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

Drug class: Toxoids
ATC class: J07AM01
VA class: IM105

Medically reviewed by Drugs.com on Nov 29, 2023. Written by ASHP.

Introduction

Fixed-combination preparations containing tetanus and diphtheria toxins (toxoids) and acellular pertussis vaccine adsorbed onto aluminum adjuvant.^{182 187 192 193} Used to stimulate active immunity to diphtheria, tetanus, and pertussis.^{100 182 187 192 193 195 196 205} Commercially available as diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed (DTaP; Daptacel, Infanrix)^{182 187} and tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed (Tdap; Adacel, Boostrix).^{192 193} Antigen potency varies depending on manufacturer.^{182 187 192 193} DTaP also commercially available in fixed-combination vaccines containing diphtheria, tetanus, pertussis, and poliovirus antigens (DTaP-IPV; Kinrix, Quadracel),^{221 223} fixed-combination vaccine containing diphtheria, tetanus, pertussis, hepatitis B, and poliovirus antigens (DTaP-HepB-IPV; Pediarix),¹⁰⁶ and combination vaccine containing diphtheria, tetanus, pertussis, poliovirus, and Hib antigens (DTaP-IPV/Hib; Pentacel).²²⁴ Although no longer available in US, diphtheria and tetanus toxoids and whole-cell pertussis vaccine adsorbed (DTP, also referred to as DTwP) may still be used in other countries.^{105 166}

Uses for Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed

Prevention of Diphtheria, Tetanus, and Pertussis

DTaP (Daptacel, Infanrix): Prevention of diphtheria, tetanus, and pertussis in infants and children 6 weeks through 6 years of age.^{105 182 187 199}

Tdap: Labeled by FDA for booster immunization against diphtheria, tetanus, and pertussis in adults and adolescents 10 through 64 years of age (Adacel) or adults and adolescents ≥10 years of age (Boostrix).^{192 193} Also recommended for use in children 7 through 10 years of age^{† [off-label]}.^{105 199}

Diphtheria is caused by toxigenic strains of Corynebacterium diphtheriae or, rarely, C. ulcerans.^{100 105 115 166 195 196 205 228} Overall case-fatality rate is 5–10%; higher death rates (up to 20%) among individuals <5 years of age and >40 years of age.¹⁶⁶ Diphtheria uncommon in US, but C. diphtheriae continues to circulate in US areas where the disease previously was endemic.^{100 105 166 228} Reported worldwide, particularly in tropical countries;¹⁶⁶ endemic in many countries in Asia, the South Pacific, the Middle East, and Eastern Europe and in Haiti and Dominican Republic.¹¹⁵ Consult CDC Travelers' Health website ([Web]) for information regarding where diphtheria is endemic.¹¹⁵ During the 1920s (before widespread immunization against diphtheria was initiated), there were approximately 100,000–200,000 cases of diphtheria and 13,000–15,000 diphtheria-related deaths each year in US.¹⁶⁶ Most diphtheria cases occur in individuals unvaccinated or incompletely vaccinated against diphtheria.^{100 105 115 166}

Tetanus is a potentially fatal disease caused by a neurotoxic exotoxin (tetanospasmin) produced by Clostridium tetani.^{105 115 166} C. tetani spores are ubiquitous in the environment worldwide; found in soil and in intestinal tracts of humans and animals (e.g., horses, sheep, cattle, dogs, cats, rats, guinea pigs, chickens).^{100 105 115 166 195} The spores can contaminate open wounds, especially puncture wounds or those with devitalized tissue; anaerobic wound conditions allow spores to germinate and produce exotoxins that disseminate through blood and lymphatic system.^{105 166 195} Neonatal tetanus (tetanus neonatorum) occurs in infants born under nonsterile conditions to inadequately vaccinated women; infection usually involves a contaminated umbilical stump and occurs because infant does not have passively acquired maternal antibodies against tetanus.^{100 105 166 195 205} Obstetric tetanus occurs within 6 weeks after delivery or termination of pregnancy because of contaminated wounds or abrasions or unclean deliveries or abortions.²⁰⁵ Generalized tetanus is characterized by rigidity and convulsive muscle spasms that usually involve the jaw (lockjaw) and neck and then become generalized.^{100 166 195} Tetanus occurs worldwide;^{115 166} reported most frequently in densely populated regions in hot, damp climates with soil rich in organic matter.¹⁶⁶ Marked decrease in mortality from tetanus occurred in US from the early 1900s to the late 1940s when immunization against tetanus became part of routine childhood immunization.¹⁶⁶ Average of 29 cases reported each year in US from 2001 through 2008 (case fatality rate 13%).¹⁶⁶ Most US cases occur following an acute wound, usually a puncture or contaminated, infected, or devitalized wound.¹⁶⁶ Almost all reported cases occur in individuals unvaccinated or inadequately vaccinated against the disease.^{105 115 166}

Pertussis (whooping cough) is an acute respiratory tract infection caused by Bordetella pertussis.^{105 115 166 197 201 205} Risk for severe pertussis and death highest among infants <1 year of age (especially those younger than 6 months of age).^{105 166 205} More than 1 million pertussis cases reported in US from 1940 through 1945 (average of 175,000 cases per year);¹⁶⁶ incidence gradually declined in US after introduction of pertussis vaccine.¹⁶⁶ Although average number of cases reported per year in US during 1980–1990 was 2900,¹⁶⁶ pertussis incidence has been gradually increasing since early 1980s.¹⁶⁶ During 2010, 27,550 pertussis cases and 27 pertussis-related deaths reported in US.^{105 166} B. pertussis infection in adults and adolescents may be asymptomatic or range from mild to severe.^{166 205} 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}

USPHS Advisory Committee on Immunization Practices (ACIP), AAP, and others recommend routine primary and booster immunization against diphtheria, tetanus, and pertussis in all individuals ≥6 weeks of age.^{105 199 200}

Combination preparation containing antigens for all 3 diseases (DTaP) preferred preparation for primary and booster immunization against these diseases in infants and children 6 weeks through 6 years of age, unless a component is contraindicated or should not be used.^{100 105 166 199}

ACIP, AAP, and others recommend that all adolescents who received primary immunization with DTaP, DTP (not commercially available in US), diphtheria and tetanus toxoids adsorbed (DT), or tetanus and diphtheria toxoids adsorbed (Td) receive a routine booster dose of Tdap (instead of Td) at 11 through 18 years of age (preferably at 11–12 years of age).^{105 195 199 201 236} If Tdap is unavailable or was administered previously, use Td for this adolescent booster dose.^{195 199 201}

Td usually preparation of choice for primary and booster immunization against diphtheria and tetanus in individuals ≥7 years of age.^{100 105 196 199 200 205} However, to reduce morbidity associated with pertussis, ACIP, AAP, and others recommend that a single dose of Tdap be used in place of a required primary or booster dose of Td in all adults, adolescents, and children 7 through 10 years of age^{† [off-label]} who have not previously received Tdap, unless pertussis antigens contraindicated or should not be used.^{105 195 196 199 200 235 236} Use Td for all subsequent primary or booster doses.^{105 195 196 199 200 236}

ACIP recommends that all adults ≥65 years of age or older who have not previously received a dose of Tdap receive a single dose of Tdap, regardless of interval since last dose of vaccine containing tetanus or diphtheria toxoids.²³⁷ Use Td for all subsequent booster doses.²³⁷

To ensure protection against pertussis, ACIP and others recommend that pregnant women receive a single dose of Tdap during each pregnancy (optimally between 27 and 36 weeks of gestation), regardless of prior vaccination history.^{200 238} (See Preexposure Vaccination Against Tetanus, Diphtheria, and Pertussis in High-risk Groups under Uses.)

DTaP-IPV (Kinrix): Can be used in children 4 through 6 years of age to provide fifth dose of DTaP vaccination series and fourth dose of IPV vaccination series in those receiving primary immunization with Infanrix (DTaP) and/or Pediarix (DTaP-HepB-IPV) when there are no contraindications to any of the individual components.²²³

DTaP-IPV (Quadracel): Can be used in children 4 through 6 years of age to provide fifth dose of DTaP vaccination series and fourth or fifth dose of IPV vaccination series in those receiving primary immunization with Pentacel (DTaP-IPV/Hib) and/or Daptacel (DTaP).^{221 222}

DTaP-HepB-IPV (Pediarix): Can be used as 3-dose primary series in infants and children 6 weeks through 6 years of age born to HBsAg-negative women when doses of DTaP, HepB, and IPV are indicated and there are no contraindications to any of the individual components.^{106 208} ACIP states also may be used to complete HBV vaccination series in infants 6 months through 6 years of age born to HBsAg-positive women^{† [off-label]}.²⁰⁸ Should not be used for initial HepB dose indicated in neonates.¹⁰⁵ For prevention of diphtheria, tetanus, and pertussis in infants and children 6 weeks through 6 years of age, may be used for initial 3 doses in DTaP series.^{105 106} Also may be used to complete first 3 doses of DTaP series in children who received 1 or 2 doses of Infanrix DTaP;¹⁰⁶ data not available regarding safety and efficacy of Pediarix used following ≥1 dose of DTaP vaccine from a different manufacturer.¹⁰⁶ Children who receive 3-dose series of Pediarix should complete DTaP and IPV series according to recommended childhood immunization schedule.^{105 106} To complete DTaP series, manufacturer recommends use of Infanrix for fourth dose of DTaP and either Infanrix DTaP or DTaP-IPV (Kinrix) for fifth dose of DTaP (these vaccines contain same pertussis antigens as Pediarix).¹⁰⁶

DTaP-IPV/Hib (Pentacel): Can be used as 4-dose series 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.^{105 224} To complete DTaP series, children who receive 4-dose series of Pentacel at 2, 4, 6, and 15 through 18 months of age should receive a dose of Daptacel at 4 through 6 years of age to provide fifth dose of DTaP.²²⁴ Pentacel also may be used in infants and children 6 weeks through 4 years of age who received ≥1 doses of Daptacel DTaP.²²⁴ Data not available on safety and immunogenicity of mixed sequences of Pentacel and Daptacel for successive doses in DTaP series or mixed sequences of Pentacel and DTaP from other manufacturers.²²⁴

Combined active immunization with a preparation containing tetanus toxoid adsorbed (Td, DT, DTaP, Tdap) and passive immunization with tetanus immune globulin (TIG) is used for postexposure prophylaxis in individuals with tetanus-prone wounds who are inadequately immunized against tetanus or whose tetanus immunization history is uncertain.^{100 105 166 195 196 201} (See Postexposure Prophylaxis of Tetanus under Uses.)

DTaP and Tdap not indicated for treatment of diphtheria, tetanus, or pertussis.^{105 166 192 201}

Because diphtheria and tetanus infections may not confer immunity against the diseases, initiate or complete primary immunization against diphtheria and tetanus at time of recovery in any previously unvaccinated or incompletely vaccinated individual.^{100 105 166 201} Although pertussis is likely to confer short-term immunity against the disease, protection wanes over time (beginning as early as 5–7 years after infection); initiate or complete immunization against pertussis at time of recovery.^{105 166 195 196 201 205}

Preexposure Vaccination Against Tetanus, Diphtheria, and Pertussis in High-risk Groups

Pregnant women should be adequately immunized against tetanus, diphtheria, and pertussis; protection is conferred to infants through transplacental transfer of maternal antibody.^{100 105 195 205 238}

Ideally, complete primary immunization and administer appropriate booster doses prior to pregnancy.^{100 105 195 205} To ensure protection against tetanus (especially against maternal and neonatal tetanus), primary immunization or booster doses of Td can be given during second or third trimester of pregnancy (and before 36 weeks of gestation).^{100 105 195}

For previously unvaccinated or incompletely vaccinated pregnant women, ACIP and others recommend that a dose of Tdap be substituted for a required Td dose, preferably during third trimester (optimally between 27 and 36 weeks of gestation).^{200 238} In addition, to ensure protection against pertussis, these experts recommend give a dose of Tdap during each pregnancy, regardless of prior vaccination history.^{200 238} (See Pregnancy under Cautions.)

Infants <12 months of age are at increased risk for pertussis (too young to be fully protected by initial DTaP doses given in early infancy).^{105 234 236} To reduce likelihood of pertussis transmission to such infants, ACIP and AAP recommend that adolescents and adults who have or anticipate having close contact with an infant <12 months of age (e.g., parents, siblings, grandparents, childcare providers, health-care personnel) receive a single dose of Tdap if they have not previously received a dose.^{105 234 236} Give Tdap dose at least 2 weeks before close contact with infant,^{105 234} regardless of interval since last Td dose.^{105 236}

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 A single dose of Tdap also recommended for all health-care personnel (regardless of age) if they have not previously received a dose.²³⁵

For health-care personnel without documentation of primary immunization, give 3-dose vaccination series using Tdap for first dose and Td for subsequent primary and booster doses.²³⁵ For previously vaccinated health-care personnel who have not received Tdap, give a single dose of Tdap as soon as feasible, regardless of interval since last Td dose;²³⁵ use Td for subsequent booster doses.²³⁵

Travelers who are unvaccinated or incompletely vaccinated against diphtheria, tetanus, and pertussis should receive remaining recommended doses prior to travel.¹¹⁵

Because tetanus, diphtheria, and pertussis occur worldwide,¹¹⁵ CDC recommends that travelers be adequately immunized against all 3 diseases before leaving US.¹¹⁵

Adults, adolescents, and children 7 through 10 years of age who are unvaccinated or incompletely vaccinated should receive a single dose of Tdap followed by remaining recommended doses of Td according to usual age-appropriate catch-up vaccination schedule.¹¹⁵ Adults and adolescents ≥11 years of age who were previously vaccinated but have not received Tdap should receive a single dose of Tdap (instead of Td) for booster dose.¹¹⁵ When indicated to provide protection against pertussis before travel, Tdap may be administered regardless of interval since last Td dose.¹¹⁵

If necessary to complete vaccination series before departure, adults, adolescents, and children can receive an accelerated immunization schedule using age-appropriate minimum intervals between doses.¹¹⁵ (See Dosage under Dosage and Administration.)

Postexposure Prophylaxis of Diphtheria

Postexposure vaccination in household and other close contacts of an individual with culture-confirmed or suspected diphtheria.^{100 105 166}

Regardless of vaccination status, all household and other close contacts of an individual with culture-confirmed or suspected diphtheria should 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} Take samples for cultures prior to giving the anti-infective and continue to observe individual for 7 days for evidence of disease.^{100 166 228}

In addition, those who previously received <3 doses of a diphtheria toxoid-containing preparation or whose vaccination status is unknown 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} Contacts who previously completed primary vaccination series should receive an immediate booster dose of age-appropriate preparation containing diphtheria toxoid adsorbed if it has been ≥5 years since last booster dose.^{100 105 166}

Diphtheria antitoxin (equine) (available in US only from 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} To obtain diphtheria antitoxin (equine), contact CDC at 404-639-8257 from 8:00 a.m. to 4:30 p.m. EST Monday–Friday or CDC Emergency Operations Center at 770-488-7100 after hours, on weekends, and holidays.^{166 204 228}

Postexposure Prophylaxis of Tetanus

Postexposure prophylaxis of tetanus in individuals with tetanus-prone wounds who previously received <3 doses of a preparation containing tetanus toxoid adsorbed or whose tetanus vaccination status is uncertain.^{100 105 166 195 196 201 205}

Postexposure prophylaxis of tetanus involves active immunization with a tetanus toxoid-containing preparation with or without passive immunization with a dose of tetanus immune globulin (TIG).^{100 105 166 195 196 201 205}

Tetanus-prone wounds include (but are not limited to) wounds contaminated with dirt, feces, soil, or saliva; deep wounds; burns; crush injuries; and wounds containing devitalized or necrotic tissue.^{100 105 166} Tetanus also has been associated with apparently clean, superficial wounds, surgical procedures, insect bites, animal bites, dental infections, compound fractures, chronic sores and infections, and IV drug abuse.^{115 166}

In the event of injury and possible exposure to tetanus, the need for active immunization against tetanus with or without passive immunization with TIG depends on the individual’s vaccination status and the likelihood of contamination with tetanus bacilli (e.g., condition of wound, source of contamination).^{100 105 195 196 205}

Table 1 summarizes ACIP guidelines for active and passive immunization against tetanus in routine wound management.

A dose of Tdap preferred instead of a dose of Td in adults and adolescents ≥11 years of age who have not previously received a dose of Tdap. Use Td in individuals in this age group who previously received a dose of Tdap. Use Td in individuals in this age group who previously received a dose of Tdap.

Td used in adults, adolescents, and children ≥7 years of age. For children 6 weeks through 6 years of age, DTaP usually indicated, but DT can be used if pertussis antigens contraindicated. Single-antigen tetanus toxoid adsorbed not commercially available in US.

If only 3 doses of tetanus toxoid fluid (no longer commercially available in US) have been received previously, give a fourth dose as a preparation containing tetanus toxoid adsorbed.

Yes, if it has been >10 years since last dose of tetanus toxoid-containing preparation.

Yes, if it has been >5 years since last dose of tetanus toxoid-containing preparation; more frequent booster doses not needed and can accentuate adverse effects.

Adapted from the Recommendations of the Immunization Practices Advisory Committee (ACIP) on prevention of diphtheria, tetanus, and pertussis published in MMWR Recomm Rep. 2006; 55(RR-3):1-43 and MMWR Recomm Rep. 2006; 55(RR-17):1-37.

Any individual whose tetanus vaccination status is unknown or uncertain should be considered to have had no previous doses of tetanus toxoid adsorbed.^{100 195 196 205}

ACIP and others recommend that a single dose of Tdap be used in place of a dose of Td for postexposure prophylaxis in individuals ≥11 years of age (including those ≥65 years of age) who have not previously received a dose of Tdap.^{195 196 199 201 205 237} Those who previously received Tdap should receive Td for postexposure prophylaxis.^{195 196 199 201 205}

Anti-infectives not indicated for tetanus postexposure prophylaxis since they do not neutralize exotoxin already formed and cannot eradicate C. tetani spores, which may revert to toxin-producing vegetative forms.^{100 166}

Postexposure Prophylaxis of Pertussis

Postexposure vaccination in household and other close contacts of an individual with pertussis.^{100 105 195 196 201}

Regardless of vaccination status or age, all household and other close contacts of an individual with suspected pertussis should 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 <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 DTaP dose ≥6 months before the exposure should receive a fourth dose.¹⁰⁵

ACIP and AAP recommend a single dose of Tdap in all adults, adolescents, and children ≥7 years of age who have not previously received a dose and are 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);^{105 195 196 201} this includes children 7 through 10 years of age^{† [off-label]} who did not complete DTaP vaccination series.¹⁰⁵

Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed Dosage and Administration

Administration

IM Administration

DTaP (Daptacel, Infanrix): Administer by IM injection.^{182 187}

Tdap (Adacel, Boostrix): Administer by IM injection.^{192 193}

DTaP-IPV (Kinrix, Quadracel), DTaP-HepB-IPV (Pediarix), DTaP-IPV/Hib (Pentacel): Administer by IM injection.^{106 221 223 224}

Do not administer DTaP, Tdap, or combination vaccines containing DTaP and other antigens IV, intradermally, or sub-Q.^{182 187 192 193 106 223 224}

To ensure delivery into muscle, make IM injections 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 injection site, and injection technique.¹³⁴

Depending on patient age, administer IM into anterolateral muscles of thigh or deltoid muscle.^{134 182 187} In infants and children 6 weeks through 2 years of age, anterolateral thigh is preferred;^{134 187} alternatively, deltoid muscle can be used in those 1 through 2 years of age if muscle mass is adequate.¹³⁴ In adults, adolescents, and children ≥3 years of age, deltoid muscle preferred.^{134 192 193 221}

Avoid administering into gluteal area or areas where there may be a major nerve trunk.^{134 182 192} If gluteal muscle is chosen for infants <12 months of age because of special circumstances (e.g., physical obstruction of other sites), it is essential that clinician identify anatomical landmarks prior to injection.¹³⁴

Syncope (vasovagal or vasodepressor reaction; fainting) may occur following vaccination;^{106 134 182 187 192 193 205 223} may be accompanied by transient neurologic signs (e.g., visual disturbance, paresthesia, tonic-clonic limb movements).^{106 182 193 223} Occurs most frequently in adolescents and young adults.^{134 205} Have procedures in place to avoid falling injury and 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, observe patient until symptoms resolve.^{134 205}

When passive immunization with 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} (See Postexposure Prophylaxis of Tetanus under Uses.)

May be given simultaneously with other age-appropriate vaccines.^{100 105 134 192 195 196 199 201} (See Interactions.)

When multiple vaccines are administered during a single health-care visit, give each parenteral vaccine with a different syringe and at different injection sites.¹³⁴ Separate injection sites by at least 1 inch (if anatomically feasible) to allow appropriate attribution of any local adverse effects that may occur.¹³⁴

DTaP (Daptacel, Infanrix)

Do not mix with any other vaccine.^{182 187}

Shake vial or prefilled syringe well immediately prior to use.^{182 187} Should appear as a uniform, turbid, white suspension after shaking;^{182 187} discard if it contains particulate matter, is discolored, or cannot be resuspended.^{182 187}

Tdap (Adacel, Boostrix)

Do not mix with any other vaccine.^{192 193}

Shake vial or prefilled syringe well immediately prior to use.^{192 193} Should appear as a uniform, turbid, white suspension after shaking;^{192 193} discard if it contains particulate matter, is discolored, or cannot be resuspended.^{192 193}

DTaP-IPV (Kinrix)

Do not mix with any other vaccine.²²³

Shake vial or prefilled syringe vigorously immediately prior to use.²²³ Should appear as a uniform, turbid, white suspension after shaking;²²³ discard if it contains particulate matter, is discolored, or cannot be resuspended.²²³

DTaP-IPV (Quadracel)

Do not mix with any other vaccine.²²¹

Shake single-dose vial well immediately prior to use.²²¹ Should appear as a uniform, white, cloudy suspension after shaking;²²¹ discard if it contains particulate matter, is discolored, or cannot be resuspended.²²¹

DTaP-HepB-IPV (Pediarix)

Do not mix with any other vaccine.¹⁰⁶

Shake prefilled syringe vigorously immediately prior to use.¹⁰⁶ Should appear as a uniform, turbid, white suspension after shaking;¹⁰⁶ discard if it contains particulate matter, is discolored, or cannot be resuspended.¹⁰⁶

DTaP-IPV/Hib (Pentacel)

Commercially available as kit containing single-dose vials of fixed-combination vaccine containing diphtheria, tetanus, pertussis, and poliovirus antigens (DTaP-IPV vaccine) and single-dose vials of lyophilized Hib vaccine (ActHIB).²²⁴

Prior to administration, reconstitute single-dose vial of lyophilized ActHIB vaccine by adding entire contents of single-dose vial of DTaP-IPV vaccine according to manufacturer’s instructions to provide a combined preparation containing diphtheria, tetanus, pertussis, poliovirus, and Hib antigens.²²⁴ Gently swirl until a cloudy, uniform white to off-white (yellow tinge) suspension is obtained.²²⁴

Administer immediately after reconstitution.²²⁴

Do not mix any component of DTaP-IPV/Hib (Pentacel) with any other vaccine or solution.²²⁴

Dosage

Dosing schedule (i.e., number of doses) and specific preparation for primary and/or booster immunization (i.e., DTaP, Tdap, combination vaccine containing DTaP) varies depending on age.^{106 182 187 192 193 199 200 221 223 224} Follow age-appropriate recommendations for specific preparation used.^{106 182 187 192 193 199 200 221 223 224}

Limited data available regarding interchangeability of different DTaP vaccines in primary or booster vaccination series.^{105 127 134 149 183 190} Although ACIP recommends that same DTaP preparation used for initial dose be used to complete primary and booster vaccination series whenever possible,^{127 134 149 183 222} any available age-appropriate DTaP vaccine should be used to complete the series if particular DTaP vaccine used previously is not known or not available.^{105 127 134 149 166 183 222}

To ensure optimal protection, give complete primary vaccination series and recommended booster doses.^{100 166 192 193 199} Interruptions resulting in an interval between doses longer than recommended should not interfere with final immunity achieved; there is no need to give additional doses or start vaccination series over.^{100 166 192 193 199}

Pediatric Patients

Prevention of Diphtheria, Tetanus, and Pertussis

Infants and Children 6 Weeks Through 6 Years of Age (DTaP; Daptacel, Infanrix)

IM

Each dose is 0.5 mL.^{182 187}

Primary immunization consists of a series of 3 primary doses and 1 or 2 booster doses.^{105 182 187 199}

ACIP, AAP, and others recommend that first 4 doses be administered at 2, 4, 6, and 15 through 18 months of age.^{105 199} Fourth (booster) dose may be given as early as 12 months of age, provided at least 6 months have elapsed since the third dose.^{105 199}

At 4 through 6 years of age (usually just prior to entry into kindergarten or elementary school), give fifth (booster) dose to those who received fourth dose of the series at <4 years of age.^{105 182 187 199} Fifth dose not necessary if fourth dose was given at ≥4 years of age.^{105 199}

If pertussis is prevalent in the community or preexposure immunization is required prior to travel, may initiate vaccination series as early as 6 weeks of age and use minimum interval of 4 weeks between first 3 doses.¹⁰⁵

If accelerated schedule needed (e.g., for catch-up or prior to travel), give a dose at first visit (minimum 6 weeks of age); give second and third doses at 4-week intervals (minimum interval) after first dose and give fourth and fifth dose at 6-month intervals (minimum interval) after third dose.^{105 199} Fifth dose not necessary if fourth dose was given at ≥4 years of age.^{105 182 199}

Infants and Children 6 Weeks through 4 Years of Age (DTaP-IPV/Hib; Pentacel)

IM

Each dose is 0.5 mL.²²⁴

May be used when immunization against diphtheria, tetanus, pertussis, poliovirus, and Hib is indicated in children 6 weeks through 4 years of age.²²⁴

In previously unvaccinated children 6 weeks through 4 years of age, Pentacel is given in a series of 4 doses.²²⁴ Give doses at 2, 4, 6, and 15 through 18 months of age.²²⁴ Initial dose usually given at 2 months of age, but may be given as early as 6 weeks of age.²²⁴

To complete recommended primary and booster vaccination series against diphtheria, tetanus, and pertussis in children who received the 4-dose Pentacel regimen at 2, 4, 6, and 15 through 18 months of age, give fifth dose as DTaP (Daptacel) at 4 through 6 years of age.²²⁴ Do not use Pentacel for DTaP booster dose indicated at 4 through 6 years of age; however, if dose of Pentacel is inadvertently given at ≥5 years of age, ACIP states the dose may be counted as a valid dose.²²⁵

To complete recommended vaccination series against poliovirus in children who received the 4-dose Pentacel regimen at 2, 4, 6, and 15 through 18 months of age, give an additional booster dose of age-appropriate vaccine containing IPV (IPV; IPOL or DTaP-IPV; Kinrix) at 4 through 6 years of age.^{224 231} This provides a 5-dose series of IPV, which is considered acceptable by ACIP.²³¹ To ensure optimum booster response, minimum interval between fourth dose of Pentacel and fifth IPV dose should be 6 months.²³¹

In infants and children 6 weeks through 4 years of age who previously received ≥1 doses of DTaP (Daptacel), Pentacel can be used to complete the DTaP vaccination series if doses of IPV and Hib vaccine also are indicated and there are no contraindications to any of the individual components.²²⁴

In infants and children 6 weeks through 4 years of age who previously received ≥1 doses of IPV, Pentacel can be used to complete the IPV vaccination series if doses of DTaP and Hib vaccine also are indicated and there are no contraindications to any of the individual components.^{224 225}

In infants and children 6 weeks through 4 years of age who previously received ≥1 doses of Hib vaccine, Pentacel can be used to complete the Hib vaccination series when doses of IPV and DTaP also are indicated and there are no contraindications to any of the individual components.²²⁴ If Hib vaccines from different manufacturers are used to complete the series, a total of 4 doses of vaccine containing Hib antigen (3 primary and a booster dose) are necessary.²²⁴

Infants and Children 6 Weeks through 6 Years of Age (DTaP-HepB-IPV; Pediarix)

IM

Each dose is 0.5 mL.¹⁰⁶

May be used when immunization against diphtheria, tetanus, pertussis, hepatitis B, and poliovirus is indicated in children 6 weeks through 6 years of age born to HBsAg-negative women.¹⁰⁶ ACIP states this fixed-combination vaccine also may be used to complete the HBV vaccination series in infants 6 weeks through 6 years of age or older born to HBsAg-positive women^{† [off-label]}.²⁰⁸

In previously unvaccinated infants and children 6 weeks through 6 years of age, Pediarix is given in a series of 3 doses.¹⁰⁶ Give doses at 2, 4, and 6 months of age (at 6- to 8-week intervals, preferably 8-week intervals).¹⁰⁶ Initial dose usually given at 2 months of age, but may be given as early as 6 weeks of age.¹⁰⁶

To complete recommended primary and booster vaccination series against diphtheria, tetanus, and pertussis in children who received the 3-dose Pediarix series, administer a fourth or fifth dose of DTaP if indicated.¹⁰⁶ Manufacturer recommends that DTaP (Infanrix) be used for fourth DTaP dose at 15 through 18 months of age and either DTaP (Infanrix) or DTaP-IPV (Kinrix) be used as fifth DTaP dose at 4 through 6 years of age since these vaccines contain the same pertussis antigens as Pediarix.^{106 223}

To complete recommended vaccination series against poliovirus in children who received the 3-dose Pediarix series, administer a dose of monovalent IPV (IPOL) at 4 through 6 years of age.^{106 199}

In infants and children 6 weeks through 6 years of age who previously received 1 or 2 doses of DTaP (Infanrix),¹⁰⁶ Pediarix may be used to complete the first 3 doses of the DTaP series if doses of IPV and HepB vaccine also are indicated and there are no contraindications to any of the individuals components.¹⁰⁶ Data not available regarding safety and efficacy of Pediarix used following ≥1 doses of DTaP vaccine from other manufacturers.¹⁰⁶

In infants and children 6 weeks through 6 years of age who previously received 1 or 2 doses of IPV from a different manufacturer, Pediarix can be used to complete the first 3 doses of the IPV vaccination series if doses of DTaP and HepB vaccine also are indicated and there are no contraindications to any of the individual components.¹⁰⁶

In infants and children 6 weeks through 6 years of age who previously received 1 or 2 doses of another HepB vaccine (monovalent or combination vaccine), Pediarix may be used to complete the 3-dose HepB vaccination series if doses of IPV and DTaP also are indicated and there are no contraindications to any of the individual components.¹⁰⁶ Do not use for the initial dose of HepB vaccine indicated in neonates.^{105 106} Although a 3-dose series of Pediarix may be used in infants who received a dose of HepB vaccine at or shortly after birth,¹⁰⁶ manufacturer states data are limited regarding safety of the vaccine in such infants.¹⁰⁶ Data not available to support use of a 3-dose series of Pediarix in those who previously received >1 dose of HepB vaccine.¹⁰⁶

Children 4 through 6 Years of Age (DTaP-IPV; Kinrix, Quadracel)

IM

Each dose is 0.5 mL.^{221 223}

May be used when immunization against diphtheria, tetanus, pertussis, and poliovirus is indicated in children 4 through 6 years of age.^{221 223}

Kinrix: Used to provide fifth dose of DTaP vaccination series and fourth dose of IPV vaccination series in children 4 through 6 years of age receiving primary immunization with DTaP (Infanrix) and/or DTaP-HepB-IPV (Pediarix).²²³

Quadracel: Used to provide fifth dose of DTaP vaccination series and fourth or fifth dose of IPV vaccination series in children 4 through 6 years of age receiving primary immunization with Pentacel (DTaP-IPV/Hib) and/or Daptacel (DTaP).^{221 222}

Previously Unvaccinated Children 7 through 10 Years of Age† (Tdap; Adacel, Boostrix)

IM

Usual dose is 0.5 mL.^{105 192 193}

Although safety and efficacy for primary immunization not established,^{192 193} ACIP recommends that primary immunization^† in previously unvaccinated or incompletely vaccinated children 7 through 10 years of age^† include a single dose of Tdap, unless pertussis antigens contraindicated or should not be used.^{105 199 236}

ACIP and others state preferred primary immunization schedule for catch-up vaccination in previously unvaccinated children 7 through 10 years of age^† is a single dose of Tdap followed by a dose of Td given 1–2 months after Tdap and a second Td dose given 6–12 months after first Td dose.^{105 199} Alternatively, substitute Tdap for any 1 of the Td doses.¹⁰⁵ Do not give these children a Tdap booster dose at 11 through 12 years of age.^{105 199}

Previously Unvaccinated Adolescents 11 through 18 Years of Age (Tdap; Adacel, Boostrix)

IM

Usual dose is 0.5 mL.^{192 193}

Although safety and efficacy of Tdap for primary immunization not established,^{192 193} ACIP recommends that primary immunization^† in previously unvaccinated or incompletely vaccinated adolescents 11 through 18 years of age include a single dose of Tdap, unless pertussis antigens contraindicated or should not be used.^{195 196}

ACIP and others state preferred primary immunization schedule for catch-up vaccination in previously unvaccinated adolescents 11 through 18 years of age is a single dose of Tdap followed by a dose of Td given at least 4 weeks after Tdap and a second Td dose given 6–12 months after first Td dose.^{105 195 196 199} Alternatively, substitute Tdap for any 1 of the 3 doses of Td.^{195 196}

Booster Dose in Adolescents 10 through 18 Years of Age (Tdap; Adacel, Boostrix)

IM

Booster dose is 0.5 mL.^{192 193}

To maintain adequate immunity against diphtheria and tetanus, ACIP and others recommend that all individuals who received primary immunization with any preparation containing diphtheria and tetanus toxoids (DTaP, DTP [not commercially available in the US], DT, Td) receive a booster dose of a preparation containing diphtheria and tetanus toxoids at 11 through 12 years of age, provided at least 5 years have elapsed since the last dose.^{100 105 199}

Because adolescents also at risk for pertussis, ACIP and others recommend Tdap (instead of Td) for adolescent booster at 11 through 18 years of age (preferably 11 through 12 years of age), unless already given or pertussis antigens contraindicated or should not be used.^{105 195 199 236} Give Tdap dose regardless of interval since last dose of diphtheria and tetanus toxoids.¹⁹⁹

Adolescents who have not previously received Tdap and who anticipate having close contact with an infant <12 months of age: Give Tdap dose at least 2 weeks before beginning close contact with the infant,²³⁴ regardless of interval since last dose of vaccine containing diphtheria and tetanus toxoids (e.g., Td).²³⁶

Postexposure Prophylaxis of Diphtheria

Household and Other Close Contacts of an Individual with Known or Suspected Diphtheria

IM

Individuals who previously received <3 doses of a diphtheria toxoid-containing preparation or whose vaccination status is unknown: Give an immediate dose of an age-appropriate preparation containing diphtheria toxoid adsorbed and complete the primary vaccination series.^{100 105 166}

Individuals who previously completed the primary vaccination series but have not received a dose within the last 5 years: Give a booster dose of an age-appropriate preparation containing diphtheria toxoid adsorbed.^{100 105 166}

Used as an adjunct to anti-infective postexposure prophylaxis.^{100 105 166} (See Postexposure Prophylaxis of Diphtheria under Uses.)

Postexposure Prophylaxis of Tetanus

Emergency dose of a preparation containing tetanus toxoid adsorbed may be indicated with or without a dose of TIG.^{100 105 166 195 196 201} (See Postexposure Prophylaxis of Tetanus under Uses.)

Wound care is an essential part of postexposure prophylaxis of tetanus.^{100 105 166 195 196} Wound care is necessary regardless of vaccination status.^{100 105} Clean and debride wounds properly, especially if dirt or necrotic tissue is present; remove all necrotic tissue and foreign material.¹⁰⁵

Adolescents 10 through 18 Years of Age (Tdap; Adacel, Boostrix)

IM

Emergency booster dose is 0.5 mL.^{100 105 192 193}

Individuals who previously received <3 doses of a tetanus toxoid-containing preparation: Give emergency booster dose of age-appropriate preparation containing tetanus toxoid adsorbed as soon as possible if an injury and possible exposure to tetanus occurs.^{100 105 166 196}

Individuals who previously received ≥3 doses of a tetanus toxoid-containing preparation: Give emergency booster dose of age-appropriate preparation containing tetanus toxoid adsorbed if injury is a clean, minor wound (not tetanus prone) and >10 years have elapsed since primary immunization against tetanus or last booster dose of tetanus toxoid-containing preparation.^{100 105 166 196} If injury is extensive (moderately or very tetanus prone), give emergency booster dose of age-appropriate preparation containing tetanus toxoid absorbed if >5 years have elapsed since primary immunization against tetanus or last booster dose.^{100 105 166 196}

For most individuals, Td indicated for emergency booster doses.^{100 105 166 196} Use single dose of Tdap (instead of Td) in those who have not previously received Tdap.^{105 166 196} If Tdap not available or administered previously, use Td.^{105 166 196}

Postexposure Prophylaxis of Pertussis

Infants and Children 6 Weeks Through 6 Years of Age (DTaP; Daptacel, Infanrix)

IM

Household and other close contacts of an individual with pertussis who have not completed primary immunization with DTaP: Complete the vaccination series with minimal intervals between doses.^{100 105} Give a fourth dose of DTaP to those who received their third DTaP dose ≥6 months before the exposure;¹⁰⁵ give a fifth dose to those who received their fourth dose ≥3 years before the exposure.¹⁰⁵

Used as adjunct to anti-infective postexposure prophylaxis.^{100 105} (See Postexposure Prophylaxis of Pertussis under Uses.)

Adolescents 10 through 18 Years of Age (Tdap; Adacel, Boostrix)

IM

Booster dose is 0.5 mL.^{105 195 196 201}

Individuals at increased risk of pertussis because of pertussis outbreaks or because they are close contacts of an individual with pertussis: Consider a booster dose of Tdap in those who have not previously received a dose.^{105 195 196 201}

Used as adjunct to anti-infective postexposure prophylaxis.^{100 105} (See Postexposure Prophylaxis of Pertussis under Uses.)

Adults

Prevention of Diphtheria, Tetanus, and Pertussis

Primary Immunization in Adults ≥19 Years of Age† (Tdap; Adacel, Boostrix)

IM

Usual dose is 0.5 mL.^{195 196}

Although safety and efficacy of Tdap for primary immunization not established,^{192 193} ACIP and others recommend that primary immunization^† against diphtheria and tetanus in previously unvaccinated or incompletely vaccinated adults ≥19 years of age include a single dose of Tdap, unless pertussis antigens contraindicated or should not be used.^{195 196 200 238}

Previously unvaccinated adults: ACIP and others state preferred primary immunization schedule is a single dose of Tdap followed by a dose of Td at least 4 weeks after Tdap and a second dose of Td 6–12 months after first Td dose.^{195 196 200} Alternatively, substitute Tdap for any 1 of the 3 doses of Td.^{195 196 200}

Booster Dose in Adults ≥19 Years of Age (Tdap; Adacel, Boostrix)

IM

Booster dose is 0.5 mL.^{192 193}

Adults who received primary immunization against diphtheria and tetanus should receive routine booster doses of Td every 10 years.^{100 200} In addition, emergency booster dose of Td may be indicated in the event of injury and possible exposure to tetanus infection.¹⁰⁰

Because adults may be at risk for pertussis, ACIP and others recommend a single dose of Tdap (instead of Td) when a booster dose is needed in adults ≥19 years of age (including those ≥65 years of age) who have not previously received Tdap, unless pertussis antigens contraindicated or should not be used.^{196 237} If indicated, give Tdap dose regardless of interval since last dose of vaccine containing diphtheria or tetanus toxoids (e.g., Td).^{200 236} Use Td for subsequent booster doses.^{196 200 236 237}

Adults ≥19 years of age who have not previously received Tdap and who have or anticipate having close contact with an infant <12 months of age: Give Tdap dose at least 2 weeks before beginning close contact with the infant,²³⁴ regardless of interval since last dose of vaccine containing diphtheria and tetanus toxoids (e.g., Td).²³⁶

Adults ≥65 years of age who have not previously received Tdap: Although only Tdap (Boostrix) labeled by FDA for this age group,¹⁹³ ACIP states either Tdap (Adacel) or Tdap (Boostrix) can be used.²³⁷

Postexposure Prophylaxis of Diphtheria

Household and Other Close Contacts of an Individual with Known or Suspected Diphtheria

IM

Individuals who previously received <3 doses of a diphtheria toxoid-containing preparation or whose vaccination status is unknown: Give an immediate dose of an age-appropriate preparation containing diphtheria toxoid adsorbed and complete the primary vaccination series.^{100 105 166}

Individuals who previously completed the primary vaccination series but have not received a dose within the last 5 years: Give a booster dose of an age-appropriate preparation containing diphtheria toxoid adsorbed.^{100 105 166}

Used as an adjunct to anti-infective postexposure prophylaxis.^{100 105 166} (See Postexposure Prophylaxis of Diphtheria under Uses.)

Postexposure Prophylaxis of Tetanus

Emergency dose of a preparation containing tetanus toxoid adsorbed may be indicated with or without a dose of TIG.^{100 105 192 193} (See Postexposure Prophylaxis of Tetanus under Uses.)

Wound care is an essential part of postexposure prophylaxis of tetanus.^{100 105 166 195 196} Wound care is necessary regardless of vaccination status.^{100 105} Clean and debride wounds properly, especially if dirt or necrotic tissue is present; remove all necrotic tissue and foreign material.¹⁰⁵

Adults ≥19 Years of Age (Tdap; Adacel, Boostrix)

IM

Emergency booster dose is 0.5 mL.^{100 105 192}

Individuals who previously received <3 doses of a tetanus toxoid-containing preparation or whose vaccination status is unknown: Give emergency booster dose of age-appropriate preparation containing tetanus toxoid adsorbed as soon as possible if injury and possible exposure to tetanus occurs.^{100 105 196}

Individuals who previously received ≥3 doses of tetanus toxoid-containing preparation: Give emergency booster dose of age-appropriate preparation containing tetanus toxoid adsorbed if injury is a clean, minor wound (not tetanus prone) and >10 years have elapsed since primary immunization against tetanus or last booster dose of tetanus toxoid-containing preparation.^{100 105 196} If injury is extensive (moderately or very tetanus prone), give emergency booster dose of age-appropriate preparation containing tetanus toxoid absorbed if >5 years have elapsed since primary immunization against tetanus or last booster dose.^{100 105 196}

For most adults, Td indicated for emergency booster doses.^{100 105 196} Use single dose of Tdap (instead of Td) in adults ≥19 years of age (including those ≥65 years of age) who have not previously received Tdap.^{100 105 196 237 238} If Tdap not available or administered previously, use Td.^{100 105 166 196}

Postexposure Prophylaxis of Pertussis

Adults 19 through 64 Years of Age (Tdap; Adacel, Boostrix)

IM

Individuals at increased risk of pertussis because of pertussis outbreaks or because they are close contacts of an individual with pertussis: Consider a booster dose of Tdap (0.5 mL) in those who have not previously received a dose.¹⁹⁵

Used as an adjunct to anti-infective postexposure prophylaxis.^{100 105} (See Postexposure Prophylaxis of Pertussis under Uses.)

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations.

Cautions for Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed

Contraindications

DTaP (Daptacel, Infanrix) or Tdap (Adacel, Boostrix)

• Severe allergic reaction (e.g., anaphylaxis) after 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.)

• Encephalopathy (e.g., coma, decreased level of consciousness, prolonged seizures) within 7 days of a previous dose of a vaccine containing pertussis antigens that is not attributable to another identifiable cause.^{182 187 192 193}

• Progressive neurologic disorder, including infantile spasms, uncontrolled epilepsy, or progressive encephalopathy.^{182 187} (See Guillain-Barré Syndrome and Other Neurologic Disorders under Cautions.)

DTaP-IPV (Kinrix, Quadracel)

• Severe allergic reaction (e.g., anaphylaxis) to any ingredient in the vaccine (e.g., neomycin, polymyxin B) or after previous dose of any vaccine containing diphtheria, tetanus, pertussis, or poliovirus antigens.^{221 223}

• Encephalopathy (e.g., coma, decreased consciousness, prolonged seizures) within 7 days of a dose of pertussis-containing vaccine that is not attributable to another identifiable cause.^{221 223}

• Progressive neurologic disorder, including infantile spasms, uncontrolled epilepsy, or progressive encephalopathy.^{221 223} (See Guillain-Barré Syndrome and Other Neurologic Disorders under Cautions and see Precautions Related to the Pertussis Component under Cautions.)

DTaP-Hib-HepB (Pediarix)

• Severe allergic reaction (e.g., anaphylaxis) to any ingredient in the vaccine (e.g., yeast, neomycin, polymyxin B) or after previous dose of any vaccine containing diphtheria, tetanus, pertussis, hepatitis B, or poliovirus antigens.¹⁰⁶

• Encephalopathy (e.g., coma, decreased consciousness, prolonged seizures) within 7 days of a dose of pertussis-containing vaccine that is not attributed to another identifiable cause.¹⁰⁶

• Progressive neurologic disorder, including infantile spasms, uncontrolled epilepsy, or progressive encephalopathy.¹⁰⁶ (See Guillain-Barré Syndrome and Other Neurologic Disorders under Cautions.)

DTaP-IPV/Hib (Pentacel)

• Severe allergic reaction (e.g., anaphylaxis) to any ingredient in the vaccine or after previous dose of the vaccine or any vaccine containing diphtheria, tetanus, pertussis, poliovirus, or Hib antigens.²²⁴

• Encephalopathy (e.g., coma, decreased consciousness, prolonged seizures) within 7 days of a dose of pertussis-containing vaccine.²²⁴

• Progressive neurologic disorder, including infantile spasms, uncontrolled epilepsy, or progressive encephalopathy.²²⁴ (See Guillain-Barré Syndrome and Other Neurologic Disorders under Cautions.)

Warnings/Precautions

Warnings

Guillain-Barré Syndrome and Other Neurologic Disorders

Guillain-Barré syndrome (GBS) reported as temporally associated with tetanus toxoid.¹¹⁴

A review by the Institute of Medicine (IOM) found evidence of a causal relationship between tetanus toxoid and brachial neuritis and GBS.^{187 192 193 224} 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}

Risk of GBS may be increased in individuals with a history of GBS within 6 weeks after receiving a prior dose of any preparation containing tetanus toxoid.^{114 187 192 224} Some manufacturers state base decision to administer subsequent doses of DTaP, Tdap, or any vaccine containing tetanus toxoid in such patients on careful consideration of potential benefits and possible risks.^{106 182 193 221 223}

ACIP states 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.^{134 195 196}

Manufacturers of Tdap (Adacel, Boostrix) state that deferral of Tdap should be considered in adults or adolescents with progressive or unstable neurologic conditions (e.g., cerebrovascular event, acute encephalopathic condition) since it is not known whether administration in such individuals might hasten manifestations of the disorder or affect prognosis.^{192 193} Administration in such individuals may result in diagnostic confusion between manifestations of the underlying illness and possible adverse effects of vaccination.^{192 193}

Precautions Related to the Pertussis Component

If any of the following events is temporally related to a dose of any vaccine containing pertussis antigens, a decision to give additional doses should be based on careful consideration of potential benefits and possible risks:^{106 182 187 221 223 224} temperature ≥40.5°C within 48 hours not due to another identifiable cause; collapse or shock-like state (hypotonic-hyporesponsive episode) within 48 hours; persistent, inconsolable crying lasting ≥3 hours occurring within 48 hours; or seizures with or without fever occurring within 3 days.^{106 182 187 221 223 224}

Some manufacturers state that administration of vaccines containing pertussis antigen should not be considered in individuals with progressive neurologic disorders until a treatment regimen has been established and the condition has stabilized.²²¹ In those with stable CNS disorders, a decision to administer a preparation containing pertussis antigens must be made by the clinician on an individual basis, with consideration of all relevant factors and assessment of potential risks and benefits.¹⁸² Advise the patient and/or patient’s parent or guardian of the potential risks.¹⁸²

A family history of seizures or other CNS disorder is not a contraindication to vaccines containing pertussis antigens.¹⁸²

To reduce the possibility of post-vaccination fever in infants or children with a history of previous seizures or at higher risk for seizures than the general population, some manufacturers suggest that an appropriate antipyretic may be given at the time of vaccination and for the next 24 hours.^{106 182 187 223 224} ACIP states that evidence does not support use of antipyretics before or at the time of vaccination for prevention of febrile seizures, but antipyretics can be used for treatment of fever or local discomfort that might occur following vaccination.¹³⁴

If pertussis vaccine is contraindicated or a decision is made to withhold pertussis vaccine, use an age-appropriate vaccine containing only tetanus and diphtheria toxoids (Td, DT).^{182 187}

Sensitivity Reactions

Hypersensitivity 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.^{100 182 187 192 193 221}

Prior to injection of DTaP, Tdap, or combination vaccine containing DTaP, review patient’s history regarding possible sensitivity and any previous adverse reactions and take all precautions known for prevention of allergic or any other adverse effects.^{106 182 187 192 193 223 224} Have epinephrine and other appropriate agents and equipment available for immediate use in case an anaphylactic reaction occurs.^{106 182 187 192 193 221 223 224}

If hypersensitivity reaction occurs, no further doses of the vaccine or any other vaccine containing diphtheria toxoid, tetanus toxoid, or pertussis vaccine should be given because of uncertainty regarding which component may have caused the reaction.^{105 187 192 193 223 224} If further doses are being considered (e.g., for tetanus postexposure prophylaxis), consider consultation with an allergist.^{187 192 193 223}

AAP states that a transient urticarial rash occurring after DTaP administration (unless it appears within a few minutes after the dose is administered) is unlikely to be anaphylactic in origin and is not a contraindication for further doses.¹⁰⁵

Arthus-type Hypersensitivity Reactions

Arthus-type hypersensitivity reactions to tetanus toxoid reported.^{192 195 196}

Reaction is an extensive local inflammatory reaction (vasculitis) that generally begins 2–12 hours after a dose.^{192 195 196} There may be severe pain, swelling, induration, edema, hemorrhage, and necrosis.^{195 196}

Arthus reactions usually resolve without sequelae.^{195 196}

Individuals who have Arthus-type hypersensitivity reactions following a dose of a tetanus toxoid-containing preparation usually have high serum tetanus antitoxin levels and should not receive doses more frequently than every 10 years, even if postexposure prophylaxis against tetanus is indicated.^{192 193 195 196}

Allergy to Neomycin or Other Anti-infectives

DTaP-IPV (Kinrix): Contains trace amounts of neomycin (≤0.05 ng) and polymyxin B (≤0.01 ng).²²³ Manufacturer states the vaccine is contraindicated in individuals with severe hypersensitivity (e.g., anaphylaxis) to neomycin and/or polymyxin B.²²³

DTaP-IPV (Quadracel): Contains trace amounts of neomycin (<4 pg) and polymyxin B (<4 pg).²²¹

DTaP-HepB-IPV (Pediarix): Contains trace amounts of neomycin (≤0.05 ng) and polymyxin B (≤0.01 ng).¹⁰⁶ Manufacturer states the vaccine is contraindicated in individuals with severe hypersensitivity (e.g., anaphylaxis) to neomycin and/or polymyxin B.¹⁰⁶

DTaP-IPV/Hib (Pentacel): Contains trace amounts of neomycin (<4 pg) and polymyxin B (<4 pg).²²⁴

Neomycin allergy usually results in delayed-type (cell-mediated) hypersensitivity reactions manifested as contact dermatitis.^{105 134} ACIP and AAP state that vaccines containing trace amounts of neomycin should not be used in individuals with a history of anaphylactic reaction to neomycin, but use of such vaccines may be considered in those with a history of delayed-type neomycin hypersensitivity if benefits of vaccination outweigh risks.^{105 134}

Allergy to Certain Preservatives

DTaP-IPV (Kinrix): Contains residual formaldehyde (≤100 mcg) from the manufacturing process.²²³

DTaP-IPV (Quadracel): Contains phenoxyethanol (0.6%) and residual formaldehyde (≤5 mcg) from the manufacturing process.²²¹

DTaP-HepB-IPV (Pediarix): Contains residual formaldehyde (≤100 mcg) from the manufacturing process.¹⁰⁶

DTaP-IPV/Hib (Pentacel): Contains trace amounts of phenoxyethanol (0.6%) and formaldehyde (≤5 mcg).²²⁴

Yeast Allergy

DTaP-HepB-IPV (Pediarix): Manufacturing process for HepB vaccine component involves baker’s yeast (Saccharomyces cerevisiae) and final product contains yeast protein (≤5%).¹⁰⁶ Manufacturer states the vaccine is contraindicated in individuals with severe hypersensitivity (e.g., anaphylaxis) to yeast.¹⁰⁶

Latex Sensitivity

Some components (i.e., tip caps) of 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 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 benefits of vaccination outweigh risk of a potential allergic reaction.¹³⁴ Contact-type allergy is the most common type of latex sensitivity.¹³⁴

General Precautions

Individuals with Altered Immunocompetence

If administered to individuals immunosuppressed as the result of disease or immunosuppressive therapy, consider possibility that immune response to the vaccine and efficacy may be reduced in these individuals.^{105 106 134 182 187 192 193 221 223 224} (See Specific Drugs under Interactions.)

Recommendations regarding use of DTaP, Tdap, or combination vaccines containing DTaP in HIV-infected individuals are the same as those for individuals who are not HIV-infected.^{105 134 155} However, immunization may be less effective in individuals with HIV infection than in immunocompetent individuals.¹⁰⁵

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 defer vaccination in individuals with moderate or severe acute illness (with or without fever).^{100 105 179 192}

Limitations of Vaccine Effectiveness

May not protect all individuals from diphtheria, tetanus, and pertussis.^{187 192 193 221 224}

Optimum protection against diphtheria and tetanus achieved with a primary series of 3 doses of preparations containing diphtheria and tetanus toxoids adsorbed.^{166 205}

Tdap (Adacel, Boostrix) labeled by FDA for booster immunization; safety and efficacy not established for primary immunization.^{192 193}

Duration of Immunity

Following primary immunization, duration of protection against diphtheria is approximately 10 years.^{100 166}

Following primary immunization, duration of protection against tetanus is approximately 10 years.^{100 166} Although some individuals may be protected for life, antitoxin levels decrease over time and only approach minimal protective level in most individuals 10 years after last dose.¹⁶⁶ The antitoxin response induced by tetanus toxoid adsorbed has a longer duration than that induced by tetanus toxoid (no longer commercially available in the US).¹⁶⁶

Duration of immunity following primary immunization against pertussis is estimated to be 5–10 years or longer, but protection wanes over time.^{105 195 196 201 205}

Pre- and Postvaccination Serologic Testing

Routine prevaccination serologic testing not recommended.^{195 196 235}

When postexposure prophylaxis against tetanus or preexposure vaccination in high-risk groups (e.g., travelers) is indicated in individuals with an unknown or uncertain history of vaccination, consider such individuals unvaccinated and give complete primary vaccination series.^{100 195}

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

Use of Fixed Combinations

When fixed-combination vaccine containing diphtheria, tetanus, pertussis, and poliovirus antigens (DTaP-IPV; Kinrix, Quadracel) used, consider cautions, precautions, and contraindications associated with each antigen.^{221 223}

When combination vaccine containing diphtheria, tetanus, pertussis, poliovirus, and Hib antigens (DTaP-IPV/Hib; Pentacel) used, consider cautions, precautions, and contraindications associated with each antigen.²²⁴

When fixed-combination vaccine containing diphtheria, tetanus, pertussis, hepatitis B virus, and poliovirus antigens (DTaP-HepB-IPV; Pediarix) used, consider cautions, precautions, and contraindications associated with each antigen.¹⁰⁶

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

Inspect all vaccines upon delivery and monitor during storage to ensure that the appropriate temperature is maintained.¹³⁴ (See Storage under Stability.)

Do not administer DTaP, Tdap, or combination vaccine containing DTaP that have been mishandled or have not been stored at the recommended temperature.¹³⁴

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

Specific Populations

Pregnancy

DTaP (Daptacel, Infanrix): Category C.^{182 187} Not indicated in adults, including pregnant women.¹⁸²

Tdap (Adacel): Category C.¹⁹²

Tdap (Boostrix): Category B.¹⁹³

DTaP-IPV (Kinrix, Quadracel), DTaP-HepB-IPV (Pediarix), DTaP-IPV/Hib (Pentacel): Category C.^{106 221 223 224} Not indicated in adults, including pregnant women.^{106 221 223 224}

Because of risks associated with diphtheria, tetanus, and pertussis, ACIP and AAP state that pregnancy not considered a contraindication for Tdap (Adacel, Boostrix).^{195 196 201 205 234}

Ideally, complete primary immunization against tetanus and diphtheria prior to pregnancy.^{100 105 195 205}

Although Td generally preferred preparation for primary immunization against diphtheria and tetanus during pregnancy,^{105 196 205} ACIP and others state that a dose of Tdap should be substituted for 1 of the required primary Td doses, preferably during third trimester (optimally between 27 and 36 weeks of gestation) in previously unvaccinated or incompletely vaccinated pregnant women.^{200 238} In addition, to ensure protection against pertussis, these experts recommend a dose of Tdap during each pregnancy, regardless of woman's prior vaccination history.^{200 238} To maximize maternal antibody response and passive antibody transfer to infant, optimal timing for Tdap dose is between 27 and 36 weeks of gestation.²³⁸

Pregnant women who were previously vaccinated but received most recent dose of a preparation containing tetanus and diphtheria toxoids ≥10 years ago should receive a booster dose of a preparation containing tetanus and diphtheria toxoid adsorbed during second or third trimester of pregnancy (and before 36 weeks of gestation).^{100 105 195 205} This dose is important if 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 Use Tdap (instead of Td) for the booster dose; preferably give Tdap during third trimester (optimally between 27 and 36 weeks gestation).^{234 238}

If postexposure prophylaxis of tetanus indicated as part of wound management in a pregnant woman, follow usual recommendations regarding emergency booster doses.²⁰⁵ (See Postexposure Prophylaxis of Tetanus under Uses.) Give booster dose of Tdap (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).^{192 193 205}

Lactation

Tdap (Adacel, Boostrix): Not known whether the antigens distributed into milk.^{192 193} Manufacturers recommend caution in nursing women.^{192 193}

ACIP states breast-feeding is not considered a contraindication for Tdap.²⁰⁵

Pediatric Use

DTaP (Daptacel, Infanrix): Safety and efficacy not established in infants <6 weeks of age or in children ≥7 years of age.^{182 187}

Tdap (Adacel, Boostrix): Safety and efficacy not established in children <10 years of age.^{192 193}

DTaP-IPV (Kinrix, Quadracel): Safety and efficacy not established in children <4 years of age or in children ≥7 years of age.^{221 223}

DTaP-HepB-IPV (Pediarix): Safety and efficacy in infants 6 weeks through 6 months of age established on the basis of clinical studies; safety and efficacy in those 7 months through 6 years of age supported by evidence in infants 6 weeks through 6 months of age.¹⁰⁶ Safety and efficacy not established in infants <6 weeks of age or in children ≥7 years of age.¹⁰⁶

DTaP-IPV/Hib (Pentacel): Safety and efficacy not established in infants <6 weeks of age or in children ≥5 years of age.²²⁴

Apnea reported following IM administration of vaccines in some infants born prematurely.^{106 182 187 224} Base decisions regarding when to administer an IM vaccine in premature infants on consideration of the individual infant’s medical status and potential benefits and possible risks of vaccination.^{106 182 187 224}

Geriatric Use

DTaP (Daptacel, Infanrix): Not indicated in adults, including geriatric adults.^{105 149 182 187}

Tdap (Adacel): Safety and efficacy not established in adults ≥65 years of age.¹⁹² Although not labeled by FDA for adults ≥65 years of age,¹⁹² ACIP states the vaccine can be used in this age group if it is the only available Tdap vaccine.²³⁷

Tdap (Boostrix): Clinical studies included adults ≥65 years of age; safety and efficacy established in this age group.¹⁹³

DTaP-IPV (Kinrix, Quadracel), DTaP-HepB-IPV (Pediarix), DTaP-IPV/Hib (Pentacel): Not indicated in adults, including geriatric adults.^{106 221 223 224}

Common Adverse Effects

DTaP (Daptacel, Infanrix): Injection site reactions (pain or tenderness,^{127 182} erythema,^{127 182} swelling),^{127 182} mild to moderate fever (38–40.4°),^{182 187} fretfulness or irritability,^{182 187} drowsiness,^{182 187} anorexia,¹⁸⁷ vomiting.¹⁸⁷

Tdap (Adacel, Boostrix): Injection site reactions (pain, erythema, swelling), headache, fatigue, sore and swollen joints, GI effects (nausea, diarrhea, vomiting, abdominal pain), chills, fever, rash.^{192 193}

DTaP-IPV (Kinrix): Injection site reactions (pain, redness, increase in arm circumference, swelling), drowsiness, fever, loss of appetite.²²³

DTaP-IPV (Quadracel): Injection site reactions (pain, redness, increase in arm circumference, swelling), myalgia, malaise, headache.²²¹

DTaP-HepB-IPV (Pediarix): Injection site reactions (pain, erythema, swelling), fever, drowsiness, fussiness/irritability, loss of appetite.¹⁰⁶

DTaP-IPV/Hib (Pentacel): Injection site reactions (tenderness, redness, swelling, increased circumference of injected arm), fever, decreased activity/lethargy, inconsolable crying, fussiness/irritability.²²⁴

Drug Interactions

Other Vaccines

Although specific data not available regarding concurrent administration of DTaP or Tdap with all other available vaccines, 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.^{100 105 134 192 193 195 196 199} However, unless commercially available 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.^{100 105 134 182 192 193 195 196 199 224}

DTaP or Tdap may be administered simultaneously with or at any interval before or after live viral vaccines, including measles, mumps, and rubella vaccine (MMR).^{105 134} In addition, DTaP or Tdap may be administered simultaneously with or at any interval before or after inactivated vaccines, including Hib vaccine, HepB vaccine, and poliovirus vaccine inactivated (IPV).^{105 134}

Specific Drugs

Stability

Storage

Parenteral

Injectable Suspension, for IM Use

DTaP (Daptacel, Infanrix): 2–8°C.^{182 187} Do not freeze;^{182 187} discard if freezing occurs.^{182 187}

Tdap (Adacel, Boostrix): 2–8°C.^{192 193} Do not freeze; discard if freezing occurs.^{192 193}

DTaP-IPV (Kinrix, Quadracel): 2–8°C.²²³ Do not freeze; discard if freezing occurs.^{221 223}

DTaP-HepB-IPV (Pediarix): 2–8°C.¹⁰⁶ Do not freeze; discarded if freezing occurs.¹⁰⁶

Adacel, Boostrix, Daptacel, Infanrix, Kinrix, Pediarix, Quadracel: Do not contain thimerosal or any other preservative.^{106 182 187 192 193 221 223}

For Injectable Suspension, for IM Use

DTaP-IPV/Hib (Pentacel): 2–8°C.²²⁴ Do not freeze; discard if freezing occurs.²²⁴

Use immediately after reconstitution.²²⁴

Does not contain thimerosal or any other preservatives.²²⁴

Actions

• DTaP and Tdap are sterile suspensions prepared by mixing suitable quantities of diphtheria and tetanus toxoids and acellular pertussis antigens which have been formaldehyde-treated, purified, and adsorbed onto an aluminum adjuvant.^{182 187 192 193}

• There are 2 different DTaP preparations commercially available in US (Daptacel, Infanrix).^{182 187} Both DTaP preparations contain similar diphtheria and tetanus toxoids, but slightly different acellular pertussis vaccine components.^{182 187} In addition, potency of each antigen varies among the preparations.^{182 187}

• There are 2 different Tdap preparations commercially available in US (Adacel, Boostrix).^{192 193} Both contain a lower content of diphtheria and pertussis antigens than that contained in DTaP.^{192 193} Tetanus antigen content is equivalent in both Tdap preparations, but diphtheria and pertussis antigen content in Adacel is different than that in Boostrix.^{192 193}

• DTaP also available as fixed-combination vaccines containing diphtheria, tetanus, pertussis, and poliovirus antigens (DTaP-IPV; Kinrix, Quadracel), fixed-combination vaccine containing diphtheria, tetanus, pertussis, hepatitis B, and poliovirus antigens (DTaP-HepB-IPV; Pediarix), and a kit that provides a combination vaccine containing diphtheria, tetanus, pertussis, poliovirus, and Hib antigens (DTaP-IPV/Hib; Pentacel).^{106 221 223 224}

• DTaP and Tdap stimulate active immunity to diphtheria and tetanus by inducing production of specific neutralizing antitoxin antibodies.^{182 187 192 193} The acellular pertussis vaccine component induces production of specific anti-pertussis antibodies, but mechanism of protection against the disease not fully determined.^{182 187 192 193}

• A complete primary immunization series with the age-appropriate preparation is needed to induce production of antitoxin antibody levels that provide protection.^{166 205}

• Diphtheria toxoid component provides protection only against the exotoxin elucidated by C. diphtheriae.^{192 193} Immunization does not prevent or eliminate colonization or carriage of C. diphtheriae in pharynx, nose, or skin.^{100 192}

• Protective levels of diphtheria antitoxin (defined as ≥0.1 international units/mL)^{134 166 195 196 205} attained in >95% of individuals after primary vaccination series.¹⁶⁶ Antitoxin levels may persist for 10 years.^{166 192}

• Protective levels of tetanus antitoxin (defined as ≥0.1 international units/mL using enzyme-linked immunoabsorbent assay [ELISA])^{195 196 205} attained in almost 100% of individuals after primary vaccination series.¹⁶⁶ Antitoxin levels persist for approximately 10 years.¹⁶⁶ Although some individuals may be protected for life, levels decrease over time and only approach minimal protective level in most individuals 10 years after last dose.¹⁶⁶

• There is no accepted serologic or laboratory correlation of protection against pertussis.^{182 195 196} Children who receive 3 doses of a preparation containing pertussis vaccine during infancy may be protected against pertussis until 6 years of age.¹⁸² There is evidence that administration of a dose of Tdap in adults results in a booster response to the pertussis antigens contained in the preparation.^{193 195 196 205}

Advice to Patients

• Prior to administration of each vaccine dose, provide a copy of the appropriate CDC Vaccine Information Statement (VIS) to the patient or patient’s legal representative as required by the National Childhood Vaccine Injury Act (VISs are available at [Web]).^{182 187 192 193 202 203 223}

• Advise patient and/or patient’s parent or guardian of the risks and benefits of vaccination against diphtheria, tetanus, and pertussis and the importance of completing the primary immunization series and receiving recommended booster doses (unless there is a contraindication to further doses).^{182 187 192 193 223}

• Importance of receiving the complete primary immunization series and recommended booster doses to ensure highest level of protection, unless contraindicated.^{182 187 192 193}

• Advise patient that the vaccines may not provide protection in all vaccinees.^{187 192 193}

• Importance of informing clinicians if child had a seizure or collapsed after a dose of DTaP, cried nonstop for ≥3 hours after a dose of DTaP, or had a fever >40.5°C or any unusual behavior after a dose of DTaP.²⁰²

• Importance of contacting clinicians if a serious allergic reaction (e.g., difficulty breathing, hoarseness, wheezing, hives, paleness, weakness, fast heartbeat, dizziness) or other adverse effects occur following a dose.^{202 223}

• Clinicians or individuals can report any adverse reactions that occur following vaccination to Vaccine Adverse Event Reporting System (VAERS) at 800-822-7967 or [Web].^{182 187 192 193 202 223}

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.^{182 187 192 193}

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{192 193}

• Importance of informing patients of other important precautionary information.^{182 187 192 193} (See Cautions.)

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.

Medical Disclaimer