Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed/Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed

[Section Outline]

Choice of Vaccines Containing Diphtheria, Tetanus, and Pertussis Antigens
Risks of Diphtheria, Tetanus, and Pertussis Exposure and Infection
Primary and Booster Immunization with Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (DTaP)
Primary and Booster Immunization with Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Tdap)
Postexposure Prophylaxis of Diphtheria
Postexposure Prophylaxis of Tetanus
Postexposure Prophylaxis of Pertussis

Diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed (DTaP) and tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed (Tdap) are used to stimulate active immunity to diphtheria, tetanus, and pertussis.100,105,182,187,192,193,195,196,201,205 The appropriate vaccine containing diphtheria, tetanus, and pertussis antigens is selected based on age and whether primary or booster immunization is indicated.105,182,187,192,193,195,196,205 (See Uses: Choice of Vaccines Containing Diphtheria, Tetanus, and Pertussis Antigens.)

DTaP or Tdap may be indicated for postexposure vaccination against diphtheria in addition to anti-infective postexposure prophylaxis in unvaccinated or inadequately vaccinated household and other close contacts of an individual with diphtheria.100,105 (See Uses: Postexposure Prophylaxis of Diphtheria.)

DTaP or Tdap may be indicated in conjunction with passive immunization with tetanus immune globulin (TIG) for postexposure prophylaxis against tetanus in individuals with tetanus-prone wounds who are inadequately immunized against tetanus or whose tetanus immunization history is unknown or uncertain.100,105,192,195,196,201,205 (See Uses: Postexposure Prophylaxis of Tetanus.)

DTaP may be indicated for postexposure prophylaxis against pertussis in infants and children who are unvaccinated or incompletely vaccinated against pertussis.100,105,166 (See Uses: Postexposure Prophylaxis of Pertussis.)

DTaP and Tdap are not indicated for treatment of diphtheria, tetanus, or pertussis.105,166,192,201 However, because diphtheria and tetanus infections do not necessarily confer immunity, initiation or completion of active immunization against these diseases is indicated at the time of recovery in any previously unvaccinated or incompletely vaccinated individual.105,166,201 In addition, although pertussis is likely to confer short-term immunity, the duration of immunity is uncertain (waning may begin as early as 5-7 years after infection) and initiation or completion of active immunization against pertussis is indicated at the time of recovery.105,166,195,196,201,205

Choice of Vaccines Containing Diphtheria, Tetanus, and Pertussis Antigens

DTaP (Daptacel^®, Infanrix^®) is used for primary and booster immunization against diphtheria, tetanus, and pertussis in infants and children 6 weeks through 6 years of age.105,149,182,187 DTaP can be used to complete the remaining required doses in the vaccination series in children through 6 years of age who received DTP (not commercially available in the US) for initial doses (e.g., children vaccinated in countries where DTP is still used).105,166 DTaP should not be used in individuals 7 years of age or older.149,187

There are no data to date indicating that any one DTaP preparation is preferred over any other DTaP preparation in terms of safety or efficacy for primary or booster immunization.166,183 The US Public Health Service Advisory Committee on Immunization Practices (ACIP) recommends that the same DTaP preparation used for the initial dose be used to complete the primary and booster immunization series since only limited data are available regarding use of different DTaP preparations interchangeably in the primary and booster vaccination series.127,134,149,183 However, these and other experts state that any age-appropriate commercially available DTaP vaccine should be used to complete the vaccination series if the particular DTaP vaccine used previously is not known or not available.105,127,149,166,183 (See Dosage and Administration: Dosage.)

DTaP also is commercially available in a fixed-combination vaccine with poliovirus antigens (DTaP-IPV; Kinrix^®, Quadracel),221,223 in a fixed-combination vaccine with poliovirus and hepatitis B antigens (DTaP-HepB-IPV; Pediarix^®),106 and in a combination vaccine with poliovirus and Hib antigens (DTaP-IPV/Hib; Pentacel^®).224 (See Combination Vaccines Containing DTaP and Other Antigens under Uses: Choice of Vaccines Containing Diphtheria, Tetanus, and Pertussis Antigens.)

Tdap (Adacel^®, Boostrix^®) is used for booster immunization in adults and adolescents 10 years of age or older.192,193,195,196,236,237 Tdap (Adacel^®) is labeled by the US Food and Drug Administration (FDA) for booster immunization in adolescents 10 years of age or older and adults 19 through 64 years of a 192 Tdap (Boostrix^®) is labeled by FDA for booster immunization in adolescents 10 years of age or older and adults 19 years of age or older.193 For adults 65 years of age or older, ACIP states that Tdap (Boostrix^®) should be used when feasible, but that Tdap (Adacel^®) would provide protection when used for booster immunization in this age group and can be used in adults 65 years of age or older† if Tdap (Boostrix^®) is not available.237 (See Uses: Primary and Booster Immunization with Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed [Tdap].)

Although safety and efficacy of Tdap for primary immunization have not been established,192,193 ACIP, the American Academy of Pediatrics (AAP), and other experts recommend that a single dose of Tdap be included in the vaccination series when adults, adolescents, or children as young as 7 years of age† require primary immunization† against diphtheria and tetanus, unless pertussis antigens are contraindicated or should not be used.195,196,199,200,201,205,236 (See Uses: Primary and Booster Immunization with Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed [Tdap].)

Combination Vaccines Containing DTaP and Other Antigens

When indicated based on the age and vaccination status of the child and when there are no contraindications to any of the individual components, combination vaccines containing DTaP and other antigens can be used instead of separate injections.134,193,199,223,224 ACIP, AAP, and other experts state that a combination vaccine generally is preferred over separate injections of the equivalent component vaccines;134,199 considerations include provider assessment (e.g., number of injections, vaccine availability, likelihood of improved coverage, likelihood of patient return, storage requirements, cost), patient preference, and potential for adverse effects.134

When there are no contraindications to any of the individual components, the commercially available fixed-combination vaccine containing diphtheria, tetanus, pertussis, and poliovirus antigens (DTaP-IPV; Kinrix^®) can be used in children 4 through 6 years of age to provide the fifth dose of the DTaP vaccination series and the fourth dose of the IPV vaccination series105,223 in those receiving primary immunization with Infanrix^® (DTaP) and/or Pediarix^® (DTaP-HepB-IPV).223 Alternatively, the commercially available fixed-combination vaccine containing diphtheria, tetanus, pertussis, and poliovirus antigens (DTaP-IPV; Quadracel^®) can be used in children 4 through 6 years of age to provide the fifth dose of the DTaP vaccination series and the fourth or fifth dose of the IPV vaccination series in those receiving primary immunization with Daptacel^® (DTaP) and/or Pentacel^® (DTaP-IPV/Hib).221,222 (For information on Kinrix^® and Quadracel^®, see Poliovirus Vaccine Inactivated 80:12.)

The commercially available fixed-combination vaccine containing diphtheria, tetanus, pertussis, hepatitis B, and poliovirus antigens (DTaP-HepB-IPV; Pediarix^®) can be used for a 3-dose immunization series in infants and children 6 weeks through 6 years of age if there are no contraindications to any of the individual components.106,208 For the prevention of diphtheria, tetanus, and pertussis in infants and children 6 weeks through 6 years of age, Pediarix^® may be used for the initial 3 doses in the DTaP series105,106 or may be used to complete the first 3 doses of the DTaP series in children who have received 1 or 2 doses of Infanrix^® DTaP;106 data are not available regarding the safety and efficacy of Pediarix^® used following 1 or more doses of a DTaP vaccine from a different manufacturer.106 Children who have received a 3-dose series of Pediarix^® should complete the DTaP and IPV series according to the recommended childhood immunization schedule.105,106 To complete the DTaP series, the manufacturer recommends that Infanrix^® be used for the fourth dose of DTaP and either Infanrix^® DTaP or DTaP-IPV (Kinrix^®) be used as the fifth dose of DTaP since these vaccines contain the same pertussis antigens as Pediarix^®.106 (For information on Pediarix^®, see Poliovirus Vaccine Inactivated 80:12 and see Hepatitis B Vaccine 80:12.)

The combination vaccine containing diphtheria, tetanus, pertussis, poliovirus, and Hib antigens (DTaP-IPV/Hib; Pentacel^®) can be used as a 4-dose series for immunization in infants and children 6 weeks through 4 years of age when doses of DTaP, IPV, and Hib vaccine are indicated and there are no contraindications to any of the individual components.224 For prevention of diphtheria, tetanus, and pertussis, Pentacel^® may be used for the initial 4 doses in the DTaP series at 2, 4, 6, and 15 through 18 months of age105,224 and a dose of Daptacel^® should be given at 4 through 6 years of age to provide the fifth dose of DTaP.224 Pentacel^® also may be used in infants and children 6 weeks through 4 years of age who have received 1 or more doses of Daptacel^® DTaP.224 However, data are not available on the safety and immunogenicity of mixed sequences of Pentacel^® and Daptacel^® for successive doses in the DTaP series or mixed sequences of Pentacel^® and DTaP from other manufacturers.224 (For information on Pentacel^®, see Poliovirus Vaccine Inactivated 80:12 and see Haemophilus b Vaccine 80:12.)

Risks of Diphtheria, Tetanus, and Pertussis Exposure and Infection

Diphtheria

Diphtheria is caused by toxigenic strains of Corynebacterium diphtheriae or, rarely, toxigenic strains of C. ulcerans .100,105,115,166,195,196,205,228 Diphtheria occurs worldwide, particularly in tropical countries.166 Although diphtheria occurs rarely in the US,115 C. diphtheriae continues to circulate in the US in areas where diphtheria previously was endemic.100,105,166,228

Before widespread immunization against the disease, diphtheria was a major cause of morbidity and mortality among children.166 During the 1920s, there were approximately 100,000-200,000 cases of diphtheria and 13,000-15,000 diphtheria-related deaths each year in the US.166 From 1980 through 2011, 55 cases of diphtheria were reported in the US with an average of 1-2 per year (range: 0-5 cases per year).166 In 1996, toxigenic C. diphtheriae was isolated from residents of a Native American community in South Dakota166,229 and toxigenic C. ulcerans was isolated from an individual in Indiana with respiratory diphtheria.229 In 1999, a resident of Washington died from an illness clinically consistent with respiratory diphtheria and toxigenic C. ulcerans was isolated from a throat swab.229 In 2003, fatal respiratory diphtheria occurred in an unvaccinated Pennsylvania resident who had returned from a trip to rural Haiti (a country where diphtheria is endemic).228,229

Most cases of diphtheria occur in individuals who are unvaccinated or incompletely vaccinated against the disease.100,105,166

Diphtheria is endemic in many countries in Asia, the South Pacific, the Middle East, and Eastern Europe and also is endemic in Haiti and the Dominican Republic.115 Since 2011, large outbreaks of diphtheria have occurred in Indonesia, Thailand, and Laos.115 Individuals who are unvaccinated or inadequately vaccinated against diphtheria, especially travelers who will live or work with local populations in countries where diphtheria is endemic, are at risk.115

The US Centers for Disease Control and Prevention (CDC) Travelers' Health website ([Web]) should be consulted for information regarding where diphtheria is endemic.115

Tetanus

Tetanus is a potentially fatal disease caused by a neurotoxic exotoxin (tetanospasmin) produced by Clostridium tetani .105,115,166 Tetanus occurs worldwide,115,166 but is reported most frequently in densely populated regions in hot, damp climates with soil rich in organic matter.166

In the US, a marked decrease in mortality from tetanus occurred from the early 1900s to the late 1940s when immunization against tetanus became part of routine childhood immunization.166 From 2001 through 2008, 233 cases of tetanus were reported in the US (average of 29 per year) with a case fatality rate of 13%.166

Tetanus is not transmitted person-to-person.115,166 C. tetani usually enters the body through a wound.166 Any open wound can become contaminated with C. tetani , including tetanus-prone wounds (wounds contaminated with dirt, feces, soil, or saliva; deep wounds; burns; crush injuries; wounds containing devitalized or necrotic tissue) and apparently clean, superficial wounds (wounds from surgical procedures, insect bites, animal bites, dental infections, compound fractures, chronic sores and infections, IV drug abuse).105,115,166 Heroin users, particularly those who inject themselves subcutaneously, appear to be at high risk for tetanus.166 Most cases of tetanus in the US occur following an acute wound, usually a puncture or contaminated, infected, or devitalized wound considered tetanus-prone.166

Almost all reported cases of tetanus occur in individuals who are unvaccinated or inadequately vaccinated against the disease (i.e., received an incomplete primary immunization series or received a complete primary series but did not receive recommended booster doses).105,115,166

Because C. tetani spores are ubiquitous in the environment worldwide, travelers can acquire tetanus anywhere in the world if they are unvaccinated or incompletely vaccinated against the disease.115 Tetanus is more common in rural and agricultural regions, areas where contact with soil or animal excreta is more likely, and areas where immunization rates are inadequate.115

Pertussis

Pertussis (whooping cough) is an acute respiratory tract infection caused by Bordetella pertussis .105,115,166,197,201,205 Pertussis remains endemic worldwide (even in areas with high vaccination rates);115 the incidence is highest in young children in developing countries and other countries where routine immunization against pertussis is not widely practiced.115 Before widespread immunization against the disease, pertussis was one of the most common childhood diseases and a major cause of morbidity and mortality among children in the US.166 There were more than 1 million cases of pertussis reported in the US from 1940 through 1945 (average of 175,000 cases per year).166 After pertussis immunization was introduced, the incidence of the disease gradually declined and the average number of cases reported per year in the US during 1980-1990 was 2900.166 However, pertussis incidence has been gradually increasing since the early 1980s.166 During 2010, there were 27,550 cases of pertussis and 27 pertussis-related deaths reported in the US.105,166 The risk for severe pertussis and death is highest among infants younger than 1 year of age (especially those younger than 6 months of age).105,166,205 In recent years, adolescents 11 years of age or older and adults have accounted for an increasing proportion of pertussis cases.166 B. pertussis infection in adults and adolescents may be asymptomatic or range from mild to severe.105,166,205 Outbreaks involving adolescents have occurred in various settings (e.g., middle and high schools, residence facilities for disabled individuals, entire communities).201 Adults and older siblings (including adolescents) with asymptomatic or mild pertussis are important sources of pertussis in unvaccinated or incompletely vaccinated infants and young children.105,166

Pertussis is highly communicable and 80-90% of nonimmune or unvaccinated household contacts acquire the disease.105,166,205 Transmission occurs via large respiratory droplets generated by coughing or sneezing or direct contact with respiratory secretions.105,115,166,205 Communicability is most likely during the catarrhal stage or early paroxysmal phase and untreated patients (especially infants) may remain infectious for 6 weeks or longer.105,166,205 Older children and adults with a history of previous pertussis infection or vaccination who develop pertussis may remain infectious for up to 14-21 days.105,166,205 Anti-infective therapy may limit the communicability of pertussis and also may ameliorate the disease if given in the catarrhal stage.105,166,205

Primary and Booster Immunization with Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (DTaP)

Infants and Children 6 Weeks through 6 Years of Age

ACIP, AAP, and other experts recommend that all infants receive primary immunization against diphtheria, tetanus, and pertussis.105,199 Therefore, a fixed-combination preparation that contains antigens for all 3 diseases (DTaP) is preferred for primary and booster immunization in infants and children 6 weeks through 6 years of age, unless a component is contraindicated or should not be used.105,134,199

The complete vaccination series against diphtheria, tetanus, and pertussis in children younger than 7 years of age generally requires 5 doses of DTaP.199 ACIP, AAP, and other experts state that DTaP doses preferably should be administered at 2, 4, 6, 15 through 18 months of age, and 4 through 6 years of age.105,199 The fourth DTaP dose (booster dose) may be given as early as 12 months of age, provided at least 6 months have elapsed since the third dose.199 The fifth dose (booster dose) is not necessary if the fourth dose was administered at 4 years of age or older.199 (See Dosage and Administration: Dosage.)

Preterm infants generally should receive primary immunization with usual doses of DTaP at the usual chronologic age (even if the child still is in the hospital).105,132,207 (See Cautions: Pediatric Precautions.)

Immunization of infants younger than 6 weeks of age against diphtheria, tetanus, and pertussis generally should not be attempted because most infants have maternal antibodies that may prevent a satisfactory immunologic response to DTaP. However, ACIP states that individual circumstances may warrant administration of the first 3 doses of vaccine at 6, 10, and 14 weeks of age to provide protection as early as possible, especially during pertussis outbreaks.100 In addition, AAP states that if pertussis is prevalent in the community, the first dose of vaccine can be given as early as 6 weeks of age, with subsequent doses given as frequently as 4 weeks apart.105

Primary immunization against diphtheria, tetanus, and pertussis can be integrated with primary immunization against Haemophilus influenzae type b (Hib), hepatitis A, hepatitis B, human papillomavirus (HPV), influenza, measles, mumps, rubella, meningococcal disease, pneumococcal disease, poliomyelitis, rotavirus, and varicella.100,105,134,185,199,200,201 (See Drug Interactions: Vaccines.)

If initiation or continuation of primary or booster immunization with DTaP is contraindicated because of the pertussis component, infants and children 6 weeks through 6 years of age should receive the fixed-combination preparation containing only diphtheria and tetanus toxoids (diphtheria and tetanus toxoids adsorbed [DT]).105,114 (See Diphtheria and Tetanus Toxoids Adsorbed/Tetanus and Diphtheria Toxoids Adsorbed 80:08.)

Children with Altered Immunocompetence

ACIP states that DTaP and other toxoids can be administered safely to individuals with altered immunocompetence and the usual doses and immunization schedules are recommended.134 However, effectiveness of immunizations may be suboptimal in such patients.134 (See Drug Interactions: Immunosuppressive Agents.)

ACIP, AAP, CDC, National Institutes of Health (NIH), HIV Medicine Association of the Infectious Diseases Society of America (IDSA), Pediatric Infectious Diseases Society, and other experts recommend that children with asymptomatic or symptomatic human immunodeficiency virus (HIV) infection, including those who are immunosuppressed in association with acquired immunodeficiency syndrome (AIDS) or other clinical manifestations of HIV infection, receive primary and booster immunization against diphtheria, tetanus, and pertussis according to the usual recommended schedules.105,156 However, immunization may be less effective in HIV-infected individuals than in immunocompetent individuals.105

Internationally Adopted Children and Other Immigrants

The number of children adopted from outside the US has increased substantially in recent years and the immune status of such children may be difficult to determine base on country of origin and medical records.134 Children adopted from other countries whose immune status is uncertain should be vaccinated according to the US Recommended Childhood and Adolescent Immunization Schedules.134 The fact that immunization schedules of other countries may differ from US schedules (e.g., different recommended vaccines, recommended ages of administration, and/or number and timing of vaccine doses) should be considered.134 Vaccines administered outside the US can generally be accepted as valid if the administration schedule was similar to that recommended in the US childhood and adolescent immunization schedules.134 Only written vaccination records should be considered as evidence of previous vaccination since such records are more likely to accurately predict protection if the vaccines administered, intervals between doses, and child's age at the time of vaccination are similar to US recommendations; however, the extent to which an internationally adopted child's immunization record reflects their protection against disease is unclear and it is possible there may be transcription errors in such records (e.g., single-antigen vaccine may have been administered although a multiple-antigen vaccine was recorded).134 Although vaccines with inadequate potency have been produced in other countries, most of vaccines used worldwide are immunogenic and produced with adequate quality control standards.134

When the immune status of an internationally adopted child is uncertain, ACIP recommends that health-care providers either repeat vaccinations (since this usually is safe and avoids the need to obtain and interpret serologic tests) and/or use selective serologic testing to determine the need for immunizations (helps avoid unnecessary injections).134 Regarding DTaP vaccination, ACIP states that health-care providers may revaccinate a child with DTaP without regard to the child's prior vaccination record; however, there is concern about this approach since data indicate increased rates of local adverse reactions after the fourth and fifth doses of DTP or DTaP (see Cautions: Local Effects).134 If a child adopted from another country is revaccinated with DTaP and experiences a severe local reaction, serologic tests for specific IgG antibody to tetanus and diphtheria toxins (if available) can be done prior to administration of additional doses.134 If protective levels of antibody are detected (defined as 0.1 international units per mL or higher for diphtheria and 0.1 international units/mL or higher for tetanus; a correlate of protection for pertussis has not been established), further DTaP doses are unnecessary and subsequent age-appropriate vaccination can occur.134

An internationally adopted child whose vaccine record indicates that 3 or more doses of DTP or DTaP have been administered may be tested for serologic evidence of IgG antibody to diphtheria and tetanus toxins to determine the need for additional DTaP doses.134 If the child has protective concentrations of diphtheria and tetanus antibodies, their prior recorded immunization record may be considered valid and the DTaP vaccination series may be completed as age-appropriate.134 Children with indeterminate antibody concentrations may have immunologic memory but waning immunity; in this situation, unnecessary revaccination with a full series may be avoided if a booster dose of DTaP is given followed by repeat serologic testing.134 If a child's vaccination record indicates that 3 or more doses of DTP or DTaP have been administered, a single booster of DTaP can be given followed 1 month later by serologic testing for specific IgG antibody to diphtheria and tetanus toxins.134 If the child has antibody concentrations considered protective, their prior recorded immunization record can be considered valid.134 Children with indeterminate antibody concentration after a booster dose should be revaccinated with the complete DTaP series.134

Travelers

Tetanus, diphtheria, and pertussis occur worldwide, and travelers are at risk if they are unvaccinated or incompletely vaccinated against these diseases.115 (See Uses: Risks of Diphtheria, Tetanus, and Pertussis Exposure and Infection.)

CDC recommends that all travelers, including children, be adequately immunized against diphtheria, tetanus, and pertussis before leaving the US.115 If necessary to complete the vaccination series before departure, an accelerated immunization schedule using the age-appropriate minimum intervals between doses can be used.105,115 (See Dosage and Administration: Dosage.)

Primary and Booster Immunization with Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Tdap)

Primary Immunization in Children 7 through 10 Years of Age

Although safety and efficacy of Tdap have not been established for primary immunization or for use in children younger than 10 years of age,192,193 ACIP, AAP and other experts recommend that a single dose of Tdap be included in the vaccination series when primary immunization† is indicated in children 7 through 10 years of age† who are unvaccinated or incompletely vaccinated against diphtheria, tetanus, and pertussis, unless pertussis antigens are contraindicated or should not be used.105,199,236 Children are considered fully vaccinated if they have received 5 doses of DTaP or have received 4 doses of DTaP with the fourth dose administered on or after the fourth birthday.236

The preferred primary immunization schedule in previously unvaccinated or incompletely vaccinated children 7 through 10 years of age† is a single dose of Tdap followed by the remaining required doses of Td;105,199 however, the Tdap dose may be substituted for any of the required doses of Td.105 These children should not receive the booster dose of Tdap usually recommended at 11 through 12 years of age.105,199

Primary Immunization in Adolescents and Adults 11 through 64 Years of Age

Although safety and efficacy of Tdap for primary immunization† have not been established,192,193 ACIP and AAP recommend that a single dose of Tdap be included in the vaccination series when primary immunization against diphtheria and tetanus is indicated in previously unvaccinated adolescents and adults 11 through 64 years of age.195,196,200,201

Adolescents and adults with an incomplete or uncertain history of primary immunization against diphtheria and tetanus should receive primary immunization with 3 doses of a preparation containing diphtheria and tetanus toxoids.195,196,200 Because such individuals also may be susceptible to pertussis, ACIP, AAP, and other experts recommend that primary immunization† against diphtheria and tetanus in previously unvaccinated adolescents and adults 11 through 64 years of age include a single dose of Tdap, unless pertussis antigens are contraindicated or should not be used.105,195,196,200 The preferred primary immunization schedule in previously unvaccinated adolescents and adults 11 through 64 years of age is a single dose of Tdap followed by a dose of Td given at least 4 weeks after the Tdap dose and a second dose of Td given 6-12 months after the first dose of Td;105,195,196,200 however, the Tdap dose may be substituted for any 1 of the 3 doses of Td.195,196 Individuals who previously received Tdap should receive Td for all subsequent primary or booster doses.192,193,195,201

Booster Immunization in Adolescents 10 through 18 Years of Age

Tdap (Adacel^®, Boostrix^®) is used for booster immunization against tetanus, diphtheria, and pertussis in adolescents 10 through 18 years of age.192,193,195,199,201,234,236

ACIP, AAP, and other experts recommend that all adolescents who received primary immunization with DTaP, DTP (not commercially available in the US), DT, or Td receive a booster dose of a preparation containing diphtheria and tetanus toxoids at 11 through 18 years of age (preferably at 11 through 12 years of age).100,105,199,201 Because adolescents also may be at risk for pertussis, ACIP, AAP, and other experts recommend that a single dose of Tdap (Adacel^®, Boostrix^®) be used (instead of Td) for the adolescent booster dose at 11 through 18 years of age (preferably at 11 through 12 years of age), unless pertussis antigens are contraindicated or should not be used.195,199,201,236 If Tdap is unavailable or was administered previously, Td should be used for this adolescent booster dose.195,199,201

Booster Immunization in Adults 19 Years of Age or Older

Tdap (Adacel^®, Boostrix^®) is used for booster immunization against tetanus, diphtheria, and pertussis in adults.192,193,236,237 Tdap (Adacel^®) is labeled by FDA for use in adults 19 through 64 years of a 192 Tdap (Boostrix^®) is labeled by FDA for use in adults 19 years of age or older (including those 65 years of age or older).193

Adults who received primary immunization against diphtheria and tetanus should receive routine booster doses of Td every 10 years.100,200 In addition, an emergency booster dose of Td may be indicated in the event of injury and possible exposure to tetanus infection.100,200 (See Uses: Postexposure Prophylaxis of Tetanus.) Because adults also may be at risk for pertussis, ACIP and other experts recommend that all adults (including those 65 years of age or older) receive a single dose of Tdap (instead of Td) when a booster dose is needed in those who have not previously received a dose of Tdap, unless pertussis antigens are contraindicated or should not be used.196,200,236,237 The Tdap booster dose can be administered regardless of the interval since the last dose of vaccine containing tetanus or diphtheria toxoids (e.g., Td).235,236,237 Although a long interval between Td and Tdap may decrease the occurrence of local reactions236 and an interval of at least 5 years usually has been recommended between the last dose of any vaccine containing diphtheria, tetanus, or pertussis antigens and Tdap,195,196,205 ACIP states that the benefits of protection against pertussis outweigh the potential risk for adverse effects.236 If Tdap is not available or was administered previously, Td should be used for booster doses.196

A single Tdap dose is recommend for all adult 65 years of age or older who have not previously received a dose.237 Because only Tdap (Boostrix^®) is labeled by FDA for booster immunization in adults 65 years of age or older,193 Tdap (Boostrix^®) should be used when feasible.237 However, ACIP states that both Tdap (Adacel^®) and Tdap (Boostrix^®) are immunogenic and either Tdap vaccine would provide protection when used for booster immunization in this age group.237 Because any opportunity to administer Tdap to adults 65 years of age or older should not be missed, ACIP states that providers may administer the Tdap (Adacel^®, Boostrix^®) that is available.237

Adolescents and Adults in Contact with Infants

ACIP and AAP recommend that adolescents and adults who have or anticipate having close contact with an infant younger than 12 months of age (e.g., parents, siblings, grandparents, childcare providers, health-care personnel) who have not previously received Tdap receive a single booster dose of Tdap to provide protection against pertussis and reduce the likelihood of pertussis transmission to the infant.105,195,196,205,234,236 Ideally, the Tdap dose should be given at least 2 weeks prior to beginning close contact with the infant.105,195,196,205,234 If indicated for pertussis vaccination, Tdap should be administered regardless of the interval since the last dose of vaccine containing diphtheria or tetanus toxoids (e.g., Td).236

Pregnant Women

Unless contraindicated, all women of childbearing potential should be adequately immunized against tetanus, diphtheria, and pertussis.100,105,195,196,200,205,234 Pregnant women who are immune to these diseases can confer protection to their infants through transplacental transfer of maternal antibody.105,195,205

Obstetric and neonatal tetanus and obstetric and neonatal diphtheria are prevented if protective levels of tetanus and diphtheria antitoxin (i.e., at least 0.1 international units when tested using enzyme-linked immunosorbent assay [ELISA]) are present in the mother.205 Although the effectiveness and optimal concentration of maternal antipertussis antibodies that would provide protection is not known, high levels of maternal antibodies in neonates during the first few weeks after birth are likely to confer protection and might prevent or modify severity of the disease.234,238

Because of the risks associated with diphtheria, tetanus, and pertussis, ACIP, AAP, and other experts state that pregnancy is not considered a contraindication for preparations containing diphtheria and tetanus toxoids, including Tdap.100,105,195,196,200,201,205,234

Ideally, primary immunization against tetanus and diphtheria should be completed prior to pregnancy.100,105,195,205 If primary immunization against these diseases is initiated in previously unvaccinated or incompletely vaccinated pregnant women, ACIP and others recommend that a dose of Tdap be substituted for one of the required Td doses, preferably during the third trimester (optimally between 27 and 36 weeks of gestation).200,238 In addition, to ensure protection against pertussis, ACIP and other experts recommend that a dose of Tdap be administered during each pregnancy, regardless of the woman's prior vaccination history.200,238 Although Tdap can be administered any time during the pregnancy, the optimal time that maximizes maternal antibody response and passive antibody transfer to the infant is between 27 and 36 weeks of gestation.238 (See Pregnancy under Cautions: Pregnancy and Lactation.)

Health-care Personnel

Health-care personnel should have documentation of age-appropriate primary immunization with a preparation containing diphtheria and tetanus toxoids and booster doses of Td every 10 years.235 In addition, ACIP recommends that all health-care personnel (regardless of age) receive a single dose of Tdap if they have not previously received a dose.235 Vaccinating health-care personnel with Tdap protects them against pertussis and also is expected to reduce transmission of pertussis to patients.195 Priority should be given to those who have direct contact with infants younger than 12 months of age.195

Health-care personnel who do not have documentation of primary immunization against diphtheria and tetanus should received a 3-dose vaccination series using Tdap for the first dose and Td for subsequent primary and booster doses.235 Previously vaccinated health-care personnel who have not received a dose of Tdap should receive a dose as soon as feasible, regardless of the interval since the last dose of vaccine containing diphtheria or tetanus toxoids (e.g., Td).235 Td should be used for subsequent booster doses.235

Hospitals and ambulatory care facilities should provide Tdap for health-care personnel and should use approaches that maximize vaccination rates (e.g., education regarding the benefits of vaccination, convenient access, provision of Tdap at no charge).235

Travelers

CDC recommends that all travelers, including adolescents and adults, be adequately immunized against diphtheria, tetanus, and pertussis before leaving the US.105,115

Adults, adolescents, and children 7 through 10 years of age† who are unvaccinated or incompletely vaccinated should receive a single dose of Tdap (unless the pertussis antigens are contraindicated or should not be used) followed by the recommended doses of Td according to the usual age-appropriate catch-up vaccination schedule.115,195,196,201,236 If necessary to complete the vaccination series before departure, an accelerated immunization schedule using the age-appropriate minimum intervals between doses can be used.105,115 (See Dosage and Administration: Dosage.)

Because immunity from childhood vaccination and natural disease wanes with time, previously vaccinated adults and adolescents 11 years of age or older who have not previously received a dose of Tdap should receive a single booster dose of Tdap.236 Individuals who have previously received Tdap should receive a booster dose of Td if indicated.115

Postexposure Prophylaxis of Diphtheria

Postexposure vaccination with a preparation containing diphtheria toxoid adsorbed may be indicated in addition to anti-infective postexposure prophylaxis in unvaccinated or inadequately vaccinated household and other close contacts of an individual with diphtheria.100,105,166

Regardless of vaccination status, ACIP, AAP, and CDC recommend that all household and other close contacts of an individual with culture-confirmed or suspected diphtheria promptly receive anti-infective postexposure prophylaxis (single IM dose of penicillin G benzathine or oral erythromycin given for 7-10 days).100,105,166,228 Samples for cultures should be taken prior to initiating anti-infective therapy and the individual should be observed for 7 days for evidence of diphtheria.100,166,228

Individuals exposed to diphtheria who previously received less than 3 doses of a preparation containing diphtheria toxoid adsorbed or whose vaccination status is unknown or uncertain should receive an immediate dose of an age-appropriate preparation containing diphtheria toxoid adsorbed, and the primary vaccination series should be completed.100,105,166 In addition, close contacts who previously completed the primary vaccination series against diphtheria should receive a booster dose of an age-appropriate preparation containing diphtheria toxoid adsorbed if it has been 5 years or longer since their last booster dose.100,105,166

Diphtheria carriers should receive an anti-infective regimen active against C. diphtheriae .100,166 Vaccination does not eliminate carriage of C. diphtheriae .100 However, diphtheria carriers who are unvaccinated or inadequately vaccinated should receive immunization using an age-appropriate preparation containing diphtheria toxoid adsorbed and those who are vaccinated but have not received a dose of a preparation containing diphtheria toxoid adsorbed within the last 5 years should receive a booster dose.105

Because diphtheria infection does not necessarily confer immunity, the primary vaccination series using an age-appropriate preparation of diphtheria toxoid adsorbed should be initiated or completed during convalescence.105

Diphtheria antitoxin (equine) (available in the US only from the CDC under an investigational new drug [IND] protocol) is no longer routinely recommended for postexposure prophylaxis of diphtheria in contacts,100,105,166 but may be recommended in exceptional circumstances for postexposure prophylaxis in individuals with known or suspected exposure to toxigenic Corynebacterium .204,228 (See Diphtheria Antitoxin (Equine) 80:04.) To obtain diphtheria antitoxin (equine), clinicians should contact the CDC at 404-639-8257 from 8:00 a.m. to 4:30 p.m. EST Monday-Friday or the CDC Emergency Operations Center at 770-488-7100 after hours, on weekends, and holidays.166,204,228

Postexposure Prophylaxis of Tetanus

When active immunization against tetanus is indicated as part of postexposure prophylaxis after injury and possible exposure to tetanus infection in infants and children 6 weeks through 6 years of age, use of DTaP is preferred; however, DT should be used in this age group if the pertussis antigen is contraindicated.100,105

Although Td usually is recommended in individuals 7 years of age or older requiring primary or booster immunization against tetanus as part of postexposure prophylaxis and wound management, a single dose of Tdap should be used instead of Td in adults and adolescents 11 years of age or older (including pregnant women and adults 65 years of age or older) who have not previously received a dose of Tdap, unless pertussis antigens are contraindicated or should not be used.100,195,196,201,237,238 If Tdap is not available or was administered previously, Td should be used for postexposure prophylaxis.195,196,201,205,237

For information on tetanus-prone wounds and associated risks of tetanus and ACIP recommendations for postexposure prophylaxis of tetanus, see Uses: Postexposure Prophylaxis of Tetanus in Diphtheria and Tetanus Toxoids Adsorbed/Tetanus and Diphtheria Toxoids Adsorbed 80:08.

Postexposure Prophylaxis of Pertussis

Postexposure vaccination with DTaP or Tdap may be indicated in addition to anti-infective postexposure prophylaxis in household and other close contacts of an individual with pertussis.100,105,195,196,201

Regardless of vaccination status or age, ACIP, AAP, and CDC recommend that all household and other close contacts of an individual with suspected pertussis receive prophylaxis with an anti-infective active against B. pertussis (usually azithromycin, clarithromycin, erythromycin; alternatively, co-trimoxazole).100,105,206 In addition, all close contacts younger than 7 years of age who have not completed primary immunization with DTaP should complete the vaccination series with minimal intervals between doses.100,105,166 Those who received their third dose of DTaP 6 months or longer before the exposure should receive a fourth dose.105

ACIP and AAP state that all individuals 7 years of age or older at increased risk of pertussis during pertussis outbreaks or because they are close contacts of an individual with pertussis (e.g., in a family, residential facility, school, school-related activity) should receive a single dose of Tdap if they have not previously received a dose.105,195,196,201 This includes children 7 through 10 years of age† who did not complete the DTaP vaccination series.105

Dosage and Administration ⬆ ⬇

[Section Outline]

Administration
Dosage

Administration

Diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed (DTaP) and tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed (Tdap) are administered only by IM injection.182,187,192,193 DTaP and Tdap should not be administered subcutaneously, intradermally, or IV.182,187,192,193

To ensure delivery into muscle, IM injections should be made at a 90° angle to the skin using a needle length appropriate for the individual's age and body mass, thickness of adipose tissue and muscle at the injection site, and the injection technique.134

Depending on patient age, IM injections of DTaP or Tdap should be made into the anterolateral muscles of the thigh or deltoid muscle of the arm.134,182,187 In adults, adolescents, and children 3 years of age or older, IM injections should preferably be made in the region of the deltoid muscle.134 In infants and children 6 weeks through 2 years of age, IM injections should preferably be made into the anterolateral thigh;134,187 alternatively, the deltoid muscle can be used in those 1 through 2 years of age if muscle mass is adequate.134

DTaP and Tdap should not be injected into the gluteal area or any area where there may be a major nerve trunk.134,182,187,192 If the gluteal muscle is chosen for infants younger than 12 months of age because of special circumstances (e.g., physical obstruction of other sites), it is essential that the clinician identify anatomic landmarks prior to injection.134

DTaP and Tdap should be inspected visually for particulate matter and discoloration prior to administration.182,187,192,193 Prior to use, vials or prefilled syringes of DTaP or Tdap should be shaken vigorously until a uniform, turbid, white suspension results.182,187,192,193 DTaP and Tdap should not be used if the vaccines cannot be resuspended.182,192,193

Syncope (vasovagal or vasodepressor reaction; fainting) may occur following vaccination;106,134,182,187,192,193,205,223 such reactions may be accompanied by transient neurologic signs (e.g., visual disturbance, paresthesia, tonic-clonic limb movements).106,182,193,223 Syncope occurs most frequently in adolescents and young adults.134,205 Procedures should be in place to avoid falling injury and to restore cerebral perfusion following syncope.106,182,193,223 Syncope and secondary injuries may be averted if vaccinees sit or lie down during and for 15 minutes after vaccination.134,205 If syncope occurs, the patient should be observed until symptoms resolve.134,205

DTaP or Tdap should not be mixed with any other vaccine or solution.182,187,192,193 Although DTaP is commercially available in a kit containing DTaP and inactivated poliovirus vaccine (DTaP-IPV) and Haemophilus b (Hib) vaccine to provide a combination vaccine containing DTaP, poliovirus, and Hib antigens (DTaP-IPV/Hib; Pentacel^®),224 extemporaneous vaccine combinations of DTaP or Tdap and other commercially available vaccines should not be prepared by admixing the vaccines.105,110,134,149

When passive immunization with tetanus immune globulin (TIG) is indicated in addition to active immunization with a preparation containing tetanus toxoid adsorbed for postexposure prophylaxis of tetanus, DTaP or Tdap may be given simultaneously with TIG using different syringes and different injection sites.100,105,134,182,192,193,195,196

DTaP or Tdap may be given simultaneously with other age-appropriate vaccines.100,105,134,182,192,195,196,199,201 (See Drug Interactions: Vaccines.) When multiple vaccines are administered during a single health-care visit, each parenteral vaccine should be given with a different syringe and at different injection sites.134 Injection sites should be separated by at least 1 inch (if anatomically feasible) to allow appropriate attribution of any local adverse effects that may occur.134

Dosage

The dosing schedule (i.e., number of doses) and specific preparation for primary and/or booster immunization (i.e., DTaP, Tdap) varies depending on age.182,187,192,193,199,200 The age-appropriate recommendations for the specific preparation used should be followed. 182,187,192,193,199,200

DTaP (Daptacel^®, Infanrix^®) is used only in infants and children 6 weeks through 6 years of age.105,149,182,187

Tdap (Adacel^®) is labeled by the US Food and Drug Administration (FDA) for booster immunization in adolescents 10 years of age or older and adults 19 through 64 years of a 192 Tdap (Boostrix^®) is labeled by FDA for booster immunization in adolescents 10 years of age or older and adults 19 years of age or older.193 Although safety and efficacy of Tdap for primary immunization or for use in children younger than 10 years of age have not been established,192,193 ACIP recommends Tdap (Adacel^®, Boostrix^®) in catch-up primary immunization† regimens in children 7 through 10 years of age†.236 In addition, although only Tdap (Boostrix^®) is labeled by FDA for use in adults 65 years of age or older, ACIP states that either Tdap (Adacel^®) or Tdap (Boostrix^®) can be used when booster immunization is indicated in this age group.237

ACIP recommends that the same DTaP preparation used for the initial dose be used to complete the primary and booster immunization series127,134,149,183 since data is limited regarding safety, efficacy, or immunogenicity of the different DTaP vaccine preparations administered interchangeably in the primary or booster immunization series.105,127,134,149,183,183 However, if the particular DTaP vaccine used previously is not known or not available, any age-appropriate commercially available DTaP vaccine should be used to complete the vaccination series.105,127,149,166,183

The complete primary vaccination series and recommended booster doses must be administered to ensure optimal protection against diphtheria and tetanus.182,187,192,193,199,200 Interruption of the recommended primary immunization schedule, regardless of length of time between doses, does not interfere with the final immunity achieved; it is not necessary to give additional doses or start the vaccine series over.100,166,192,193,199

Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (DTaP)

DTaP (Daptacel^®, Infanrix^®) is administered in 0.5-mL doses.182,187

Each 0.5-mL dose of Daptacel^® contains 15 Lf units of diphtheria toxoid, 5 Lf units of tetanus toxoid, and pertussis antigens consisting of 10 mcg of detoxified pertussis toxoid, 5 mcg of filamentous hemagglutinin (FHA), 3 mcg of pertactin, and 5 mcg of fimbriae types 2 and 3.187

Each 0.5 mL of Infanrix^® contains 25 Lf units of diphtheria toxoid, 10 Lf units of tetanus toxoid, and pertussis antigens consisting of 25 mcg of inactivated pertussis toxin, 25 mcg of FHA, and 8 mcg of pertactin.182

Primary and Booster Immunization in Infants and Children 6 Weeks through 6 Years of Age

For primary immunization in infants and children 6 weeks through 6 years of age, ACIP, AAP, and other experts recommend that DTaP be given in a series of 3 primary doses and 1 or 2 booster doses.105,149 The first 3 doses of DTaP should be given at 4- to 8-week intervals (usually at 2, 4, and 6 months of age) and the fourth dose (booster dose) given approximately 6-12 months after the third dose (usually at 15 through 18 months of age).105,182,183,199 The fourth dose may be administered as early as 12 months of age, provided at least 6 months have elapsed since the third dose.105,199 Some manufacturers recommend that this dose be given at 15-20 months.182,187

At 4 through 6 years of age (usually just prior to entry into school), children who received the fourth dose of the DTaP vaccination series at younger than 4 years of age should receive a fifth dose (booster dose).105,182,187,199 The fifth dose is not necessary if the fourth dose was given at 4 years of age or older.105

For accelerated vaccination (e.g., for catch-up or prior to travel) in children 6 weeks to 6 years of age who did not receive DTaP at the usually recommended time in early infancy, a dose of DTaP should be given at the first visit and the second and third doses given at 4-week intervals after first dose.105,199 The fourth and fifth of DTaP doses should then be given at 6-month intervals after third dose.105,199 A fifth dose is not necessary if the fourth dose was given at 4 years of age or older.105,182

Deferral of Pertussis Vaccination in Children 6 Weeks through 6 Years of Age

When initiation or continuation of DTaP vaccination is contraindicated because of the pertussis component of the vaccine (see Cautions: Precautions and Contraindications), children younger than 7 years of age should receive diphtheria and tetanus toxoids adsorbed (DT) to complete the vaccination series.105,182 If DTaP administration is deferred (e.g., while the neurologic status of the child is evaluated) and it is subsequently decided to proceed with the vaccination series following individual assessment in these children, there is no need to restart the series regardless of the time elapsed between doses.105

Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Tdap)

Tdap (Adacel^®, Boostrix^®) is administered in a 0.5-mL dose.192,193

Each 0.5-mL dose of Tdap (Adacel^®) contains 5 Lf units of tetanus toxoid, 2 Lf units of diphtheria toxoid, and pertussis antigens consisting of 2.5 mcg of detoxified pertussis toxin, 5 mcg of FHA, 3 mcg of pertactin, and 5 mcg of fimbriae types 2 and 3.192

Each 0.5 mL of Tdap (Boostrix^®) contains 5 Lf of tetanus toxoid, 2.5 Lf units of diphtheria toxoid, and pertussis antigens consisting of 8 mcg of detoxified pertussis toxin, 2.5 mcg of FHA, and 2.5 mcg of pertactin.193

Primary Immunization in Children 7 through 10 Years of Age

Although safety and efficacy of Tdap have not been established for primary immunization or for use in children younger than 10 years of age,192,193 ACIP, AAP, and other experts recommend that primary immunization† against diphtheria, tetanus, and pertussis in previously unvaccinated or incompletely vaccinated children 7 through 10 years of age† include a single dose of Tdap, unless pertussis antigens are contraindicated or should not be used.105,199,236

The preferred primary immunization schedule recommended by ACIP, AAP, and other experts for catch-up vaccination in children 7 through 10 years of age is a single dose of Tdap followed by a dose of Td given 1-2 months after the Tdap dose and a second Td dose given 6-12 months after the first Td dose.105,199 Alternatively, Tdap may be substituted for any 1 of the Td doses.105 Children who receive a dose of Tdap at 7 through 10 years of age† should not receive a Tdap booster dose at 11 through 12 years of age.105,199

Primary Immunization in Adolescents and Adults 11 through 64 Years of Age

Although safety and efficacy of Tdap for primary immunization have not been established,192,193 ACIP recommends that primary immunization† against diphtheria and tetanus in previously unvaccinated or incompletely vaccinated adolescents and adults 11 through 64 years of age include a single dose of Tdap, unless pertussis antigens are contraindicated or should not be used.195,196

The preferred primary immunization schedule recommended by ACIP, AAP, and other experts for previously unvaccinated adolescents and adults 11 through 64 years of age is a single dose of Tdap followed by a dose of Td given at least 4 weeks after the Tdap dose and a second dose of Td given 6-12 months after the first Td dose.105,195,196,200 Alternatively, the Tdap dose may be substituted for any 1 of the 3 doses of Td.195,196 Td should be used for all subsequent booster doses.192,193,195,201

Booster Doses in Adolescents 10 through 18 Years of Age

All individuals who received primary immunization with DTaP, DTP (not commercially available in the US), DT, or Td receive a booster dose of a preparation containing diphtheria and tetanus toxoids at 11 through 18 years of age (preferably at 11 through 12 years of age) and routine booster dose of Td every 10 years to maintain adequate immunity against diphtheria and tetanus.100,105,199

Because adolescents also may be at risk for pertussis, ACIP, AAP, and other experts recommend that a single dose of Tdap (Adacel^®, Boostrix^®) be used (instead of Td) for the adolescent booster dose at 11 through 18 years of age (preferably at 11 through 12 years of age), unless Tdap has already been given or the pertussis antigens are contraindicated or should not be used.195,199,201 If Tdap is unavailable or was administered previously, Td should be used for this adolescent booster dose.195,199,201

Booster Doses in Adults 19 through 64 Years of Age

Adults who have received primary immunization against diphtheria and tetanus should receive routine booster doses of Td every 10 years.100,200 In addition, an emergency booster dose of Td may be indicated in the event of injury and possible exposure to tetanus infection.100,200 Because adults may be at risk for pertussis, ACIP and other experts recommend that a single dose of Tdap be used (instead of Td) when a booster dose is needed in adults 19 through 64 years of age who have not previously received Tdap, unless pertussis antigens are contraindicated or should not be used.196 If Tdap is not available or was administered previously, Td should be used for booster doses.196

Booster Doses in Adults 65 Years of Age or Older

A single dose of Tdap should be used (instead of Td) when a booster dose of vaccine containing tetanus and diphtheria toxoids is needed in adults 65 years of age or older who have not previously received Tdap.193,237 Although only Tdap (Boostrix^®) is labeled for use in adults 65 years of age or older,193 ACIP states that either Tdap (Adacel^®) or Tdap (Boostrix^®) can be used when a dose of Tdap is indicated in this age group.237 If Tdap was administered previously, Td should be used for subsequent booster doses.237 (See Uses: Primary and Booster Immunization with Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed [Tdap].)

Combination Vaccines Containing DTaP and Other Antigens

For information on dosage and administration of the fixed-combination vaccines containing DTaP and poliovirus antigens (DTaP-IPV; Kinrix^®, Quadracel),221,223 see Poliovirus Vaccine Inactivated 80:12.

For information on dosage and administration of the fixed-combination vaccine containing DTaP and hepatitis B and poliovirus antigens (DTaP-HepB-IPV; Pediarix^®),106 see Poliovirus Vaccine Inactivated 80:12 and see Hepatitis B Vaccine 80:12.

For information on dosage and administration of the combination vaccine containing DTaP and poliovirus and Hib antigens (DTaP-IPV/Hib; Pentacel^®),224 see Poliovirus Vaccine Inactivated 80:12 and see Haemophilus b Vaccine 80:12.

Cautions ⬆ ⬇

[Section Outline]

Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (DTaP)
Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Tdap)
Precautions and Contraindications
Pediatric Precautions
Geriatric Precautions
Mutagenicity and Carcinogenicity
Pregnancy and Lactation

Diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed (DTaP) is associated with a lower incidence of adverse local reactions and a lower incidence of adverse systemic effects (including severe adverse effects) than diphtheria and tetanus toxoids and whole-cell pertussis vaccine adsorbed (DTP, also referred to as DTwP; not commercially available in the US).105,127,166,182,183

The incidence and severity of adverse reactions reported to date with use of a single dose of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed (Tdap) in adolescents and adults have been similar to that reported with use of tetanus and diphtheria toxoids adsorbed (Td) in this age group.192,193

Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (DTaP)

Local Effects

Local adverse effects, including pain or tenderness,127,182 erythema,127,182 and swelling,127,182 have been reported following administration of DTaP. Adverse local effects are reported more frequently and are more severe following booster doses of DTaP (fourth and fifth doses) than following the initial 3 doses in the vaccination series.127,134,182,187 This increased incidence of adverse effects with the fourth and fifth doses has been reported with all commercially available DTaP vaccines.127,182,187 Although additional safety data are needed to determine the frequency and severity of adverse events after a fifth dose of Daptacel^® in children who have previously received 4 doses of the DTaP vaccine,127,187 data from studies evaluating Infanrix^® indicate that higher rates of local injection site reactions (redness, swelling, pain) and larger local reactions occur following a fifth dose of the vaccine compared with the fourth dose.182 Adverse local reactions usually occur within 1-3 days after vaccination and resolve within about 5-7 days without sequelae.127,187

In one study in infants and children who received Daptacel^® at 2, 4, 6, and 17-18 months of age, the incidence of tenderness, erythema, or swelling was 4.3-12.7% after the first dose, 4.3-20.6% after the second dose, 4.7%-22.2% after the third dose, and 18.6-36.5% after the fourth dose.187

In one study in US infants and children who received primary immunization with Infanrix^® at 2, 4, and 6 months of age, the incidence of pain, erythema, or swelling at the injection site was 9.6-31.9% after the first dose, 20.4-32.8% after the second dose, and 24.8-39% after the third dose.182 When a booster dose of Infanrix^® was given at 15-18 months of age in a US study in children who previously received 3 doses of the vaccine, 32.8-48.2% had pain, erythema, or swelling at the injection site and 33.2% had an increase in mid-thigh circumference on the leg where the dose was given.182 When the fifth consecutive dose of Infanrix^® (booster dose) was given at 4-6 years of age, 27-53.3% had pain, erythema, or swelling at the injection site and 37.8% had an increase in arm circumference on the arm where the dose was given.182

Edematous swelling, sometimes involving the entire injected thigh or upper arm has been reported following booster doses of DTaP (fourth or fifth doses).127,182 In US studies evaluating local reactions to the fourth and fifth consecutive doses of Infanrix^®, 2.3% of infants 15-18 months of age had large swelling reactions (defined as swelling more than 50 mm in diameter, more than a 50 mm increase in thigh circumference, and/or any diffuse swelling that interfered with or prevented daily activities) occurring within 4 days of the fourth dose and 1% of children 4-6 years of age had large swelling reactions (defined as involving more than 50% of the upper arm length and associated with more than a 30 mm increase in mid-upper arm circumference) occurring within 4 days of the fifth dose.182

The pathogenesis of these substantial local reactions and limb swelling is unknown.127 Analysis of data from one study indicated that swelling that increased limb circumference more than 5 cm after the fourth dose was associated with the pertussis toxoid content of the vaccine administered; swelling after the fifth dose was associated with the aluminum content of the vaccine; and entire thigh swelling after the fourth dose was associated with the diphtheria toxoid content of the vaccine.127 Prevaccination antibody titers to diphtheria, tetanus, or pertussis toxins were not predictive of these reactions.127 The inconsistent pattern of associations of vaccine content and swelling possibly could indicate that the associations were a statistical artifact attributable to a limited sample size or to differential reporting of entire thigh swelling among the DTaP vaccine groups.127 Whether children who experience entire limb swelling after a fourth dose of DTaP are at increased risk for this reaction after the fifth dose is unknown.127

Systemic Effects

Mild to moderate fever (38-40.4°),182,187 fretfulness or irritability,182,187 and drowsiness,182,187 have been reported following administration of DTaP. These systemic effects have been reported in 8.9-61.6% of children receiving the first 4 doses of Infanrix^®182 and 7.7-43.2% of children receiving the first 4 doses of Daptacel^®.187 Anorexia and vomiting187 have been reported in 4.3-11.2% of children receiving the first 3 doses of Daptacel^®.187 Data are limited to date regarding the incidence of adverse systemic effects following the fifth dose of DTaP.187 In a study in US children, fever (37.5°C or greater), drowsiness, or loss of appetite was reported in14.8-17.5% after the fifth dose of Infanrix^®.182

Severe adverse effects, including fever (40°C or higher);182 unusual or persistent crying (lasting 3 hours or longer),182 seizures (febrile or nonfebrile),182 or hypotonic-hyporesponsive episodes,182 have been reported only rarely to date with DTaP. The incidence of these adverse effects appears to be substantially lower than that reported for DTP.182,187 In one large German study in which 22,505 infants received 66,867 doses of Infanrix^®, severe adverse effects (in rates per 1000 doses) occurring within 8 days (including events interpreted by investigators as related as well as those interpreted as unrelated to vaccination) were unusual crying (0.09), febrile seizures (0.0), afebrile seizures (0.13), and hypotonic/hyporesponsive episodes (0.01).182 In a study in which 2587 infants received Daptacel^® at 2, 4, and 6 months, serious adverse effects (rate per 1000 doses at 2, 4, and 6 months) reported were fever of 40°C or higher within 48 hours of vaccination (0.39), persistent crying 3 hours or longer within 24 hours of vaccination (0.39-1.16), seizures within 72 hours of vaccination (0), and hypotonic/hyporesponsive episodes occurring within 24 hours of vaccination (0.39).187

Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Tdap)

Local Effects

In adolescents and adults 11 through 64 years of age who received a single dose of Tdap (Adacel^®), pain at the injection site occurred in 66-78% and was the most frequently reported adverse effect.192 In addition, erythema occurred in 21-25% and injection site swelling occurred in 21%.192 Following a single dose of Tdap (Adacel^®), rates of adverse effects at the injection site reported in adolescents 10 to less than 11 years of age are similar to rates reported in adolescents 11 to less than 12 years of age.192

The most common local effects reported in adolescents and adults 10 through 64 years of age who received a single dose of Tdap (Boostrix^®) were pain (61-75%), erythema (21-48%), swelling (18-39%), and increase in arm circumference of the injected arm (28%).193 In adults 65 years of age or older who received a single dose of Tdap (Boostrix^®), pain, erythema, and swelling at the injection site were reported in 21.5, 10.8, and 7.5%, respectively.193

Systemic Effects

In adolescents and adults 11 through 64 years of age who received a single dose of Tdap (Adacel^®), headache occurred in 34-44%, body ache or muscle weakness occurred in 22-30%, fatigue occurred in 24-30%, sore and swollen joints occurred in 9-11%, GI effects (nausea, diarrhea, vomiting) occurred in 3-13%, chills occurred in 8-15%, fever (38°C or higher) occurred in 1-5%, and rash occurred in 2-3%.192 Serious adverse events were reported in 1.5% of vaccine recipients, including neuropathic events such as severe migraine with unilateral facial paralysis and nerve compression in neck and left arm.192 Following a single dose of Tdap (Adacel^®), rates of adverse systemic effects reported in adolescents 10 to less than 11 years of age are similar to rates reported in adolescents 11 to less than 12 years of age.192

The most common systemic effects reported in adolescents and adults 10 through 64 years of age who received a single dose of Tdap (Boostrix^®) were headache (30-43%), fatigue (28-37%), GI symptoms such as nausea, vomiting, diarrhea, and abdominal pain (16-26%), and fever (6-14%).193 In adults 65 years of age or older who received a single dose of Tdap (Boostrix^®), fatigue, headache, GI symptoms, and fever occurred in 2-12.5%.193

Precautions and Contraindications

DTaP and Tdap are contraindicated in individuals who have had severe allergic reactions (e.g., anaphylaxis) after a previous dose of DTaP, any vaccine component, or any vaccine containing tetanus, diphtheria, or pertussis antigens.182,187,192,193 (See Sensitivity Reactions under Cautions: Precautions and Contraindications.)

DTaP and Tdap are contraindicated in individuals who have had encephalopathy (e.g., coma, decreased level of consciousness, prolonged seizures) within 7 days of a previous dose of a vaccine containing pertussis antigens that could not be attributable to another identifiable cause.134,182,187,192,193 The vaccines also are contraindicated in individuals with progressive neurologic disorder, including infantile spasms, uncontrolled epilepsy, or progressive encephalopathy.182,187,193 (See Precautions Related to Pertussis Components under Cautions: Precautions and Contraindications.)

To determine whether any contraindications to administration of DTaP or Tdap exist and to accurately assess the benefits and risks of the vaccines for each patient, the patient and/or the patient's parent or guardian should be questioned about the health status of the patient and questioned regarding the occurrence of any adverse effect after a previous dose.105,134,182

The patient and/or the patient's parent or guardian should be informed of the benefits and risks of immunization with DTaP and Tdap and the importance of completing the primary immunization series and receiving recommended booster doses (unless there is a contraindication to further doses).182,187,192,193,202 The patients and/or the patient's parent or guardian should be provided with a copy of the appropriate Vaccine Information Statement (available at the CDC website [Web]).182,187,192,193,202,203 Patients and/or the patient's parent or guardian also should be instructed to report any adverse reactions to their health-care provider.134,182,187,192,193 Clinicians or individuals can report any adverse reactions that occur following vaccination to VAERS at 800-822-7967 or [Web].134,182,187,192,193

When further doses of preparations containing pertussis antigens are contraindicated, DT should be used to complete the vaccination series in infants and children 6 weeks through 6 years of age and Td should be used in adults, adolescents, and children 7 years of age or older.105,179,182

Precautions Related to Pertussis Components

The pertussis components (antigens) contained in DTaP and Tdap are prepared from inactivated acellular pertussis and appear to be less reactogenic than the pertussis antigens prepared from inactivated or disrupted whole cells of Bordetella pertussis that are contained in DTP (no longer commercially available in the US).111,112,150,192,193

Encephalopathy

ACIP, AAP, and the manufacturers state that encephalopathy (not due to another identifiable cause) that occurs within 7 days following a dose of any preparation that contains pertussis antigens (e.g., DTaP, Tdap, DTP) is a contraindication to doses of DTaP or Tdap, regardless of whether causation is established.105,182,192,193 Encephalopathy is defined as an acute, severe CNS disorder which may be manifested by coma or major alterations in consciousness or generalized or focal seizures that persist more than a few hours without recovery within 24 hours.105,179,182

Progressive or Unstable Neurologic Disorders

ACIP, AAP, and the manufacturers state that DTaP and Tdap are contraindicated in individuals with progressive neurologic disorder, including infantile spasms, uncontrolled epilepsy, or progressive encephalopathy.182,187,192,193 DTaP and Tdap should be deferred in individuals with progressive or unstable neurologic conditions (e.g., cerebrovascular event, acute encephalopathic condition).182,192,193 It is not known whether administration to individuals with an unstable or progressive neurologic disorder might hasten manifestations of the disorder or affect the prognosis; administration in such individuals may result in diagnostic confusion between manifestations of the underlying illness and possible adverse effects of vaccination.192,193

AAP states that pertussis immunization should be deferred (possibly permanently) in infants and children with progressive neurologic disorders characterized by developmental delay or neurologic findings (e.g., infantile spasms, other epilepsies beginning in infancy).105 Administration of DTaP in infancy may coincide with or hasten the recognition of inevitable manifestations of the disorder, with resulting confusion over causation.105 Such disorders should be differentiated from those that are nonprogressive with symptoms that may change as the child matures.105

Stable neurologic conditions (e.g., cerebral palsy, well-controlled seizure disorder, developmental delay) are not considered contraindications for DTaP or Tdap.134

Unexplained Fever, Collapse, or Crying

ACIP, AAP, and the manufacturers state that the following adverse reactions reported in temporal relation to previous doses of a preparation containing pertussis antigens (e.g., DTaP, Tdap, DTP) should be considered precautions for, rather than absolute contraindications to, doses of DTaP or Tdap: a temperature of 40.5°C or greater within 48 hours of a dose that is unexplained by another cause; collapse or a shock-like state (i.e., a hypotonic-hyporesponsive episode) within 48 hours of a dose; or persistent, severe, inconsolable screaming or crying lasting 3 hours or more occurring within 48 hours of a dose.100,105,179,182,192,193,201 Although many of these adverse effects previously were considered contraindications for pertussis vaccine, they are now considered precautions because they have not been proven to cause permanent sequelae.105

The risks of giving subsequent doses of a pertussis vaccine to a child who has had one of these events are unknown; the possibility of another reaction of similar or greater severity may justify discontinuing pertussis immunization.105 However, in certain circumstances (e.g., during a community pertussis outbreak), the potential benefits of vaccination may outweigh the risks of another reaction.105,179 Whenever one of these adverse effects occurs in temporal relation to administration of a dose of DTaP, the decision to administer subsequent doses of DTaP or a dose of Tdap should be based on the clinical assessment of the prior reaction, the likelihood of pertussis exposure in the child's community, and the potential benefits and risks of pertussis vaccine.105,179,182,192,193

Personal or Family History of Seizures

ACIP, AAP, and the manufacturers state that a seizure (with or without fever) occurring within 3 days of a dose of a preparation containing pertussis antigens (e.g., DTaP, Tdap, DTP) is considered a precaution (not a contraindication) for doses of DTaP or Tdap.100,105,179,192,193,201 Available data to date provide no convincing evidence that seizures alone, temporally associated with DTP administration, result in permanent brain damage, cause epilepsy, aggravate neurologic disorders, or affect the prognosis for children with underlying disorders.105,179

Although there are uncertainties in reported studies, data suggest that infants and young children with a personal seizure history (whether febrile or not) appear to be more likely to have a seizure following administration of a pertussis-containing vaccine than those without such history.105,179 A seizure occurring within 3 days of DTP administration in a child with a seizure history may result from vaccine-induced fever (in children prone to febrile seizures), may be related to the pertussis component of the vaccine, or may be unrelated to the vaccine.179

ACIP states that the decision whether and, if so, when to vaccinate children with a history of seizures must be decided on an individual basis.179 AAP states that because the risk of a postimmunization seizure is increased, pertussis immunization of children with recent seizures should be deferred until a progressive neurologic disorder is excluded;105 DTaP may be used in infants and children with well-controlled seizures or those in whom a seizure is unlikely to recur.105

ACIP and AAP state that a family history of seizures in parents or siblings is not a contraindication or precaution for preparations containing pertussis antigens and that children with such family histories should receive DTaP according to the usual recommended schedule.122,123,130,134,146 AAP states that, although the risk of seizures in children with a family history of seizures may be increased, these seizures are usually febrile in origin and generally benign, and a family history of seizure disorders or a severe reaction following receipt of a pertussis-containing vaccine in another family member is not a contraindication.105 This recommendation is based on the risks of pertussis disease, the large number of children with a family history of seizures (5-7%), the clustering of these children within families, and the low risk of seizures following pertussis vaccination.105,122,130

AAP states that prematurity is not believed to increase the risk of seizures following immunization, but the risk associated with certain types of prematurity (e.g., that with intracranial bleeding of varying severity) has not been fully determined. ACIP states that a history of prematurity generally is not a reason to defer immunization.179

Although it is not known whether prophylactic use of antipyretics following administration of preparations containing pertussis antigens can decrease the risk of febrile seizures, some manufacturers state that acetaminophen or other appropriate antipyretic can be given at the time of DTaP vaccination and then every 4 hours for 24 hours after the dose to reduce the possibility of postvaccination fever.182,187 ACIP states that use of antipyretics in children with previous febrile seizures does not appear to be effective in preventing febrile seizures.134 Although evidence does not support use of antipyretics before or at the time of vaccination, antipyretics can be used for the treatment of fever or local discomfort that might occur following vaccination.134 Fever that does not begin until 24 hours or longer after vaccination or that persists for more than 24 hours following vaccination should not be assumed to be caused by vaccination; other causes for such new or persistent fever should be sought so that treatment is not delayed for serious conditions such as otitis media or meningitis.100,179

Sensitivity Reactions

Anaphylactic or anaphylactoid reactions, characterized by urticaria and angioedema, difficulty breathing, hypotension, and/or shock, have been reported following administration of preparations containing tetanus and/or diphtheria toxoids.100,182,187,192,193

Prior to administration of DTaP or Tdap, the clinician should review the patient's history regarding possible sensitivity and any previous adverse reactions and should take all precautions known for prevention of allergic or any other adverse effects.182,187,192,193 Epinephrine and other appropriate agents and equipment should be available for immediate use in case an anaphylactic reaction occurs.182,187,192,193

DTaP and Tdap are contraindicated in individuals hypersensitive to any ingredient in the formulations.105,179,182,193

DTaP and Tdap are contraindicated in any individual who has had a severe allergic reaction (e.g., anaphylaxis) temporally associated with a dose of any preparation containing tetanus, diphtheria, or pertussis antigens.105,182,192,193,201 Because of the uncertainty as to which component might be responsible for the sensitivity reaction, no further doses of diphtheria, tetanus, or pertussis antigens should be administered.105,182,192,193,223 Alternatively, such individuals may be referred to an allergist for evaluation if further doses are being considered.182,192,193,201,223

Arthus-type Hypersensitivity Reactions

Rarely, extensive local reactions (Arthus-type hypersensitivity reactions) may occur after injection of preparations containing tetanus toxoid.114,192 These reactions generally begin 2-12 hours after administration and are a local inflammatory reaction (vasculitis) that can include severe pain, swelling, induration, edema, hemorrhage, and necrosis.114,192,195,196 (See Cautions: Local Effects in Diphtheria and Tetanus Toxoids Adsorbed/Tetanus and Diphtheria Toxoids Adsorbed 80:08.)

Individuals who experience Arthus-type hypersensitivity reactions or fever greater than 39.4°C after administration of a preparation containing tetanus toxoid adsorbed usually have very high serum tetanus antitoxin levels and usually should not receive additional routine or emergency booster doses of a preparation containing tetanus toxoid adsorbed more frequently than every 10 years, even if postexposure prophylaxis of tetanus is indicated.100,114,192,193,195,196

Latex Sensitivity

Some components (i.e., tip caps) of the single-dose prefilled syringes of DTaP (Infanrix^®) Tdap (Adacel^®, Boostrix^®), DTaP-IPV (Kinrix^®), and DTaP-HepB-IPV (Pediarix^®) may contain natural rubber latex which may cause sensitivity reactions in susceptible individuals.106,182,192,193,223

ACIP states that vaccines supplied in vials or syringes containing dry natural rubber or natural rubber latex may be administered to individuals with latex allergies other than anaphylactic allergies (e.g., history of contact allergy to latex gloves), but should not be used in those with a history of severe (anaphylactic) allergy to latex, unless the benefits of vaccination outweigh the risk of a potential allergic reaction.134 Contact-type allergy is the most common type of latex sensitivity.134

Precautions Related to Booster Doses

Parents or caregivers of children receiving booster doses of DTaP (fourth or fifth doses) should be informed that increases in reactogenicity have been reported with these doses compared with the first 3 doses of the vaccination series.127 Parents also should be informed that edematous swelling involving the entire thigh or upper arm has been reported.127 Whether children who experience entire limb swelling after a fourth dose of DTaP are at increased risk for this reaction after the fifth dose is unknown.127 However, because reports to date indicate that the reactions are self-limited and resolve without sequelae and because of the benefits provided by the preschool booster dose of DTaP (fifth dose), ACIP states that a history of extensive swelling after the fourth dose should not be considered a contraindication for receipt of the fifth dose of DTaP.127 The fact that these reactions may be clinically indistinguishable from other conditions (e.g., cellulitis) that require treatment should be considered.127 Therefore, ACIP recommends that providers make decisions regarding evaluation and management of children with suspected reactions to DTaP on a case-by-case basis.127

Individuals with Altered Immunocompetence

DTaP and Tdap may be administered to individuals immunosuppressed as the result of disease or immunosuppressive therapy.105,134,155,156,187 However, the possibility that the immune response to the vaccine and efficacy may be reduced in these individuals should be considered.105,134,156,182,187,192,193 (See Drug Interactions: Immunosuppressive Agents.)

Recommendations regarding use of DTaP or Tdap in adults, adolescents, or children with human immunodeficiency virus (HIV) infection are the same as those for individuals who are not HIV-infected.155,156 However, immunization may be less effective in HIV-infected individuals than in immunocompetent individuals.156

Guillain-Barré Syndrome and Brachial Neuritis

If Guillain-Barré syndrome (GBS) occurs within 6 weeks after receipt of a vaccine containing tetanus toxoid, the risk for GBS may be increased following a dose of DTaP or Tdap.187,192 Some manufacturers state that a decision to administer subsequent doses of DTaP, Tdap, or any vaccine containing tetanus toxoid in such patients should be based on careful consideration of the potential benefits and possible risks.182,193

A review by the Institute of Medicine (IOM) found evidence of a causal relationship between tetanus toxoid and brachial neuritis and GBS.114,187,192,193 Analysis of active surveillance data collected during 1991 failed to demonstrate an increased risk of GBS in children or adults within 6 weeks following vaccination with a preparation containing tetanus toxoid adsorbed.195,196,230

ACIP states that a history of GBS occurring within 6 weeks after a previous dose of a preparation containing tetanus toxoid adsorbed should be considered a precaution for subsequent doses of such preparations.134,195,196

ACIP does not consider brachial neuritis a precaution or contraindication for further doses of preparations containing tetanus toxoid adsorbed.134,195,196

Concomitant Illnesses

A decision to administer or delay vaccination in an individual with a current or recent febrile illness depends on the severity of symptoms and etiology of the illness.105,134,179

Minor acute illness, such as mild diarrhea or mild upper respiratory tract infection (with or without fever), generally does not preclude vaccination, but vaccination should be deferred in individuals with moderate or severe acute illness (with or without fever).100,105,134,179,192

Limitations of Vaccine Effectiveness

DTaP or Tdap may not protect all individuals from diphtheria, tetanus, and pertussis.187,192,193

Optimum protection against diphtheria and tetanus is achieved with a primary series of 3 doses of preparations containing diphtheria and tetanus toxoids adsorbed.205

Duration of Immunity

Following primary immunization, the duration of protection against diphtheria is approximately 10 years.166

Following primary immunization, the duration of protection against tetanus is approximately 10 years.105,166 Although some individuals may be protected for life, antitoxin levels decrease over time and only approach the minimal protective level in most individuals 10 years after last dose.166

The duration of immunity against pertussis is estimated to be about 5-10 years or longer, but protection wanes over time.105,195,196,201,205 (See Pharmacology.)

Pre- and Postvaccination Serologic Testing

Routine prevaccination serologic testing is not recommended prior to administration of DTaP or Tdap.195,196,235

When postexposure prophylaxis against tetanus or preexposure vaccination in high-risk groups (e.g., travelers) is indicated, individuals with an unknown or uncertain history of vaccination generally should be considered unvaccinated and should receive the complete primary vaccination series.100,115,195

To avoid unnecessary vaccination, ACIP states that prevaccination serologic testing for tetanus and diphtheria antitoxin antibodies can be considered in adults, adolescents, or children 7 years of age or older who probably were vaccinated but cannot produce vaccination records.195,196 If levels of tetanus and diphtheria antitoxin are both at least 0.1 international units/mL, previous vaccination with diphtheria and tetanus toxoids adsorbed can be assumed.195,196

Use of Fixed Combinations

When a fixed-combination vaccine containing diphtheria, tetanus, pertussis, and poliovirus antigens (DTaP-IPV; Kinrix^®, Quadracel) is used, the cautions, precautions, and contraindications associated with each antigen should be considered.221,223 (See Poliovirus Vaccine Inactivated 80:12.)

When the fixed-combination vaccine containing diphtheria, tetanus, pertussis, hepatitis B virus, and poliovirus antigens (DTaP-HepB-IPV; Pediarix^®) is used, the cautions, precautions, and contraindications associated with each antigen should be considered.106 (See Poliovirus Vaccine Inactivated 80:12 and see Hepatitis B Vaccine 80:12.)

When the combination vaccine containing diphtheria, tetanus, pertussis, poliovirus, and Haemophilus b (Hib) antigens (DTaP-IPV/Hib; Pentacel^®) is used, the cautions, precautions, and contraindications associated with each antigen should be considered.224 (See Poliovirus Vaccine Inactivated 80:12 and see Haemophilus b Vaccine 80:12.)

Improper Storage and Handling

Improper storage or handling of vaccines may reduce vaccine potency and can result in reduced or inadequate immune responses in vaccinees.134

All vaccines should be inspected upon delivery and monitored during storage to ensure that the appropriate temperature is maintained.134 (See Chemistry and Stability: Stability.)

DTaP or Tdap that has been mishandled or has not been stored at the recommended temperature should not be administered.134

If there are concerns about mishandling, the manufacturer or state or local immunization or health departments should be contacted for guidance on whether the vaccine is usable.134

Pediatric Precautions

Safety and efficacy of DTaP (Daptacel^®, Infanrix^®) in children younger than 6 weeks of age or in children 7 years of age or older have not been established.182,187

Safety and efficacy of Tdap (Adacel^®, Boostrix^®) in children younger than 10 years of age have not been established.192,193

Apnea has been reported following IM administration of vaccines in some infants born prematurely.182,187,224 Decisions regarding when to administer an IM vaccine in infants born prematurely should be based on consideration of the individual infant's medical status and potential benefits and possible risks of vaccination.182,187,224

Geriatric Precautions

Clinical studies evaluating the safety and efficacy of Tdap (Boostrix^®) included adults 65 years of age or older, and this preparation is labeled by the US Food and Drug Administration (FDA) for booster immunization in geriatric adults.193

Safety and efficacy of Tdap (Adacel^®) have not been established in adults 65 years of age or older.192 Although Tdap (Adacel^®) is not labeled by FDA for use in adults 65 years of age or older,192 ACIP states the vaccine can be used in this age group if it is the only Tdap vaccine available.237 (See Booster Immunization in Adults 19 Years of Age or Older under Uses: Primary and Booster Immunization with Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed [Tdap].)

Mutagenicity and Carcinogenicity

Studies have not been performed to date to evaluate the mutagenic or carcinogenic potential of DTaP (Infanrix^®) or Tdap (Adacel^®, Boostrix^®).182,192,193

Pregnancy and Lactation

Pregnancy

Animal reproduction studies have not been performed with Tdap (Adacel^®).192 A developmental toxicity study in female rats using Tdap (Boostrix^®) at a dose approximately 40 times the human dose (on a mL/kg basis) did not reveal evidence of harm to the fetus.193 Animal fertility studies have not been conducted with Tdap (Adacel^®, Boostrix^®).192,193

There are no adequate and well-controlled studies using Tdap in pregnant women,193 and it is not known whether the vaccine can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity.192 The manufacturers state that Tdap should be used during pregnancy only when clearly needed.192,193

ACIP and AAP state that pregnancy is not generally considered a contraindication to Tdap if a dose is indicated to provide protection against pertussis.195,196,201,205,234 ACIP states that available data do not suggest any elevated frequency or unusual patterns of adverse events in pregnant women who received Tdap and the few serious adverse events reported were unlikely to have been caused by the vaccine.234,238 These experts state that the potential benefit of preventing pertussis morbidity and mortality in infants outweighs theoretical concerns of possible severe adverse events.238

Ideally, primary immunization against tetanus and diphtheria should be completed prior to pregnancy.100,105,195,205 Pregnant women who have not received primary immunization with DTaP, DTP (not commercially available in the US), DT, Td, or single-antigen tetanus toxoid adsorbed and those with unknown or incomplete tetanus immunization should receive a primary series of 3 doses of vaccine containing diphtheria and tetanus toxoids beginning during pregnancy.205,234,238 Although Td usually is the preferred preparation for primary or booster immunization against diphtheria and tetanus in adults, ACIP, AAP, and other experts state that all pregnant women should receive a dose of Tdap, regardless of prior vaccination.105,195,196,200,205,234,238

When primary or booster immunization against diphtheria and tetanus is indicated during pregnancy in previously unvaccinated or incompletely vaccinated pregnant women, ACIP and other experts state that a dose of Tdap should be substituted for one of the required Td doses, preferably during the third trimester (optimally between 27 and 36 weeks of gestation).105,196,200,205,238 In addition, to ensure protection against pertussis, these experts recommend that a dose of Tdap be administered during each pregnancy, regardless of the woman's prior vaccination history.200,238 To maximize the maternal antibody response and passive antibody transfer to the infant, the optimal timing for the Tdap dose is between 27 and 36 weeks of gestation.238

Pregnant women who were previously vaccinated but received the most recent dose of a preparation containing tetanus and diphtheria toxoids 10 or more years previously should receive a booster dose of a preparation containing tetanus toxoid during the second or third trimester of pregnancy (and before 36 weeks of gestation).100,105,195,196,205 This dose is important if the woman does not have sufficient tetanus immunity to protect against maternal and neonatal tetanus or if protection against diphtheria is needed (e.g., for travel to an area where diphtheria is endemic).205 ACIP and other experts state that Tdap should be used for the booster dose (instead of Td).234

If postexposure prophylaxis of tetanus is indicated as part of wound management in a pregnant woman, the usual recommendations regarding emergency booster doses should be followed.205 (See Uses: Postexposure Prophylaxis of Tetanus.) Tdap should be used for the booster dose (instead of Td).234,238

Clinicians are encouraged to register pregnant women who receive Tdap with the manufacturer's pregnancy registry at 800-822-2463 (Adacel^®) or 888-452-9622 (Boostrix^®).192,193

Lactation

It is not known whether Tdap (Adacel^®, Boostrix^®) is distributed into milk.192,193 The manufacturers state that Tdap should be used with caution in nursing women.192,193

ACIP states that breast-feeding is not a contraindication for Tdap and women, including those who are breastfeeding, should receive a single dose of Tdap during the immediate postpartum period if they have not previously received a dose.195,196,205

Drug Interactions ⬆ ⬇

[Section Outline]

Diphtheria Antitoxin (Equine)
Immune Globulins
Immunosuppressive Agents
Vaccines

Diphtheria Antitoxin (Equine)

If both diphtheria antitoxin (equine) (available in the US only from the US Centers for Disease Control and Prevention (CDC) under an investigational new drug [IND] protocol) and a dose of diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed (DTaP) or tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed (Tdap) are required, they should be given at separate sites using different syringes.100 Although specific studies are not available, diphtheria antitoxin (equine) is unlikely to impair the immune response to diphtheria toxoid adsorbed.100

Immune Globulins

DTaP or Tdap may be administered simultaneously with (using different syringes and injection sites) or at any time before or after immune globulin (e.g., immune globulin IM [IGIM], immune globulin IV [IGIV]) or specific hyperimmune globulin (e.g., hepatitis B immune globulin [HBIG], rabies immune globulin [RIG], tetanus immune globulin [TIG], varicella zoster immune globulin [VZIG]).100,134,192,193

When both active and passive immunization against tetanus is indicated, DTaP or Tdap may be administered concomitantly with TIG at a different site using a separate syringe.100,105,134,192,193,195,196

Immunosuppressive Agents

Individuals receiving immunosuppressive agents (e.g., corticotropin, corticosteroids, alkylating agents, antimetabolites, radiation therapy) may have a diminished immunologic response to DTaP and Tdap.187,192,193 Short-term (less than 2 weeks), low- to moderate-dose systemic corticosteroid therapy; long-term, alternate-day, systemic corticosteroid therapy using low to moderate doses of short-acting drugs; topical corticosteroid therapy (e.g., nasal, cutaneous, ophthalmic); or intra-articular, bursal, or tendon injections with corticosteroids should not be immunosuppressive.134,179 If immunosuppressive therapy is to be discontinued shortly, it is reasonable to defer routine DTaP vaccination until 1 month after the immunosuppressive agent is discontinued.179 If immunosuppressive therapy is likely to continue, routine vaccination should be initiated.179

Vaccines

Although specific data are not available regarding concurrent administration of DTaP or Tdap with all other available vaccines,192,193 the US Public Health Service Advisory Committee on Immunization Practices (ACIP), American Academy of Pediatrics (AAP), and American Academy of Family Physicians (AAFP) state that primary immunization against diphtheria, tetanus, and pertussis can be integrated with primary immunization against Haemophilus influenzae type b (Hib), hepatitis A, hepatitis B, human papillomavirus (HPV), influenza, measles, mumps, rubella, meningococcal disease, pneumococcal disease, poliomyelitis, rotavirus, and varicella.105,134,195,199,201 However, unless combination vaccines appropriate for the age and vaccination status of the recipient are used, each parenteral vaccine should be administered using a different syringe and different injection site.100,105,134,182,192,193,195,196,199

Haemophilus b Vaccines

DTaP can be administered concurrently with haemophilus b (Hib) conjugate (meningococcal protein conjugate) vaccine (PRP-OMP; PedvaxHIB^®)136 or Hib conjugate (tetanus toxoid conjugate) vaccine (PRP-T; ActHIB^®)159,160,174 at a different site using different syringes without a decrease in the antibody response or an increase in adverse reactions to either vaccine.134,136,182 Alternatively, depending on the age and vaccination status of the child and if there are no contraindications to any of the individual components, commercially available combination vaccines that contain DTaP and Hib antigens can be used instead of separate injections.149,224

Alternatively, the combination vaccine containing DTaP and Hib and poliovirus antigens (DTaP-IPV/Hib; Pentacel^®) can be used for primary or booster immunization in infants and children 6 weeks through 4 years of age when doses of DTaP, poliovirus vaccine inactivated (IPV), and Hib vaccine are indicated and there are no contraindications to any of the individual components.224 (For information on Pentacel^®, see Poliovirus Vaccine Inactivated 80:12 and see Haemophilus b Vaccine 80:12.)

There is some evidence that extemporaneous combinations of Hib vaccine and other vaccines administered to infants 2-6 months of age may result in suboptimal immune responses to the Hib vaccine.110 Therefore, other commercially available DTaP and Hib vaccines should not be mixed extemporaneously.160

Although an increase in serum concentrations of tetanus antitoxin may occur following administration of PRP-T, this Hib conjugate vaccine is not considered an immunizing agent against tetanus.105,136

Hepatitis B Vaccine

DTaP or Tdap may be given concurrently with hepatitis B vaccine using different syringes and different injection sites.105,134,149,182,192 Alternatively, depending on the age and vaccination status of the child and if there are no contraindications to any of the individual components, the commercially available fixed-combination vaccine containing DTaP and hepatitis B and poliovirus antigens (DTaP-HepB-IPV; Pediarix^®) can be used instead of separate injections for primary immunization in infants and children 6 weeks through 6 years of age.106,208 (For information on Pediarix^®, see Poliovirus Vaccine Inactivated 80:12 and see Hepatitis B Vaccine 80:12.)

Tdap (Adacel^®) has been administered concurrently with hepatitis B vaccine in adolescents 11 through 14 years of age without a decrease in the antibody response to any of the antigens.192 Although the incidence of fever and injection site pain were similar when the vaccines were given concurrently or 4-6 weeks apart, the incidence of injection site erythema and swelling and swollen and/or sore joints and generalized body aches were slightly higher with concurrent administration.192

Human Papillomavirus Vaccine

Tdap (Adacel^®) may be administered concurrently with human papillomavirus (HPV) vaccine using different syringes and different injection sites.105,134,199,232

Human Papillomavirus Quadrivalent Vaccine (4vHPV; Gardasil®)

Tdap (Adacel^®) was administered concurrently with 4vHPV (Gardasil^®) and meningococcal polysaccharide (serogroups A, C, Y and W-135) diphtheria toxoid conjugate vaccine (MCV4; Menactra^®) in an open-label, randomized controlled study in 1040 boys and girls 11 through 17 years of age (mean age 12.6 years).232,233 Concurrent administration of these 3 vaccines at different injection sites did not interfere with the antibody response to any of the vaccine antigens compared with administration of 4vHPV (Gardasil^®) alone followed by administration of Tdap (Adacel^®) and MCV4 (Menactra^®) concurrently at different sites 1 month after the 4vHPV (Gardasil^®) dose.232,233 Although the overall incidence of adverse injection site and systemic reactions in those who received all 3 vaccines concurrently at different sites was similar to that reported when 4vHPV (Gardasil^®) was given alone followed by Tdap (Adacel^®) and MCV4 (Menactra^®) 1 month later,233 concurrent administration was associated with an increased incidence of swelling at the 4vHPV (Gardasil^®) injection site232,233 and an increased incidence of bruising or pain at the other injection sites.233

Human Papillomavirus 9-valent Vaccine (9vHPV; Gardasil® 9)

Tdap (Adacel^®) was administered concurrently with human papillomavirus 9-valent vaccine, recombinant (9vHPV; Gardasil^® 9) and MCV4 (Menactra^®) in a randomized study in 1237 boys and girls 11 through 15 years of age.219 These adolescents received 9vHPV (Gardasil^® 9) in one limb concurrently with Tdap (Adacel^®) and MCV4 (Menactra^®) given at different sites in the opposite limb or received 9vHPV (Gardasil^® 9) in one limb followed 1 month later by Tdap (Adacel^®) and MCV4 (Menactra^®) given concurrently at different sites in the opposite limb.219 Although overall rates of adverse reactions at the injection sites in those who received all 3 vaccines on the same day (at separate sites) were similar to the overall rates reported when 9vHPV (Gardasil^® 9) was given 1 month before the other 2 vaccines, an increased rate of swelling at the 9vHPV (Gardasil^® 9) injection site occurred when all 3 vaccines were administered concurrently compared with administration of 9vHPV (Gardasil^® 9) alone.219 Concurrent administration of all 3 vaccines did not interfere with antibody responses to 9vHPV (Gardasil^® 9) or the other vaccines compared with administration 1 month apart.219

Influenza Vaccine

DTaP or Tdap may be given concurrently with influenza virus vaccine inactivated using a different syringe and different injection site.105,134

Tdap (Adacel^®) has been administered concurrently with influenza virus vaccine inactivated (Fluzone^®) in adults 19 through 64 years of age without a clinically important decrease in the antibody response to tetanus, diphtheria, and influenza antigens.192 There was a lower antibody response to pertactin when Tdap (Adacel^®) was administered concurrently with influenza virus vaccine inactivated, but responses to the other pertussis antigens (detoxified pertussis toxin, fimbriae types 2 and 3, filamentous hemagglutinin) were not affected.192 Although the booster response to the tetanus antigen was lower in those receiving Tdap and influenza vaccine concurrently compared with those who received the vaccines 4-6 weeks apart, at least 98% of individuals in both groups achieved seroprotective levels of tetanus antitoxin.192 The incidence of fever and injection site erythema and swelling were similar when the vaccines were given concurrently or 4-6 weeks apart; however, the incidence of injection site pain and swollen and/or sore joints were slightly higher with concurrent administration.192

Concurrent administration of Tdap (Boostrix^®) and influenza virus vaccine inactivated (Fluarix^®) was evaluated in adults 19 through 64 years of age randomized to receive the vaccines concurrently (at different injection sites) or 1 month apart.193 The immune responses to the diphtheria, tetanus, and influenza antigens and the pertussis toxin antigen were noninferior following concurrent administration.193 However, the immune responses to the pertussis filamentous hemagglutinin (FHA) and pertactin antigens (measured as geometric mean antibody concentrations [GMCs] of anti-FHA and anti-pertactin) were lower when Tdap (Boostrix^®) was administered concurrently with Fluarix^® compared with administration 1 month apart; however, it is not known whether efficacy of the vaccine is affected by the reduced response to these pertussis antigens.193

Measles, Mumps, Rubella, and Varicella Vaccines

DTaP may be administered simultaneously with measles, mumps, and rubella virus vaccine live (MMR) and varicella virus vaccine live (using different syringes and different injection sites) or at any interval before or after the live viral vaccines.134,149,150,199

Meningococcal Vaccine

ACIP and AAP state that Tdap may be administered concurrently with MCV4 (Menactra^®) using different syringes and different injection sites.195,196,201 If not given concurrently, ACIP states that the meningococcal vaccine may be given at any interval before or after Tdap;195,196,201 however, AAP states that the vaccines should be given at least 1 month apart if not given concurrently .201

Tdap (Adacel^®) was administered concurrently with MCV4 (Menactra^®) and either 4vHPV (Gardasil^®) or 9vHPV (Gardasil^® 9) in randomized studies in adolescent boys and girls.219,232,233 Concurrent administration of the 3 vaccines at different injection sites did not interfere with the antibody response to any of the vaccine antigens.219,232,233 Although the overall incidence of adverse reactions in those who received all 3 vaccines concurrently at different sites was similar to that reported when 4vHPV (Gardasil^®) or 9vHPV (Gardasil^® 9) was given alone followed by Tdap (Adacel^®) and MCV4 (Menactra^®) 1 month later,219,233 concurrent administration was associated with an increased incidence of adverse local reactions at the 4vHPV (Gardasil^®) or 9vHPV (Gardasil^® 9) injection sites.219,232,233 (See Human Papillomavirus Vaccine under Drug Interactions: Vaccines.)

Concurrent administration of Tdap (Boostrix^®) and MCV4 (Menactra^®) was evaluated in a study in adolescents 11-18 years of age randomized to receive the vaccines concurrently (at different injection sites) or 1 month apart.193 The immune responses to the diphtheria, tetanus, and meningococcal antigens were noninferior following concurrent administration.193 However, the immune response to the pertactin pertussis antigen (measured as GMCs of anti-pertactin) was lower when Tdap (Boostrix^®) was administered concurrently with MCV4; however, it is not known whether efficacy of the vaccine is affected by the reduced response to pertactin.193

Concurrent administration of MCV4 (Menveo^®) and Tdap (Boostrix^®) and 4vHPV (Gardasil^®) in adolescents 11 through 18 years of age did not interfere with the immune response to the meningococcal antigens.220 Although the clinical importance is unclear, the antibody response to some pertussis antigens was decreased when MCV4 (Menveo^®), Tdap (Boostrix^®), and 4vHPV (Gardasil^®) were administered concurrently compared with Tdap (Boostrix^®) alone.220 Systemic adverse reactions were more frequent in those receiving all 3 vaccines concurrently compared with administration of MCV4 (Menveo^®) alone.220

Pneumococcal Vaccine

Pneumococcal 13-valent Conjugate Vaccine

DTaP may be administered concurrently with pneumococcal 13-valent conjugate vaccine (diphtheria CRM₁₉₇ protein) (PCV13; Prevnar^® 13) using different syringes and different injection sites.105,134

Pneumococcal 23-valent Vaccine

Concurrent administration of DTaP and pneumococcal vaccine, polyvalent (pneumococcal 23-valent vaccine; PPSV23; Pneumovax^® 23) does not increase the severity of adverse reactions or diminish the antibody responses to the vaccines.105 DTaP may be administered concurrently with PPSV23 (Pneumovax^® 23) using different syringes and different injection sites.105,134

Poliovirus Vaccine Inactivated

DTaP may be administered concurrently with IPV using different syringes and different injection sites.134,149,150 Alternatively, depending on the age and vaccination status of the child and if there are no contraindications to any of the individual components, a commercially available fixed-combination vaccine containing DTaP and IPV (DTaP-IPV; Kinrix^®, Quadracel^®),221,222,223 the fixed-combination vaccine containing DTaP, IPV, and hepatitis B virus antigens (DTaP-HepB-IPV; Pediarix^®),106 or the combination vaccine containing DTaP, IPV, and Hib antigens (DTaP-IPV/Hib; Pentacel^®)224 can be used instead of separate injections. (For information on Kinrix^® and Quadracel, see Poliovirus Vaccine Inactivated 80:12; for information on Pediarix^®, see Poliovirus Vaccine Inactivated 80:12 and see Hepatitis B Vaccine 80:12; for information on Pentacel^®, see Poliovirus Vaccine Inactivated 80:12 and see Haemophilus b Vaccine 80:12.)

Although data regarding the immunologic response are not available, IPV has been safely administered concurrently (at a separate site) with DTaP (Infanrix^®).182

Other Information ⬆ ⬇

[Section Outline]

Response to Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccines Adsorbed (DTaP)
Response to Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Tdap)
Chemistry
Stability

Pharmacology

Response to Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccines Adsorbed (DTaP)

Diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed (DTaP) stimulates active immunity to diphtheria, tetanus, and pertussis by inducing production of specific antitoxins and antibodies.182,187,192,193 A complete primary immunization series with the age-appropriate preparations is needed to induce optimum levels of antitoxin antibodies that provide protection.100,105,166,195,196,205

The diphtheria toxoid adsorbed component provides protection against the exotoxin elucidated by Corynebacterium diphtheriae .100,166 Primary immunization against diphtheria reduces the risk of developing diphtheria and the severity of clinical illness,100 but does not prevent or eliminate colonization or carriage of C. diphtheriae in the pharynx, nose, or skin of vaccinees.100 Protective levels of diphtheria antitoxin (defined as at least 0.1 international units/mL)166,195,196,205 are attained in at least 95% of individuals after the primary vaccination series.166 Following primary immunization, protective levels of diphtheria antitoxin levels may persist for about 10 years.166

Tetanus toxoid adsorbed induces production of specific antitoxin antibodies that neutralize exotoxin produced by Clostridium tetani .105 A complete primary series of a preparation containing tetanus toxoid adsorbed results in protective levels of tetanus antitoxin that persist for approximately 10 years.100,105,166,195,196,205 Protective levels of tetanus antitoxin were previously defined as at least 0.01 international units/mL when measured by in vivo neutralization assay,205 but are currently defined as at least 0.1 international units/mL when measured by enzyme-linked immunosorbent assay (ELISA) or other methods.195,196,205 Although some individuals may be protected against tetanus for life following primary immunization with a preparation containing tetanus toxoid adsorbed, antitoxin levels decrease over time and only approach the minimal protective level in most individuals 10 years after the last dose of tetanus toxoid adsorbed.166 The antitoxin response induced by tetanus toxoid adsorbed has a longer duration than that induced by tetanus toxoid fluid (no longer commercially available in the US).166

The acellular pertussis vaccine component includes several pertussis antigens and induces production of specific anti-pertussis antibodies; however, the mechanism of protection against the disease has not been fully determined.182,187,192,193 There is no accepted serologic or laboratory correlation of protection against pertussis.182,195,196 The duration of immunity following primary immunization against pertussis is estimated to be 5-10 years or longer, but protection wanes over time and vaccinated individuals may become susceptible to infection or reinfection.105,195,196,201,205 Residual immunity from previous infection or vaccination can lessen the severity of B. pertussis infection.205

Response to Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Tdap)

Adolescents and Adults 10 through 64 Years of Age

The immunologic response to a booster dose of Tdap (Adacel^®) has been evaluated in adolescents and adults 11 through 64 years of age who were randomized to receive a dose of Tdap or tetanus and diphtheria toxoids adsorbed (Td); participants had not received a preparation containing diphtheria or tetanus toxoid within the last 5 years.192 One month after the booster dose, antibody responses to the tetanus and diphtheria antigens in individuals who received Tdap were similar to that in individuals who received Td.192 In addition, the antibody response to the pertussis antigens in Tdap was similar to that reported in infants who receive a 3-dose primary immunization series of DTaP (Daptacel^®).192

The immunologic response to a booster dose of Tdap (Boostrix^®) has been evaluated in adolescents 10-18 years of age who were randomized to receive a dose of Tdap or Td; 98% had received the recommended series of 4 or 5 doses of DTaP and/or DTP (not commercially available in the US) in childhood.193 One month after the booster dose of Tdap, antibody responses to the tetanus and diphtheria antigens were similar in both groups and there also was an acceptable booster response to the pertussis antigens in Tdap (i.e., the response was similar to that reported in infants who receive a 3-dose primary immunization series of DTaP [Infanrix^®]).193 In adults 19 through 64 years of age who had not received a dose of a preparation containing diphtheria and tetanus toxoids adsorbed within the last 5 years, a single booster dose of Tdap (Boostrix^®) resulted in tetanus and diphtheria antitoxin levels 1 month after the dose that were seroprotective (i.e., at least 0.1 international units/mL) in 95.9 and 85.2% of patients, respectively.193 There also was an acceptable booster response to the pertussis antigens.193

Adults 65 Years of Age or Older

Based on prespecified criteria, administration of a dose of Tdap (Adacel^®) in adults 65 years of age or older† was associated with lower geometric mean antibody concentrations (GMCs) to the pertussis antigens (pertussis toxin, filamentous hemagglutinin, pertactin) compared with GMCs reported in infants who received a primary immunization series of DTaP (Daptacel^®).192

In a randomized study in adults 65 years of age or older who had not received a dose of Td within 5 years, immune responses to the tetanus and diphtheria antigens measured 1 month after a single dose of Tdap (Boostrix^®) were comparable to those attained in those who received a dose of Td.193 In addition, the GMCs to the pertussis antigens 1 month following a single dose of Tdap (Boostrix^®) in adults 65 years of age or older were noninferior to those reported in infants following a primary immunization series of DTaP (Infanrix^®).193

Chemistry and Stability

Chemistry

Diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed (DTaP) and tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed (Tdap) contain diphtheria and tetanus toxoids and a pertussis vaccine component that is prepared from inactivated acellular pertussis.111,166,182,183,192,193 In contrast to the many pertussis antigens present in the pertussis component of diphtheria and tetanus toxoids and whole-cell pertussis vaccine adsorbed (DTP, also referred to as DTwP; no longer commercially available in the US), only several biologically active components of B. pertussis are present in DTaP or Tdap.111,166,192,193 DTaP and Tdap, therefore, contain less endotoxin relative to DTP and, although immunogenic, are less reactogenic than DTP.111,112,150,192,193

Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (DTaP)

DTaP is a sterile suspension prepared by mixing suitable quantities of the two toxoids and acellular pertussis vaccine that have been adsorbed onto an aluminum adjuvant.182,187 There are 2 different DTaP preparations commercially available in the US.182,187 These preparations contain similar diphtheria and tetanus toxoids but slightly different acellular pertussis vaccine components.182,187 DTaP (Daptacel^®) contains 5 distinct acellular antigens derived from B. pertussis ;187 DTaP (Infanrix^®) contains 3 distinct acellular antigens derived from B. pertussis .182

DTaP (Daptacel®)

DTaP (Daptacel^®) contains diphtheria and tetanus toxoids prepared from toxins that are detoxified with formalin and purified by ammonium sulfate fractionation and diafiltration.187 The acellular pertussis vaccine component of DTaP (Daptacel^®) contains 5 acellular pertussis antigens isolated from B. pertussis grown in modified Stainer-Scholte liquid media.187 The fimbriae types 2 and 3 are extracted from the bacterial cells and the pertussis toxin (PT), filamentous hemagglutinin (FHA), and pertactin (PRN) are prepared from the supernatant.187 The pertussis antigens are then purified using sequential filtration, salt-precipitation, ultrafiltration and chromatography.187 PT is detoxified with glutaraldehyde and FHA is treated with formaldehyde.187 Potency of the pertussis component is evaluated by measurement of the antibody response to PT, FHA, PRN, and fimbriae types 2 and 3 in immunized mice using ELISA; the diphtheria and tetanus toxoids are measured in a guinea pig potency test.187 The diphtheria, tetanus, and pertussis antigens are individually adsorbed onto aluminum phosphate.187

After shaking, DTaP (Daptacel^®) occurs as a homogeneous, white, cloudy suspension.187 Each 0.5 mL of DTaP (Daptacel^®) contains 15 Lf units of diphtheria toxoid, 5 Lf units of tetanus toxoid, 23 mcg of pertussis antigens (10 mcg of detoxified PT, 5 mcg of FHA, 3 mcg of PRN, 5 mcg of fimbriae types 2 and 3) and 1.5 mg of aluminum phosphate adjuvant (0.33 mg of aluminum).187 Each 0.5 mL also contains not more than 5 mcg of residual formaldehyde, less than 0.05 mcg of residual glutaraldehyde, and 3.3 mg of 2-phenoxyethanol (not as a preservative).187 DTaP (Daptacel^®) does not contain thimerosal.187

DTaP (Infanrix®)

DTaP (Infanrix^®) contains diphtheria and tetanus toxoids that are concentrated by ultrafiltration, purified by precipitation, sterile filtration, and dialysis, and detoxified using formaldehyde.182 Any bovine materials used in preparation of the diphtheria and tetanus toxoids are obtained from countries which the US Department of Agriculture (USDA) has determined do not have and are not at risk of bovine spongiform encephalopathy (BSE).182 The acellular pertussis vaccine component of Infanrix^® contains 3 acellular pertussis antigens isolated from B. pertussis grown in modified Stainer-Scholte liquid media.182 PT and FHA are extracted from the fermentation broth and PRN is extracted by heat treatment and flocculation.182 The pertussis antigens are then purified using successive chromatography steps.182 PT is detoxified using formaldehyde and glutaraldehyde; FHA and PRN are treated with formaldehyde.182 Potency of the pertussis component is evaluated by measurement of the antibody response to PT, FHA, and PRN in immunized mice using ELISA.182 The diphtheria, tetanus, and pertussis antigens are individually adsorbed onto aluminum hydroxide.182

After shaking, DTaP (Infanrix^®) occurs as a homogeneous, turbid, white suspension.182 Each 0.5 mL of DTaP (Infanrix^®) contains 25 Lf units of diphtheria toxoid, 10 Lf units of tetanus toxoid, and 58 mcg of pertussis antigens (25 mcg of inactivated PT, 25 mcg of FHA, 8 mcg of PRN) and aluminum hydroxide adjuvant (not more than 0.625 mg of aluminum).182 Each 0.5 mL also contains 4.5 mg sodium chloride, not more than 100 mcg of residual formaldehyde, and not more than 100 mcg of polysorbate 80.182 Infanrix^® does not contain thimerosal or any other preservatives.182

Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Tdap)

Tdap is a sterile suspension prepared by mixing suitable quantities of tetanus toxoid, diphtheria toxoid, and acellular pertussis vaccine that have been adsorbed onto an aluminum adjuvant.192,193 Tdap contains a lower content of diphtheria and pertussis antigens than that contained in DTaP.192,193,201 There are 2 different Tdap preparations commercially available in the US: Adacel^® and Boostrix^®.192,193,201

Tdap (Adacel®)

Tdap (Adacel^®) contains the same tetanus toxoid, diphtheria toxoid, and acellular pertussis antigens as DTaP (Daptacel^®); however, Adacel^® contains a lower content of the diphtheria and pertussis antigens compared with Daptacel^®.192,201

After shaking, Tdap (Adacel^®) occurs as a homogeneous white cloudy suspension.192 Each 0.5 mL of Tdap (Adacel^®) contains 5 Lf units of tetanus toxoid, 2 Lf units of diphtheria toxoid, 15.5 mcg of pertussis antigens (2.5 mcg of detoxified PT, 5 mcg of FHA, 3 mcg of PRN, 5 mcg of fimbriae types 2 and 3) and 1.5 mg of aluminum phosphate adjuvant (0.33 mg of aluminum).192 Each 0.5 mL also contains not more than 5 mcg of residual formaldehyde, less than 0.05 mcg of residual glutaraldehyde, and 3.3 mg of 2-phenoxyethanol (not as a preservative).192 Tdap (Adacel^®) does not contain thimerosal or any other preservatives.192

Tdap (Boostrix®)

Tdap (Boostrix^®) contains the same tetanus toxoid, diphtheria toxoid, and acellular pertussis antigens as DTaP (Infanrix^®); however, Boostrix^® contains a lower content of all 3 antigens compared with Infanrix^®.193,201

After shaking, Tdap (Boostrix^®) occurs as a homogeneous white turbid suspension.193 Each 0.5 mL of Tdap (Boostrix^®) contains 5 Lf units of tetanus toxoid, 2.5 Lf units of diphtheria toxoid, 18.5 mcg of pertussis antigens (8 mcg of detoxified PT, 8 mcg of FHA, 2.5 mcg of PRN) and aluminum hydroxide adjuvant (not more than 0.39 mg of aluminum). Each 0.5 mL also contains 4.5 mg of sodium chloride, not more than 100 mcg of residual formaldehyde, and not more than 100 mcg of polysorbate 80.193 Tdap (Boostrix^®) does not contain thimerosal or any other preservatives.193

Stability

DTaP (Daptacel^®187 , Infanrix^®)182 and Tdap (Adacel^®192 , Boostrix^®)193 should be stored at 2-8°C and should not be frozen. Any DTaP or Tdap vaccine that has been frozen should be discarded.182,187,192,193

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations ⬆ ⬇

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (DTaP)

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injectable suspension, for IM use	Diphtheria Toxoid 15 Lf units, Tetanus Toxoid 5 Lf units, and Acellular Pertussis Vaccine 23 mcg (of pertussis antigens) per 0.5 mL	Daptacel^®	Sanofi Pasteur
		Diphtheria Toxoid 25 Lf units, Tetanus Toxoid 10 Lf units, and Acellular Pertussis Vaccine 58 mcg (of pertussis antigens) per 0.5 mL	Infanrix^®	GlaxoSmithKline

Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Tdap)

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injectable suspension, for IM use	Tetanus Toxoid 5 Lf units, Diphtheria Toxoid 2 Lf units, and Acellular Pertussis Vaccine 15.5 mcg (of pertussis antigens) per 0.5 mL	Adacel^®	Sanofi Pasteur
		Tetanus Toxoid 5 Lf units, Diphtheria Toxoid 2.5 Lf units, and Acellular Pertussis Vaccine 18.5 mcg (of pertussis antigens) per 0.5 mL	Boostrix^®	GlaxoSmithKline

Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed and Inactivated Poliovirus Vaccine (DTaP-IPV)

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection, for IM use	Diphtheria Toxoid 15 Lf units, Tetanus Toxoid 5 Lf units, Acellular Pertussis Vaccine 48 mcg (of pertussis antigen) and Poliovirus Type 1 40 DU, Poliovirus Type 2 8 DU, and Poliovirus Type 3 32 DU per 0.5 mL	Quadracel^®	Sanofi Pasteur
		Diphtheria Toxoid 25 Lf units, Tetanus Toxoid 10 Lf units, Acellular Pertussis Vaccine 58 mcg (of pertussis antigen) and Poliovirus Type 1 40 DU, Poliovirus Type 2 8 DU, and Poliovirus Type 3 32 DU per 0.5 mL	Kinrix^®	GlaxoSmithKline

Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Hepatitis B (Recombinant) and Inactivated Poliovirus Vaccine Combined (DTaP-HepB-IPV)

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injectable suspension, for IM use	Diphtheria Toxoid 25 Lf units, Tetanus Toxoid 10 Lf units, Acellular Pertussis Vaccine 58 mcg (of pertussis antigen), Hepatitis B Surface Antigen 10 mcg, Poliovirus Type 1 40 DU, Poliovirus Type 2 8 DU, and Poliovirus Type 3 32 DU per 0.5 mL	Pediarix^®	GlaxoSmithKline

Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate (Tetanus Toxoid Conjugate) Vaccine (DTaP-IPV/Hib)

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Kit, for IM use	Injection, for IM use, Diphtheria Toxoid 15 Lf units, Tetanus Toxoid 5 Lf units, Acellular Pertussis Vaccine 48 mcg (of pertussis antigen), Poliovirus Type 1 40 DU, Poliovirus Type 2 8 DU, and Poliovirus Type 3 32 DU per 0.5 mL For injectable suspension, for IM use, Haemophilus b Polysaccharide 10 mcg, Tetanus Toxoid 24 mcg per 0.5 mL, ActHIB^®	Pentacel^®	Sanofi Pasteur

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Kit, for IM use

Injection, for IM use, Diphtheria Toxoid 15 Lf units, Tetanus Toxoid 5 Lf units, Acellular Pertussis Vaccine 48 mcg (of pertussis antigen), Poliovirus Type 1 40 DU, Poliovirus Type 2 8 DU, and Poliovirus Type 3 32 DU per 0.5 mL

For injectable suspension, for IM use, Haemophilus b Polysaccharide 10 mcg, Tetanus Toxoid 24 mcg per 0.5 mL, ActHIB^®

Pentacel^®

Sanofi Pasteur

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References ⬆

Only references cited for selected revisions after 1984 are available electronically.

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105. American Academy of Pediatrics. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012.

106. GlaxoSmithKline. Pediarix^® (diphtheria and tetanus toxoids and acellular pertussis adsorbed, hepatitis B [recombinant] and inactivated poliovirus vaccine combined) suspension for intramuscular injection prescribing information. Research Triangle Park, NC; 2013 Nov.

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155. Panel on Opportunistic Infections in HIV-infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America (May 7, 2013). Updates may be available at HHS AIDS Information (AIDSinfo) website. [Web]

156. Panel on Opportunistic Infections in HIV-exposed and HIV-infected children, US Department of Health and Human Services (HHS). Guidelines for the prevention and treatment of opportunistic infections in HIV-exposed and HIV-infected children: recommendations from the National Institutes of Health, Centers for Disease Control and Prevention, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics (Nov 6, 2013). Updates may be available at HHS AIDS Information (AIDSinfo) website. [Web]

159. Centers for Disease Control and Prevention. Recommendations for use of Haemophilus b conjugate vaccines and a combined diphtheria, tetanus, pertussis, and Haemophilus b vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep . 1993; 42(No. RR-13):1-15. [PubMed 8418395][Fulltext MMWR]

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section name header

Introduction ⬇

AHFS Class:

Generic Name(s):

Uses ⬆ ⬇

Dosage and Administration ⬆ ⬇

Cautions ⬆ ⬇

Drug Interactions ⬆ ⬇

Other Information ⬆ ⬇

Preparations ⬆ ⬇

Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (DTaP)

Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Tdap)

Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed and Inactivated Poliovirus Vaccine (DTaP-IPV)

Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Hepatitis B (Recombinant) and Inactivated Poliovirus Vaccine Combined (DTaP-HepB-IPV)

Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate (Tetanus Toxoid Conjugate) Vaccine (DTaP-IPV/Hib)

Copyright ⬆ ⬇

References ⬆