Vaccine Information: FLUZONE QUADRIVALENT SOUTHERN HEMISPHERE

FLUZONE QUADRIVALENT SOUTHERN HEMISPHERE- influenza a virus a/sydney/5/2021 san-013 (h1n1) antigen (formaldehyde inactivated), influenza a virus a/darwin/9/2021 san-010 (h3n2) antigen (formaldehyde inactivated), influenza b virus b/michigan/01/2021 antigen (formaldehyde inactivated) and influenza b virus b/phuket/3073/2013 antigen (formaldehyde inactivated) injection, suspension
Sanofi Pasteur Inc.

1 INDICATIONS AND USAGE

Fluzone^® Quadrivalent Southern Hemisphere is a vaccine indicated for active immunization for the prevention of influenza disease caused by influenza A subtype viruses and type B viruses contained in the vaccine.

Fluzone Quadrivalent Southern Hemisphere is approved for use in persons 6 months of age and older.

2 DOSAGE AND ADMINISTRATION

For intramuscular use only

2.1 Dose and Schedule

The dose and schedule for Fluzone Quadrivalent Southern Hemisphere are presented in Table 1.

Prior to vaccination, always refer to the current Advisory Committee on Immunization Practices annual recommendations on prevention and control of influenza.

Table 1: Dose and Schedule for Fluzone Quadrivalent Southern Hemisphere

Age	Vaccination Status	Dose	Schedule
“-” Indicates information is not applicable
* The schedule can be completed as two 0.25-mL doses ≥4 weeks apart, two 0.5-mL doses ≥4 weeks apart, or any combination of 2 doses (either 0.25 mL or 0.5 mL) administered ≥4 weeks apart † To determine if 1 or 2 doses are required, refer to Advisory Committee on Immunization Practices annual recommendations on prevention and control of influenza
6 months through 35 months	Not previously vaccinated with influenza vaccine or unknown vaccination history	Two doses, either 0.25 mL or 0.5 mL *	Administer at least 4 weeks apart
	Previously vaccinated with influenza vaccine	One or two doses †, either 0.25 mL or 0.5 mL *	If two doses, administer at least 4 weeks apart
36 months through 8 years	Not previously vaccinated with influenza vaccine or unknown vaccination history	Two 0.5 mL doses	Administer at least 4 weeks apart
	Previously vaccinated with influenza vaccine	One or two 0.5 mL doses †	If two doses, administer at least 4 weeks apart
9 years and older	–	One 0.5 mL dose	–

2.2 Administration

Parenteral drug products should be inspected visually for particulate matter and/or discoloration prior to administration, whenever solution and container permit. If any of these defects or conditions exist, Fluzone Quadrivalent Southern Hemisphere should not be administered.

Before administering a dose of vaccine, shake the prefilled syringe or multi-dose vial. Use a separate sterile needle and syringe for each dose withdrawn from the multi-dose vial. A maximum of ten doses can be withdrawn from the multi-dose vial.

The preferred sites for intramuscular injection are the anterolateral aspect of the thigh in infants 6 months through 11 months of age, the anterolateral aspect of the thigh (or the deltoid muscle if muscle mass is adequate) in persons 12 months through 35 months of age, or the deltoid muscle in persons ≥36 months of age. The vaccine should not be injected into the gluteal area or areas where there may be a major nerve trunk.

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

Fluzone Quadrivalent Southern Hemisphere should not be combined through reconstitution or mixed with any other vaccine.

3 DOSAGE FORMS AND STRENGTHS

Fluzone Quadrivalent Southern Hemisphere is a suspension for injection.

Fluzone Quadrivalent Southern Hemisphere is supplied in 2 presentations:

1) Prefilled single-dose syringe (clear syringe plunger rod), 0.5 mL, for persons 6 months of age and older.

2) Multi-dose vial, 5 mL, for persons 6 months of age and older.

4 CONTRAINDICATIONS

Do not administer Fluzone Quadrivalent Southern Hemisphere to anyone with a history of a severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine [see Description (11)] , including egg protein, or to a previous dose of any influenza vaccine.

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. (See ref. 1) If GBS has occurred within 6 weeks following previous influenza vaccination, the decision to give Fluzone 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 Fluzone Quadrivalent Southern Hemisphere.

5.3 Altered Immunocompetence

If Fluzone Quadrivalent Southern Hemisphere is administered to immunocompromised persons, including those receiving immunosuppressive therapy, the expected immune response may not be obtained.

5.4 Limitations of Vaccine Effectiveness

Vaccination with Fluzone Quadrivalent Southern Hemisphere may not protect all recipients.

5.5 Syncope

Syncope (fainting) has been reported following vaccination with Fluzone Quadrivalent Southern Hemisphere . Procedures should be in place to avoid injury from fainting.

6 ADVERSE REACTIONS

Fluzone Quadrivalent Southern Hemisphere and Fluzone Quadrivalent are manufactured using the same process. This section summarizes data obtained from clinical studies with Fluzone Quadrivalent.

In children 6 months through 35 months of age receiving a 0.25-mL dose of Fluzone Quadrivalent in Study 1 (NCT01240746, see http://clinicaltrials.gov), the most common (≥10%) injection-site reactions were pain (57%)1 or tenderness (54%)2, erythema (37%), and swelling (22%); the most common solicited systemic adverse reactions were irritability (54%)2, abnormal crying (41%)2, malaise (38%)1, drowsiness (38%)2, appetite loss (32%)2, myalgia (27%)1, vomiting (15%)2, and fever (14%). In children 3 years through 8 years of age, the most common (≥10%) injection-site reactions were pain (67%), erythema (34%), and swelling (25%); the most common solicited systemic adverse reactions were myalgia (39%), malaise (32%), and headache (23%). In adults 18 years and older, the most common (≥10%) injection-site reaction was pain (47%); the most common solicited systemic adverse reactions were myalgia (24%), headache (16%), and malaise (11%). In adults 65 years of age and older, the most common (≥10%) injection-site reaction was pain (33%); the most common solicited systemic adverse reactions were myalgia (18%), headache (13%), and malaise (11%).

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1

Assessed in children 24 months through 35 months of age

2

Assessed in children 6 months through 23 months of age

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse event rates observed in the clinical trial(s) of a vaccine cannot be directly compared to rates in the clinical trial(s) of another vaccine and may not reflect the rates observed in practice.

Children 6 Months Through 8 Years of Age

Study 1 (NCT01240746, see http://clinicaltrials.gov) was a single-blind, randomized, active- controlled multi-center safety and immunogenicity study conducted in the US. In this study, children 6 months through 35 months of age received one or two 0.25 mL doses of either Fluzone Quadrivalent or one of two formulations of a comparator trivalent influenza vaccine (TIV-1 or TIV-2), and children 3 years through 8 years of age received one or two 0.5 mL doses of either Fluzone Quadrivalent, TIV-1, or TIV-2. Each of the trivalent formulations contained an influenza type B virus that corresponded to one of the two type B viruses in Fluzone Quadrivalent (a type B virus of the Victoria lineage or a type B virus of the Yamagata lineage). For participants who received two doses, the doses were administered approximately 4 weeks apart. The safety analysis set included 1841 children 6 months through 35 months of age and 2506 children 3 years through 8 years of age. Among participants 6 months through 8 years of age in the three vaccine groups combined, 49.3% were female (Fluzone Quadrivalent, 49.2%; TIV-1, 49.8%; TIV-2, 49.4%), 58.4% Caucasian (Fluzone Quadrivalent, 58.4%; TIV-1, 58.9%; TIV-2, 57.8%), 20.2% Black (Fluzone Quadrivalent, 20.5%; TIV-1, 19.9%; TIV-2, 19.1%), 14.1% Hispanic (Fluzone Quadrivalent, 14.3%; TIV-1, 13.2%; TIV-2, 14.7%), and 7.3% were of other racial/ethnic groups (Fluzone Quadrivalent, 6.8%; TIV-1, 8.0%; TIV-2, 8.5%). Table 2 and Table 3 summarize solicited injection-site and systemic adverse reactions reported within 7 days post-vaccination via diary cards. Participants were monitored for unsolicited adverse events for 28 days after each dose and serious adverse events (SAEs) during the 6 months following the last dose.

Table 2: Study 1*: Percentage of Solicited Injection-site and Systemic Adverse Reactions Within 7 Days After Vaccination in Children 6 Months Through 35 Months of Age (Safety Analysis Set)†

	Fluzone Quadrivalent ‡, §(N ¶=1223)			TIV-1§, #(B Victoria)(N ¶=310)			TIV-2§, Þ(B Yamagata)(N ¶=308)
	Any(%)	Grade 2ß(%)	Grade 3à(%)	Any(%)	Grade 2ß(%)	Grade 3à(%)	Any(%)	Grade 2ß(%)	Grade 3à(%)
* NCT01240746 † The safety analysis set includes all persons who received at least one dose of study vaccine ‡ Fluzone Quadrivalent (0.25 mL) containing A/California/07/2009 (H1N1), A/Victoria/210/2009 (H3N2), B/Brisbane/60/2008 (Victoria lineage), and B/Florida/04/2006 (Yamagata lineage) § Participants received 1 or 2 doses according to ACIP recommendations ¶ N is the number of participants in the safety analysis set # 2010-2011 Fluzone TIV (0.25 mL) containing A/California/07/2009 (H1N1), A/Victoria/210/2009 (H3N2), and B/Brisbane/60/2008 (Victoria lineage), licensed Þ Investigational TIV (0.25 mL) containing A/California/07/2009 (H1N1), A/Victoria/210/2009 (H3N2), and B/Florida/04/2006 (Yamagata lineage), non-licensed ß Grade 2 — Injection-site pain: sufficiently discomforting to interfere with normal behavior or activities; Injection-site tenderness: cries and protests when injection-site is touched; Injection-site erythema, Injection-site swelling: ≥2.5 cm to <5 cm; Fever: >101.3°F to ≤103.1°F (6 months through 23 months); ≥101.2°F to ≤102.0°F (24 months through 35 months); Malaise, Myalgia, and Headache: some interference with activity; Irritability: requiring increased attention; Crying abnormal: 1 to 3 hours; Drowsiness: not interested in surroundings or did not wake up for a feed/meal; Appetite loss: missed 1 or 2 feeds/meals completely; Vomiting: 2 to 5 episodes per 24 hours à Grade 3 — Injection-site pain: incapacitating, unable to perform usual activities; Injection-site tenderness: cries when injected limb is moved, or the movement of the injected limb is reduced; Injection-site erythema, Injection-site swelling: ≥5 cm; Fever: >103.1°F (6 months through 23 months); ≥102.1°F (24 months through 35 months); Malaise, Myalgia, and Headache: Significant; prevents daily activity; Irritability: inconsolable; Crying abnormal: >3 hours; Drowsiness: sleeping most of the time or difficult to wake up; Appetite loss: refuses ≥3 feeds/meals or refuses most feeds/meals; Vomiting: ≥6 episodes per 24 hours or requiring parenteral hydration è Assessed in children 24 months through 35 months of age ð Assessed in children 6 months through 23 months of age ø Fever measured by any route
Injection-site adverse reactions
Pain è	57.0	10.2	1.0	52.3	11.5	0.8	50.3	5.4	2.7
Tenderness ð	54.1	11.3	1.9	48.4	8.2	1.9	49.7	10.3	0.0
Erythema	37.3	1.5	0.2	32.9	1.0	0.0	33.3	1.0	0.0
Swelling	21.6	0.8	0.2	19.7	1.0	0.0	17.3	0.0	0.0
Systemic adverse reactions
Fever (≥100.4°F) ø	14.3	5.5	2.1	16.0	6.6	1.7	13.0	4.1	2.0
Malaise è	38.1	14.5	4.6	35.2	14.8	4.7	32.4	12.8	6.8
Myalgia è	26.7	6.6	1.9	26.6	9.4	1.6	25.0	6.8	2.7
Headache è	8.9	2.5	0.6	9.4	3.9	0.0	12.2	4.7	0.0
Irritability ð	54.0	26.4	3.2	52.8	20.1	3.1	53.5	22.9	2.8
Crying abnormal ð	41.2	12.3	3.3	36.5	8.2	1.9	29.9	10.4	2.1
Drowsiness ð	37.7	8.4	1.3	32.1	3.8	0.6	31.9	5.6	0.7
Appetite loss ð	32.3	9.1	1.8	33.3	5.7	1.9	25.0	8.3	0.7
Vomiting ð	14.8	6.2	1.0	11.3	4.4	0.6	13.9	6.3	0.0

Table 3: Study 1*: Percentage of Solicited Injection-site and Systemic Adverse Reactions Within 7 Days After Vaccination in Children 3 Years Through 8 Years of Age (Safety Analysis Set)†

	Fluzone Quadrivalent ‡(N §=1669)			TIV-1¶(B Victoria)(N §=424)			TIV-2#(B Yamagata)(N §=413)
	Any(%)	Grade 2Þ(%)	Grade 3ß(%)	Any(%)	Grade 2Þ(%)	Grade 3ß(%)	Any(%)	Grade 2Þ(%)	Grade 3ß(%)
* NCT01240746 † The safety analysis set includes all persons who received at least one dose of study vaccine ‡ Fluzone Quadrivalent containing A/California/07/2009 (H1N1), A/Victoria/210/2009 (H3N2), B/Brisbane/60/2008 (Victoria lineage), and B/Florida/04/2006 (Yamagata lineage) § N is the number of participants in the safety analysis set ¶ 2010-2011 Fluzone TIV containing A/California/07/2009 (H1N1), A/Victoria/210/2009 (H3N2), and B/Brisbane/60/2008 (Victoria lineage), licensed # Investigational TIV containing A/California/07/2009 (H1N1), A/Victoria/210/2009 (H3N2), and B/Florida/04/2006 (Yamagata lineage), non-licensed Þ Grade 2 — Injection-site pain: sufficiently discomforting to interfere with normal behavior or activities; Injection-site erythema, Injection-site swelling: ≥2.5 cm to <5 cm; Fever: ≥101.2°F to ≤102.0°F; Headache, Malaise, and Myalgia: some interference with activity ß Grade 3 — Injection-site pain: incapacitating, unable to perform usual activities; Injection-site erythema, Injection-site swelling: ≥5 cm; Fever: ≥102.1°F; Headache, Malaise, and Myalgia: Significant; prevents daily activity à Fever measured by any route
Injection-site adverse reactions
Pain	66.6	15.8	2.1	64.6	9.5	2.0	63.8	11.6	2.8
Erythema	34.1	2.9	1.8	36.8	3.4	1.2	35.2	2.5	1.8
Swelling	24.8	2.8	1.4	25.4	1.5	1.2	25.9	2.5	1.8
Systemic adverse reactions
Fever(≥100.4°F) à	7.0	2.1	2.1	7.1	2.2	1.2	7.6	2.8	0.8
Headache	23.1	6.8	2.2	21.2	5.1	2.7	24.4	7.5	2.0
Malaise	31.9	11.2	5.5	32.8	11.4	5.6	33.4	10.8	5.0
Myalgia	38.6	12.2	3.3	34.1	9.0	2.7	38.4	11.1	2.8

Among children 6 months through 8 years of age, unsolicited non-serious adverse events were reported in 1360 (47.0%) recipients in the Fluzone Quadrivalent group, 352 (48.0%) recipients in the TIV-1 group, and 346 (48.0%) recipients in the TIV-2 group. The most commonly reported unsolicited non-serious adverse events were cough, vomiting, and pyrexia. During the 28 days following vaccination, a total of 16 (0.6%) recipients in the Fluzone Quadrivalent group, 4 (0.5%) recipients in the TIV-1 group, and 4 (0.6%) recipients in the TIV-2 group, experienced at least one SAE. Throughout the study period, a total of 41 (1.4%) recipients in the Fluzone Quadrivalent group, 7 (1.0%) recipients in the TIV-1 group, and 14 (1.9%) recipients in the TIV-2 group, experienced at least one SAE. Three SAEs were considered to be possibly related to vaccination: croup in a Fluzone Quadrivalent recipient and 2 episodes of febrile seizure, 1 each in a TIV-1 recipient and a TIV-2 recipient.

0.5-mL Dose of Fluzone Quadrivalent in Children 6 Months through 35 Months of Age

Study 2 (NCT02915302 see http://clinicaltrials.gov) was a randomized, observer-blinded, 2-arm, multi-center safety and immunogenicity study conducted in the US. In this study, 1950 children 6 months through 35 months of age were randomly assigned to receive Fluzone Quadrivalent administered in either a volume of 0.25 mL (Group 1) or 0.5 mL (Group 2). For participants recommended to receive two doses of influenza vaccine as per Advisory Committee on Immunization Practices guidance, the same dose was administered 4 weeks after the first. The safety analysis set included 1941 participants who received at least 1 dose of study vaccine. Of these participants, 49.7% were female, 74.3% were Caucasian, 19.2% were Black, 6.5% were of other racial groups, and 22.0% were Hispanic/Latino.

Table 4 summarizes solicited injection-site and systemic adverse reactions reported within 7 days post-vaccination via diary cards for the 0.25 mL and 0.5 mL volumes of Fluzone Quadrivalent in children 6 months through 35 months of age.

Table 4: Study 2*: Percentage of Solicited Injection-site and Systemic Adverse Reactions Within 7 Days After Vaccination in Children 6 Months Through 35 Months of Age (Safety Analysis Set)†

	Fluzone Quadrivalent0.25 mL ‡(N §=949)		Fluzone Quadrivalent0.5 mL ‡(N §=992)
	Any(%)	Grade 3¶(%)	Any(%)	Grade 3¶(%)
* NCT02915302 † The safety analysis set includes all persons who received at least one dose of study vaccine ‡ Participants received 1 or 2 doses according to ACIP recommendations § N is the number of participants in the safety analysis set ¶ Grade 3 — Injection-site tenderness: Cries when injected limb is moved, or the movement of the injected limb is reduced; Injection-site redness, Injection-site swelling: ≥50 mm; Irritability: inconsolable; Abnormal Crying: >3 hours; Drowsiness: sleeping most of the time or difficult to wake up; Loss of Appetite: refuses ≥3 feeds/meals or refuses most feeds/meals; Fever: >103.1°F; Vomiting: ≥6 episodes per 24 hours or requiring parenteral hydration # Fever measured by any route
Injection-site adverse reactions
Tenderness	47.3	1.7	50.4	1.2
Redness	23.1	0.0	24.3	0.2
Swelling	12.9	0.1	14.7	0.0
Systemic adverse reactions
Irritability	47.4	3.6	48.6	4.0
Abnormal Crying	33.3	3.1	34.1	2.6
Drowsiness	31.9	2.1	31.3	1.6
Loss of Appetite	27.3	1.4	28.3	2.2
Fever(≥100.4°F)#	11.3	0.6	12.2	1.2
Vomiting	10.0	0.4	10.2	0.5

The difference in fever rate (Group 2 minus Group 1) was 0.84% (95% CI: -2.13%; 3.80%), meeting the prespecified non-inferiority criterion (upper limit of the 2-sided 95% CI of the difference in fever rates <5%). Participants were monitored for unsolicited adverse events and SAEs during the 28 days following vaccination. Unsolicited non-serious adverse events were reported in 417 (44%) participants in Group 1 and 394 (40%) participants in Group 2. The most commonly reported unsolicited non-serious adverse events in both groups were cough and rhinorrhea. Ten SAEs were reported during the 28-day follow-up period: 5 (0.5%) in Group 1 and 5 (0.5%) in Group 2.

Adults

In Study 3 (NCT00988143), a multi-centered randomized, open-label trial conducted in the US, adults 18 years of age and older received one dose of either Fluzone Quadrivalent or one of two formulations of comparator trivalent influenza vaccine (TIV-1 or TIV-2). Each of the trivalent formulations contained an influenza type B virus that corresponded to one of the two type B viruses in Fluzone Quadrivalent (a type B virus of the Victoria lineage or a type B virus of the Yamagata lineage). The safety analysis set included 570 recipients, half aged 18-60 years and half aged 61 years or older. Among participants in the three vaccine groups combined, 67.2% were female (Fluzone Quadrivalent, 68.4%; TIV-1, 67.9%; TIV-2, 65.3%), 88.4% Caucasian (Fluzone Quadrivalent, 91.1%; TIV-1, 86.8%; TIV-2, 87.4%), 9.6% Black (Fluzone Quadrivalent, 6.8%; TIV-1, 12.1%; TIV-2, 10.0%), 0.4% Hispanic (Fluzone Quadrivalent, 0.0%; TIV-1, 0.5%; TIV-2, 0.5%), and 1.7% were of other racial/ethnic groups (Fluzone Quadrivalent, 2.1%; TIV-1, 0.5%; TIV-2, 2.2%). Table 5 summarizes solicited injection-site and systemic adverse reactions reported within 3 days post-vaccination via diary cards. Participants were monitored for unsolicited adverse events and SAEs during the 21 days following vaccination.

Table 5: Study 3*: Percentage of Solicited Injection-site and Systemic Adverse Reactions Within 3 Days After Vaccination in Adults 18 Years of Age and Older (Safety Analysis Set)†

	Fluzone Quadrivalent ‡(N §=190)			TIV-1¶(B Victoria)(N §=190)			TIV-2#(B Yamagata)(N §=190)
	Any (%)	Grade 2Þ(%)	Grade 3ß(%)	Any (%)	Grade 2Þ(%)	Grade 3ß(%)	Any (%)	Grade 2Þ(%)	Grade 3ß(%)
* NCT00988143 † The safety analysis set includes all persons who received study vaccine ‡ Fluzone Quadrivalent containing A/California/07/2009 (H1N1), A/Victoria/210/2009 (H3N2), B/Brisbane/60/2008 (Victoria lineage), and B/Florida/04/2006 (Yamagata lineage) § N is the number of participants in the safety analysis set ¶ 2009-2010 Fluzone TIV containing A/Brisbane/59/2007 (H1N1), A/Uruguay/716/2007 (H3N2), and B/Brisbane/60/2008 (Victoria lineage), licensed # 2008-2009 Fluzone TIV containing A/Brisbane/59/2007 (H1N1), A/Uruguay/716/2007 (H3N2), and B/Florida/04/2006 (Yamagata lineage), licensed Þ Grade 2 — Injection-site pain: Some interference with activity; Injection-site erythema, Injection-site swelling, Injection-site induration, and Injection-site ecchymosis: ≥5.1 to ≤10 cm; Fever: ≥101.2°F to ≤102.0°F; Myalgia, Headache, Malaise, and Shivering: some interference with activity ß Grade 3 — Injection-site pain: Significant; prevents daily activity; Injection-site erythema, Injection-site swelling, Injection-site induration, and Injection-site ecchymosis: >10 cm; Fever: ≥102.1°F; Myalgia, Headache, Malaise, and Shivering: Significant; prevents daily activity à Fever measured by any route
Injection-site adverse reactions
Pain	47.4	6.8	0.5	52.1	7.9	0.5	43.2	6.3	0.0
Erythema	1.1	0.0	0.0	1.6	0.5	0.0	1.6	0.5	0.0
Swelling	0.5	0.0	0.0	3.2	0.5	0.0	1.1	0.0	0.0
Induration	0.5	0.0	0.0	1.6	0.5	0.0	0.5	0.0	0.0
Ecchymosis	0.5	0.0	0.0	0.5	0.0	0.0	0.5	0.0	0.0
Systemic adverse reactions
Myalgia	23.7	5.8	0.0	25.3	5.8	0.0	16.8	5.8	0.0
Headache	15.8	3.2	0.5	18.4	6.3	0.5	18.0	4.2	0.0
Malaise	10.5	1.6	1.1	14.7	3.2	1.1	12.1	4.7	0.5
Shivering	2.6	0.5	0.0	5.3	1.1	0.0	3.2	0.5	0.0
Fever(≥100.4°F)à	0.0	0.0	0.0	0.5	0.5	0.0	0.5	0.5	0.0

Unsolicited non-serious adverse events were reported in 33 (17.4%) recipients in the Fluzone Quadrivalent group, 45 (23.7%) recipients in the TIV-1 group, and 45 (23.7%) recipients in the TIV-2 group. The most commonly reported unsolicited non-serious adverse events were headache, cough, and oropharyngeal pain. In the follow-up period, there were two SAEs, 1 (0.5%) in the Fluzone Quadrivalent group and 1 (0.5%) in the TIV-2 group.

Geriatric Adults

In Study 4 (NCT01218646), a multi-center, randomized, double-blind trial conducted in the US, adults 65 years of age and older received one dose of either Fluzone Quadrivalent, or one of two formulations of comparator trivalent influenza vaccine (TIV-1 or TIV-2). Each of the trivalent formulations contained an influenza type B virus that corresponded to one of the two type B viruses in Fluzone Quadrivalent (a type B virus of the Victoria lineage or a type B virus of the Yamagata lineage). The safety analysis set included 675 recipients. Among participants in the three vaccine groups combined, 55.7% were female (Fluzone Quadrivalent, 57.3%; TIV-1, 56.0%; TIV-2, 53.8%), 89.5% Caucasian (Fluzone Quadrivalent, 87.6%; TIV-1, 89.8%; TIV-2, 91.1%), 2.2% Black (Fluzone Quadrivalent, 4.0%; TIV-1, 1.8%; TIV-2, 0.9%), 7.4% Hispanic (Fluzone Quadrivalent, 8.4%; TIV-1, 7.6%; TIV-2, 6.2%) and 0.9% were of other racial/ethnic groups (Fluzone Quadrivalent, 0.0%; TIV-1, 0.9%; TIV-2, 1.8%).

Table 6 summarizes solicited injection-site and systemic adverse reactions reported within 7 days post-vaccination via diary cards. Participants were monitored for unsolicited adverse events and SAEs during the 21 days following vaccination.

Table 6: Study 4*: Percentage of Solicited Injection-site and Systemic Adverse Reactions Within 7 Days After Vaccination in Adults 65 Years of Age and Older (Safety Analysis Set)†

	Fluzone Quadrivalent ‡(N §=225)			TIV-1¶(B Victoria)(N §=225)			TIV-2#(B Yamagata)(N §=225)
	Any (%)	Grade 2Þ(%)	Grade 3ß(%)	Any (%)	Grade 2Þ(%)	Grade 3ß(%)	Any (%)	Grade 2Þ(%)	Grade 3ß(%)
* NCT01218646 † The safety analysis set includes all persons who received study vaccine ‡ Fluzone Quadrivalent containing A/California/07/2009 (H1N1), A/Victoria/210/2009 (H3N2), B/Brisbane/60/2008 (Victoria lineage), and B/Florida/04/2006 (Yamagata lineage) § N is the number of participants in the safety analysis set ¶ 2010-2011 Fluzone TIV containing A/California/07/2009 (H1N1), A/Victoria/210/2009 (H3N2), and B/Brisbane/60/2008 (Victoria lineage), licensed # Investigational TIV containing A/California/07/2009 (H1N1), A/Victoria/210/2009 (H3N2), and B/Florida/04/2006 (Yamagata lineage), non-licensed Þ Grade 2 — Injection-site pain: some interference with activity; Injection-site erythema and Injection-site swelling: ≥5.1 to ≤10 cm; Fever: ≥101.2°F to ≤102.0°F; Myalgia, Headache, and Malaise: some interference with activity ß Grade 3 — Injection-site pain: Significant; prevents daily activity; Injection-site erythema and Injection-site swelling: >10 cm; Fever: ≥102.1°F; Myalgia, Headache, and Malaise: Significant; prevents daily activity à Fever measured by any route
Injection-site adverse reactions
Pain	32.6	1.3	0.9	28.6	2.7	0.0	23.1	0.9	0.0
Erythema	2.7	0.9	0.0	1.3	0.0	0.0	1.3	0.4	0.0
Swelling	1.8	0.4	0.0	1.3	0.0	0.0	0.0	0.0	0.0
Systemic adverse reactions
Myalgia	18.3	4.0	0.4	18.3	4.0	0.0	14.2	2.7	0.4
Headache	13.4	1.3	0.4	11.6	1.3	0.0	11.6	1.8	0.4
Malaise	10.7	4.5	0.4	6.3	0.4	0.0	11.6	2.7	0.9
Fever(≥100.4°F)à	1.3	0.0	0.4	0.0	0.0	0.0	0.9	0.4	0.4

Unsolicited non-serious adverse events were reported in 28 (12.4%) recipients in the Fluzone Quadrivalent group, 22 (9.8%) recipients in the TIV-1 group, and 22 (9.8%) recipients in the TIV-2 group. The most commonly reported adverse events were oropharyngeal pain, rhinorrhea, injection-site induration, and headache. Three SAEs were reported during the follow-up period, 2 (0.9%) in the TIV-1 group and 1 (0.4%) in the TIV-2 group.