the H1N1 Vaccine - Know it in detail! (Part2)

Other Internet Sources:

CDC - Emerging Infectious Diseases

http://www.cdc.gov/ncidod/eid/vol12no01/05-1254.htm

United States Government National Cancer Institute

http://www.cancer.gov/cancertopics/factsheet/risk/formaldehyde

International Agency for Research on Cancer (World Health Organization) 

http://monographs.iarc.fr/ENG/Monographs/vol88/index.php 

(http://monographs.iarc.fr/ENG/Monographs/vol88/mono88-6B.pdf) 

United States Department of Labor

Occupational Safety and Health Administration 

http://www.osha.gov/SLTC/formaldehyde/

Formaldehyde and cancer morbidity among male employees in Denmark

http://www.springerlink.com/content/w632326683541334/

Warnings: (Courtesy of the following websites:)

http://www.rumormillnews.com/cgi-bin/archive.cgi?read=150745

FLU VACCINE RECOMMENDATIONS FOR ALL PREGNANT WOMEN (CDC)

The Advisory Committee on Immunization Practices (ACIP):
Vaccination of pregnant women is recommended by the Centers for Disease Control Advisory Committee on Immunization Practices (ACIP).
< http://www.cdc.gov/vaccines/pubs/vis/default.htm#flu > http://www.cdc.gov/vaccines/pubs/vis/default.htm#flu

FDA approved manufacturers package insert: Manufacturers warnings

Sanofi Pasteurs Fluzone package insert, WARNING
www.vaccinesafety.edu/package_inserts.htm" TARGET="_blank">http://www.vaccinesafety.edu/package_inserts.htm>www.vaccinesafety.edu/package_inserts.htm>

8.1 Pregnancy Category C: Animal reproduction studies have not been conducted with Fluzone vaccine. It is also not known whether Fluzone vaccine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Fluzone vaccine should be given to a pregnant woman only if clearly needed.

8.2 Nursing Mothers: It is not known whether Fluzone vaccine is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Fluzone vaccine is administered to a nursing woman.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility: Fluzone vaccine has not been evaluated for carcinogenic or mutagenic potential, or for impairment of fertility.

NOTE: CDC does not require providers to inform pregnant women of the Thimerosal (mercury) content.

Appendix A - Sanofi Pasteur Packaging Insert - 

Courtesy of the FDA - 

http://www.fda.gov/downloads/biologicsbloodvaccines/vaccines/approvedproducts/ucm182404.pdf

sanofi pasteur 449/454 Influenza A (H1N1) 2009 Monovalent Vaccine

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use Influenza A (H1N1) 2009 Monovalent Vaccine safely and effectively. See full prescribing information for Influenza A (H1N1) 2009 Monovalent Vaccine.

Influenza A (H1N1) 2009 Monovalent Vaccine Manufactured by Sanofi Pasteur Inc. Suspension for Intramuscular Injection Initial US Approval: 1980

----------------------------RECENT MAJOR CHANGES------------------------------ Indications and Usage ( 1 ) [9/2009] Dosage and Administration ( 2.2 ) [9/2009]

----------------------------INDICATIONS AND USAGE------------------------------- Influenza A (H1N1) 2009 Monovalent Vaccine is an inactivated influenza virus vaccine indicated for active immunization of persons 6 months of age and older against influenza disease caused by pandemic (H1N1) 2009 virus. (1)

--------------------------DOSAGE AND ADMINISTRATION------------------------- Based on currently available information the vaccination regimen is as follows:

Children ▪ 6 through 35 months of age (0.25 mL dose, intramuscular injection): - Two 0.25 mL doses approximately one month apart. (2.2) ▪ 36 months through 9 years of age (0.5 mL dose, intramuscular injection): - Two 0.5 mL doses approximately one month apart. (2.2) ▪ 10 years of age and older - A single 0.5 mL dose, intramuscular injection. (2.2) Adults - A single 0.5 mL dose, intramuscular injection. (2.2)

---------------------DOSAGE FORMS AND STRENGTHS--------- Influenza A (H1N1) 2009 Monovalent Vaccine, a sterile suspension for intramuscular injection, is supplied in four presentations: ␣ Prefilled syringe, 0.25 mL, no preservative; distinguished by a pink syringe

plunger rod (3) ␣ Prefilled syringe, 0.5 mL, no preservative (3) ␣ Single-dose vial, 0.5 mL, no preservative (3) ␣ Multi-dose vial, 5 mL, contains thimerosal, a mercury derivative, added as a

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-------------------------------CONTRAINDICATIONS------------ ␣ Severe hypersensitivity to egg proteins or any component of the vaccine

or life-threatening reactions after previous administration of any influenza vaccine. (4, 11)

-----------------------WARNINGS AND PRECAUTIONS--------------------- ␣ If Guillain-Barr? syndrome (GBS) has occurred within 6 weeks of

previous influenza vaccination, the decision to give Influenza A (H1N1) 2009 Monovalent Vaccine should be based on careful consideration of the potential benefits and risks. (5.1)

␣ Immunocompromised persons may have a reduced immune response to Influenza A (H1N1) 2009 Monovalent Vaccine. (5.2)

------------------------------ADVERSE REACTIONS-------------- Adverse reaction information is based on studies conducted with seasonal trivalent Influenza Virus Vaccine. ␣ Most common (≥10%) local reactions were soreness at injection site,

tenderness, pain, and swelling. (6) ␣ Most common (≥10%) systemic events were malaise, headache, and

myalgia. (6)

To report SUSPECTED ADVERSE REACTIONS, contact Sanofi Pasteur Inc., Discovery Drive, Swiftwater, PA 18370 at 1-800-822-2463 (1-800-VACCINE) or VAERS at 1-800-822-7967 or http://vaers.hhs.gov.

------------------------------DRUG INTERACTIONS-------------- ␣ Do not mix with other vaccines in the same syringe or vial. (7.1) ␣ Immunosuppressive therapies may reduce the immune response to

Influenza A (H1N1) 2009 Monovalent Vaccine. (7.2)

-----------------------USE IN SPECIFIC POPULATIONS------- Information in this section is based on seasonal trivalent Influenza Virus Vaccine manufactured by Sanofi Pasteur Inc. (Fluzone vaccine). ␣ Safety and effectiveness of Influenza A (H1N1) 2009 Monovalent

Vaccine have not been established in pregnant women or nursing mothers

or children <6 months of age. (8.1, 8.3, 8.4) ␣ Antibody responses to Fluzone vaccine were lower in the geriatric

population than in younger adults. (8.5) See 17 PATIENT_COUNSELING_INFORMATION.

preservative. Each 0.5 mL dose contains 25 mcg mercury. (3, 11 ) _______________________________________________________________________________________________________________________________________

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE 2 DOSAGE AND ADMINISTRATION

2.1 Preparation for Administration

2.2 Recommended Dose and Schedule 3 DOSAGE FORMS AND STRENGTHS 4 CONTRAINDICATIONS 5 WARNINGS AND PRECAUTIONS

5.1 Guillain-Barr? Syndrome 5.2 Altered Immunocompetence 5.3 Preventing and Managing Allergic Reaction 5.4 Limitations of Vaccine Effectiveness

6 ADVERSE REACTIONS

6.1 Clinical Trial Experience 6.2 Post-Marketing Experience 6.3 Other Adverse Events Associated with Influenza Vaccines

7 DRUG INTERACTIONS

7.1 Concomitant Administration with other Vaccines 7.2 Immunosuppressive Therapies

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy 8.3 Nursing Mothers 8.4 Pediatric Use 8.5 Geriatric Use

11 DESCRIPTION 12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action 13 NON-CLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 14 CLINICAL STUDIES

14.1 Immunogenicity in the Adult and Geriatric Population

14.2 Immunogenicity in Children 15 REFERENCES 16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

16.2 Storage and Handling 17 PATIENT COUNSELING INFORMATION

*Sections or subsections omitted from the full prescribing information are not listed.

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Revised: September 2009

sanofi pasteur 10 September 2009_v0.3 449/454 Influenza A (H1N1) 2009 Monovalent Vaccine LE5860-5862

1 FULL PRESCRIBING INFORMATION: 

2 1. INDICATIONS AND USAGE

3 Influenza A (H1N1) 2009 Monovalent Vaccine is an inactivated influenza virus vaccine 4 indicated for active immunization of persons 6 months of age and older against influenza disease 5 caused by pandemic (H1N1) 2009 virus. 6

7 2. DOSAGE AND ADMINISTRATION

8

2.1. Preparation for Administration

9 Inspect Influenza A (H1N1) 2009 Monovalent Vaccine syringes and vials visually for particulate 10 matter and/or discoloration prior to administration. If either of these conditions exist, the vaccine 11 should not be administered. 12

13 Shake the syringe and single-dose vials well before administering the vaccine and shake the 14 multi-dose vial each time before withdrawing a dose of vaccine. 15 16 2.2. Recommended Dose and Schedule

17 Clinical studies are ongoing with Influenza A (H1N1) 2009 Monovalent Vaccine to determine 18 the optimal dosage, number of doses and schedule. 19 20 Available data show that children 9 years of age and younger are largely serologically naive to 21 the pandemic (H1N1) 2009 virus. (1) Based upon these data Influenza A (H1N1) 2009

22 Monovalent Vaccine should be administered as follows:

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1 2 Children 3 Children 6 through 35 months of age should receive two 0.25 mL intramuscular doses 4 approximately 1 month apart. (1) 5 6 Children 36 months through 9 years of age should receive two 0.5 mL intramuscular doses 7 approximately 1 month apart. (1) 8 9 Children 10 years of age and older should receive a single 0.5 mL intramuscular dose. (1)

10 11 The preferred sites for intramuscular injections are the anterolateral aspect of the thigh in infants 12 or the deltoid muscle of the upper arm in toddlers and young children. 13 14 The vaccine should not be injected into the gluteal region or into areas where there may be a 15 major nerve trunk. 16 17 Adults 18 Persons 18 years of age and older should receive a single 0.5 mL intramuscular dose. 19 20 In adults, the preferred site for intramuscular injection is the deltoid muscle. 21

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1 The vaccine should not be injected into the gluteal region or into areas where there may be a 2 major nerve trunk. 3

4 3. DOSAGE FORMS AND STRENGTHS 5 Influenza A (H1N1) 2009 Monovalent Vaccine is a sterile suspension for intramuscular

6 injection. [See Description (11)] 7 8 Influenza A (H1N1) 2009 Monovalent Vaccine is supplied in 4 presentations:

Prefilled syringe, 0.25 mL, no preservative, for 6 through 35 months of age; distinguished by a pink syringe plunger rod; Prefilled syringe, 0.5 mL, no preservative, for 36 months of age and older; Single-dose vial, 0.5 mL, no preservative, for 36 months of age and older;

Multi-dose vial, 5 mL, for 6 months of age and older, contains thimerosal, a mercury derivative, added as a preservative. Each 0.5 mL dose contains 25 micrograms (mcg) mercury.

17 4. 18 Do not administer Influenza A (H1N1) 2009 Monovalent Vaccine to anyone with a known severe hypersensitivity to egg proteins or any component of the vaccine or life-threatening reactions after previous administration of any influenza vaccine. [See Warnings and Precautions 21 (5) and Description (11)] 

5. WARNINGS AND PRECAUTIONS

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CONTRAINDICATIONS

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1 5.1. Guillain-Barr? Syndrome

2 Recurrence of Guillain-Barr? syndrome (GBS) has been temporally associated with the 3 administration of influenza vaccine. The decision to give Influenza A (H1N1) 2009 Monovalent 4 Vaccine to individuals who have a prior history of Guillain-Barr? syndrome should be based on 5 careful consideration of the potential benefits and risks. 6 7 5.2. Altered Immunocompetence

8 If Influenza A (H1N1) 2009 Monovalent Vaccine is administered to immunocompromised

9 persons, including those receiving immunosuppressive therapy, the immune response may be 10 diminished. 11 12

5.3. Preventing and Managing Allergic Reaction

13 Appropriate medical treatment and supervision must be available to manage possible 14 anaphylactic reactions following administration of the vaccine. 15 16 5.4. Limitations of Vaccine Effectiveness

17 Vaccination with Influenza A (H1N1) 2009 Monovalent Vaccine may not protect all recipients. 18

19

6. ADVERSE REACTIONS 

20 Sanofi Pasteur?s Influenza A (H1N1) 2009 Monovalent Vaccine and seasonal trivalent Influenza

21 Virus Vaccine (Fluzone?) are manufactured by the same process. The following sub-sections

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sanofi pasteur 10 September 2009_v0.3 449/454 Influenza A (H1N1) 2009 Monovalent Vaccine LE5860-5862

1 summarize safety data from clinical experience with seasonal trivalent inactivated influenza 2 vaccines, including Fluzone vaccine. 3

6.1. Clinical Trial Experience

4 Adverse event information from clinical trials provides the basis for identifying adverse events 5 that appear to be related to vaccine use and for approximating the rates of these events. However, 6 because clinical trials are conducted under widely varying conditions, adverse event rates 7 observed in the clinical trials of a vaccine cannot be directly compared to rates in the clinical trial 8 of another vaccine, and may not reflect the rates observed in practice. 9

10 Adults and Geriatrics 11 In placebo-controlled studies among adults, the most frequent side effect of vaccination is soreness 12 at the vaccination site (affecting 10%?64% of patients) that lasts <2 days, local pain and swelling. 13 These local reactions typically are mild. Fever, malaise, myalgia, and other systemic symptoms can 14 occur following vaccination and most often affect persons who have had no prior exposure to the 15 influenza virus antigens in the vaccine (e.g., young children). These reactions begin 6?12 hours 16 after vaccination and can persist for 1?2 days. Placebo-controlled trials demonstrate that among 17 older persons and healthy young adults, administration of split-virus influenza vaccine is not 18 associated with higher rates of systemic symptoms (e.g., fever, malaise, myalgia, and headache) 19 when compared with placebo injections. (2) 20

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1 Children 2 The 2003-2004 formulation of Fluzone vaccine was studied in 19 children 6 to 23 months of age 3 and in 12 children 24 to 36 months of age, given in 2 doses one month apart. Local reactions and 4 systemic events were solicited for 3 days after each dose. Most local and systemic reactions were 5 mild. The proportions of local and systemic reactions in children were similar to the proportions 6 in adults. No reported local or systemic reaction required a therapeutic intervention other than 7 analgesics. (3) 8 9

6.2. Post-Marketing Experience

10 The following additional events have been reported during post-approval use of Fluzone vaccine. 11 Because these events are reported voluntarily from a population of uncertain size, it is not always 12 possible to reliably estimate their frequency or establish a causal relationship to vaccine 13 exposure.

14 15 Blood and Lymphatic System Disorders: Thrombocytopenia, lymphadenopathy 16 17 Immune System Disorders: Anaphylaxis, other allergic/hypersensitivity reactions (including 18 urticaria, angioedema) 19 20 Nervous System Disorders: GBS, convulsions, myelitis (including encephalomyelitis and 21 transverse myelitis), facial palsy (Bell?s palsy), optic neuritis/neuropathy, brachial neuritis, 22 syncope (shortly after vaccination), dizziness, paresthesia

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1 2 Vascular Disorders: Vasculitis, vasodilation/flushing 3 4 Respiratory, Thoracic and Mediastinal Disorders: Dyspnea, pharyngitis, rhinitis 5 6 Skin and Subcutaneous Tissue Disorders: Stevens-Johnson syndrome 7 8 General Disorders and Administration Site Conditions: Fever, pain, pruritis, asthenia/fatigue, 9 pain in extremities, chest pain

10 11

6.3. Other Adverse Events Associated with Influenza Vaccines

12 Anaphylaxis has been reported after administration of influenza vaccines. Although Influenza A 13 (H1N1) 2009 Monovalent Vaccine contains only a limited quantity of egg protein, this protein 14 can induce immediate hypersensitivity reactions among persons who have severe egg allergy. 15 Allergic reactions include hives, angioedema, allergic asthma, and systemic anaphylaxis. [See 16 Contraindications (4)]

17 18 The 1976 swine influenza vaccine was associated with an increased frequency of Guillain-Barr? 19 syndrome (GBS). Evidence for a causal relation of GBS with subsequent vaccines prepared from 20 other influenza viruses is unclear. If influenza vaccine does pose a risk, it is probably slightly 21 more than 1 additional case/1 million persons vaccinated. 22

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1 Neurological disorders temporally associated with influenza vaccination such as encephalopathy, 2 optic neuritis/neuropathy, partial facial paralysis, and brachial plexus neuropathy have been 3 reported. 4

5 Microscopic polyangitis (vasculitis) has been reported temporally associated with influenza 6 vaccination. 7

8

7. DRUG INTERACTIONS

9

7.1. Concomitant Administration with Other Vaccines

10 There are no data on the concomitant administration of Influenza A (H1N1) 2009 Monovalent 11 V accine with seasonal trivalent influenza vaccines. 12 13 Influenza A (H1N1) 2009 Monovalent Vaccine should not be mixed with any other vaccine in 14 the same syringe or vial.

15 16 If Influenza A (H1N1) 2009 Monovalent Vaccine is to be given at the same time as another 17 injectable vaccine(s), the vaccine(s) should always be administered at different injection sites. 18 19 7.2. Immunosuppressive Therapies

20 If Influenza A (H1N1) 2009 Monovalent Vaccine is administered to immunosuppressed persons 21 or persons receiving immunosuppressive therapy, immunologic response may be diminished. 22

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1

8. USE IN SPECIFIC POPULATIONS 2 Sanofi Pasteur?s Influenza A (H1N1) 2009 Monovalent Vaccine and seasonal trivalent Influenza

3 Virus Vaccine (Fluzone vaccine) are manufactured by the same process. Available information 4 for Fluzone vaccine is provided in this section. 5

8.1. Pregnancy

6 Pregnancy Category C: Animal reproduction studies have not been conducted with Influenza A 7 (H1N1) 2009 Monovalent Vaccine or Fluzone vaccine. It is also not known whether these 8 vaccines can cause fetal harm when administered to a pregnant woman or can affect reproduction 9 capacity. Influenza A (H1N1) 2009 Monovalent Vaccine should be given to a pregnant woman

10 only if clearly needed. 11 12

8.3. Nursing Mothers

13 It is not known whether Influenza A (H1N1) 2009 Monovalent Vaccine or Fluzone vaccine is 14 excreted in human milk. Because many drugs are excreted in human milk, caution should be 15