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  • CLASSES

    Influenza Vaccines

    DEA CLASS

    Rx

    DESCRIPTION

    Inactivated influenza vaccine (IIV)
    Used to confer immunity against 3 (2 type A and 1 type B) or 4 (2 type A and 2 type B) strains likely to circulate during annual flu season
    Annual immunizations required; recommended for all people at least 6 months of age

    COMMON BRAND NAMES

    Afluria, Alfuria, FLUAD, Fluarix, Fluarix Quadrivalent, Flublok, FLUCELVAX, Flulaval, Fluvirin, Fluzone, Fluzone High-Dose, Fluzone Intradermal

    HOW SUPPLIED

    Afluria/Alfuria/FLUAD/Fluarix Quadrivalent/FLUCELVAX/Flulaval/Fluvirin/Fluzone/Fluzone High-Dose Intramuscular Inj Susp: 0.5mL, 15-15-15mcg, 45-45-45mcg, 60-60-60mcg
    Flublok Intramuscular Inj Sol: 0.5mL, 45-45-45mcg
    Fluzone Intradermal Intradermal Inj Susp

    DOSAGE & INDICATIONS

    For annual seasonal influenza prophylaxis.
    Intramuscular dosage (Fluzone High-Dose)
    Geriatric 65 years and older

    0.5 mL IM as a single dose. Each 0.5 mL dose of Fluzone High-Dose contains influenza split virus antigens that are formulated to contain a total of 180 mcg of influenza virus hemagglutinin, 60 mcg each from the 3 influenza virus strains in the vaccine. In one study, Fluzone-High Dose showed statistical superiority to Fluzone in reducing the incidence of influenza-like illness among patients 65 years of age and older [relative efficacy 24.2% (95% CI 9.7; 36.5)].

    Intramuscular dosage (Fluad)
    Geriatric 65 years and older

    0.5 mL IM as a single dose.

    Intramuscular dosage (Fluzone Trivalent and Quadrivalent)
    Adults, Adolescents, and Children 9 years and older

    0.5 mL IM as a single dose.

    Children 3 to 8 years

    0.5 mL IM. For children who have not received at least 2 doses of trivalent or quadrivalent influenza vaccine before July 1, 2016, administer a second dose of 0.5 mL IM at least 4 weeks after the initial dose. The Advisory Committee on Immunization Practices (ACIP) recommends that children aged 6 months through 8 years who have previously received at least 2 doses of  influenza vaccine before July 1, 2016, receive only 1 dose for 2016 to 2017. The two previous doses need not have been given during the same season or consecutive seasons.

    Infants and Children 6 to 35 months

    0.25 mL IM. For infants and children who have not received at least 2 doses of trivalent or quadrivalent influenza vaccine before July 1, 2016, administer a second dose of 0.25 mL IM at least 4 weeks after the initial dose. The Advisory Committee on Immunization Practices (ACIP) recommends that children aged 6 months through 8 years who have previously received at least 2 doses of influenza vaccine before July 1, 2016, receive only 1 dose for 2016 to 2017. The two previous doses need not have been given during the same season or consecutive seasons.

    Intramuscular dosage (Fluarix Quadrivalent)
    Adults, Adolescents, and Children 9 years and older

    0.5 mL IM as a single dose. 

    Children 3 to 8 years

    0.5 mL IM. For children who have not received at least 2 doses of trivalent or quadrivalent influenza vaccine before July 1, 2016, administer a second dose of 0.5 mL IM at least 4 weeks after the initial dose. The Advisory Committee on Immunization Practices (ACIP) recommends that children aged 6 months through 8 years who have previously received at least 2 doses of influenza vaccine before July 1, 2016, receive only 1 dose for 2016 to 2017. The two previous doses need not have been given during the same season or consecutive seasons.

    Intramuscular dosage (Flulaval Quadrivalent)
    Adults, Adolescents, and Children 9 years and older

    0.5 mL IM as a single dose.

    Infants and Children 6 months to 8 years

    0.5 mL IM. For children who have not received at least 2 doses of trivalent or quadrivalent influenza vaccine before July 1, 2016, administer a second dose of 0.5 mL IM at least 4 weeks after the initial dose. The Advisory Committee on Immunization Practices (ACIP) recommends that children aged 6 months through 8 years who have previously received at least 2 doses of influenza vaccine before July 1, 2016, receive only 1 dose for 2016 to 2017. The two previous doses need not have been given during the same season or consecutive seasons.

    Neonates and Infants younger than 6 months

    Safety and efficacy have not been established.

    Intramuscular dosage (Afluria)
    Adults, Adolescents, and Children 9 years and older

    0.5 mL IM as a single dose. NOTE: The Afluria PharmaJet Stratis Needle-Free injection system is NOT approved in patients less than 18 years of age.

    Children 5 to 8 years

    0.5 mL IM is the FDA-approved dosage ; however, the ACIP recommends that Afluria not be used in children younger than 9 years due to an increased risk of febrile reactions in 2010 with a similar southern hemisphere vaccine from the same manufacturer. If no other licensed inactivated vaccine is available and the child has a medical condition that may increase the risk of influenza complications, Afluria may be used. For children who have not received at least 2 doses of trivalent or quadrivalent influenza vaccine before July 1, 2016, administer a second dose of 0.5 mL IM at least 4 weeks after the initial dose. The two previous doses need not have been given during the same season or consecutive seasons.

    Intramuscular dosage (Fluvirin, Flucelvax Quadrivalent)
    Adults, Adolescents, and Children 9 years and older

    0.5 mL IM as a single dose.

    Children 4 to 8 years

    0.5 mL IM. For children who have not received at least 2 doses of trivalent or quadrivalent influenza vaccine before July 1, 2016, administer a second dose of 0.5 mL IM at least 4 weeks after the initial dose. The Advisory Committee on Immunization Practices (ACIP) recommends that children aged 6 months through 8 years who have previously received at least 2 doses of influenza vaccine before July 1, 2016, receive only 1 dose for 2016 to 2017. The two previous doses need not have been given during the same season or consecutive seasons.

    Intramuscular dosage (Afluria Quadrivalent)
    Adults

    0.5 mL IM as a single dose. NOTE: The Afluria Quadrivalent PharmaJet Stratis Needle-Free injection system is only approved in Adults 18 through 64 years.

    Intramuscular dosage (Flucelvax)
    Adults

    0.5 mL IM as a single dose.

    Intramuscular dosage (Flublok)
    Adults

    0.5 mL IM as a single dose.

    Intramuscular dosage (Flublok Quadrivalent)
    Adults

    0.5 mL IM as a single dose.

    Intradermal dosage (Fluzone Intradermal)
    Adults 18 to 64 years

    0.1 mL intradermally as a single dose.

    MAXIMUM DOSAGE

    Adults

    0.5 mL/dose IM; 0.1 mL/dose intradermal (Fluzone Intradermal only). Safety and efficacy of IM Fluad and Fluzone High-Dose have not been established.

    Geriatric

    0.5 mL/dose IM. Safety and efficacy of intradermal administration have not been established.

    Adolescents

    0.5 mL/dose IM for Fluzone Trivalent and Quadrivalent, Fluarix Trivalent and Quadrivalent, FluLaval Quadrivalent, Afluria (excluding the needle-free injection system), Flucelvax Quadrivalent, and Fluvirin. Safety and efficacy of IM Fluzone High-Dose, Agriflu, Flublok, Flublok Quadrivalent, Flucelvax, Fluad, and intradermal administration have not been established.

    Children

    5 years and older: 0.5 mL/dose IM for Fluzone Trivalent and Quadrivalent, Fluarix Trivalent and Quadrivalent, FluLaval  Quadrivalent, Afluria (excluding the needle-free injection system), Flucelvax Quadrivalent, and Fluvirin. Safety and efficacy of IM Fluzone High-Dose, Agriflu, Flublok, Flublok Quadrivalent, Flucelvax, Fluad, and intradermal administration have not been established.
    4 years: 0.5 mL/dose IM for Fluzone Trivalent and Quadrivalent, Fluarix Trivalent and Quadrivalent, FluLaval Quadrivalent, Flucelvax Quadrivalent and Fluvirin. Safety and efficacy of IM Fluzone High-Dose, Agriflu, Flublok, Flublok Quadrivalent, Flucelvax, Afluria, Fluad, and intradermal administration have not been established.
    3 years: 0.5 mL/dose IM for Fluzone Trivalent and Quadrivalent, Fluarix Trivalent and Quadrivalent, and FluLaval  Quadrivalent. Safety and efficacy of IM Fluvirin, Fluzone High-Dose, Agriflu, Flublok, Flublok Quadrivalent, Flucelvax, Afluria, Fluad, Flucelvax Quadrivalent, and intradermal administration have not been established.
    1 to 2 years: 0.25 mL/dose IM for Fluzone Trivalent and Quadrivalent; 0.5 mL/dose IM for FluLaval Quadrivalent. Safety and efficacy of IM Fluarix Trivalent and Quadrivalent, Fluvirin, Fluzone High-Dose, Agriflu, Flublok, Flublok Quadrivalent, Flucelvax, Afluria, Fluad, Flucelvax Quadrivalent, and intradermal administration have not been established.

    Infants

    6 to 11 months: 0.25 mL/dose IM for Fluzone Trivalent and Quadrivalent; 0.5 mL/dose IM for Flulaval Quadrivalent. Safety and efficacy of IM Fluarix Trivalent and Quadrivalent, Fluvirin, Fluzone High-Dose, Agriflu, Flublok, Flublok Quadrivalent, Flucelvax, Afluria, Flucelvax Quadrivalent, and intradermal administration have not been established.
    1 to 5 months: Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    For storage information, see the specific product information within the How supplied section.
     
    NOTE: According to U.S. federal laws, the healthcare provider must record in the patient's permanent record: the manufacturer, lot number, date of administration, and the name and address of the person administering the vaccine.
    Obtain a patient's current health status and immunization history to determine vaccine adverse reactions. Complete a Vaccine Adverse Event Reporting System (VAERS) report form if adverse events have been identified. The reporting of events is required by the National Childhood Vaccine Injury Act of 1986. The toll-free number for VAERS is 1-800-822-7967. Depending on the adverse reaction, subsequent vaccination, if needed, may be contraindicated.
    The health care professional should have immediate availability of epinephrine injection and other agents used in the treatment of anaphylaxis in the event of a serious allergic reaction.
    Inform the patient, parent, guardian, or responsible adult of the benefits and risks of the vaccine. The vaccine cannot cause influenza.
    Provide the Vaccine Information Statements from the manufacturer to the recipient or guardian before each immunization; materials are free of charge from the Centers for Disease Control. Provision of the Vaccine Information Statements is required by the National Childhood Vaccine Injury Act of 1986.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
    Do not mix with any other vaccine.
    When concomitant administration of other vaccines is required, they should be given with different syringes and at different injection sites.

    Intramuscular Administration

    Prior to administration, clean skin over the injection site with a suitable cleansing agent.
    For products supplied as a suspension, shake well immediately before use.
    For vials, use a sterile syringe and needle to withdraw vaccine from vial. It is recommended that small syringes (0.5 mL) be used to minimize product loss. For prefilled syringes, attach a sterile needle.
    For adults and older children, a needle length >= 1 inch can be considered; needles < 1 inch might be of insufficient length to penetrate muscle tissue in certain adults and children.
    For children >= 3 years, the needle size required for deltoid injection ranges from 5/8- to 1-inch.
    For children 1 to 2 years, a needle at least 1 inch long is preferred for administration into the thigh; a 5/8 inch needle is sufficient for administration into the deltoid if the skin is stretched flat and the needle is inserted at a 90 degree angle.
    For the majority of infants < 1 year, a 1-inch, 22- to 25-gauge needle is sufficient to penetrate thigh muscle.
    Inject into the anterolateral aspect of the mid-thigh (for infants < 1 year of age) or the deltoid muscle of the upper arm (for children and adults). Do NOT administer in the gluteal muscle.
    Aspirate prior to injection to avoid injection into a blood vessel. If a vessel is penetrated, withdraw the needle and use a new syringe and needle at a different injection site.
    Doses from Afluria vials may be administered to adults (18 to 64 years) using the PharmaJet Stratis needle-free injection system. This spring loaded device delivers a single IM dose by creating a narrow fluid stream that rapidly penetrates the skin. Safety and efficacy of needless injectors have not been established in geriatric (> 64 years) nor pediatric (< 18 years) patients.
    Storage of opened vials: Acceptable storage varies depending on vaccine formulation and brand. See How Supplied section or directly contact the manufacturer for specific vaccine being used.

    Other Injectable Administration

    Intradermal administration (Fluzone Intradermal only):
    Gently shake the device and remove the needle cap.
    Insert the needle perpendicular to the skin in the region of the deltoid. Maintain light pressure on the surface of the skin and push the plunger to inject the dose. Do not aspirate.
    After needle removal from the skin, firmly push the plunger to activate the needle shield.

    STORAGE

    Afluria :
    - Discard entered multi-dose vial after 28 days
    - Discard if product has been frozen
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Protect from light
    - Refrigerate (between 36 and 46 degrees F)
    Agriflu:
    - Do not freeze
    - Protect from light
    - Store between 36 to 46 degrees F
    Alfuria:
    - Discard if product has been frozen
    - Do not freeze
    - Protect from light
    - Refrigerate (between 36 and 46 degrees F)
    FLUAD:
    - Discard if product has been frozen
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Protect from light
    - Store between 36 to 46 degrees F
    - Store in original container
    Fluarix:
    - Discard if product has been frozen
    - Do not freeze
    - Protect from light
    - Refrigerate (between 36 and 46 degrees F)
    - Store in original container
    Fluarix Quadrivalent:
    - Discard if product has been frozen
    - Do not freeze
    - Protect from light
    - Store between 36 to 46 degrees F
    - Store in original package until time of use
    Flublok:
    - Discard if product has been frozen
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Protect from light
    - Store between 36 to 46 degrees F
    FLUCELVAX:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Protect from light
    - Store between 35 to 46 degrees F
    Flulaval:
    - Discard if product has been frozen
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Protect from light
    - Refrigerate (between 36 and 46 degrees F)
    - Store in original container
    Fluvirin:
    - Discard if product has been frozen
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Protect from light
    - Store between 36 to 46 degrees F
    Fluzone:
    - Discard if product has been frozen
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Store between 35 to 46 degrees F
    Fluzone High-Dose:
    - Discard if product has been frozen
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Store between 35 to 46 degrees F
    Fluzone Intradermal:
    - Discard if product has been frozen
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Store between 35 to 46 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Prior to administration, inform the parent, guardian, or responsible adult of the benefits and risks of the vaccine, and provide the Vaccine Information Statement, accessible at the Centers for Disease Control and Prevention (CDC) website. These actions are required by the National Childhood Vaccine Injury Act of 1986. If a dose of influenza virus vaccine, inactivated has been previously given, question the parent or guardian about previous adverse reactions that may preclude further administration. Report all adverse reactions to the Vaccine Adverse Event Reporting System (VAERS), as well as the manufacturer. The toll-free number for VAERS is 1—800—822—7967. Educate the responsible adult(s) to promptly report any adverse reaction after vaccine administration to a health care provider.

    Intravenous administration, subcutaneous administration

    Influenza virus vaccine should not be given via intravenous administration or subcutaneous administration, it is for intramuscular (IM) administration only, with the exception of the intradermal Fluzone products. All other formulations should not be given by intradermal administration. Incorrect administration may result in inadequate immunity.

    Fever, respiratory infection

    The decision to administer or to delay vaccination with the influenza virus vaccine because of current or recent febrile illness depends on the severity of symptoms and on the etiology of the disease. The Advisory Committee on Immunization Practices recommends that vaccinations be delayed during the course of a moderate or severe acute febrile illness and administered after the acute phase of illness has resolved, unless the patient is at immediate risk of infection. Use caution when administering the vaccine to patients with severely compromised cardiopulmonary status. All vaccines can be administered to persons with minor illnesses such as diarrhea, mild upper-respiratory infection with or without low-grade fever, or other low-grade febrile illness. Persons with moderate or severe febrile illness should be vaccinated as soon as they have recovered from the acute phase of the illness.

    Egg hypersensitivity, kanamycin hypersensitivity, latex hypersensitivity, neomycin hypersensitivity

    All formulations of the inactivated influenza vaccine (IIV), with the exception of Flucelvax and Flublok, are contraindicated for use in persons with a known history of a severe allergic reaction (e.g., anaphylaxis) to the vaccine or any of its components, persons who have had a life-threatening reaction to any previous influenza vaccination, or persons with egg hypersensitivity. Agriflu is also contraindicated in persons with kanamycin hypersensitivity and/or neomycin hypersensitivity. Due to differences in manufacturing processes, Flucelvax and Flublok do not use eggs to propagate the virus; thus, they are only contraindicated in persons with a known history of a severe allergic reaction (e.g., anaphylaxis) to the vaccine or any of its components. Flucelvax, however, cannot be considered 100% egg-free because the initial seed virus is created using reference virus stains from the World Health Organization, which have been passaged in eggs. Flublok is egg-free, and thus, is recommended by the Advisory Committee on Immunization Practices (ACIP) for use in all egg allergic patients aged 18—49 years without other contraindications. If Flublok is unavailable/contraindicated, and the patient experienced only hives following ingestion of lightly cooked eggs (e.g., scrambled eggs), another IIV should be used with additional safety measures (observe for >= 30 minutes after immunization for symptoms of a reaction and the should be administered by a health care provider familiar with the clinical manifestations of egg hypersensitivity). In patients unable to receive Flublok and who have experienced angioedema, respiratory distress, lightheadedness, repeated emesis, or who required treatment with emergency interventions such as epinephrine, the inactivated influenza vaccine should only be administered by a physician experienced in the recognition and management of severe allergic conditions.  Patients with no known egg exposure, but who are suspected of being egg-allergic based on previous allergy testing and who are unable to receive Flublok, should be referred to an allergist. Although the ACIP recommends these additional safety measures for patients with egg allergy, the American College of Allergy, Asthma, and Immunology considers these special precautions (i.e., waiting periods after administration beyond those recommended for any vaccine and administration in a specialized medical setting) as unnecessary due to the extremely rare risk of anaphylactic reactions after vaccination. In a study in which 4172 patients with egg allergy received 4729 doses of inactivated influenza vaccine, including 513 patients with severe egg allergy who received 597 doses, no cases of anaphylaxis were reported. As with any biologic product, the prescriber or health care professional should have procedures in place to manage allergic reactions. The health care professional should have immediate availability of epinephrine (1:1000) injection and other agents used in the treatment of severe anaphylaxis in the event of a serious allergic reaction to the influenza virus vaccine. Additionally, caution must be exercised when using any Agriflu, Flucelvax, Fluad, and Fluvirin prefilled syringes, as the tip caps may contain natural latex rubber which may cause reactions in patients with latex hypersensitivity. Latex is not contained in Fluarix Trivalent or Quadrivalent, the vial stoppers of Fluvirin, Flublok, Flulaval Trivalent or Quadrivalent, nor in any Fluzone or Afluria products.

    Guillain-Barre syndrome

    Persons with a history of Guillain-Barre syndrome (GBS) have a substantially greater likelihood of subsequently developing GBS than persons without such a history. Thus, the likelihood of coincidentally developing GBS after influenza vaccination is expected to be greater among persons with a history of GBS than among persons with no history of this syndrome. It is not known if influenza vaccination is causally associated with this risk for recurrence of GBS. Nevertheless, the Advisory Committee on Immunization Practices (ACIP) recommends against influenza immunization in non-high risk patients who have developed GBS within 6 weeks of a previous influenza vaccination. However, for persons with a history of GBS who are at high risk for severe complications from influenza, the benefits of the influenza vaccination may justify the risks.

    Geriatric

    Geriatric persons may develop lower postvaccination antibody titers than healthy young adults and, thus, may remain susceptible to influenza-related upper respiratory tract infection (see Pharmacokinetics). However, even if such persons develop influenza illness despite vaccination, the vaccine can be effective in preventing lower respiratory tract infection or other secondary complications, thereby reducing the risk for hospitalization and death. In a retrospective study of data from 1990—2000, influenza vaccination was associated with significant reductions in the risk of hospitalization for pneumonia or influenza and in the risk of death among community-dwelling patients at least 65 years of age as compared with unvaccinated patients. Specifically, vaccination was associated with a 27% reduction in the risk of hospitalization for pneumonia or influenza and a 48% reduction in the risk of death. Statistically significant reductions in the risk of both hospitalization and death were also found by sensitivity analyses, which modeled the effect of a hypothetical unmeasured confounder that would have caused overestimation of vaccine effectiveness. In elderly nursing home residents, administration of the flu vaccine annually prior to October should generally be avoided because antibody concentrations can decrease within a few months of immunization.

    Children, infants

    Use caution when using the Afluria formulation of inactivated influenza virus vaccine in children < 9 years of age. In 2010, the Southern Hemisphere 2010 Afluria formulation was associated with increased post-marketing reports of fever and febrile seizures in children predominantly below the age of 5 years as compared to previous years; accordingly, Afluria is no longer FDA approved in infants and children < 5 years, and no longer recommended by the ACIP in children < 9 years. If no other licensed inactivated vaccine is available and the child has a medical condition that may increase the risk of influenza complications, Afluria may be used. During the 2010/2011 influenza season, increases in reports of febrile seizures in children 6 months to 4 years of age (most commonly in children 12 to 23 months of age) receiving the inactivated influenza vaccine and the conjugated pneumococcal vaccine (Prevnar 13) concomitantly occurred. Data from the 2011/2012 influenza season (which used the same formulation as the 2010/2011 season) resulted in similar findings; however, an increased risk for febrile seizures was not observed during the 2012/2013 influenza season. Although this observational data may suggest association of the seizure with the simultaneous administration of the vaccines, immunization should not be delayed (e.g., by separating administration across multiple healthcare visits) due to the threat of disease.

    Pregnancy

    The influenza virus vaccine is classified in FDA pregnancy risk category C (Fluzone Trivalent and Fluzone High-Dose) or B (Afluria, Agriflu, Fluarix Trivalent and Quadrivalent, Flublok, Flucelvax, FluLaval Trivalent and Quadrivalent, Fluvirin, Fluad, and Fluzone Quadrivalent and Intradermal). No adequate and well-controlled studies have been conducted in pregnant women and the ability of the vaccine to cause fetal harm or to affect reproductive capacity is unknown. During animal studies, no evidence of impaired fertility or fetal harm was noted with Afluria, Agriflu, Fluarix, Flublok, Flucelvax, FluLaval, Fluvirin, or Fluzone Quadrivalent or Intradermal. Pregnancy may increase the risk of serious medical complications from influenza. It is estimated that 12 hospitalizations among pregnant women could be prevented for every 1000 pregnant women who are vaccinated. Therefore, the Advisory Committee on Immunization Practices (ACIP) recommends that all women who are or will be pregnant (in any trimester) during the influenza season be routinely vaccinated with an inactivated influenza vaccine (vs. live-attenuated influenza vaccine). Although more data are needed, studies of more than 2000 pregnant women have demonstrated no adverse fetal effects associated with influenza virus vaccine. Many experts consider influenza vaccination safe during any stage of pregnancy. However, because spontaneous abortion is common in the first trimester and unnecessary drug-exposures have traditionally been avoided during this time, some experts prefer waiting until the second trimester of pregnancy to vaccinate. In addition to benefits to the mother, influenza vaccine administration during pregnancy appears to help protect newborns and infants. Fewer cases of laboratory-confirmed influenza occurred during the first 6 months of life among infants of the 159 mothers who received the inactivated influenza vaccine (6 cases) as compared with infants of 157 mothers who received the pneumococcal polysaccharide vaccine (16 cases). The clinical judgment of the physician is paramount in the determination of whether to vaccinate a pregnant woman. GlaxoSmithKline (GSK), the manufacturer of FluLaval and Fluarix, and Sanofi Pasteur, the manufacturer of Fluzone, have established pregnancy registries to monitor pregnancy outcomes and newborn health following vaccination. Patients who receive these vaccines during pregnancy are encouraged to contact GSK by telephone at 888 - 452 - 9622 or Sanofi Pasteur at 800 - 822 - 2463.

    Breast-feeding

    Data are limited regarding use of the influenza virus vaccine during breast-feeding and its' excretion in human breast milk is unknown. The manufacturers recommend caution when administering to nursing mothers; however according to the Advisory Committee on Immunization Practices (ACIP), inactivated virus vaccines pose no risk for mothers or their infants. Additionally, breast-feeding does not adversely affect immunization; limited data suggest breast-feeding may enhance the immune response to certain vaccine antigens. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.

    Anticoagulant therapy, coagulopathy, hemophilia, thrombocytopenia, vitamin K deficiency

    Patients with thrombocytopenia or a coagulopathy (e.g., hemophilia), vitamin K deficiency, or who are on anticoagulant therapy should be monitored closely when given influenza virus vaccine because bleeding can occur at the IM injection site.

    Acquired immunodeficiency syndrome (AIDS), agammaglobulinemia, human immunodeficiency virus (HIV) infection, hypogammaglobulinemia, immunosuppression, neoplastic disease, radiation therapy, severe combined immunodeficiency (SCID)

    Patients with significant immunosuppression may not have an adequate antibody response to the influenza virus vaccine. Immunosuppressed persons may include patients with severe combined immunodeficiency (SCID); hypogammaglobulinemia; agammaglobulinemia; altered immune states due to generalized neoplastic disease; or an immune system compromised by radiation therapy or drug therapy (e.g., chemotherapy or corticosteroid therapy with greater than physiologic doses). Short-term (< 2 weeks) corticosteroid therapy or intra-articular, bursal, or tendon injections with corticosteroids should not be immunosuppressive. Patients vaccinated with influenza virus vaccine within 2 weeks before starting immunosuppressive therapy or while receiving immunosuppressive therapy should be considered unvaccinated and should be revaccinated at least 3 months after therapy is discontinued if immune competence has been restored. Although patients with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) could have a diminished response, 1 randomized, placebo controlled trial noted that the administration of influenza virus vaccine was highly effective in preventing hospitalization due to influenza in patients with HIV infection and was not associated with changes in viral load or CD4 counts (mean count 400 cells/mm3). The CDC recommends immunization of HIV-infected individuals with the inactivated vaccine, as this measure is safe and may confer protection against influenza. Inactivated influenza vaccination should be offered to all patients with HIV infection.  However, because of the theoretical concern that increases in HIV plasma RNA following vaccination during pregnancy might increase the risk of perinatal transmission of HIV, providers may wish to defer vaccination for HIV-positive pregnant patients until after HAART is initiated.

    Syncope

    Injectable vaccines, including influenza virus vaccine, have been associated with episodes of syncope and fainting. These events may be accompanied by transient tonic-clonic limb movements, visual disturbances, and paresthesias. Prior to administration, ensure procedures are in place to prevent falls and restore cerebral perfusion. Monitor vaccine recipients after administration of the dose. If syncope occurs, place the patient in a supine or Trendelenburg position to restore cerebral perfusion.

    ADVERSE REACTIONS

    Severe

    bronchospasm / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    anaphylactic shock / Rapid / Incidence not known
    Guillain-Barre syndrome / Delayed / Incidence not known
    muscle paralysis / Delayed / Incidence not known
    myelitis / Delayed / Incidence not known
    optic neuritis / Delayed / Incidence not known
    vasculitis / Delayed / Incidence not known
    seizures / Delayed / Incidence not known

    Moderate

    erythema / Early / 1.0-76.4
    migraine / Early / 1.0-1.0
    wheezing / Rapid / 1.0-1.0
    confusion / Early / Incidence not known
    encephalopathy / Delayed / Incidence not known
    neuropathic pain / Delayed / Incidence not known
    dysphonia / Delayed / Incidence not known
    dysphagia / Delayed / Incidence not known
    dyspnea / Early / Incidence not known
    lymphadenopathy / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    photophobia / Early / Incidence not known
    conjunctivitis / Delayed / Incidence not known
    sinus tachycardia / Rapid / Incidence not known

    Mild

    injection site reaction / Rapid / 1.0-89.0
    pruritus / Rapid / 0.2-52.1
    irritability / Delayed / 3.0-42.9
    malaise / Early / 1.0-38.1
    drowsiness / Early / 13.0-37.7
    myalgia / Early / 1.0-36.4
    anorexia / Delayed / 1.0-32.3
    headache / Early / 1.0-24.7
    fatigue / Early / 1.0-18.0
    fever / Early / 0-16.0
    ecchymosis / Delayed / 0.5-15.2
    arthralgia / Delayed / 0.3-15.0
    vomiting / Early / 1.4-14.8
    shivering / Rapid / 2.6-12.1
    nausea / Early / 0.4-12.0
    diaphoresis / Early / 1.0-10.0
    rhinitis / Early / 1.0-10.0
    chills / Rapid / 2.0-7.3
    nasal congestion / Early / 1.0-7.0
    rhinorrhea / Early / 2.7-7.0
    diarrhea / Early / 1.0-4.8
    back pain / Delayed / 1.5-1.5
    abdominal pain / Early / 1.4-1.4
    dysmenorrhea / Delayed / 1.3-1.3
    cough / Delayed / 1.0
    infection / Delayed / 1.0
    pharyngitis / Delayed / 1.0
    throat irritation / Early / Incidence not known
    rash (unspecified) / Early / Incidence not known
    urticaria / Rapid / Incidence not known
    insomnia / Early / Incidence not known
    paresthesias / Delayed / Incidence not known
    tremor / Early / Incidence not known
    hypoesthesia / Delayed / Incidence not known
    laryngitis / Delayed / Incidence not known
    syncope / Early / Incidence not known
    dizziness / Early / Incidence not known
    chest pain (unspecified) / Early / Incidence not known
    flushing / Rapid / Incidence not known
    pallor / Early / Incidence not known
    vertigo / Early / Incidence not known

    DRUG INTERACTIONS

    Adalimumab: It is not clear if adalimumab interferes with the effectiveness of influenza virus vaccine. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients receiving such therapies.
    Amantadine: Although no data exist, there is a theoretical interaction between intranasal influenza vaccine and antiviral drugs used for influenza prophylaxis or treatment, such as amantadine. An interval of at least 48 hours between the administration of one of amantadine and the vaccine is recommended. If needed, the antiviral drug should not be restarted for at least 2 weeks after vaccine administration, unless medically needed.
    Carbamazepine: The elimination of some medications that are metabolized by cytochrome P-450, including carbamazepine, may be altered following administration of influenza virus vaccine. Reports concerning impaired drug clearance and possible toxicity are conflicting, and the clinical importance of the potential interaction is not clear.
    Fosphenytoin: Although influenza virus vaccine has been reported to inhibit the clearance of medications metabolized by cytochrome P-450 including phenytoin (or fosphenytoin), the reports concerning possible toxicity are conflicting. Most recent reports have noted no adverse clinical outcomes from the use of influenza virus vaccine in patients taking these medications; the use of these medications should not prohibit influenza immunization if indicated. Isolated reports of increased or decreased phenytoin serum concentrations secondary to the administration of influenza virus vaccine exist, but these interactions appear to be rare. Interactions, when they occur, are usually noted between 7 and 14 days post-vaccination. Although not routinely expected, it may be prudent to inform patients of how to recognize and manage the symptoms of phenytoin toxicity or the symptoms of decreased phenytoin efficacy after receiving flu vaccination.
    Phenytoin: Although influenza virus vaccine has been reported to inhibit the clearance of medications metabolized by cytochrome P-450 including phenytoin, the reports concerning possible toxicity are conflicting. The use of these medications should not prohibit influenza immunization if indicated.
    Pneumococcal Vaccine, Polyvalent: Higher risk of fever has been noted with simultaneous administration of trivalent inactivated influenza vaccine (TIV) and pneumococcal vaccine, polyvalent. An observational study found that that pediatric patients aged 6 to 23 months receiving simultaneous trivalent inactivated influenza vaccine (TIV) and 13-valent pneumococcal vaccine (PCV13) were 2.7 times (CI 1.3 to 5.6) more likely to have a day 0 to 1 temperature of >= 100.4 degrees F than those receiving TIV without PCV13. A temperature of 102.2 degrees F was 3.92 times (CI 1.09 to 14.14) more likely to occur on day 0 to 1 when TIV and PCV13 are administered together vs. TIV alone. If concomitant administration of other vaccines is required with the influenza virus vaccine, the vaccines should be administered at different injection sites.
    Rituximab: The safety of immunization with live virus vaccines following rituximab therapy has not been studied. Vaccination with live virus vaccines before or during rituximab receipt is not recommended. Before rituximab initiation, review the vaccination status of patients with rheumatoid arthritis and follow the Centers for Disease Control and Prevention guidelines for adult vaccination with non-live vaccines; administer non-live vaccines at least 4 weeks before a course of rituximab.The effect of rituximab on immune responses after vaccination was assessed in a trial of patients with rheumatoid arthritis randomized to receive either methotrexate alone or in combination with rituximab. Responses to pneumococcal vaccination were lower in the rituximab/methotrexate arm than in the methotrexate alone arm (19% v. 61%). Responses to tetanus toxoid vaccination were similar between the two treatment arms (39% v. 42%). Most patients who received rituximab had B-cell counts below the lower limit of normal at the time of immunization. The clinical implications of these findings are not known.
    Theophylline, Aminophylline: Influenza virus vaccine has been reported to inhibit the clearance of medications metabolized by cytochrome P-450 including theophylline or aminophylline. The use of these medications should not prohibit influenza immunization if indicated. However, because an occasional predisposed patient may experience an increase in the effects of theophylline or aminophylline, monitoring for theophylline toxicity may be warranted; a temporary dosage adjustment may be needed if an interaction occurs.

    PREGNANCY AND LACTATION

    Pregnancy

    The influenza virus vaccine is classified in FDA pregnancy risk category C (Fluzone Trivalent and Fluzone High-Dose) or B (Afluria, Agriflu, Fluarix Trivalent and Quadrivalent, Flublok, Flucelvax, FluLaval Trivalent and Quadrivalent, Fluvirin, Fluad, and Fluzone Quadrivalent and Intradermal). No adequate and well-controlled studies have been conducted in pregnant women and the ability of the vaccine to cause fetal harm or to affect reproductive capacity is unknown. During animal studies, no evidence of impaired fertility or fetal harm was noted with Afluria, Agriflu, Fluarix, Flublok, Flucelvax, FluLaval, Fluvirin, or Fluzone Quadrivalent or Intradermal. Pregnancy may increase the risk of serious medical complications from influenza. It is estimated that 12 hospitalizations among pregnant women could be prevented for every 1000 pregnant women who are vaccinated. Therefore, the Advisory Committee on Immunization Practices (ACIP) recommends that all women who are or will be pregnant (in any trimester) during the influenza season be routinely vaccinated with an inactivated influenza vaccine (vs. live-attenuated influenza vaccine). Although more data are needed, studies of more than 2000 pregnant women have demonstrated no adverse fetal effects associated with influenza virus vaccine. Many experts consider influenza vaccination safe during any stage of pregnancy. However, because spontaneous abortion is common in the first trimester and unnecessary drug-exposures have traditionally been avoided during this time, some experts prefer waiting until the second trimester of pregnancy to vaccinate. In addition to benefits to the mother, influenza vaccine administration during pregnancy appears to help protect newborns and infants. Fewer cases of laboratory-confirmed influenza occurred during the first 6 months of life among infants of the 159 mothers who received the inactivated influenza vaccine (6 cases) as compared with infants of 157 mothers who received the pneumococcal polysaccharide vaccine (16 cases). The clinical judgment of the physician is paramount in the determination of whether to vaccinate a pregnant woman. GlaxoSmithKline (GSK), the manufacturer of FluLaval and Fluarix, and Sanofi Pasteur, the manufacturer of Fluzone, have established pregnancy registries to monitor pregnancy outcomes and newborn health following vaccination. Patients who receive these vaccines during pregnancy are encouraged to contact GSK by telephone at 888 - 452 - 9622 or Sanofi Pasteur at 800 - 822 - 2463.

    Data are limited regarding use of the influenza virus vaccine during breast-feeding and its' excretion in human breast milk is unknown. The manufacturers recommend caution when administering to nursing mothers; however according to the Advisory Committee on Immunization Practices (ACIP), inactivated virus vaccines pose no risk for mothers or their infants. Additionally, breast-feeding does not adversely affect immunization; limited data suggest breast-feeding may enhance the immune response to certain vaccine antigens. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Influenza virus vaccine imparts immunity against the influenza virus by stimulating production of antibodies that are specific to the disease. Vaccine recipients develop immunity only to those strains of the virus from which the vaccine was prepared. Influenza viruses are recognized by the surface antigens they carry, and two such antigens, hemagglutinin (H) and neuraminidase (N) have been identified and are used to classify the various viruses. Subtypes of these strains (H1, H2, H3, N1, N2) are associated with influenza A virus and have been recognized to cause disease in humans. Immunity to these surface antigens increases resistance to infection and decreases the severity of the disease if infection occurs. Eventually, antigenic variation can occur, and immunity to one strain may no longer impart immunity to distantly related subtypes of the virus. Influenza B viruses also exhibit antigenic variation, and new variants of both types of viruses continue to cause widespread epidemics of respiratory disease.

    PHARMACOKINETICS

    The inactivated influenza virus vaccine (IIV) is usually administered intramuscularly; intradermal vaccines are also available. The vaccine usually imparts a protective effect within 10 to 14 days of administration. Post-vaccine antibody titers are generally high enough in healthy young adults and children to provide resistance against infection by strains found in the vaccine as well as related strains. A hemagglutination-inhibiting antibody titer of at least 1:40 may be protective against influenza infection in up to 50% of people. Among 1007 patients 18 to 64 years of age who got Afluria, 94.2 to 99.9% had a postvaccination titer of at least 1:40. The duration of immunity imparted by the influenza vaccine generally lasts 6 to 12 months.