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Influenza Virus Vaccine (001533)

CATEGORIES:

Indications: Immunization, influenza

Pregnancy Category C

WHO Formulary

FDA Pre 1938 Drugs

FDA DRUG CLASS: Vaccines/Antisera

BRAND NAMES: Agrippal (Italy, South-Africa); Alorbat (Germany); Begrivac (Austria, Germany); Begrivac F (Israel); Flu Shield (US); Fluarix (New-Zealand, Mexico, Hong-Kong); Fluimmune (US); Fluogen (US); Flushield (US); Fluvax (Australia, New-Zealand, Korea); Fluvirin (US); Fluvirine (France); Fluzone (US); Hiberix (Australia); Inflexal (Spain, Austria, Italy); Inflexal Berna (Philippines, South-Africa); Inflexal Berna Polyvalent Vaccine (Malaysia); Influvac (Benin, Burkina-Faso, Ethiopia, Gambia, Ghana, Guinea, Ivory-Coast, Kenya, Liberia, Malawi, Mali, Mauritania, Mauritius, Morocco, Niger, Nigeria, Senegal, Seychelles, Sierra-Leone, Sudan, Tanzania, Tunia, Uganda, Zambia, Zimbabwe; Bahrain, Cyprus, Egypt, Iran, Iraq, Israel, Jordan, Kuwait, Lebanon, Libya, Oman, Qatar, Republic-of-Yemen, Saudi-Arabia, Syria, United-Arab-Emirates);

Mutagrip (Germany, Belgium, Spain, Netherlands, France); Sandovac (Austria); Vaxigrip (New-Zealand, Denmark, Netherlands, France, Greece, Belgium, Bulgaria, Norway, Austria, Hong-Kong, Korea, Philippines, South-Africa, Israel); X-Flu (South-Africa);

(International brand names outside U.S. in italics)

DESCRIPTION:

Influenza Virus Vaccine, Trivalent, Types A and B (chromatograph- and filter-purified subvirion antigen)

1993-94 formula

DO NOT INJECT INTRAVENOUSLY Influenza virus vaccine, trivalent, types A and B (purified subvirion) is a sterile injectable for administration intramuscularly.

Influenza virus vaccine, trivalent, types A and B (purified subvirion) is prepared from the allantoic fluids of chick embryos inoculated with a specific type of influenza virus. During processing, not more than 5 mcg of gentamicin sulfate per ml is added. The harvested virus is inactivated with formaldehyde and is concentrated and purified.

Influenza virus vaccine, trivalent, types A and B (purified subvirion) is concentrated and refined by a column-chromatographic procedure. At the same time, addition of tri(n)butylphosphate and polysorbate 80, to the column-eluting fluids effects disruption and inactivation of a significant proportion of the virus to smaller subunit particles. The recovered subvirion (split-virus) suspension is freed of substantial portions of the disrupting agents by dialysis and of other undesirable materials by selective filtration through membranes of controlled pore size.

The viral antigen content has been standardized by immunodiffusion tests, according to current U.S. Public Health Service requirements. Each dose (0.5 ml) contains the proportions and not less than the microgram amounts of hemagglutinin antigens (mcg HA) representative of the specific components recommended for the current influenza season.

The vaccine contains 1:10,000 thimerosal (mercury derivative) as a preservative. Gentamicin sulfate is used during manufacturing but is not detectable in the final product by current assay procedures.

CLINICAL PHARMACOLOGY:

The administration of inactivated influenza vaccine to high-risk persons

each year before the influenza season is the single most important

influenza-control measure.1

The injection of antigens prepared from inactivated influenza virus stimulates the production of specific antibodies. Protection is afforded only against those strains of virus from which the vaccine is prepared or closely related strains. With the passing of time, there may be major antigenic changes in the prevalent strains, or there may be continuous and progressive antigenic variation within a given virus subtype over time (antigenic drift), so that infection or immunization with one strain may not induce immunity to distantly related strains. Field studies of influenza vaccines conducted on many occasions since the 1940’s have shown marked variation in efficacy, as measured by protection from disease, ranging from undemonstrable to 70-80%. The PHS regularly reviews the antigenic characteristics of current strains in order to select those to be included in the contemporary vaccine.

INDICATIONS AND USAGE:

Influenza virus vaccine is recommended for 1) high-risk persons 6 months of age or older and for their medical-care providers or household contacts; 2) for children and teenagers receiving long-term aspirin therapy who, therefore, may be at increased risk of developing Reye’s syndrome after an influenza virus infection; and 3) for other persons who wish to reduce their chances of acquiring influenza.

Guidelines for the use of vaccine among different groups are given below.

Target Groups for Vaccination

Groups at Increased Risk for Influenza-Related Complications:

1.   Otherwise healthy persons 65 years of age or older.

2.   Residents of nursing homes and other chronic-care facilities housing patients of any age with chronic medical conditions.

3.   Adults and children with chronic disorders of the pulmonary or cardiovascular systems requiring regular medical follow-up or hospitalization during the preceding year, including children with asthma.

4.   Adults and children 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).

5.   Children and teenagers (aged 6 months to 18 years) who are receiving long-term aspirin therapy and, therefore, may be at risk of developing Reye’s syndrome after influenza infection.

 

Elderly persons and persons with certain chronic diseases may develop lower post-vaccination antibody titers than healthy young adults and thus may remain susceptible to influenza upper-respiratory-tract infections.  Nevertheless, even if such persons develop influenza illness, the vaccine has been shown to be effective in preventing lower-respiratory-tract involvement or other complications, thereby reducing the risk of hospitalization and death.

Groups Potentially Capable of Nosocomial Transmission of Influenza To

High-Risk Persons

Individuals attending high-risk persons can transmit influenza infections to them while they are themselves incubating infection, undergoing subclinical infection, or working despite the existence of symptoms. Some high-risk persons, (e.g., the elderly, transplant recipients, persons with acquired immunodeficiency syndrome (AIDS)), can have relatively low antibody responses to influenza vaccine. Efforts to protect them against influenza may be improved by reducing the chances that their care providers may expose them to influenza. Therefore, the following groups should be vaccinated:

1.   Physicians, nurses, and other personnel in both hospital and outpatient settings.

2.   Providers of home care to high-risk persons (e.g., visiting nurses, volunteer workers) as well as all household members of high-risk persons, including children, whether or not they provide care.

 

Vaccination of Other Groups

General Population: Physicians should administer influenza vaccine to any person who wishes to reduce his/her chances of acquiring influenza infection. Persons who provide essential community services and students or other healthy individuals in institutional settings (i.e., schools and colleges) should be encouraged to receive vaccine to minimize the disruption of routine activity during outbreaks.

Pregnant Women: Influenza-associated excess mortality among pregnant women has not been documented, except in the largest pandemics of 1918-19 and 1957-58. However, pregnant women who have medical conditions increasing their risks of complications from influenza should be vaccinated, as the vaccine is considered safe for pregnant women. Administering the vaccine after the first trimester is a reasonable precaution to minimize any concern over the theoretical possibility of teratogenicity. However, it is undesirable to delay vaccination of pregnant women with high-risk conditions who will still be in the first trimester of pregnancy when the influenza season begins.

Persons Infected With Human Immunodeficiency Virus (HIV): Little information exists regarding the frequency and severity of influenza illness in human immunodeficiency virus (HIV)-infected persons, but recent reports suggest that symptoms may be prolonged and the risk of complications increased for this high-risk group. Because influenza may result in serious illness and complications, vaccination is a prudent precaution and will result in protective antibody levels in many recipients. However, the antibody response to vaccine may be low in persons with advanced HIV-related illnesses; a booster dose of vaccine has not improved the immune response for these individuals.

Foreign Travelers: The risk of exposure to influenza during foreign travel

varies, depending on, among other factors, season of travel and

destination. Influenza can occur throughout the year in the tropics; the

season of greatest influenza activity in the Southern Hemisphere is

April-September. Because of the short incubation period for influenza,

exposure to the virus during travel will often result in clinical illness

that begins during travel, an inconvenience or potential danger, especially

for persons at increased risk for complications. Persons preparing to

travel to the tropics at any time of year or to the Southern Hemisphere

during April-September should review their vaccination histories. If not

vaccinated the previous fall/winter, they should be considered for

influenza vaccination prior to travel. Persons in the high-risk categories

especially should be encouraged to receive the vaccine. The most current

available vaccine should be used. High-risk persons given the previous

season’s vaccine prior to travel should be revaccinated in the fall/winter

with current vaccine.1

Immunization Programs

If this product is to be used in an immunization program sponsored by an

organization WHERE A TRADITIONAL PHYSICIAN/PATIENT RELATIONSHIP DOES NOT

EXIST, each participant (or legal guardian) should be made aware of the possible risks that have been associated with the use of influenza virus vaccines, including the possible risk of a form of paralysis sometimes known as Guillain-Barre syndrome. Information about possible side effects and adverse reactions is presented below, and consent, preferably written, should be obtained from the intended recipient (or legal guardian) before vaccine administration.

Simultaneous Administration of Pneumoccal or Pediatric Vaccines:

Pneumococcal vaccine and influenza vaccine can be given at the same time at

different sites without increased side effects. However, it should be

emphasized that whereas influenza vaccine is given annually, it is

currently recommended that, with few exceptions, pneumococcal vaccine be

given only once.1

It may be desirable to simultaneously administer influenza vaccine, if indicated, with routine pediatric vaccine but at different sites. Although studies have not been done, no diminution of immunogenicity or enhancement of adverse reactions should be expected.1 Influenza vaccine should not be given within 3 days of vaccination with pertussis vaccine.

CONTRAINDICATIONS:

INFLUENZA VIRUS VACCINE SHOULD NOT BE ADMINISTERED TO INDIVIDUALS WITH A

HISTORY OF HYPERSENSITIVITY (ALLERGY) TO CHICKEN EGG OR OTHER COMPONENTS OF

INFLUENZA VIRUS VACCINES WITHOUT FIRST CONSULTING A PHYSICIAN (SEE ADVERSE

REACTIONS). Before being vaccinated, persons known to be hypersensitive to

egg protein should be given a skin test or other allergy-evaluating test,

using the Influenza Virus Vaccine as the antigen. Persons with adverse

reactions to such testing should not be vaccinated. Chemoprophylaxis may be

indicated for prevention of influenza A in such persons. However, persons

with a history of anaphylactic hypersensitivity to vaccine components but

who are also at highest risk for complications of influenza infections may

benefit from vaccine after appropriate evaluation and desensitization.1

Although gentamicin sulfate is not detectable in the final product by current assay procedures, the vaccine should not be administered to persons with known sensitivity to gentamicin or other aminoglycosides.

Persons with a past history of Guillain-Barre syndrome (GBS) should not be given influenza virus vaccine.

Persons with acute febrile illnesses usually should not be vaccinated until

their symptoms have abated. However, minor illness with or without fever

should not contraindicate the use of influenza vaccine, particularly in

children with a mild upper-respiratory-tract infection or allergic

rhinitis.3

WARNINGS:

Patients with impaired immune responsiveness, whether due to the use of immunosuppressive therapy (including irradiation, large amounts of corticosteroids, antimetabolites, alkylating agents, and cytotoxic agents), a genetic defect, human immunodeficiency virus (HIV) infection, leukemia, lymphoma, generalized malignancy, or other causes, may have a reduced antibody response to active immunization procedures.1 Short-term (less than 2 weeks) corticosteroid therapy or intra-articular, bursal, or tendon injections with corticosteroids should not be immunosuppressive.  Inactivated vaccines are not a risk to immunocompromised individuals, although their efficacy may be substantially reduced. Because patients with immunodeficiencies may not have an adequate response to immunizing agents, they may remain susceptible despite having received an appropriate vaccine.

If feasible, specific serum antibody titers or other immunologic responses

may be determined after immunization to assess immunity.3 Chemoprophylaxis

may be indicated for high-risk persons who are expected to have a poor

antibody response to influenza vaccine.1

PRECAUTIONS:

General

Influenza virus is remarkably capricious antigenically, and significant changes may occur from time to time. It is known definitely that influenza vaccine, as now constituted, is not effective against all possible strains of influenza virus. Protection is afforded most people only against those strains of virus from which the vaccine is prepared or against closely related strains .

Influenza vaccine often contains one or more antigens used in previous years. However, immunity declines during the year following immunization.  Therefore, revaccination on a yearly basis is necessary to provide optimal protection for the current season. REMAINING VACCINE FROM THE PREVIOUS YEAR SHOULD NOT BE USED.

Epinephrine injection (1:1000) must be immediately available should an acute anaphylactoid reaction occur due to any component of the vaccine.

A separate sterile syringe and needle should be used for each patient to prevent transmission of hepatitis B virus or other infectious agents from one person to another. Reusable glass syringes and needles should be heat-sterilized.

Pregnancy Category C

Animal reproduction studies have not been conducted with influenza virus vaccine. It is also not known whether influenza virus vaccine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Influenza virus vaccine should be given to a pregnant woman only if clearly needed. (See INDICATIONS AND USAGE).

DRUG INTERACTIONS:

There have been conflicting reports4-13 on the effects of influenza virus vaccine on the elimination of some drugs metabolized by the hepatic cytochrome P-450 system. Hypoprothrombinemia in patients receiving warfarin and elevated theophylline serum concentrations have occurred. Most studies have failed to show any adverse effects of influenza vaccine in patients receiving these drugs. Nevertheless, observation for possible enhanced drug effect or toxicity is indicated for those persons taking theophylline preparations or warfarin sodium.

Individuals receiving therapy with immunosuppressive agents (large amounts of corticosteroids, antimetabolites, alkylating agents, cytotoxic agents) may not respond optimally to active immunization procedures. (See WARNINGS.)

ADVERSE REACTIONS:

Side effects of influenza vaccine are generally inconsequential in adults and occur at low frequency, but at younger ages side effects may be more common.

BECAUSE INFLUENZA VACCINE CONTAINS ONLY NONINFECTIOUS VIRUSES, IT CANNOT

CAUSE INFLUENZA. Occasional cases of respiratory disease following vaccination represent coincidental illnesses unrelated to influenza vaccination.

The most frequent side effect of vaccination is soreness around the vaccination site for up to 2 days; this occurs in less than one-third of vaccinees.

In addition, the following three types of systemic reactions have occurred:

1.   Fever, malaise, myalgia, and other systemic symptoms occur infrequently and most often affect persons who have had no exposure to the influenza virus antigens in the vaccine (e.g., young children).  These reactions begin 6 to 12 hours after vaccination and can persist for 1 or 2 days.

2.   Immediate, presumably allergic, reactions such as hives; angioedema, allergic asthma, or systemic anaphylaxis occur extremely rarely after influenza vaccination. These reactions probably result from hypersensitivity to some vaccine component - the majority are most likely residual egg protein. Although current influenza vaccines contain only a small quantity of egg protein, this protein may induce immediate hypersensitivity reactions in persons with severe egg allergy. Persons who have developed those who have developed hives, have had swelling of the lips or tongue, or experienced acute respiratory distress or collapse after eating eggs should consult a physician for appropriate evaluation to assist in determining whether vaccination may proceed or should be deferred. Persons with a documented immunoglobulin E (IgE)-mediated hypersensitivity to eggs, including those who have experienced occupational asthma or other allergic responses from occupational exposure to egg protein, may also be at increased risk for reactions from influenza vaccine, and similar consultation should be considered. The protocol for influenza vaccination developed by Murphy and Strunk may be considered for patients who have egg allergies and medical conditions that place them at increased risk for influenza infection or its complications.15 The potential exists for hypersensitivity reactions to any vaccine component. Although exposure to vaccines containing thimerosal can lead to induction of hypersensitivity, most patients do not develop reactions to thimerosal administered as a component of vaccines even when patch or intradermal tests for thimerosal indicate hypersensitivity. When it has been reported, hypersensitivity to thimerosal has usually consisted of local delayed type hypersensitivity reactions.1

3.   Guillain-Barre syndrome (GBS). This is an uncommon illness characterized by ascending paralysis which is usually self-limited and reversible. Though most persons with GBS recover without residual weakness, approximately 5% of cases are fatal. Before 1976, no association of GBS with influenza vaccine use was recognized.

 

Except for the 1976-77 swine influenza vaccine, subsequent vaccines prepared from other virus strains have not been clearly associated with an increased frequency of Guillain-Barre syndrome.1, 16-19 Although, in 1990-91, there may have been a small increase in GBS cases in vaccinated persons 18 to 64 years of age, the epidemiologic features of the possible association of the 1990-91 vaccine with GBS were not as convincing as those found with the swine influenza vaccine. It is difficult to make a precise estimate of risk for a rare condition such as GBS.1 Therefore, candidates for influenza virus vaccine should be made aware of the possible risks, including GBS, and the benefits of administration.

Other neurologic disorders, including encephalopathies, not defined as GBS,

have been temporarily associated with influenza vaccination.20

DOSAGE AND ADMINISTRATION:

Although influenza virus vaccine often contains one or more antigens used in previous years, immunity declines during the year following vaccination.

Therefore, a history of vaccination in any previous year with a vaccine

containing one or more antigens included in the current vaccine does NOT

preclude the need for revaccination for the 1993-1994 influenza season to

provide optimal protection. REMAINING VACCINE FROM THE PREVIOUS YEAR SHOULD

NOT BE USED.

Influenza vaccine may be offered to high-risk persons presenting for routine care or hospitalization beginning in September, but not until new vaccine is available (see INDICATIONS AND USAGE, Vaccination of Other Groups for foreign travel, related exceptions). Opportunities to vaccinate persons at high risk for complications of influenza should not be missed.  In the United States, influenza activity generally peaks between late December and early March, and high levels of influenza activity infrequently occur in the contiguous 48 states before December. Therefore, the optimal time for organized vaccination campaigns for high-risk persons usually is the period between mid-October and mid-November. In facilities such as nursing homes it is particularly important to avoid administering vaccine too far in advance of the influenza season because antibody may begin to decline within a few months. Such vaccination programs may be undertaken as soon as current vaccine is available in September or October if regional influenza activity is expected to begin earlier than normal.

Children less than 9 years of age who have not been vaccinated previously should receive two doses with at least 1 month between doses to maximize the chance of a satisfactory antibody response to all three vaccine antigens. The second dose should be given before December if possible.  Vaccine should continue to be offered to both children and adults up to and even after influenza virus activity is documented in a community which may be as late as April in some years.

Parenteral drug products should be inspected visually for particulate matter and discoloration, whenever solution and container permit.

DO NOT INJECT INTRAVENOUSLY. Injections of FluShield are recommended to be given intramuscularly. The recommended site is the deltoid muscle for adults and older children. The preferred site for infants and young children is the anterolateral aspect of the thigh musculature. Because of lack of adequate evaluation of other route in high-risk persons, the preferred route of vaccination is intramuscularly whenever possible. Before injection, the skin over the site to be injected should be cleansed with a suitable germicide. After insertion of the needle, aspirate to help avoid inadvertent injection into a blood vesseL. SeeTABLE 1 for pediatric dosages.

TABLE 1

 AGE GROUP                                       DOSAGE SCHEDULE

 9 years and older                              0.5 ml (one dose)

 3 to 8 years                                0.5 ml (1 or 2 doses)*

 6 to 35 months                              0.25 ml (1 or 2 doses)*

For those under 13 years, only split-virus (subvirion) vaccine is recommended.

·        A single dose is considered sufficient for those under 9 years who have received at least 1 dose of influenza virus vaccine. With the 2-dose regimen, allow 4 weeks or more between doses. Both doses are recommended for maximum protection.

 

Immunogenicity and reactogenicity of split- and whole-virus vaccines are

similar in adults when used according to the recommended dosage.1

Storage: Store between 2°-8°C (35°-46° F). Potency is destroyed by freezing; do not use Influenza Virus Vaccine that has been frozen.

REFERENCES:

1.   Recommendations of the Advisory Committee on Immunization Practices—

Prevention and Control of Influenza: Part 1, vaccines. MMWR 1993: 42 (no.

RR-7).

2.   ACIP. Pneumococcal polysaccharride vaccine. MMWR 1989: 38: 64- 8, 73-6.

3.   American Academy of Pediatrics: Report of the Committee on Infectious Diseases, 22nd ed. Elk Grove Village, IL, American Academy of Pediatrics, 1991.

4.   KRAMER, P. and McCLAIN, C.: Depression of aminopyrine metabolism by influenza vaccination. NEJM 305: 1262, 1981.

5.   RENTON, K. et al: Decreased elimination of theophylline after influenza vaccination. Canadian Med. Assoc. J. 123: 288, 1980.

6.   GOLDSTEIN, R. S. et al: Decreased elimination of theophylline after influenza vaccination. Canadian Med. Assoc. J. 126: 470, 1982.

7.   BRITTON, L. and RUBEN, F. L.: Serum and theophylline levels after influenza vaccination. Canadian Med. Assoc. J. 126: 1375, 1982.

8.   FISCHER, R. G. et al: Influence of trivalent influenza vaccine on serum theophylline levels. Canadian Med. Assoc. J. 126: 1312-1313, 1982.

9.   SAN JOAQUIN, V. H., REYES, S., and MARKS, M. I.: Influenza vaccination in asthmatic children on maintenance theophylline therapy. Clin. Pediatrics 21: 724-726, 1982.

10. STULTS, B. and HASISAKI, P.: Influenza vaccination and theophylline pharmacokinetics in patients with chronic obstructive lung disease. West J.  Med. 139: 651-654, 1983.

11. PATRIARCA, P.A. et al: Influenza vaccination and warfarin or theophylline toxicity in nursing-home residents. New Eng. J. Med.308: 1601, 1983.

12. MEREDITH, C. G. et al: Effects of influenza virus vaccine on hepatic drug metabolism. Clin. Pharm. Ther. 37: 396-401, 1985.

13. LIPSKY, B. A. et al: Influenza vaccination and warfarin anticoagulation. Ann. Int. Med. 100: 835-837, 1984.

14. KRAMER, P. et al: Effect of Influenza vaccine on warfarin anticoagulation. Clin. Pharmacol. Ther. 35: 416, 1984.

15. MURPHY, K. R. and STRUNK, R. L.: Safe administration of Influenza vaccine in asthmatic children hypersensitive to egg proteins. J.  Pediatr.106: 931-3, 1985.

16. SCHONBERGER, L. et al: Guillain-Barre syndrome following vaccination in the National Influenza Immunization Program, United States 1976-1977. Am.  J. Epidemiol. 110: 105, 1979.

17. SCHONBERGER, L. et al: Guillain-Barre syndrome: Its epidemiology and associations with influenza vaccination. Ann. Neurol. 9 (Supplement: 31, 1981).

18. HURWITZ, E. et al: Guillain-Barre syndrome and the 1978-1979 influenza vaccine. New Eng. J. Med. 304: 1557, 1981.

19. KAPLAN, J. et al: Guillain-Barre syndrome in the United States, 1979-1980 and 1980-1981. Lack of association with influenza vaccination.

JAMA 248: 698, 1982.

20. RETAILLIAU, H. et al: Illness after influenza vaccination reported through a nation-wide surveillance system, 1976-1977. Am. J. Epidemiol.111:

170, 1980.

 

 

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ALL INFORMATION, DATA, AND MATERIAL CONTAINED, PRESENTED, OR PROVIDED HERE IS FOR GENERAL INFORMATION PURPOSES ONLY AND IS NOT TO BE CONSTRUED AS REFLECTING THE KNOWLEDGE OR OPINIONS OF THE PUBLISHER, AND IS NOT TO BE CONSTRUED OR INTENDED AS PROVIDING MEDICAL OR LEGAL ADVICE.  THE DECISION WHETHER OR NOT TO VACCINATE IS AN IMPORTANT AND COMPLEX ISSUE AND SHOULD BE MADE BY YOU, AND YOU ALONE, IN CONSULTATION WITH YOUR HEALTH CARE PROVIDER.