0

Redness

1.7

0.0

2.9

0.0

1.4

0.0

Systemic Adverse Events

Muscle aches

26.3

0.8

25.0

0.5

18.5

1.4

Headache

21.5

0.9

19.7

0.5

22.7

0.0

Fatigue

21.5

0.8

21.6

1.0

17.1

1.9

Arthralgia

14.8

0.8

16.7

1.0

14.6

2.9

Gastrointestinal symptomsg

9.3

0.8

10.1

1.9

6.9

0.5

Shivering

8.8

0.6

7.7

0.5

6.0

0.9

Feverh

1.3

0.4

0.5

0.0

1.4

0.5

Unsolicited adverse events occurring within 21 days of vaccination were reported in 19%, 23%, and 23% of subjects who received FLULAVAL QUADRIVALENT (n = 1,272), TIV-1 (B Victoria) (n = 213), or TIV-2 (B Yamagata) (n = 218), respectively. The unsolicited adverse events that occurred most frequently (≥1% for FLULAVAL QUADRIVALENT) included nasopharyngitis, upper respiratory tract infection, headache, cough, and oropharyngeal pain. Serious adverse events occurring within 21 days of vaccination were reported in 0.4%, 0%, and 0% of subjects who received FLULAVAL QUADRIVALENT, TIV-1 (B Victoria), or TIV-2 (B Yamagata), respectively.

FLULAVAL QUADRIVALENT in Children

Trial 4 (NCT02242643) was a randomized, observer-blind, active-controlled immunogenicity and safety trial. The trial included subjects aged 6 through 35 months who received FLULAVAL QUADRIVALENT (n = 1,207) or FLUZONE QUADRIVALENT, a U.S.-licensed inactivated influenza vaccine (n = 1,217) used as comparator, manufactured by Sanofi Pasteur Inc. Children with no history of influenza vaccination received 2 doses of FLULAVAL QUADRIVALENT or the comparator vaccine approximately 28 days apart. Children with a history of influenza vaccination received one dose of FLULAVAL QUADRIVALENT or the comparator vaccine. In the overall population, 53% were male; 64% were white, 16% were black, 3% were Asian, and 17% were of other racial/ethnic groups. The mean age of subjects was 20 months. Subjects were followed for safety for 6 months; solicited local adverse reactions and systemic adverse events were collected for 7 days (day of vaccination and the next 6 days) post vaccination. The incidence of local adverse reactions and systemic adverse events occurring within 7 days of vaccination in children are shown in Table 3.

Table . FLULAVAL QUADRIVALENT: Incidence of Solicited Local Adverse Reactions and Systemic Adverse Events within 7 Daysa of 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 (i.e., diary card completed for solicited symptoms). n = number of subjects with diary card completed.a 7 days included day of vaccination and the subsequent 6 days.b Trial 4: NCT02242643.c U.S.-licensed quadrivalent, inactivated influenza vaccine (manufactured by Sanofi Pasteur Inc).d Grade 3 pain: Defined as cried when limb was moved/spontaneously painful. Grade 3 swelling, redness: Defined as >100 mm. Grade 3 irritability: Defined as crying that could not be comforted/prevented normal activity. Grade 3 drowsiness: Defined as prevented normal activity. Grade 3 loss of appetite: Defined as not eating at all. Grade 3 (or higher) fever: Defined as >102.2°F (39.0°C). e Fever: Defined as ≥100.4°F (38.0°C).

Adverse Reaction/ Adverse Event

FLULAVAL QUADRIVALENT

%

Active Comparatorc

%

Any

Grade 3d

Any

Grade 3d

Local Adverse Reactions

n = 1,151

n = 1,146

Pain

40.3

2.4

37.4

1.4

Swelling

1.0

0.0

0.4

0.0

Redness

1.3

0.0

1.3

0.0

Systemic Adverse Events

n = 1,155

n = 1,148

Irritability

49.4

3.8

45.9

3.0

Drowsiness

36.7

2.7

36.9

2.6

Loss of appetite

28.9

1.6

28.6

1.3

Fevere

5.6

1.4

5.8

1.0

In children who received a second dose of FLULAVAL QUADRIVALENT or the comparator vaccine, the incidences of solicited adverse events following the second dose were generally similar or lower than those observed after the first dose.

Unsolicited adverse events occurring within 28 days of vaccination were reported in 46% and 44% of subjects who received FLULAVAL QUADRIVALENT (n = 1,207) and the comparator vaccine (n = 1,217), respectively. The unsolicited adverse reactions that occurred most frequently (≥1%) for FLULAVAL QUADRIVALENT included upper respiratory tract infection, cough, diarrhea, pyrexia, vomiting, and rash. Serious adverse events occurring during the study period (approximately 6 months) were reported in 2% of subjects who received FLULAVAL QUADRIVALENT and in 2% of subjects who received the comparator vaccine. There were no deaths reported during the study period.

Trial 2 (NCT01198756) was a randomized, double-blind, active-controlled trial. In this trial, subjects received FLULAVAL QUADRIVALENT (n = 932) or one of 2 formulations of a comparator trivalent influenza vaccine [FLUARIX (Influenza Vaccine), TIV-1 (B Victoria), n = 929 or TIV-2 (B Yamagata), n = 932], each containing an influenza type B virus that corresponded to one of the 2 B viruses in FLULAVAL QUADRIVALENT (a type B virus of the Victoria lineage or a type B virus of the Yamagata lineage). The population was aged 3 through 17 years (mean age: 9 years) and 53% were male; 65% were white, 13% were Asian, 9% were black, and 13% 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 for 7 days (day of vaccination and the next 6 days). The incidence of local adverse reactions and systemic adverse events occurring within 7 days of vaccination in children are shown in Table 4.

Table . FLULAVAL QUADRIVALENT: Incidence of Solicited Local Adverse Reactions and Systemic Adverse Events within 7 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 7 days included day of vaccination and the subsequent 6 days.b Trial 2: NCT01198756.c Contained 2 A strains and 2 B strains, one of Victoria lineage and one of Yamagata lineage.d Contained the same 2 A strains as FLULAVAL QUADRIVALENT and a B strain of Victoria lineage.e Contained the same 2 A strains as FLULAVAL QUADRIVALENT and a B strain of Yamagata lineage.f Grade 3 pain: Defined as cried when limb was moved/spontaneously painful (children ˂5 years), or significant pain at rest, prevented normal everyday activities (children ≥5 years). Grade 3 swelling, redness: Defined as >100 mm. Grade 3 irritability: Defined as crying that could not be comforted/prevented normal activity. Grade 3 drowsiness: Defined as prevented normal activity. Grade 3 loss of appetite: Defined as not eating at all. Grade 3 (or higher) fever: Defined as ≥102.2°F (39.0°C). Grade 3 muscle aches, fatigue, headache, arthralgia, gastrointestinal symptoms, shivering: Defined as prevented normal activity.g Fever: Defined as ≥100.4°F (38.0°C). h Gastrointestinal symptoms included nausea, vomiting, diarrhea, and/or abdominal pain.

Adverse Reaction/Adverse Event

Trivalent Influenza Vaccine (TIV)

FLULAVAL

TIV-1

TIV-2

QUADRIVALENTc

(B Victoria)d

(B Yamagata)e

%

%

%

Any

Grade 3f

Any

Grade 3f

Any

Grade 3f

Aged 3 through 17 Years

Local Adverse Reactions

n = 913

n = 911

n = 915

Pain

65.4

3.2

54.6

1.8

55.7

2.4

Swelling

6.2

0.1

3.3

0.0

3.8

0.0

Redness

5.3

0.1

3.2

0.0

3.5

0.0

Aged 3 through 4 Years

Systemic Adverse Events

n = 185

n = 187

n = 189

Irritability

25.9

0.5

16.6

0.0

21.7

1.6

Drowsiness

21.1

0.0

19.8

1.6

23.3

0.5

Loss of appetite

17.3

0.0

16.0

1.6

13.2

1.1

Feverg

4.9

0.5

5.9

1.1

3.7

1.6

Aged 5 through 17 Years

Systemic Adverse Events

n = 727

n = 724

n = 725

Muscle aches

28.5

0.7

24.9

0.6

24.7

1.0

Fatigue

22.1

0.7

23.6

1.8

23.0

1.0

Headache

22.0

1.0

22.1

1.0

20.1

1.2

Arthralgia

12.9

0.4

11.9

0.6

10.5

0.1

Gastrointestinal symptomsh

9.6

1.0

9.7

1.0

9.0

0.7

Shivering

7.0

0.4

6.9

1.2

6.9

0.6

Feverg

1.9

0.6

3.6

1.1

2.5

0.3

In children who received a second dose of FLULAVAL QUADRIVALENT, FLUARIX TIV-1 (B Victoria), or TIV-2 (BºYamagata), the incidences of adverse events 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 30%, 31%, and 30% of subjects who received FLULAVAL QUADRIVALENT (n = 932), FLUARIX TIV-1 (B Victoria) (n = 929), or TIV-2 (B Yamagata) (n = 932), respectively. The unsolicited adverse events that occurred most frequently (≥1% for FLULAVAL QUADRIVALENT) included vomiting, pyrexia, bronchitis, nasopharyngitis, pharyngitis, upper respiratory tract infection, headache, cough, oropharyngeal pain, and rhinorrhea. Serious adverse events occurring within 28 days of any vaccination were reported in 0.1%, 0.2%, and 0.2% of subjects who received FLULAVAL QUADRIVALENT, FLUARIX TIV-1 (B Victoria), or TIV-2 (B Yamagata), respectively.

Trial 3 (NCT01218308) was a randomized, observer-blind, non-influenza vaccine-controlled trial evaluating the efficacy of FLULAVAL QUADRIVALENT. The trial included subjects aged 3 through 8 years who received FLULAVAL QUADRIVALENT (n = 2,584) or HAVRIX (Hepatitis A Vaccine) (n = 2,584) as a control vaccine. Children with no history of influenza vaccination received 2 doses of FLULAVAL QUADRIVALENT or HAVRIX approximately 28 days apart (this dosing regimen for HAVRIX is not a U.S.-licensed schedule). Children with a history of influenza vaccination received one dose of FLULAVAL QUADRIVALENT or HAVRIX. In the overall population, 52% were male; 60% were Asian, 5% were white, and 35% were of other racial/ethnic groups. The mean age of subjects was 5 years. Solicited local adverse reactions and systemic adverse events were collected for 7 days (day of vaccination and the next 6 days). The incidence of local adverse reactions and systemic adverse events occurring within 7 days of vaccination in children are shown in Table 5.

Table . FLULAVAL QUADRIVALENT: Incidence of Solicited Local Adverse Reactions and Systemic Adverse Events within 7 Daysa of First Vaccination in Children Aged 3 through 8 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 7 days included day of vaccination and the subsequent 6 days.b Trial 3: NCT01218308.c Hepatitis A Vaccine used as a control vaccine.d Grade 3 pain: Defined as cried when limb was moved/spontaneously painful (children ˂5 years), or significant pain at rest, prevented normal everyday activities (children ≥5 years). Grade 3 swelling, redness: Defined as >100 mm. Grade 3 loss of appetite: Defined as not eating at all. Grade 3 irritability: Defined as crying that could not be comforted/prevented normal activity. Grade 3 drowsiness: Defined as prevented normal activity. Grade 3 (or higher) fever: Defined as ≥102.2°F (39.0°C). Grade 3 muscle aches, headache, fatigue, arthralgia, gastrointestinal symptoms, shivering: Defined as prevented normal activity.e Fever: Defined as ≥100.4°F (38.0°C). f Gastrointestinal symptoms included nausea, vomiting, diarrhea, and/or abdominal pain.

Adverse Reaction/Adverse Event

FLULAVAL

QUADRIVALENT

HAVRIXc

%

%

Any

Grade 3d

Any

Grade 3d

Aged 3 through 8 Years

Local Adverse Reactions

n = 2,546

n = 2,551

Pain

39.4

0.9

27.8

0.7

Swelling

1.0

0.0

0.3

0.0

Redness

0.4

0.0

0.2

0.0

Aged 3 through 4 Years

Systemic Adverse Events

n = 898

n = 895

Loss of appetite

9.0

0.3

8.2

0.4

Irritability

8.1

0.4

7.5

0.1

Drowsiness

7.7

0.4

7.3

0.0

Fevere

3.8

1.2

4.4

1.3

Aged 5 through 8 Years

Systemic Adverse Events

n = 1,648

n = 1,654

Muscle aches

12.0

0.1

9.7

0.2

Headache

10.5

0.4

10.6

0.8

Fatigue

8.4

0.1

7.1

0.3

Arthralgia

6.3

0.1

4.5

0.1

Gastrointestinal symptomsf

5.5

0.2

5.9

0.3

Shivering

3.0

0.1

2.5

0.1

Fevere

2.7

0.6

2.7

0.7

In children who received a second dose of FLULAVAL QUADRIVALENT or HAVRIX, the incidences of adverse events following the second dose were generally lower than those observed after the first dose.

The frequency of unsolicited adverse events occurring within 28 days of vaccination was similar in both groups (33% for both FLULAVAL QUADRIVALENT and HAVRIX). The unsolicited adverse events that occurred most frequently (≥1% for FLULAVAL QUADRIVALENT) included diarrhea, pyrexia, gastroenteritis, nasopharyngitis, upper respiratory tract infection, varicella, cough, and rhinorrhea. Serious adverse events occurring within 28 days of any vaccination were reported in 0.7% of subjects who received FLULAVAL QUADRIVALENT and in 0.2% of subjects who received HAVRIX.

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