Boostrix

Tell your healthcare provider if you or your child:

• had a severe allergic reaction (e.g., anaphylaxis) after a previous dose of any tetanus toxoid-, diphtheria toxoid-, or pertussis antigen-containing vaccine or any component of this vaccine
• had encephalopathy (e.g., coma, decreased level of consciousness, prolonged seizures) within 7 days of administration of a previous dose of a pertussis antigen-containing vaccine that is not attributable to another identifiable cause
• are pregnant or plan to become pregnant
• are breastfeeding
• are allergic to latex

Tell you doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. 

• If you have an allergy to any part of Boostrix (diphtheria and tetanus toxoids, and acellular pertussis vaccine).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have seizures or any other brain or nervous system problem.
• If you have had a brain problem like coma, lowered level of awareness, or seizures from an unknown cause within 7 days of a previous vaccine that has pertussis.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Boostrix with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• This medicine may not protect all people who use it. Talk with the doctor.
• If you have a latex allergy, talk with your doctor.
• Not all brands of vaccines are for children. Talk with your child's doctor.
• Some children may need to have more than 1 dose of this vaccine. Talk with your child's doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using Boostrix while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Pain where the shot was given.
• Redness or swelling where the shot is given.
• Headache.
• Feeling tired or weak.
• Fever or chills.
• Upset stomach or throwing up.
• Belly pain.
• Loose stools (diarrhea).
• Joint pain or swelling.
• Swollen gland.

Young children:

• Feeling fussy.
• Not hungry.
• Feeling sleepy.
• Crying that is not normal.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Hypersensitivity

A severe allergic reaction (e.g., anaphylaxis) after a previous dose of any tetanus toxoid-, diphtheria toxoid-, or pertussis antigen-containing vaccine or any component of this vaccine is a contraindication to administration of Boostrix2,3[see Description (11)]. Because of the uncertainty as to which component of the vaccine might be responsible, none of the components should be administered. Alternatively, such individuals may be referred to an allergist for evaluation if immunization with any of these components is considered.

Encephalopathy

Encephalopathy (e.g., coma, decreased level of consciousness, prolonged seizures) within 7 days of administration of a previous dose of a pertussis antigen-containing vaccine that is not attributable to another identifiable cause is a contraindication to administration of any pertussis antigen-containing vaccine, including Boostrix.2,3

Carcinogenesis, Mutagenesis, Impairment of Fertility

Boostrix has not been evaluated for carcinogenic or mutagenic potential, or for impairment of fertility.

BOOSTRIX (Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine, Adsorbed) (Tdap) is a noninfectious, sterile, vaccine for intramuscular administration manufactured by GlaxoSmithKline Biologicals. It contains tetanus toxoid, diphtheria toxoid, and pertussis antigens (inactivated pertussis toxin [PT] and formaldehyde-treated filamentous hemagglutinin [FHA] and pertactin [69 kiloDalton outer membrane protein]) adsorbed onto aluminum hydroxide. The antigens are the same as those in INFANRIX (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed), but BOOSTRIX is formulated with reduced quantities of these antigens.

Tetanus toxin is produced by growing Clostridium tetani in a modified Latham medium derived from bovine casein. The diphtheria toxin is produced by growing Corynebacterium diphtheriae in Fenton medium containing a bovine extract. The bovine materials used in these extracts are sourced from countries which the United States Department of Agriculture (USDA) has determined neither have nor are at risk of bovine spongiform encephalopathy (BSE). Both toxins are detoxified with formaldehyde, concentrated by ultrafiltration, and purified by precipitation, dialysis, and sterile filtration.

The 3 acellular pertussis antigens (PT, FHA, and pertactin) are isolated from Bordetella pertussis culture grown in modified Stainer-Scholte liquid medium. PT and FHA are isolated from the fermentation broth; pertactin is extracted from the cells by heat treatment and flocculation. The antigens are purified in successive chromatographic and precipitation steps. PT is detoxified using glutaraldehyde and formaldehyde. FHA and pertactin are treated with formaldehyde.

Each antigen is individually adsorbed onto aluminum hydroxide. All antigens are then diluted and combined to produce the final formulated vaccine. Each 0.5-mL dose is formulated to contain 2.5 Lf of diphtheria toxoid, 5 Lf of tetanus toxoid, 2.5 mcg of pertactin, 8 mcg of FHA, and 8 mcg of inactivated PT.

Tetanus and diphtheria toxoid potency is determined by measuring the amount of neutralizing antitoxin in previously immunized guinea pigs. The potency of the acellular pertussis components (inactivated PT and formaldehyde-treated FHA and pertactin) is determined by enzyme-linked immunosorbent assay (ELISA) on sera from previously immunized mice.

Each 0.5-mL dose also contains 4.5 mg of NaCl, aluminum adjuvant (not more than 0.39 mg aluminum by assay), </=100 mcg of residual formaldehyde, and </=100 mcg of polysorbate 80 (Tween 80).

This vaccine does not contain a preservative.

The vaccine must be well shaken before administration to obtain a homogeneous, turbid, white suspension.

Diphtheria and Tetanus Toxoids Adsorbed Combined Bulk (For Further Manufacturing Use) and Tetanus Toxoid Concentrate (For Further Manufacturing Use) are manufactured by Chiron Behring GmbH & Co KG, Marburg, Germany. The acellular pertussis antigens are manufactured by GlaxoSmithKline Biologicals, Rixensart, Belgium. Formulation, filling, testing, packaging, and release of the vaccine are also performed by GlaxoSmithKline Biologicals.

Tetanus:   Tetanus is a condition manifested primarily by neuromuscular dysfunction caused by a potent exotoxin released by C. tetani . Spores of C. tetani are ubiquitous. Naturally acquired immunity to tetanus toxin does not occur. Thus, universal primary immunization and timed booster doses to maintain adequate tetanus antitoxin levels are necessary to protect all age groups. 1 Protection against disease is due to the development of neutralizing antibodies to the tetanus toxin. A serum tetanus antitoxin level of at least 0.01 IU/mL, measured by neutralization assays, is considered the minimum protective level. 2,3 A level >/=0.1 to 0.2 IU/mL has been considered as protective. 4 Following immunization, protection persists for at least 10 years. 1

Efficacy of tetanus toxoid used in BOOSTRIX was determined on the basis of a US immunogenicity study (see Immunological Evaluation of BOOSTRIX).

Diphtheria:   Diphtheria is an acute toxin-mediated infectious disease caused by toxigenic strains of C. diphtheriae . Diphtheria in the United States has been controlled through the use of diphtheria toxoid-containing vaccines. Protection against disease is due to the development of neutralizing antibodies to the diphtheria toxin. Following adequate immunization with diphtheria toxoid, protection persists for at least 10 years. A serum diphtheria antitoxin level of 0.01 IU/mL is the lowest level giving some degree of protection; a level of 0.1 IU/mL is regarded as protective. 5 Levels of 1.0 IU/mL are associated with long-term protection. 5 Immunization with diphtheria toxoid does not, however, eliminate carriage of C. diphtheriae in the pharynx or nares or on the skin. 1

Efficacy of diphtheria toxoid used in BOOSTRIX was determined on the basis of a US immunogenicity study (see Immunological Evaluation of BOOSTRIX).

Pertussis:   Pertussis (whooping cough) is a disease of the respiratory tract caused by B. pertussis . The role of the different components produced by B. pertussis in either the pathogenesis of, or the immunity to, pertussis is not well understood. However, the pertussis components in BOOSTRIX (i.e., inactivated PT and formaldehyde-treated FHA and pertactin) have been shown to prevent pertussis in clinical trials of INFANRIX (for details see INFANRIX prescribing information). 6,7

The efficacy of a 3-dose primary series of INFANRIX in infants has been assessed in 2 clinical studies: A prospective efficacy trial conducted in Germany employing a household contact study design and a double-blind, randomized, active Diphtheria and Tetanus Toxoids (DT)-controlled trial conducted in Italy sponsored by the National Institutes of Health (NIH) (for details see INFANRIX prescribing information). 6,7 Serological data from a subset of infants immunized with INFANRIX in the household contact study were compared to the sera of adolescents immunized with BOOSTRIX (see Immunological Evaluation of BOOSTRIX ). In the household contact study, the protective efficacy of INFANRIX, in infants, against WHO-defined pertussis (21 days or more of paroxysmal cough with infection confirmed by culture and/or serologic testing) was calculated to be 89% (95% CI: 77% to 95%). When the definition of pertussis was expanded to include clinically milder disease, with infection confirmed by culture and/or serologic testing, the efficacy of INFANRIX against >/=7 days of any cough was 67% (95% CI: 52% to 78%) and against >/=7 days of paroxysmal cough was 81% (95% CI: 68% to 89%) (for details see INFANRIX prescribing information). 6

Immunological Evaluation of BOOSTRIX:   The efficacy of the tetanus and diphtheria toxoid components of BOOSTRIX is based on the immunogenicity of these antigens compared to a US-licensed Tetanus and Diphtheria Toxoids Adsorbed For Adult Use (Td) vaccine manufactured by Massachusetts Public Health Biologic Laboratories using established serologic correlates of protection. The efficacy of the pertussis components of BOOSTRIX was evaluated by comparison of the immune response of adolescents following a single dose of BOOSTRIX to the immune response of infants following a 3-dose primary series of INFANRIX. In addition, the ability of BOOSTRIX to induce a booster response to each of the antigens was evaluated.

In a multicenter, randomized, controlled study conducted in the United States, the immune responses to each of the antigens contained in BOOSTRIX were evaluated in sera obtained approximately one month after administration of a single dose of vaccine to adolescent subjects (10 to 18 years of age). Of the subjects enrolled in this study, approximately 76% were 10 to 14 years of age and 24% were 15 to 18 years of age. Approximately 98% of participants in this study had received the recommended series of 4 or 5 doses of either Diphtheria and Tetanus Toxoids and Pertussis Vaccine Adsorbed (DTwP) or a combination of DTwP and Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (DTaP) in childhood. The racial/ethnic demographics were as follows: Caucasian 85.8%, Black 5.7%, Hispanic 5.6%, Oriental 0.8% and other 2.1%.

Response to the Tetanus and Diphtheria Toxoids:   The antibody responses to the tetanus and diphtheria toxoids of BOOSTRIX compared to Td vaccine are shown in Table 1.

One month after a single dose, non-inferiority of BOOSTRIX compared to the control Td vaccine was demonstrated for anti-tetanus and anti-diphtheria seroprotective rates (>/=0.1 IU/mL) and booster response rates.

Response to the Pertussis Antigens of BOOSTRIX:   The booster response rates of adolescents to the pertussis antigens are shown in Table 2.

For each of the pertussis antigens the lower limit of the two-sided 95% CI for the percentage of subjects with a booster response exceeded the pre-defined lower limit of 80% for demonstration of an acceptable booster response.

Immune Response of Adolescents to BOOSTRIX Compared to the Immune Response of Infants to INFANRIX:   The geometric mean concentrations (GMCs) to each of the pertussis antigens one month following a single dose of BOOSTRIX in the US adolescent study (N = 2,941-2,979) were compared to the GMCs of infants following a 3-dose primary series of INFANRIX administered at 3, 4, and 5 months of age (N = 631-2,884). Table 3 presents the results for the total immunogenicity cohort in both studies (vaccinated subjects with serology data available for at least one pertussis antigen; the majority of subjects in the INFANRIX study had anti-PT serology data only). These infants were a subset of those who formed the cohort for the German household contact study in which the efficacy of INFANRIX was demonstrated (see CLINICAL PHARMACOLOGY ).

Although a serologic correlate of protection for pertussis has not been established, anti-PT, anti-FHA, and anti-pertactin antibody concentrations of adolescents one month after a single dose of BOOSTRIX were non-inferior to those of infants following a primary vaccination series with INFANRIX.

Immune Response to Concomitantly Administered Vaccines:   Immunogenicity data are not available on the concurrent administration of BOOSTRIX with other vaccines.

BOOSTRIX is indicated for active booster immunization against tetanus, diphtheria, and pertussis as a single dose in individuals 10 through 18 years of age.

The use of BOOSTRIX as a primary series or to complete the primary series has not been studied.

As with any vaccine, BOOSTRIX may not protect 100% of individuals receiving the vaccine. BOOSTRIX is not recommended for treatment of actual infections.