In addition to reports in clinical trials for BOOSTRIX, the following adverse events have been identified in persons aged 10 years and older during postapproval use of BOOSTRIX worldwide. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to the vaccine.
Blood and Lymphatic System Disorders
Immune System Disorders
Allergic reactions, including anaphylactic and anaphylactoid reactions.
General Disorders and Administration Site Conditions
Extensive swelling of the injected limb, injection site induration, injection site inflammation, injection site mass, injection site pruritus, injection site nodule, injection site warmth, injection site reaction.
Musculoskeletal and Connective Tissue Disorders
Arthralgia, back pain, myalgia.
Nervous System Disorders
Convulsions (with and without fever), encephalitis, facial palsy, loss of consciousness, paresthesia, syncope.
Skin and Subcutaneous Tissue Disorders
Angioedema, exanthem, Henoch-Schönlein purpura, rash, urticaria.
BOOSTRIX was administered concomitantly with MENACTRA in a clinical study of subjects aged 11 to 18 years [see Clinical Studies (14.5)]. Post-vaccination geometric mean antibody concentrations (GMCs) to PRN were lower following BOOSTRIX administered concomitantly with meningococcal conjugate vaccine compared with BOOSTRIX administered first. It is not known if the efficacy of BOOSTRIX is affected by the reduced response to PRN.
BOOSTRIX was administered concomitantly with FLUARIX (Influenza Virus Vaccine) in a clinical study of subjects aged 19 to 64 years [see Clinical Studies (14.5)]. Lower GMCs for antibodies to the pertussis antigens filamentous hemagglutinin (FHA) and PRN were observed when BOOSTRIX was administered concomitantly with FLUARIX as compared with BOOSTRIX alone. It is not known if the efficacy of BOOSTRIX is affected by the reduced response to FHA and PRN.
When BOOSTRIX is administered concomitantly with other injectable vaccines or Tetanus Immune Globulin, they should be given with separate syringes and at different injection sites. BOOSTRIX should not be mixed with any other vaccine in the same syringe or vial.
Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs, and corticosteroids (used in greater than physiologic doses), may reduce the immune response to BOOSTRIX.
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to BOOSTRIX during pregnancy. Healthcare providers are encouraged to register women by calling 1-888-452-9622.
All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. There are no adequate and well-controlled studies of BOOSTRIX in pregnant women in the U.S.
Available data suggest that the rates of major birth defects and miscarriage in women who received BOOSTRIX within 28 days prior to conception or during pregnancy are consistent with estimated background rates (see Data).
A developmental toxicity study was performed in female rats administered INFANRIX prior to mating and BOOSTRIX during gestation, 0.1 mL at each occasion (a single human dose is 0.5 mL). In a second study, female rats were administered 0.2 mL of BOOSTRIX prior to mating and during the gestation and lactation period. In a third study, female New Zealand White rabbits were given 0.5 mL (full human dose) of BOOSTRIX (non-U.S. formulation) prior to mating and during gestation. These studies revealed no evidence of harm to the fetus due to BOOSTRIX. (See Data)
Human Data: An assessment of data from the ongoing U.S. pregnancy registry over approximately 13 years (2005-2018) included 1,388 prospective reports of exposure to BOOSTRIX within 28 days prior to conception or during pregnancy. Of these reports, 240 had known pregnancy outcomes available. After excluding those with exposure in the third trimester (n = 186) and those with an unknown exposure timing (n = 9), there were 45 pregnancies with known outcomes with exposure within 28 days prior to conception through the second trimester. Outcomes among these prospectively followed pregnancies included 3 cases of miscarriage in women exposed in the first trimester and no major birth defects in infants born to women with exposure within 28 days prior to conception or during pregnancy.
An assessment of spontaneous and postmarketing data through August 2018 included 595 prospective reports of exposure to non-U.S. formulations of BOOSTRIX/Tdap or BOOSTRIX-Polio/Tdap-IPV within 28 days prior to conception or during pregnancy. Of these reports, 146 had known pregnancy outcomes available. After excluding elective terminations (n = 3), those with exposure in the third trimester (n = 56), and those with an unknown exposure timing (n = 4), there were 83 pregnancies with known outcomes with exposure during the 28 days prior to conception through the second trimester. Outcomes among these prospectively followed pregnancies included 1 live infant with a major birth defect born to a woman with exposure during the first trimester, 1 stillbirth in a woman exposed in the first trimester, and 4 cases of miscarriage in women exposed in the first trimester.
Animal Data: Developmental toxicity studies were performed in female rats and New Zealand White rabbits. In one study, female rats were administered 0.1 mL of INFANRIX (a single human dose is 0.5 mL) by intramuscular injection 30 days prior to mating and 0.1 mL of BOOSTRIX (a single human dose is 0.5 mL) by intramuscular injection on Gestation Days 6, 8, 11, and 15. The antigens in INFANRIX are the same as those in BOOSTRIX, but INFANRIX is formulated with higher quantities of these antigens. In a second study, female rats were administered 0.2 mL of BOOSTRIX by intramuscular injection 28 days and 14 days prior to mating, on Gestation Days 3, 8, 11, and 15, and on Lactation Day 7. In these studies, no adverse effects on embryo-fetal or pre-weaning development up to Postnatal Day 25 were observed; there were no fetal malformations or variations observed. In a third study, female New Zealand White rabbits were administered 0.5 mL (full human dose) of BOOSTRIX (non-U.S. formulation) by intramuscular injection on Premating Days -28 and -14 and on Gestation Days 3, 8, 11, 15, and 24. In this study, no adverse effects on embryo-fetal development related to BOOSTRIX were observed; postnatal development was not evaluated.
It is not known whether the vaccine components of BOOSTRIX are excreted in human milk. Data are not available to assess the effect of administration of BOOSTRIX on breastfed infants or on milk production/excretion. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for BOOSTRIX and any potential adverse effects on the breastfed child from BOOSTRIX or from the underlying maternal condition. For preventive vaccines, the underlying maternal condition is susceptibility to disease prevented by the vaccine.
BOOSTRIX is not indicated for use in children aged younger than 10 years. Safety and effectiveness of BOOSTRIX in this age group have not been established.
In clinical trials, 1,104 subjects aged 65 years and older received BOOSTRIX; of these subjects, 299 were aged 75 years and older. Adverse events following BOOSTRIX were similar in frequency to those reported with the comparator Td vaccine [see Adverse Reactions (6.1)].
BOOSTRIX (Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine, Adsorbed) is a noninfectious, sterile, vaccine for intramuscular administration. It contains tetanus toxoid, diphtheria toxoid, and pertussis antigens (inactivated pertussis toxin [PT] and formaldehyde-treated FHA and PRN). The antigens are the same as those in INFANRIX, 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 acellular pertussis antigens (PT, FHA, and PRN) are isolated from Bordetella pertussis culture grown in modified Stainer-Scholte liquid medium. PT and FHA are isolated from the fermentation broth; PRN 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 PRN are treated with formaldehyde.
Each antigen is individually adsorbed onto aluminum hydroxide. Each 0.5-mL dose is formulated to contain 5 Lf of tetanus toxoid, 2.5 Lf of diphtheria toxoid, 8 mcg of inactivated PT, 8 mcg of FHA, and 2.5 mcg of PRN (69 kiloDalton outer membrane protein).
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 contains aluminum hydroxide as adjuvant (not more than 0.39 mg aluminum by assay), 4.4 mg of sodium chloride, ≤100 mcg of residual formaldehyde, and ≤100 mcg of polysorbate 80 (Tween 80).
BOOSTRIX is available in vials and prefilled syringes. The tip caps of the prefilled syringes contain natural rubber latex; the plungers are not made with natural rubber latex. The vial stoppers are not made with natural rubber latex.
BOOSTRIX is formulated without preservatives.
Tetanus is a condition manifested primarily by neuromuscular dysfunction caused by a potent exotoxin released by Clostridium tetani (C. tetani). 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 A level ≥0.1 IU/mL by ELISA has been considered as protective.
Diphtheria is an acute toxin-mediated infectious disease caused by toxigenic strains of Corynebacterium diphtheriae (C. diphtheriae). Protection against disease is due to the development of neutralizing antibodies to the diphtheria toxin. A serum diphtheria antitoxin level of 0.01 IU/mL, measured by neutralization assays, is the lowest level giving some degree of protection; a level of 0.1 IU/mL by ELISA is regarded as protective.3 Diphtheria antitoxin levels ≥1.0 IU/mL by ELISA have been associated with long-term protection.3
Pertussis (whooping cough) is a disease of the respiratory tract caused by Bordetella pertussis (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.
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