Professional Drug Information > Influenza Virus Vaccine

Influenza Virus Vaccine (Systemic)

VA CLASSIFICATION
Primary: IM100


Note: This monograph refers to the current (2002–2003 season) inactivated whole-virus influenza vaccine prepared from intact, purified virus particles. Purified surface-antigen and subvirion preparations are available.^{34} Manufacturer's prescribing information should be consulted for additional information regarding specific manufacturing processes. ^{34}
Based on the detected antigenic changes in the circulating strains of influenza viruses in the U.S. and worldwide, the U.S. Food and Drug Administration's Vaccines and Related Biological Products Advisory Committee (VRBPAC) and the World Health Organization (WHO) recommended that the 2002–2003 trivalent influenza virus vaccine contain A/Moscow/10/99 (H3N2)-like, A/New Caledonia/20/99 (H1N1)-like, and B/Hong Kong/330/2001-like antigens. ^{34}
Influenza vaccine with reduced thimerosal content will be available for the 2002–2003 influenza season, however supplies may be limited. ^{34}
However, as in previous years, the specific viruses used in vaccine manufacturing in each country must be approved by the national control authorities.^{04}

Commonly used brand name(s): FluShield; Fluviral; Fluviral S/F; Fluvirin; Fluzone.

Another commonly used name is
flu vaccine.
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Immunizing agent (active)—

Indications

General considerations
Influenza A viruses are classified into subtypes on the basis of their two surface antigens: hemagglutinin (H) and neuraminidase (N) ^{{03} {28}}. Three subtypes of hemagglutinin (H1, H2, and H3) and two types of neuraminidase (N1 and N2) are recognized among influenza A viruses that have caused widespread human disease ^{{02} {03} {05}}. Immunity to these antigens, especially to the hemagglutinin, reduces the likelihood of infection and lessens the severity of disease if infection occurs ^{{02} {05}}.

Note: Unlike influenza A, the influenza B viruses are not segregated into sub-types^{28}


Infection with a virus of one subtype confers little or no protection against viruses of other subtypes. ^{{02} {05}} Furthermore, over time, antigenic variation (antigenic drift) within a subtype may be so marked that infection or vaccination with one strain may not induce immunity to distantly related strains of the same subtype. ^{{02} {05}}

Although influenza B viruses have shown more antigenic stability than influenza A viruses, antigenic variations do occur in influenza B viruses. ^{{02} {05}} For these reasons, major epidemics of respiratory disease caused by new variants of influenza continue to occur. ^{{02} {05}} The antigenic characteristics of circulating strains provide the basis for selecting the virus strains included in each year's vaccine. ^{{02} {05}}

Typical influenza illness is characterized by abrupt onset of fever, myalgia, headache, rhinitis, sore throat, and nonproductive cough. ^{{02} {05}{34}} Unlike other common respiratory illnesses, influenza can cause severe malaise lasting for several days. ^{{02} {05}}Cough and malaise can persist for greater than 2 weeks in some persons infected with influenza. ^{34} More severe illness can result if either primary influenza develops into viral pneumonia or if secondary bacterial pneumonia occurs. ^{{02} {05}} During influenza epidemics, high attack rates of acute illness result in increased numbers of visits to physicians' offices, walk-in clinics, and emergency rooms, and increased hospitalizations for management of lower respiratory tract complications. ^{{02} {05}}

Elderly persons and persons with underlying chronic health problems are at increased risk for complications of influenza. ^{{02} {05} {08} {14} {15} {28}} If they become ill with influenza, such members of high-risk groups are more likely than the general population to require hospitalization. ^{{02} {05} {28}} During major epidemics, hospitalization rates for persons at high risk may increase twofold to fivefold, depending on the age group. ^{{02} {05}} Previously healthy children and younger adults may also require hospitalization for influenza-related complications, but the relative increase in their hospitalization rates is less than for persons who belong to high-risk groups. ^{{02} {05}}

An increase in mortality further indicates the impact of influenza epidemics. ^{{02} {05}} Increased mortality results not only from influenza and pneumonia, but also from cardiopulmonary and other chronic diseases that can be exacerbated by influenza. ^{{02} {05}} More than 90% of the deaths attributed to pneumonia and influenza occur among persons ³ 65 years of age. ^{{02} {05}}

Because the proportion of elderly persons in the U.S. population is increasing, and because age and its associated chronic diseases are risk factors for severe influenza illness, the number of deaths attributed to influenza can be expected to increase unless control measures are implemented more vigorously. ^{{02} {05}} In addition, the number of persons < 65 years of age at increased risk for influenza-related complications is increasing. ^{{02} {05}{28}} Better survival rates for organ-transplant recipients, the success of neonatal intensive-care units, and better management of diseases such as cystic fibrosis and acquired immunodeficiency syndrome (AIDS) contribute to a growing population of younger persons at high risk. ^{{02} {05}}

More than 8 million children and adolescents in the U.S., including 2.2 million persons 10 to 18 years of age who have asthma, have at least one medical condition that places them at high risk for complications associated with influenza. ^{16} Such children and adolescents should be vaccinated annually against influenza; currently, however, few actually receive the vaccine. ^{16}

Adolescents who meet any of the following criteria should be vaccinated against influenza:

   • Adolescents who have chronic disorders of the pulmonary system (including those who have asthma) or the cardiovascular system. ^{16}
   • Adolescents who reside in long-term facilities. ^{16}
   • Adolescents who have required regular medical follow-up or hospitalization during the preceding year because of chronic metabolic disease (including those who have diabetes mellitus), renal dysfunction, hemoglobinopathy, or immunosuppression (including those who have immunosuppression caused by medication). ^{16}
   • Adolescents who receive long-term aspirin therapy and, therefore, may be at risk for contracting Reye's syndrome after an influenza infection. ^{16}
   • In addition, adolescents who have close contact with persons who meet any of these conditions or with persons ³ 65 years of age should be administered influenza virus vaccine annually, to reduce the likelihood of their acquiring influenza infection. ^{16}


In the U.S., influenza virus vaccine campaigns are targeted at approximately 35 million persons ³ 65 years of age, and 33–39 million persons < 65 years of age who are at high risk for influenza-associated complications. ^{28} National health objectives for the year 2000 include vaccination of at least 60% of persons at risk for severe influenza-related illnesses. ^{{02} {05} {28}} Influenza virus vaccination levels among persons ³ 65 years of age improved substantially from 1989 (33%) to 1999 (66%), thereby exceeding the year 2000 target for this age class; the national health objective for this age group has now been upgraded to achieve vaccination coverage of at least 90% of all persons ³ 65 years of age by the year 2010. ^{34} In 2000, vaccination levels among all persons at high risk < 65 years of age was 32% and 44% for persons 50 to 64 years of age with chronic medical conditions. ^{34}

Successful vaccination programs have combined education for health care workers, publicity and education targeted at potential recipients, a plan for identifying persons at high risk (usually by medical record review), and efforts to remove administrative and financial barriers that prevent persons from receiving the vaccine. ^{{02} {05}} Persons for whom influenza virus vaccine is recommended can be identified and vaccinated in the following settings ^{{02} {05}}:

   • Outpatient clinics and physicians' offices. ^{{02} {05}{28}} Staff in physicians' offices, clinics, health maintenance organizations, and employee health clinics should be instructed to identify and label the medical records of patients who should receive vaccination. ^{{02} {05}} Vaccination should be offered during visits beginning in September and lasting throughout the influenza season. ^{{02} {05}} The offer of vaccination and its receipt or refusal should be documented in the medical records. ^{{02} {05}} Patients in high-risk groups who do not have regularly scheduled visits during the fall should be reminded by mail or telephone of the need for vaccination. ^{{02} {05}} If possible, arrangements should be made to provide vaccination with minimal waiting time and at the lowest possible cost. ^{{02} {05}}
   • Facilities providing episodic or acute care. ^{{02} {05} {12}} Health care providers in these settings (e.g., emergency rooms and walk-in clinics) should be familiar with influenza virus vaccine recommendations. ^{{02} {05}} They should offer vaccination to persons in high-risk groups or should provide written information giving the reason for this vaccination, the locations where it is available, and the health care personnel to contact. ^{{02} {05}} Written information should be available in language(s) appropriate for the population served by the facility. ^{{02} {05}}
   • Nursing homes and other residential long-term care facilities. ^{{02} {05} {12}} Vaccination should be routinely provided to all residents of long-term care facilities with the concurrence of the attending physicians rather than by obtaining individual vaccination orders for each patient. ^{{02} {05}} Consent for vaccination should be obtained from the resident or a family member at the time of admission to the facility, and all residents should be vaccinated at one time, immediately preceding the influenza season. ^{{02} {05}} Residents admitted during the winter months after completion of the vaccination program should be vaccinated when they are admitted. ^{{02} {05}}
   • Acute care hospitals. ^{28} All persons ³ 50 years of age and younger persons (including children) with-high risk conditions who are hospitalized at any time from September through March should be offered and strongly encouraged to receive the influenza virus vaccine before they are discharged. ^{28} Household members and others with whom they will have contact also should receive written information about the need for influenza virus vaccination, and where it is available. ^{{02} {05}}
   • Outpatient facilities providing continuing care to patients at high risk. ^{{02} {05}} All patients should be offered vaccination before the beginning of the influenza season. ^{{02} {05}} Patients admitted to such programs (e.g., hemodialysis centers, hospital specialty care clinics, and outpatient rehabilitation programs) during the winter months after the earlier vaccination program has been conducted should be vaccinated at the time of admission. ^{{02} {05}} Household members and others with whom they will have contact also should receive written information about the need for influenza virus vaccination, and where it is available. ^{{02} {05}}
   • Visiting nurses and others providing home care to persons at high risk. ^{{02} {05}} Nursing care plans should identify patients in high-risk groups, and vaccination should be provided in the home if necessary. ^{{02} {05}} Caregivers and other persons in the household (including children) should be referred for vaccination. ^{{02} {05}{28}}
   • Facilities providing services to persons ³50 years of age. ^{28} In these facilities (e.g., retirement communities, assisted living facilities, and recreation centers), all unvaccinated residents/attendees should be offered vaccination on site before the influenza season begins. ^{28} Education/publicity programs should also be provided; these programs should emphasize the need for influenza virus vaccination and provide specific information on the vaccination programs, their schedules, and locations. ^{{02} {05}}
   • Clinics and other settings providing health care for travelers. ^{{02} {05}} Indications for influenza virus vaccination should be reviewed before travel, and vaccination should be offered, if appropriate. ^{{02} {05}}
   • Health care workers. ^{{02} {05}} Administrators of all health care facilities should arrange for influenza vaccination to be offered to all personnel before the influenza season begins. ^{{02} {05}} Personnel should be provided with appropriate educational materials, and should be strongly encouraged to receive the vaccine. ^{{02} {05}} Particular emphasis should be placed on vaccination of persons who care for members of high risk groups (e.g., staff of intensive care units [including neonatal intensive care units], staff of medical/surgical units, and employees of nursing homes and long-term care facilities). Using a mobile cart to carry the vaccine doses to hospital wards or other work sites and making the vaccine available during night and weekend work shifts can enhance compliance, as can a follow-up campaign early in the course of a community outbreak. ^{{02} {05}}


An alternative strategy for controlling influenza type A infection among high-risk patients is the use of the antiviral agents amantadine and rimantadine, especially for chronically ill, institutionalized, or severely debilitated persons who have been or may be exposed to influenza type A during an outbreak. ^{{02} {05} {09}} Amantadine and rimantadine are equally effective in the prevention and treatment of influenza type A infections.^{{02} {05} {09}{28}} The neuraminadase inhibitors oseltamivir and zanamivir have also proven effective in reducing the duration of uncomplicated influenza A and B illness when administered within 2 days of symptom onset; however, neither have been approved for influenza prophylaxis. None of the four antiviral agents have been effective in the prevention of serious influenza-related complications^{28}.

Accepted

Influenza (prophylaxis)—Influenza virus vaccine is indicated for any person ³ 6 months of age who, because of age or underlying medical condition, is at increased risk of complications of influenza ^{{02} {08}}, including:    • Targeted high-risk children. ^{{03} {20} {21} {22}} Yearly immunization is recommended for children 6 months of age and older with one or more specific risk factors. ^{03} Data are insufficient regarding the potential severity of influenza in several of these groups of children; however, based on available data and knowledge of the pathophysiology of these disorders, children with the following risk factors warrant immunization:    —Those with asthma and other chronic pulmonary diseases. ^{03} Influenza vaccination can be given safely and effectively to children with asthma regardless of asthma symptoms or concurrent prednisone therapy. ^{07} Vaccination of all patients with moderate to severe asthma who visit clinics or emergency departments would improve the overall vaccination rate significantly. ^{07}
   —Those with hemodynamically significant cardiac disease. ^{03}
   —Those undergoing immunosuppressive therapy. ^{03}
   —Those with sickle-cell anemia and other hemoglobinopathies. ^{03}

   • Other high-risk children. ^{03} Children who are potentially at increased risk for complicated influenza illness and who may benefit from influenza immunization are those with one or more of the following conditions ^{03}:    —Human immunodeficiency virus (HIV) infection. ^{03}
   —Diabetes mellitus. ^{03}
   —Chronic metabolic diseases. ^{03}
   —Recipients of long-term aspirin therapy, such as children with rheumatoid arthritis or Kawasaki disease, who may have an increased risk of developing Reye's syndrome. ^{03}
   —Influenza virus vaccination also may be considered for children who are marginally immunocompromised as a result of any underlying condition, since even uncomplicated influenza can have adverse effects on the course of an underlying illness. ^{03}

   • Adults at increased risk for influenza-related complications ^{{20} {21} {22}{28}}:    —Persons ³50 years of age. ^{28}
   —Residents of nursing homes and other long-term care facilities that house persons of any age with chronic medical conditions. ^{{02} {05}}
   —Those with chronic disorders of the pulmonary or cardiovascular systems. ^{{02} {05}}
   —Those who have required regular medical follow-up or hospitalization during the preceding year because of chronic metabolic diseases (including diabetes mellitus), renal dysfunction, hemoglobinopathies, or immunosuppression (including immunosuppression caused by medications). ^{{02} {05}}
   —Women who will be in the second or third trimester of pregnancy during the influenza season. ^{05}

   • Persons who can transmit influenza to others who are at high risk. ^{{02} {03} {05} {20} {21} {22}} Persons who are clinically or subclinically infected with influenza and who care for or live with members of high-risk groups can transmit influenza virus to them. ^{{02} {05}} Some persons at high risk (e.g., the elderly, transplant recipients, and persons with AIDS) can have a low antibody response to influenza vaccine. ^{{02} {05}} Efforts to protect these members of high-risk groups against influenza may be improved by reducing the likelihood of influenza virus exposure from their caregivers. ^{{02} {05}} Immunization of adults who are in close contact with children at high risk may be an important means of protecting these children, especially for infants < 6 months of age for whom vaccination is not recommended. ^{03} Immunization of pregnant women may be beneficial to the neonates, as well, since transplacentally acquired antibody appears to protect neonates from infection with influenza A virus. ^{03} Therefore, the following groups should be immunized. ^{{02} {03} {05}}:    —Physicians, nurses, and other personnel in both hospital and outpatient settings, including medical emergency response workers. ^{{02} {03} {05} {28}{34}}
   —Employees of nursing homes and long-term care facilities who have contact with patients or residents. ^{{02} {05}{28}}
   —Employees of assisted living and other residences for persons at high risk. ^{34}
   —Providers of home care to persons at high risk (e.g., visiting nurses and volunteer workers). ^{{02} {05}{28}}
   —Household contacts of persons at high risk, ^{{02} {03} {05}} including children, ^{{02} {05}} siblings, and primary caretakers of children at high risk. ^{{02} {05}} HIV-infected children who are members of households with adults at high risk also should be immunized. ^{{02} {05}}

   • General population. ^{{02} {05} {20} {21} {22}} Physicians should administer influenza virus vaccine to any person who wishes to reduce the likelihood of becoming ill with influenza. ^{{02} {05}{28}} Persons who provide essential community services should be considered for vaccination, to minimize disruption of essential activities during influenza outbreaks. ^{{02} {05}{28}} Vaccination should be considered for groups of individuals whose close contact with each other facilitates rapid transmission of the virus infection resulting in disruption of routine activities. ^{{02} {03} {05}} Examples are students in colleges, schools, and other institutions of learning, particularly those who reside in dormitories or who are members of athletic teams, and those living in residential institutions. ^{{02} {03} {05}{28}}
   • Healthy young children. Recent studies, which attempt to separate the effects of RSV and influenza, report otherwise healthy children aged 0 to 4 years may be at increased risk for influenza-related hospitalization compared with older healthy children or older children with high-risk conditions. ^{34} Vaccination of all children aged 6 to 23 months is encouraged when feasible. ^{34}Healthy children aged less than 6 months, the pediatric group at greatest risk for influenza-related complications, are not vaccinated because the influenza vaccine is not FDA approved for use in this population. Risk of transmission of influenza can be reduced if household contacts and out-of-home care givers are vaccinated. ^{34}
   • Persons infected with HIV. ^{{02} {05} {20} {21} {22}{28}} Limited information exists regarding the frequency and severity of influenza illness among HIV-infected persons, but reports suggest that symptoms may be prolonged and the risk for complications increased for some HIV-infected persons. ^{{02} {05}} Influenza vaccine has produced protective antibody titers against influenza in vaccinated HIV-infected persons who have minimal AIDS-related symptoms and high CD4+ T-lymphocyte cell counts. ^{28} In patients who have advanced HIV infection–related disease and low CD4+ T-lymphocyte cell counts, however, influenza virus vaccine may not induce protective antibody titers; furthermore, a second dose of vaccine does not improve the immune response for these persons. ^{28} Recent studies have examined the effect of influenza virus vaccination on replication of HIV type 1 (HIV-1). ^{{02} {05}} Although some studies have demonstrated a transient (i.e., 2- to 4-week) increase in replication of HIV-1 in the plasma or peripheral blood mononuclear cells of HIV-1–infected persons after vaccine administration, other studies using similar laboratory techniques have not indicated any substantial increase in replication. ^{28} Decline in CD4+ T-lymphocyte cell counts and progression of clinical HIV infection–related disease have not been demonstrated among HIV-infected persons who receive influenza virus vaccine. ^{28} Since influenza can result in serious illness and complications, and because influenza virus vaccination may result in protective antibody titers, vaccination will benefit many HIV-infected patients, including HIV-infected pregnant women. ^{28}{34}
   • International travelers. ^{{02} {03} {05} {20} {21} {22}{28}} The risk of exposure to influenza during foreign travel varies, depending on the season and destination. ^{{02} {05}} In the tropics, influenza outbreaks can occur throughout the year; in the southern hemisphere, most outbreaks occur between April and September. ^{{02} {05}{28}} Because of the short incubation period for influenza, exposure to the virus during travel can result in clinical illness that begins while traveling, which could be an inconvenience or a potential danger, especially for persons at increased risk for complications. ^{{02} {05}} Travelers with organized tourist groups at any time of year may also be at risk for exposure if the group includes persons from areas of the world where influenza viruses are circulating. ^{34}Persons preparing to travel should review their influenza vaccination histories. ^{{02} {05}{28}} If they were not vaccinated during the previous fall or winter, they should consider receiving influenza vaccination before travel. ^{28}



Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Source—
    Each year's influenza vaccine contains three virus strains (usually two type A strains and one type B strain) representing the influenza viruses that are likely to circulate in the U.S. in the upcoming winter. ^{{02} {05}} The vaccine is made from highly purified, egg-grown viruses that have been made noninfectious (inactivated). ^{{02} {05}} Whole-virus, subvirion, and purified-surface-antigen preparations are available. ^{{02} {05}}
    In collaboration with the World Health Organization (WHO), its international network of collaborating laboratories, and state and local health departments, the Centers for Disease Control and Prevention (CDC) conducts surveillance to monitor influenza activity and detect antigenic changes in the circulating strains of influenza viruses. ^{{01} {10} {11} {13}}

Mechanism of action/Effect:

Humoral defenses against influenza infection are mainly conferred by serum and local immune globulin G (IgG) and immune globulin A (IgA) antibodies to the surface glycoproteins, hemagglutinin (H) and neuraminidase (N). ^{17} Anti-H antibodies inhibit the attachment of the influenza virus to target cell membrane receptors and thus neutralize viral infectivity. ^{17} Depending on their concentration, these antibodies can either provide complete protection from the acquisition of infection or prevent the development of serious illness. ^{17} Protection studies have indicated that an anti-H antibody titer of ³ 40 is the protection threshold beyond which serious illness is unlikely to develop. ^{17}


Protective effect

Most vaccinated children and young adults develop high titers of postvaccination hemagglutinin-inhibition (HI) antibody. ^{02} These antibodies protect the individual against illness caused by strains similar to those in the vaccine. ^{02} Elderly persons and persons with certain chronic diseases may develop lower postvaccination antibody titers than healthy young adults and thus may remain susceptible to influenza-related upper respiratory tract infection. ^{02} However, even if such persons develop influenza illness despite vaccination, the vaccine can be effective in preventing lower respiratory tract involvement or other complications, thereby reducing the risks of hospitalization and death. ^{02}

The effectiveness of influenza vaccine in preventing or attenuating illness varies, depending primarily on the age and immunocompetence of the vaccine recipient and the degree of similarity between the virus strains included in the vaccine and those that circulate during the influenza season. ^{02} When there is a good match between the vaccine and circulating viruses, influenza virus vaccine has been shown to prevent illness in approximately 70% of healthy persons < 65 years of age. ^{02} In these circumstances, studies have also indicated that the effectiveness of influenza virus vaccine in preventing hospitalization for pneumonia and influenza among elderly persons living in settings other than nursing homes or similar long-term care facilities ranges from 30 to 70%. ^{02}

Among elderly persons residing in nursing homes, influenza virus vaccine is very effective in preventing severe illness, secondary complications, and death. ^{02} Studies in this population have indicated that the vaccine can be 50 to 60% effective in preventing hospitalization and pneumonia, and 80% effective in preventing death, even though the vaccine's efficacy in preventing influenza illness may only be in the range of 30 to 40% among the frail elderly. ^{02} Achieving a high rate of vaccination among nursing home residents can reduce the spread of infection in a facility, thus preventing disease through herd immunity. ^{02}.


Time to protective effect

Peak antibody protection against influenza strains included in the vaccine develops 2 weeks after vaccination in adults. ^{34}


Duration of protective effect

Since the antigenic properties of influenza virus surface antigens frequently change, the vaccine-induced protective immunity is short-lived. ^{17} For this reason, health authorities recommend annual revaccination of persons at risk, using influenza virus vaccines containing the expected epidemic strains for the next season. ^{17}


Precautions to Consider

Pregnancy/Reproduction

Pregnancy—
Influenza-associated excess mortality among pregnant women has not been documented except during the pandemics of 1918–19 and 1957–58. ^{05} However, because death-certificate data often do not indicate whether a woman was pregnant at the time of death, studies conducted during interpandemic periods may underestimate the impact of influenza in this population. ^{05} Case reports and limited studies suggest that pregnancy may increase the risk of serious medical complications of influenza, as a result of increases in heart rate, increases in stroke volume and oxygen consumption, decreases in lung capacity, and changes in immunologic functions. ^{05} A recent study of the impact of influenza during 17 interpandemic influenza seasons documented that the relative risk of hospitalization for selected cardiorespiratory conditions among pregnant women increased from 1.4 during weeks 14 to 20 of gestation to 4.7 during weeks 37 to 42, as compared with rates among women who were 1 to 6 months postpartum. ^{05} Women in their third trimesters of pregnancy were hospitalized at a rate comparable to that of nonpregnant women with high-risk medical conditions for whom influenza virus vaccine has traditionally been recommended. ^{05} Using data from this study, it was estimated that an average of 1 to 2 hospitalizations among pregnant women could be prevented for every 1000 pregnant women immunized. ^{05}

On the basis of these and other data suggesting that influenza infection may cause increased morbidity in women during the second and third trimesters of pregnancy, the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) recommends that women who will be beyond the first trimester of pregnancy (14 weeks of gestation) during the influenza season be vaccinated. ^{05} Pregnant women who have medical conditions that increase the risk of complications from influenza should be vaccinated before the influenza season, regardless of the stage of pregnancy. ^{05} Studies of influenza immunization of more than 2000 pregnant women have demonstrated no adverse fetal effects associated with influenza virus vaccine; however, more data are needed. ^{05} Because influenza virus vaccine is not a live virus vaccine and major systemic reactions are rare, many experts consider influenza vaccination safe during any stage of pregnancy. ^{05} However, because spontaneous abortion is common in the first trimester and unnecessary exposures have traditionally been avoided during this time, some experts prefer influenza vaccination during the second trimester to avoid coincidental association of the vaccine with early pregnancy loss. ^{05}

No data or evidence exists of any harm caused by the level of mercury exposure that might occur from influenza vaccination of pregnant women despite thimerosal use in U.S. vaccines since the 1930s. The benefit of influenza vaccine with reduced or standard thimerosal content to pregnant women for prevention of influenza-related complications outweighs the potential risk, if any, for thimerosal. ^{34}

Influenza vaccination of HIV-infected pregnant women can result in the production of protective antibody titers and will benefit HIV-infected pregnant women by preventing serious influenza-related illness. ^{34}

Studies have not been done in animals ^{{20} {21} {22}}.

FDA Pregnancy Category C ^{{20} {21} {22}}.

Breast-feeding

Influenza vaccine does not affect the safety of breast-feeding for mothers or infants. ^{05} Breast-feeding does not adversely affect the immune response and is not a contraindication for vaccination. ^{05}

Pediatrics

In immunosuppressed children receiving chemotherapy, influenza immunization with a new vaccine antigen results in a sufficient immune response in only a minority of children. ^{03} The optimal time to immunize children with malignancies who still must undergo chemotherapy is 3 to 4 weeks after chemotherapy has been discontinued and the peripheral granulocyte and lymphocyte counts are greater than 1000 per cubic millimeter. ^{03} Children who are no longer receiving chemotherapy generally have high rates of seroconversion. ^{03}

The immune response and safety of influenza vaccine in children with hemodynamically unstable cardiac disease (another large group of children potentially at high risk for complications of influenza) are comparable to those in healthy children. ^{03}

The effect of corticosteroid therapy on influenza vaccine immunogenicity is unknown. ^{03} Since a high dose of corticosteroids (i.e., a dose equivalent to either 2 mg per kg of body weight or a total of 20 mg per day of prednisone) may impair antibody responses, particularly in unvaccinated or previously uninfected persons, vaccination may be deferred temporarily during high-dose corticosteroid therapy, provided deferral does not compromise the likelihood of immunization before the start of the influenza season. ^{03} Corticosteroid therapy should not unnecessarily delay the administration of influenza vaccine, particularly in children with asthma who require intermittent or maintenance corticosteroid therapy. ^{03}

Infants younger than 6 months of age with high-risk conditions, especially those with compromised cardiopulmonary function may have the same or greater risk from influenza complications as of older children. ^{03} However, no information is available about the reactivity, immunogenicity, or the efficacy of the influenza vaccine in infants during the first 6 months of life. ^{03} In addition, the effect of influenza antigens in an inactivated vaccine on the infant's future immune response to influenza is unknown. ^{03} Therefore, alternative methods of protection for young infants should be considered, ^{03} including vaccination of household contacts and out-of-home care givers. ^{34}

Recent studies, which attempt to separate the effects of RSV and influenza, report otherwise healthy children aged 0 to 4 years may be at increased risk for influenza-related hospitalization compared with older healthy children or older children with high-risk conditions. ^{34} Vaccination of all children aged 6 to 23 months is encouraged when feasible. ^{34}

Children and young adults with cystic fibrosis (CF) will benefit from annual influenza vaccination. ^{06} In a 10-year observational study with a cohort design of 38 children and young adults with CF, serum hemagglutinin-inhibition (HI) antibody titers were determined at the time of vaccination, and 4 weeks later each year in the fall before the influenza epidemic. ^{06} While the prevaccination and postvaccination geometric mean serum HI antibody titers varied from year to year, no upward or downward trend was evident over the 10-year period. ^{06} In addition, the majority of vaccinees had a presumably protective postvaccination serum HI titer ³ 1:40 each year for all three vaccine strains. ^{06}

In children with little previous experience with influenza, two doses of vaccine, administered 1 month apart, are necessary to produce a satisfactory antibody response. ^{03} Children previously primed with a related strain of influenza virus by infection or vaccination almost uniformly exhibit a brisk antibody response to one dose of the vaccine. ^{03}

Only the subvirion or purified surface-antigen vaccines, i.e., those termed “split-virus” vaccines, should be used for children younger than 12 years of age. ^{23}


Geriatrics


Although influenza vaccine reportedly provides 65 to 85% protection against influenza illness in young, healthy adults, studies of its effectiveness in high-risk groups, such as the elderly, have yielded inconsistent results. ^{13} In observational studies of high-risk patients, respiratory illness during influenza epidemics occurred often, despite vaccination. ^{13} A review of studies of influenza vaccination in nursing homes disclosed that the median protective effect in 16 outbreaks of influenza A was 26%, and it was only 19% in seven studies of influenza B outbreaks. ^{13} Among noninstitutionalized elderly persons, the number of medical care visits for upper respiratory illnesses during two influenza outbreaks was the same for those who had received influenza vaccine and those who had not. ^{13}

Despite the apparent ineffectiveness of influenza vaccination in preventing respiratory infection, other nonrandomized studies have shown that it reduces serious complications and mortality due to influenza in the elderly or chronically ill. ^{13} In nursing homes, for example, significant reductions in pneumonia and mortality among vaccinees were documented during influenza A outbreaks. ^{13}

Among noninstitutionalized elderly persons, compelling evidence for the effectiveness of influenza vaccine comes from retrospective studies of more than 10,000 elderly members of a prepaid health plan during four influenza epidemics from 1968 to 1981 ^{13}. Hospitalizations and deaths from influenza and pneumonia among elderly vaccinees with chronic illnesses were reduced by more than 70% during two of these outbreaks. ^{13} Healthy elderly persons who received the vaccine also had fewer hospitalizations and deaths than their unvaccinated counterparts, although the differences were not statistically significant. ^{13} During a third epidemic in which there was pronounced antigenic drift, a statistically insignificant trend toward protection against hospitalization and death among vaccine recipients was observed. ^{13} Antigenic shift to a subtype different from that in the vaccine occurred during the fourth epidemic studied, and no protection from vaccination was observed. ^{13} More recently, several case-control studies during the influenza seasons from 1989 to 1992 showed that influenza vaccination was 31 to 45% effective in preventing hospitalizations for pneumonia. ^{13}

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Aminophylline or
Carbamazepine or
Phenobarbital or
Phenytoin or
Theophylline preparations or
Warfarin sodium    (influenza virus vaccine is listed in some references among the therapeutic agents that may increase theophylline levels or the anticoagulant effects of warfarin. ^{13} Such warnings are apparently based on a report that influenza vaccination depresses hepatic cytochrome P450 activity and on case reports of complications or altered pharmacologic characteristics in vaccinated patients taking these medications. ^{13} More recent studies have failed to show a significant impact of influenza virus vaccine on the laboratory or clinical effects of warfarin or theophylline, and patients taking these medications can be vaccinated safely without special precautions or monitoring. ^{{13} {20} {21} {22}})


Immunosuppressive agents or
Radiation therapy    (since normal defense mechanisms are suppressed, the patient's antibody response to influenza virus vaccine may be decreased. The precaution does not apply to corticosteroids used as replacement therapy, for short-term [less than 2 weeks] systemic therapy, or by other routes of administration that do not cause immunosuppression. ^{{20} {21} {22}})



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

Human immunodeficiency virus (HIV), serum and
Hepatitis C virus (HCV), serum    (it was reported that patients who receive influenza virus vaccine may develop false-positive results of enzyme-linked immunosorbent assays for HIV and HCV. ^{13} Such false-positive test results are uncommon, probably occurring in less than 2% of vaccine recipients; results usually revert to negative within several months. ^{13} There is no evidence that recipients of influenza virus vaccine are at increased risk of acquiring HIV or HCV infection. However, physicians should be aware of this laboratory test interaction in evaluating the results of the screening tests. ^{13})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problems exist:
» Febrile illness, severe    (to avoid confusing the manifestations of illness with possible side/adverse effects of vaccine. ^{20})


» Respiratory disease, acute    (influenza virus vaccine should not be administered until the acute symptoms of the patient's illness have abated, since the symptoms of the condition may be confused with the possible side effects of the vaccine ^{20})


Risk-benefit should be considered when the following medical problems exist
» Allergy to eggs    (immediate, presumably allergic, reactions [e.g., hives, angioedema, allergic asthma, and systemic anaphylaxis] occur rarely after influenza vaccination. ^{{02} {05}} These reactions probably result from hypersensitivity to some vaccine component; the majority of reactions are most likely related to residual egg protein in the vaccine. ^{{02} {05}})

    (although current influenza vaccines contain only a small quantity of egg protein, this protein can induce immediate hypersensitivity reactions among persons who have severe egg allergy. ^{{02} {05}} Persons who have developed hives, have had swelling of the lips or tongue, or have experienced acute respiratory distress or collapse after eating eggs should consult a physician for appropriate evaluation to determine if influenza virus vaccine should be administered. ^{{02} {05}})

    (persons with documented immunoglobulin E [IgE]-mediated hypersensitivity to eggs, including those who have had occupational asthma or other allergic responses due to exposure to egg protein, may also be at increased risk of reactions from influenza vaccine, and similar consultation with a physician should be considered. ^{{02} {05}} The protocol for influenza virus vaccination developed by Murphy and Strunk may be considered for patients who have egg allergies and other medical conditions that place them at increased risk for influenza-associated complications. ^{{02} {05}})


» Guillain-Barré syndrome (GBS), history of    (patients with a prior history of GBS have shown a greater likelihood of developing a recurrence of GBS following administration of influenza virus vaccine; although not absolutely contraindicated for patients with a history of GBS, certain authorities have recommended against vaccination in patients who are known to have developed GBS within 6 weeks of receiving the influenza virus vaccine, and who are not known to be at high risk for severe influenza-related complications; most authorities otherwise believe that the benefits of influenza virus vaccine justify the risk in patients with a history of GBS who are at high risk for development of severe complications associated with influenza ^{28}{29}{30})


Neurologic disorders, active    (influenza vaccine should not be administered to a patient with an active neurologic disorder; the vaccine should be considered only after the disease process has been stabilized. ^{{20} {21} {22}})


Sensitivity to influenza virus vaccine
Sensitivity to thimerosal, sodium bisulfite, gentamicin sulfate, streptomycin sulfate, or other aminoglycosides    (hypersensitivity reactions to any vaccine component can occur; although exposure to vaccines containing thimerosal can lead to induction of hypersensitivity, most patients do not develop reactions to thimerosal when administered as a component of vaccines, even when patch or intradermal tests for thimerosal indicate hypersensitivity; when reported, hypersensitivity to thimerosal usually has consisted of local, delayed-type hypersensitivity reactions ^{05})






Side/Adverse Effects

Note: Because influenza vaccine contains only noninfectious viruses, it cannot cause influenza ^{{02} {05}}. Respiratory disease after vaccination represents coincidental illness unrelated to influenza vaccination ^{{02} {05}}.
Unlike the 1976 swine influenza vaccine, subsequent vaccines prepared from other virus strains have not been clearly associated with an increased frequency of Guillain-Barré syndrome (GBS) ^{{02} {05} {13}}. However, a precise estimate of risk is difficult to determine for a rare condition such as GBS, which has an annual background incidence of only one to two cases per 100,000 in the adult population ^{02}. Among persons who received the swine influenza vaccine, the rate of GBS that exceeded the background rate was slightly less than one case per 100,000 vaccinations ^{02}.
An investigation of GBS cases in 1990–91 indicated no overall increase in frequency of GBS among persons who were administered influenza vaccine; a slight increase in GBS cases among vaccinated persons may have occurred in the age group of 18 to 64 years, but not among persons ³ 65 years of age ^{02}. In contrast to the swine influenza vaccine, the epidemiologic features of the possible associations of the 1990–91 vaccine and GBS were not as convincing ^{02}. The rate of GBS cases after vaccination that was passively reported to the Vaccine Adverse Event Reporting System (VAERS) during 1993–94 was estimated to be approximately twice the average rate reported during other seasons (i.e., 1990–91, 1991–92, 1992–93, and 1994–5) ^{02}. The data currently available are not sufficient to determine whether this represents an actual risk ^{02}. However, even if GBS were a true side effect, the very low estimated risk for GBS is less than that of severe influenza prevented by vaccination ^{02}.
Whereas the incidence of GBS in the general population is very low, persons with a history of GBS have a substantially greater likelihood of subsequently developing GBS than persons without such a history ^{02}. 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 ^{02}. Whether influenza vaccination is causally associated with the risk for recurrence is not known ^{02}. Although it would seem prudent to avoid a subsequent influenza vaccination in a person known to have developed GBS within 6 weeks of a previous influenza vaccination, for most persons with a history of GBS who are at high risk of severe complications from influenza, the established benefits of influenza virus vaccination justify their yearly immunization ^{02}. ^{05}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence rare
    
Anaphylactic reaction, most likely to residual egg protein in the influenza virus vaccine ^{{02}{05}{20}{21}{22}}(difficulty in breathing or swallowing; hives; itching, especially of feet or hands; reddening of skin, especially around ears; swelling of eyes, face, or inside of nose; unusual tiredness or weakness, sudden and severe)



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Tenderness, redness, or induration at the site of injection, lasting 1 or 2 days (tenderness, redness, or hard lump at place of injection)—incidence approximately 30%^{20}{21}{22}

Incidence less frequent
    
Fever, malaise, myalgia, and headache starting 6 to 12 hours after administration and persisting 1 or 2 days ^{{02}{05}{13}{20}{21}{22}}(aches or pains in muscles; general feeling of discomfort or illness)—most often affecting children and adults who have had no previous exposure to the influenza virus antigens in the vaccine^{05}

Note: Recent placebo-controlled trials suggest that in elderly persons and healthy young adults, split-virus influenza vaccine is not associated with higher rates of systemic symptoms (e.g., fever, malaise, myalgia, and headache) when compared with placebo injections ^{05}.






Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Influenza Virus Vaccine (Systemic).
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to influenza virus vaccine or allergy to eggs, sodium bisulfite, thimerosal, gentamicin sulfate, streptomycin sulfate, or other aminoglycosides





Use in children—Use is not recommended for infants up to 6 months of age; for children 6 months to 12 years of age, only the split-virus vaccines (split, subvirion, or purified-surface-antigen type) should be used; if two doses are needed, they should be spaced 4 weeks apart






Use in the elderly—Influenza vaccine may be less effective in elderly persons; however, vaccine may be still effective in preventing other complications of influenza in these persons
Other medical problems, especially acute respiratory disease, allergy to eggs, Guillain-Barré syndrome, or severe febrile illness

Proper use of this medication

» Proper dosing


Side/adverse effects
Signs of potential side effects, especially anaphylactic reaction


General Dosing Information
Appropriate precautions should be taken prior to vaccine injection to prevent allergic or any other unwanted reactions. This should include a review of the patient's history regarding possible sensitivity, and the ready availability of epinephrine 1:1000 and other appropriate agents (e.g., antihistamines) used to control immediate allergic reactions. ^{20}

Inactivated influenza virus vaccine should not be administered to persons known to have anaphylactic hypersensitivity to eggs or to other components of the influenza vaccine without first consulting a physician. ^{02} Use of an antiviral agent (i.e., amantadine, oseltamivir, rimantadine, or zanamivir) instead of influenza virus vaccine is an option for prevention of influenza A in such persons. ^{02}{28} However, persons who have a history of anaphylactic hypersensitivity to vaccine components but who are also at high risk of complications of influenza can benefit from the vaccine after appropriate allergy evaluation and desensitization procedures. ^{02}

Children with severe chronic asthma at risk for adverse reactions to influenza virus vaccine should be identified, and appropriate steps should be taken to assure their proper immunization. ^{26} With the protocol of administering increasing doses of the influenza virus vaccine in small increments, individuals with hypersensitivity to egg proteins can be safely and effectively immunized. ^{26} Therefore, the following desensitization protocol for influenza virus vaccination developed by Murphy and Strunk may be considered for patients who have egg allergies and other medical conditions that place them at increased risk of influenza-associated complications. ^{{24} {26}}

Desensitization of the patient should be carried out by serial injections of diluted and undiluted influenza virus vaccine as indicated below at intervals of 15 minutes for a total cumulative dose of 0.5 mL undiluted influenza virus vaccine. ^{26}

Schedules for desensitization:    • 0.05 mL of 1:100 dilution intramuscularly. ^{26}
   • 0.05 mL of 1:10 dilution intramuscularly. ^{26}
   • 0.05 mL of undiluted vaccine intramuscularly. ^{26}
   • 0.1 mL of undiluted vaccine intramuscularly. ^{26}
   • 0.15 mL of undiluted vaccine intramuscularly. ^{26}
   • 0.2 mL of undiluted vaccine intramuscularly. ^{26}


Because of their decreased potential for causing febrile reactions, only split-virus vaccines should be used for children younger than 13 years of age. ^{05} They may be labeled as split, subvirion, or purified-surface-antigen type vaccine. ^{05} Immunogenicity and side effects of split- and whole-virus vaccines are similar among adults when vaccines are administered at the recommended dosage. ^{05}

Elderly patients may develop lower antibody titers after immunization than healthy young adults and, therefore, may remain susceptible to influenza infection of the upper respiratory tract. ^{{20} {21} {22}} Nonetheless, influenza virus vaccine may still be effective in preventing lower respiratory tract involvement or other complications of influenza. ^{{20} {21} {22}}

During recent decades, data on influenza virus vaccine immunogenicity and side effects have been obtained for intramuscularly administered vaccine. ^{{02} {05}} Because recent influenza vaccines have not been adequately evaluated when administered by other routes, the intramuscular route is recommended. ^{{02} {05}}Inactivated influenza virus vaccine should not be injected intravenously.^{35}{36} Adults and older children should be vaccinated in the deltoid muscle and infants and young children in the anterolateral aspect of the thigh. ^{{02} {05}}

Remaining influenza virus vaccine from the previous influenza season should not be used to provide protection for the current influenza season. ^{35}{36}

Beginning each September, when vaccine for the upcoming influenza season becomes available, persons at high risk who are seen by health care providers for routine care or as a result of hospitalization should be offered influenza virus vaccine. ^{{02} {05}} Opportunities to vaccinate persons at high risk of complications of influenza should not be missed. ^{{02} {05}}

The optimal time for organized vaccination campaigns for persons in high-risk groups is usually the period from October through mid-November. ^{05} This period has been extended to include the first 2 weeks in October. ^{{02} {05}} In the U.S., influenza activity generally peaks between late December and early March. ^{{02} {05}} High levels of influenza activity infrequently occur in the contiguous 48 states before December. ^{{02} {05}} Administering the vaccine too far in advance of the influenza season should be avoided in facilities such as nursing homes, because antibody levels might begin to decline within a few months of vaccination. ^{{02} {05}} Vaccination programs can be undertaken as soon as the current vaccine is available, if regional influenza activity is expected to begin earlier than December. ^{{02} {05}}

Children younger than 9 years of age who have not been vaccinated previously should receive two doses of vaccine at least 1 month apart, to maximize the likelihood of a satisfactory antibody response to all three vaccine antigens. ^{{02} {05}{28}} The second dose should preferably be administered before December. ^{{02} {05}}
Note: Studies among adults receiving a second dose of vaccine during the same influenza season have shown little or no improvement in antibody response^{28}



Individuals at high risk for complications of influenza who were not vaccinated with influenza vaccine during the preceding fall or winter should consider receiving influenza vaccine before travel if they plan to: travel to the tropics; travel with large organized tourist groups at any time of year; or travel to the Southern Hemisphere during April to September. ^{36}

Vaccine should be offered to both children and adults prior to, and even after, influenza activity is documented in a community. ^{{02} {05}}

The target groups for influenza and pneumococcal vaccination overlap considerably. ^{{02} {05}} For persons at high risk who have not been previously vaccinated with pneumococcal vaccine, health care providers should strongly consider administering both pneumococcal and influenza virus vaccines concurrently. ^{{02} {05}} Both vaccines can be administered at the same time at different body sites without increasing potential side effects. ^{{02} {05}} However, influenza virus vaccine is administered each year, whereas the pneumococcal vaccine is not. ^{{02} {05}} Children at high risk of influenza-related complications can receive influenza virus vaccine at the same time they receive other routine vaccinations, including pertussis vaccine (as DTP or as DTaP). ^{{02} {05}} Because influenza virus vaccine can cause fever when administered to young children, DTaP (which is less frequently associated with fever and other adverse reactions) is preferable. ^{{02} {05}}

For treatment of adverse effects
Recommended treatment includes:    • For mild hypersensitivity reaction—Administering antihistamines and, if necessary, corticosteroids. ^{18} In mild anaphylaxis, antihistamines or subcutaneous epinephrine may be all that is necessary if the condition is progressing slowly and is not life-threatening, regardless of the organ or system affected. ^{18} Under these circumstances, the risks associated with intravenous epinephrine administration outweigh the benefits. ^{18}
   • For severe hypersensitivity or anaphylactic reaction—Administering epinephrine. Antihistamines and/or corticosteroids also may be administered as required. ^{18} Epinephrine is the treatment of choice for severe hypersensitivity or anaphylactic reaction. ^{18} If the patient's condition is not stable, epinephrine may be infused. ^{18} Norepinephrine may be preferable if there is no bronchospasm. For bronchospasm, epinephrine should be given with corticosteroids. ^{18} Other bronchodilators, such as intravenous aminophylline or albuterol by nebulization, also should be considered. ^{18}



Parenteral Dosage Forms

INFLUENZA VIRUS VACCINE (Injection—Split virus [purified-surface-antigen type]) USP

Usual adult and adolescent dose
Influenza prophylaxis
Adults and children 12 years ^{23} of age and older: Intramuscular, 0.5 mL as a single dose. ^{{20} {21} {22}}


Usual pediatric dose
Influenza prophylaxis
Infants up to 6 months of age: Use is not recommended. ^{{20} {21} {22}}

Infants 6 to 35 months ^{23} of age: Two doses of 0.25 mL each, 4 weeks apart. ^{22}

Children 3 to 8 ^{23} years of age: Intramuscular, 0.5 mL of the split-virus vaccine. ^{22} Two doses of 0.5 mL each, 4 weeks apart, are recommended for maximum protection in persons under 9 years of age who have not been previously vaccinated. ^{{20} {21} {22}}

Children 8 to 12 ^{23} years of age: Intramuscular, 0.5 mL as a single dose of the split-virus vaccine. ^{{20} {21} {22}}


Usual geriatric dose
See Usual adult and adolescent dose.

Strength(s) usually available
U.S.—


Each 0.5-mL dose contains the proportions, and not less than the microgram amounts, of hemagglutinin antigens (mcg HA) representative of the specific components recommended for the present year's vaccine (Rx) [Fluvirin ( thimerosal 0.01%)^{22}]

Canada—
Not commercially available.

Packaging and storage:
Store between 2 and 8 °C (36 and 46 °F), unless otherwise specified by manufacturer. ^{{19} {20} {21} {22}} Do not freeze. ^{{19} {20} {21} {22}}

Stability:
Potency is destroyed by freezing; vaccine that has been frozen should not be used. ^{{19} {20} {21} {22}}

Auxiliary labeling:
   • Shake well. ^{{19} {20} {21} {22}}
   • Do not freeze. ^{{19} {20} {21} {22}}



INFLUENZA VIRUS VACCINE (Injection—Split virus [split or subvirion type]) USP

Usual adult and adolescent dose
Influenza prophylaxis
Adults and children 12 years ^{23} of age and older: Intramuscular, 0.5 mL as a single dose. ^{{20} {21} {22}}


Usual pediatric dose
Influenza prophylaxis
Infants up to 6 months of age: Use is not recommended ^{{20} {21} {22}}.

Infants 6 to 35 months ^{23} of age: Intramuscular, 0.25 mL of the split-virus vaccine. Dose should be repeated in four or more weeks if the patient has not been previously vaccinated. ^{{20} {21} {22}}

Children 3 to 8 years ^{23} of age: Intramuscular, 0.5 mL of the split-virus vaccine. Two doses of 0.5 mL each, 4 weeks apart, are recommended for maximum protection in children under 8 years ^{23} of age who have not been previously vaccinated. ^{{20} {21} {22}}

Children 8 to 12 ^{23} years of age: Intramuscular, 0.5 mL as a single dose of the split-virus vaccine. ^{{20} {21} {22}}


Usual geriatric dose
See Usual adult and adolescent dose .

Strength(s) usually available
U.S.—


Each 0.25-mL dose contains the proportions, and not less than the microgram amounts, of hemagglutinin antigens (mcg HA) representative of the specific components recommended for the present year's vaccine (Rx) [Fluzone ( contains NO preservative)]^{36}


Each 0.5-mL dose contains the proportions, and not less than the microgram amounts, of hemagglutinin antigens (mcg HA) representative of the specific components recommended for the present year's vaccine (Rx) [Fluzone ( contains NO preservative)]^{36}

Note: Both of the preservative-free formulations contain a trace amount of thimerosal (£ 0.5 micrograms Hg per 0.25 mL dose and £ 1.0 micrograms Hg per 0.5 mL dose) from the manufacturing process.^{36}
The 0.25-mL prefilled syringe is used for pediatric dosing. An alternative immunization method for children when one dose of 0.25 mL is indicated and the 0.5 mL prefilled syringe is being used, is to push the plunger of the 0.5 mL prefilled syringe exactly to the edge of the mark so that half of the volume is discarded. The remaining volume should then be injected. ^{36}



Each 0.5-mL dose contains the proportions, and not less than the microgram amounts, of hemagglutinin antigens (mcg HA) representative of the specific components recommended for the present year's vaccine (Rx) [FluShield ( 1:10,000 thimerosal) (gentamicin sulfate)] [Fluzone (1:10,000 thimerosal)][Generic](may contain gentamicin sulfate)(1:10,000 thimerosal)^{20}{21}

Canada—


Each 0.5-mL dose contains the proportions, and not less than the microgram amounts, of hemagglutinin antigens (mcg HA) representative of the specific components recommended for the present year's vaccine (Rx) [Fluviral S/F ( thimerosal 0.01%)] [Fluzone (thimerosal ^{20})]

Note: Gentamicin sulfate, streptomycin sulfate, neomycin, polymyxin, and/or sodium bisulfite may be used in the production of influenza virus vaccine. By current assay procedures, concentrations of these products are not detectable in the final vaccine; however, even in trace amounts they may be able to cause hypersensitivity reactions in susceptible persons ^{{20} {21} {22}}.


Packaging and storage:
Store between 2 and 8 °C (36 and 46 °F), unless otherwise specified by the manufacturer ^{{19} {20} {21} {22}}. Do not freeze ^{{19} {20} {21} {22}}.

Preparation of dosage form:
This product should be visually inspected for particulate matter and/or discoloration prior to administration. Samples containing visible particulates should not be used. ^{36}

Stability:
Potency is destroyed by freezing; vaccine that has been frozen should not be used.

Auxiliary labeling:
   • Shake well ^{{19} {20} {21} {22}}.
   • Do not freeze ^{{19} {20} {21} {22}}.



INFLUENZA VIRUS VACCINE (Injection—Whole virus) USP

Usual adult and adolescent dose
Influenza prophylaxis
Adults and children 13 years of age and older: Intramuscular, 0.5 mL as a single dose ^{20}.


Usual pediatric dose
Influenza prophylaxis
Use is not recommended in children up to 12 years ^{23} of age ^{{05} {20} {21} {22}}.


Note: Only split-virus influenza vaccines (split, subvirion, or purified-surface-antigen type) should be used for children up to 12 years ^{23} of age because of the vaccines' lower potential for causing febrile adverse reactions when compared to the whole-virus influenza vaccine. None of the influenza virus vaccines is recommended for infants up to 6 months of age.


Usual geriatric dose
See Usual adult and adolescent dose .

Strength(s) usually available
U.S.—


Each 0.5-mL dose contains the proportions, and not less than the microgram amounts, of hemagglutinin antigens (mcg HA) representative of the specific components recommended for the present year's vaccine (Rx) [Fluzone ( 1:10,000 thimerosal)^{20}]

Canada—


Each 0.5-mL dose contains the proportions, and not less than the microgram amounts, of hemagglutinin antigens (mcg HA) representative of the specific components recommended for the present year's vaccine (Rx) [Fluviral ( thimerosal 0.01%)] [Fluzone (thimerosal)^{20}]

Packaging and storage:
Store between 2 and 8 °C (35 and 46 °F), unless otherwise specified by manufacturer ^{{20} {21} {22}}. Do not freeze ^{{19} {20} {21} {22}}.

Stability:
Potency is destroyed by freezing; vaccine that has been frozen should not be used ^{{19} {20} {21} {22}}.

Auxiliary labeling:
   • Shake well ^{{19} {20} {21} {22}}.
   • Do not freeze ^{{19} {20} {21} {22}}.

Revised: 12/30/2002

References

1. Centers for Disease Control and Prevention (CDC). Update: influenza activity—United States and worldwide, 1996-97 season, and composition of the 1997-98 influenza vaccine. MMWR Morb Mortal Wkly Rep 1996; 46(15): 325-30.
   

2. Centers for Disease Control and Prevention (CDC). Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 1996; 45(RR-5): 1-24.
   

3. American Academy of Pediatrics. Influenza. In: Pickering LK, ed. 2000 Red book: report of the Committee on Infectious Diseases. 23rd ed. Elk Grove Village, IL: American Academy of Pediatrics, 2000: 352–9.
   

4. World Health Organization. WHO announces influenza vaccine formula for 1997/1998. In: Press Release WHO/14, 1997 Feb 20.
   

5. Centers for Disease Control and Prevention (CDC). Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 1997; 46(RR-9): 1-25.
   

6. Gross PA, Denning CR, Gaerlan PF. Annual influenza vaccination: response in patients over 10 years. Vaccine 1996; 14(13): 1280-4.
   

7. Park CL, Frank AL, Sullivan M, et al. Influenza vaccination of children during acute asthma exacerbation and concurrent prednisone therapy. Pediatrics 1996; 98(2): 196-200.
   

8. Centers for Disease Control and Prevention (CDC). Influenza surveillance—United States, 1992-3 and 1993-94. MMWR Morb Mortal Wkly Rep 1997; 46(SS-1): 1-12.
   

9. Centers for Disease Control and Prevention (CDC). Decreased antibody response to influenza vaccine among nursing-home residents who received recalled vaccine—New York, 1996. MMWR Morb Mortal Wkly Rep 1996; 45(50): 1100-2.
   

10. Centers for Disease Control and Prevention (CDC). Update: influenza activity—United States, 1996-97 season. MMWR Morb Mortal Wkly Rep 1996; 45(50): 1102-5.
    

11. Centers for Disease Control and Prevention (CDC). Update: influenza activity—United States, 1996-7 season. MMWR Morb Mortal Wkly Rep 1997; 46(4): 76-8.
    

12. Centers for Disease Control and Prevention (CDC). Update: influenza activity—United States, 1996-7 season. MMWR Morb Mortal Wkly Rep 1997; 46(8): 173-6.
    

13. Fiebach N, Beckett W. Prevention of respiratory infections in adults: influenza and pneumococcal vaccines. Arch Intern Med 1994; 154: 2545-57.
    

14. Nichol KL, Margolis KL, Wuorenma J, et al. The efficacy and cost effectiveness of vaccination against influenza among elderly persons living in the community. N Engl J Med 1994; 331(12): 778-84.
    

15. Monto AS. Influenza vaccines for the elderly. N Engl J Med 1994; 331(12): 807-8.
    

16. Centers for Disease Control and Prevention (CDC). Immunization of adolescents: recommendations of the Advisory Committee on Immunization Practices (ACIP), the American Academy of Pediatrics (AAP), the American Academy of Family Physicians (AAFP), and the American Medical Association (AMA). MMWR Morb Mortal Wkly Rep 1996; 45(RR-13): 1-16.
    

17. Kunzel W, Glathe H, Engelmann, et al. Kinetics of humoral antibody response to trivalent inactivated split influenza vaccine in subjects previously vaccinated or vaccinated for the first time. Vaccine 1996; 14(12): 1108-10.
    

18. Fisher M. Treatment of acute anaphylaxis. BMJ 1995; 311: 731-3.
    

19. The United States pharmacopeia. The national formulary. USP 23rd revision (January 1, 1995). Rockville, MD: The United States Pharmacopeial Convention, Inc.; 1994. p. 806-7.
    

20. Fluzone package insert (Connaught—US), Rev 5/96, Rec 3/97.
    

21. Flushield package insert (Wyeth-Ayerst—US), Rev 5/96, Rec 4/97.
    

22. Fluvirin package insert (Evans—UK), Rev 4/95, Rec 6/95.
    

23. Panel Comment, 7/97.
    

24. Centers for Disease Control and Prevention (CDC). Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 1998; 47(RR-6): 1-26.
    

25. World Health Organization. WHO announces influenza vaccine formula for 1998/1999. In: Press Release WHO/25, 1998 Feb 18.
    

26. Murphy KR, Strunk RC. Safe administration of influenza vaccine in asthmatic children hypersensitive to egg proteins. J Pediatr 1985 Jun; 106(6): 931-3.
    

27. Centers for Disease Control and Prevention (CDC). Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 1999; 48(RR-4): 5.
    

28. Centers for Disease Control and Prevention (CDC). Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2000; 49(RR–03): 1–38.
    

29. Panel Comment, 6/00.
    

30. Panel Comment, 7/00.
    

31. Panel Comment, 7/00.
    

32. Centers for Disease Control and Prevention (CDC). Press release: possible flu vaccine supply reduction and delay; June 22, 2000. URL: http://www.cdc.gov/od/oc/media/pressrel/r2k0622a.htm.
    

33. Centers for Disease Control and Prevention (CDC). Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2001; 50(RR-4): 1-44.
    

34. Centers for Disease Control and Prevention (CDC). Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2002; 51(RR–3): 1-31.
    

35. Product Information: FluShield®, influenza virus vaccine (2002–2003 Formula). Wyeth Laboratories, Marietta, PA, (PI revised 06/2002) reviewed 12/2002.
    

36. Product Information: Fluzone®, influenza virus vaccine (2002–2003 Formula). Aventis Pasteur Inc., Swiftwater, PA, (PI revised 07/2002) reviewed 12/2002.