Vaccine Information: FLUZONE High-Dose

FLUZONE HIGH-DOSE- 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) and influenza b virus b/maryland/15/2016 bx-69a antigen (formaldehyde inactivated) injection, suspension
FLUZONE HIGH-DOSE- influenza a virus a/michigan/45/2015 x-275 (h1n1) antigen (formaldehyde inactivated), influenza a virus a/singapore/infimh-16-0019/2016 ivr-186 (h3n2) antigen (formaldehyde inactivated) and influenza b virus b/maryland/15/2016 bx-69a antigen (formaldehyde inactivated) injection, suspension
Sanofi Pasteur Inc.

1 INDICATIONS AND USAGE

Fluzone^® High-Dose is a vaccine indicated for active immunization for the prevention of influenza disease caused by influenza A subtype viruses and type B virus contained in the vaccine.

Fluzone High-Dose is approved for use in persons 65 years of age and older.

2 DOSAGE AND ADMINISTRATION

• For intramuscular use only

2.1 Dose and Schedule

Fluzone High-Dose should be administered as a single 0.5 mL injection by the intramuscular route in adults 65 years of age and older.

2.2 Administration

Inspect Fluzone High-Dose visually for particulate matter and/or discoloration prior to administration. If either of these conditions exist, the vaccine should not be administered.

Before administering a dose of vaccine, shake the prefilled syringe.

The preferred site for intramuscular injection is the deltoid muscle. 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 or subcutaneously.

Fluzone High-Dose should not be combined through reconstitution or mixed with any other vaccine.

3 DOSAGE FORMS AND STRENGTHS

Fluzone High-Dose is a suspension for injection.

Fluzone High-Dose is supplied in prefilled syringes (gray syringe plunger rod), 0.5 mL, for adults 65 years of age and older.

4 CONTRAINDICATIONS

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 is a contraindication to administration of Fluzone High-Dose.

5 WARNINGS AND PRECAUTIONS

5.1 Guillain-Barré Syndrome

If Guillain-Barré syndrome (GBS) has occurred within 6 weeks following previous influenza vaccination, the decision to give Fluzone High-Dose 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 per 1 million persons vaccinated. (See references 1 and 2.)

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 Altered Immunocompetence

If Fluzone High-Dose 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 High-Dose may not protect all recipients.

6 ADVERSE REACTIONS

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.

Two clinical studies have evaluated the safety of Fluzone High-Dose.

Study 1 (NCT00391053, see http://clinicaltrials.gov) was a multi-center, double-blind pre-licensure trial conducted in the US. In this study, adults 65 years of age and older were randomized to receive either Fluzone High-Dose or Fluzone (2006-2007 formulation). The study compared the safety and immunogenicity of Fluzone High-Dose to those of Fluzone. The safety analysis set included 2573 Fluzone High-Dose recipients and 1260 Fluzone recipients.

Table 1 summarizes solicited injection-site reactions and systemic adverse events reported within 7 days post-vaccination via diary cards. Onset was usually within the first 3 days after vaccination and a majority of the reactions resolved within 3 days. Solicited injection-site reactions and systemic adverse events were more frequent after vaccination with Fluzone High-Dose compared to Fluzone.

Table 1: Study 1*: Frequency of Solicited Injection-Site Reactions and Systemic Adverse Events Within 7 Days After Vaccination with Fluzone High-Dose or Fluzone, Adults 65 Years of Age and Older

	Fluzone High-Dose (N †=2569-2572)Percentage			Fluzone (N †=1258-1260)Percentage
	Any	Moderate ‡	Severe §	Any	Moderate ‡	Severe §
* NCT00391053 † N is the number of vaccinated participants with available data for the events listed ‡ Moderate — Injection-site pain: sufficiently discomforting to interfere with normal behavior or activities; Injection-site erythema and Injection-site swelling: ≥2.5 cm to <5 cm; Fever: >100.4°F to ≤102.2°F; Myalgia, Malaise, and Headache: interferes with daily activities § Severe — Injection-site pain: incapacitating, unable to perform usual activities; Injection-site erythema and Injection-site swelling: ≥5 cm; Fever: >102.2°F; Myalgia, Malaise, and Headache: prevents daily activities ¶ Fever — The percentage of temperature measurements that were taken by oral route or not recorded were 97.9% and 2.1%, respectively, for Fluzone High-Dose; and 98.6% and 1.4%, respectively, for Fluzone
Injection-Site Pain	35.6	3.7	0.3	24.3	1.7	0.2
Injection-Site Erythema	14.9	1.9	1.8	10.8	0.8	0.6
Injection-Site Swelling	8.9	1.6	1.5	5.8	1.3	0.6
Myalgia	21.4	4.2	1.6	18.3	3.2	0.2
Malaise	18.0	4.7	1.6	14.0	3.7	0.6
Headache	16.8	3.1	1.1	14.4	2.5	0.3
Fever ¶ (≥99.5°F)	3.6	1.1	0.0	2.3	0.2	0.1

Within 6 months post-vaccination, 156 (6.1%) Fluzone High-Dose recipients and 93 (7.4%) Fluzone recipients experienced a serious adverse event (SAE). No deaths were reported within 28 days post-vaccination. A total of 23 deaths were reported during Days 29 – 180 post-vaccination: 16 (0.6%) among Fluzone High-Dose recipients and 7 (0.6%) among Fluzone recipients. The majority of these participants had a medical history of cardiac, hepatic, neoplastic, renal, and/or respiratory diseases. These data do not provide evidence for a causal relationship between deaths and vaccination with Fluzone High-Dose.

Study 2 (NCT01427309, see http://clinicaltrials.gov) was a multi-center, double-blind post-licensure efficacy trial conducted in the US and Canada over two influenza seasons. In this study, adults 65 years of age and older were randomized to receive either Fluzone High-Dose or Fluzone (2011-2012 and 2012-2013 formulations). The study compared the efficacy and safety of Fluzone High-Dose to those of Fluzone. The safety analysis set included 15,992 Fluzone High-Dose recipients and 15,991 Fluzone recipients.

Within the study surveillance period (approximately 6 to 8 months post-vaccination), 1323 (8.3%) Fluzone High-Dose recipients and 1442 (9.0%) Fluzone recipients experienced an SAE. Within 30 days post-vaccination, 204 (1.3%) Fluzone High-Dose recipients and 200 (1.3%) Fluzone recipients experienced an SAE. The majority of these participants had one or more chronic comorbid illnesses. A total of 167 deaths were reported within 6 to 8 months post-vaccination: 83 (0.5%) among Fluzone High-Dose recipients and 84 (0.5%) among Fluzone recipients. A total of 6 deaths were reported within 30 days post-vaccination: 6 (0.04%) among Fluzone High-Dose recipients and 0 (0%) among Fluzone recipients. These data do not provide evidence for a causal relationship between deaths and vaccination with Fluzone High-Dose.