Influenza H1N1 Vaccine: Package Insert / Prescribing Info

2.1 Preparation for Administration

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

Shake the syringe vigorously before administering the vaccine and shake the multidose vial preparation each time before withdrawing a dose of vaccine.

Between uses, return the multidose vial to the recommended storage conditions between 2º and 8ºC (36º and 46ºF). Do not freeze. Discard if the vaccine has been frozen.

A separate syringe and needle or a sterile disposable unit should be used for each injection to prevent transmission of infectious agents from one person to another. Needles should be disposed of properly and not recapped.

It is recommended that small syringes (0.5-mL or 1-mL) should be used to minimize any product loss.

2.2 Recommended Dose and Schedule

Clinical studies are ongoing with Influenza A (H1N1) 2009 Monovalent Vaccine to determine the optimal dosage, number of doses and schedule.

Available data show that children 9 years of age and younger are largely serologically naïve to the pandemic (H1N1) 2009 virus (15.1). Based upon these data Influenza A (H1N1) 2009 Monovalent Vaccine should be administered as follows:

4.1 Hypersensitivity

Influenza A (H1N1) 2009 Monovalent Vaccine should not be administered to anyone with known systemic hypersensitivity reactions to egg proteins (eggs or egg products), or to any component of Influenza A (H1N1) 2009 Monovalent Vaccine, or who has had a life-threatening reaction to previous influenza vaccinations [see DESCRIPTION (11)].

5.1 Guillain-Barré Syndrome

If Guillain-Barré syndrome has occurred within 6 weeks of receipt of prior influenza vaccine, the decision to give Influenza A (H1N1) 2009 Monovalent Vaccine should be based on careful consideration of the potential benefits and risks.

5.2 Altered Immunocompetence

If Influenza A (H1N1) 2009 Monovalent Vaccine is administered to immunocompromised persons, including individuals receiving immunosuppressive therapy, the expected immune response may not be obtained.

5.3 Preventing and Managing Allergic Reactions

Prior to administration of any dose of Influenza A (H1N1) 2009 Monovalent Vaccine, the healthcare provider should review the patient’s prior immunization history for possible adverse events, to determine the existence of any contraindication to immunization with Influenza A (H1N1) 2009 Monovalent Vaccine and to allow an assessment of benefits and risks. Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of the vaccine.

5.4 Limitations of Vaccine Effectiveness

Vaccination with Influenza A (H1N1) 2009 Monovalent Vaccine may not protect all individuals.

6.1 Overall Adverse Reaction Profile

Serious allergic reactions, including anaphylactic shock, have been observed in individuals receiving FLUVIRIN during postmarketing surveillance.

6.2 Clinical Trial Experience

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

6.3 Postmarketing Experience

The following additional adverse reactions have been reported during post-approval use of FLUVIRIN. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccine exposure. Adverse events described here are included because: a) they represent reactions which are known to occur following immunizations generally or influenza immunizations specifically; b) they are potentially serious; or c) the frequency of reporting.

• Body as a whole: Local injection site reactions (including pain, pain limiting limb movement, redness, swelling, warmth, ecchymosis, induration), hot flashes/flushes; chills; fever; malaise; shivering; fatigue; asthenia; facial edema.
• Immune system disorders: Hypersensitivity reactions (including throat and/or mouth edema). In rare cases, hypersensitivity reactions have lead to anaphylactic shock and death.
• Cardiovascular disorders: Vasculitis (in rare cases with transient renal involvement), syncope shortly after vaccination.
• Digestive disorders: Diarrhea; nausea; vomiting; abdominal pain.
• Blood and lymphatic disorders: Local lymphadenopathy; transient thrombocytopenia.
• Metabolic and nutritional disorders: Loss of appetite.
• Musculoskeletal: Arthralgia; myalgia; myasthenia.
• Nervous system disorders: Headache; dizziness; neuralgia; paraesthesia; confusion; febrile convulsions; Guillain-Barré Syndrome; myelitis (including encephalomyelitis and transverse myelitis); neuropathy (including neuritis); paralysis (including Bell’s Palsy).
• Respiratory disorders: Dyspnea; chest pain; cough; pharyngitis; rhinitis.
• Skin and appendages: Stevens-Johnson syndrome; sweating; pruritus; urticaria; rash (including non-specific, maculopapular, and vesiculobulbous).

6.4 Other Adverse Reactions Associated with Influenza Vaccination

Anaphylaxis has been reported after administration of FLUVIRIN. Although FLUVIRIN and Influenza A (H1N1) 2009 Monovalent Vaccine contain only a limited quantity of egg protein, this protein can induce immediate hypersensitivity reactions among persons who have severe egg allergy. Allergic reactions include hives, angioedema, allergic asthma, and systemic anaphylaxis [see CONTRAINDICATIONS (4)].

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

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

Microscopic polyangiitis (vasculitis) has been reported temporally associated with influenza vaccination.

7.1 Concomitant Administration with Other Vaccines

There are no data to assess the concomitant administration of Influenza A (H1N1) 2009 Monovalent Vaccine with other vaccines. If Influenza A (H1N1) 2009 Monovalent Vaccine is to be given at the same time as another injectable vaccine(s), the vaccines should always be administered at different injection sites.

Influenza A (H1N1) 2009 Monovalent Vaccine should not be mixed with any other vaccine in the same syringe or vial.

7.2 Concurrent Use with Immunosuppressive Therapies

Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs, and corticosteroids (used in greater than physiologic doses), may reduce the immune response to Influenza A (H1N1) 2009 Monovalent Vaccine.

8.1 Pregnancy

Pregnancy Category C: Animal reproduction studies have not been conducted with Influenza A (H1N1) 2009 Monovalent Vaccine or FLUVIRIN. It is also not known whether Influenza A (H1N1) 2009 Monovalent Vaccine or FLUVIRIN can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Influenza A (H1N1) 2009 Monovalent Vaccine should be given to a pregnant woman only if clearly needed.

8.3 Nursing Mothers

It is not known whether FLUVIRIN or Influenza A (H1N1) 2009 Monovalent Vaccine is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Influenza A (H1N1) 2009 Monovalent Vaccine is administered to a nursing woman.

8.4 Pediatric Use

Safety and effectiveness in pediatric subjects below the age of 4 years have not been established. [see ADVERSE REACTIONS (6) and CLINICAL STUDIES (14)]

8.5 Geriatric Use

Since 1997, of the total number of geriatric subjects (n = 397) in clinical studies of FLUVIRIN, 29% of adult subjects were 65 years and over, while 2.1% were 75 years and over.

Antibody responses were lower in the geriatric population than in younger subjects. Adverse events occurred less frequently in geriatric subjects (≥65 years) than in younger adults. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. [See ADVERSE REACTION (6) and CLINICAL STUDIES (14)].

12.1 Mechanism of Action

Influenza illness and its complications follow infection with influenza viruses. Global surveillance of influenza identifies yearly antigenic variants. For example, since 1977, antigenic variants of influenza A (H1N1 and H3N2) viruses and influenza B viruses have been in global circulation. Specific levels of hemagglutination inhibition (HI) antibody titers post-vaccination with inactivated influenza virus vaccine have not been correlated with protection from influenza illness. In some human studies, antibody titer of ≥1:40 have been associated with protection from influenza illness in up to 50% of subjects [see REFERENCES (15.2, 15.3)].

Antibody against one influenza virus type or subtype confers limited or no protection against another. Furthermore, antibody to one antigenic variant of influenza virus might not protect against a new antigenic variant of the same type or subtype.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Neither FLUVIRIN nor the Influenza A (H1N1) 2009 Monovalent Vaccine have been evaluated for carcinogenic or mutagenic potential, or for impairment of fertility.

14.1 Immunogenicity in Adults (18 to 64 years of age)

Tables 4 and 5 show the immunogenicity data for the adult age group. The seven clinical studies presented enrolled a total of 774 adult subjects. In the adult group, for all antigens (A/H1N1, A/H3N2 and B) at least one of the following point estimate criteria was met: the proportion of subjects with seroconversion (post-vaccination titer ≥1:40 from a pre-vaccination titer <1:10) or significant increase (at least a four-fold increase from pre-vaccination titer ≥1:10) in antibody titer was greater than 40%; the geometric mean titer (GMT) increase was >2.5; the proportion of subjects with a post-vaccination hemagglutination inhibition (HI) antibody titer ≥1:40 was greater than 70%.

14.2 Immunogenicity in Geriatric Subjects (65 years of age and older)

Tables 6 and 7 show the immunogenicity of FLUVIRIN in the geriatric age group. The six clinical studies presented enrolled a total of 296 geriatric subjects. For each of the influenza antigens, the percentage of subjects who achieved seroconversion and the percentage of subjects who achieved HI titers of ≥1:40 are shown, as well as the fold increase in GMT.

For all antigens (A/H1N1, A/H3N2 and B) at least one of the following point estimate criteria was met: the proportion of subjects with seroconversion (post-vaccination titer ≥1:40 from a pre-vaccination titer <1:10) or significant increase (at least a four-fold increase from pre-vaccination titer ≥1:10) in antibody titer was greater than 30%; the geometric mean titer (GMT) increase was >2.0; the proportion of subjects with a post-vaccination hemagglutination inhibition (HI) antibody titer ≥1:40 was greater than 60%. The pre-specified efficacy criteria were met in each study, although a relatively lower immunogenicity of A/H1N1 strain was seen in the last four studies (the same strain was in each of the formulations).

14.3 Immunogenicity in Pediatric Subjects

A small-scale study was conducted in 1987 to evaluate safety and immunogenicity of FLUVIRIN in 38 ‘at risk’ children, with diabetes and/or asthma, or lymphoid leukemia. Thirty-eight participants aged between 4 and 12 years of age were assessed. Ten subjects had diabetes, 21 had asthma, two had both diabetes and asthma, and one had lymphoid leukemia. There were four healthy control subjects. All participants received a single 0.5-mL dose of FLUVIRIN.

Immunogenicity results were obtained for 19 of the 38 subjects enrolled in the study. The point estimate of the percentage of subjects achieving a titer of ≥ 1:40 was 84% for the A/H1N1 strain 79% for the B strain, and 53% for the A/H3N2 strain. The GMT fold increases were 5.8 for the A/H1N1 strain, 40 for the B strain and 17.7 for the A/H3N2 strain.

Three clinical studies were carried out between 1995 and 2004 in a total of 520 pediatric subjects (age range 6-47 months). Of these, 285 healthy subjects plus 41 ‘at risk’ pediatric subjects, received FLUVIRIN.

In a 1995/1996 clinical study, 41 subjects (aged 6-36 months) at increased risk for influenza-related complications received two 0.25-mL doses of FLUVIRIN. At least 49% of subjects showed a ≥4-fold increase in HI antibody titer to all three strains. HI antibody titers of 1:40 or greater were seen in at least 71% of the subjects for all three influenza strains, with increases in geometric mean titer of 6.0-fold or greater to all three strains.

Two clinical studies (1999-2000 and 2004) indicated a lower immunogenicity profile for FLUVIRIN compared with two commercial split vaccines; in a study in the age group 6-48 months the comparator was a US licensed vaccine, Fluzone®, and in another study in the age group 6-36 months the comparator was a non-US licensed inactivated influenza vaccine. Despite the small sample size (a total of 285 healthy subjects received FLUVIRIN in these two clinical studies) the lower immunogenicity profile of FLUVIRIN was greatest versus the comparator vaccines in children <36months but was also evident in those 36-48 months of age, though the differences were less.

Influenza A (H1N1) 2009 Monovalent Vaccine should only be used for the immunization of persons aged 4 years and older.

16.1 How Supplied

Influenza A (H1N1) 2009 Monovalent Vaccine is supplied as a 0.5-mL prefilled single dose syringe, package of 10 syringes per carton. NDC 66521-200-02

Influenza A (H1N1) 2009 Monovalent Vaccine is supplied as a 5-mL multidose vial, individually packaged in a carton. NDC 66521-200-10

16.2 Storage and Handling

Store Influenza A (H1N1) 2009 Monovalent Vaccine refrigerated between 2º and 8ºC (36º and 46ºF).

Do not freeze. Discard if the vaccine has been frozen.

Store in the original package to protect from light.

Do not use after the expiration date.

Between uses, return the multidose vial to the recommended storage conditions.