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

Class: Toxoids
ATC Class: J07AM01
VA Class: IM105
Brands: Adacel, Boostrix, Daptacel, Infanrix, Kinrix, Pediarix, Pentacel, TriHIBit, Tripedia

Introduction

Fixed-combination preparations containing formaldehyde-treated tetanus and diphtheria toxins (toxoids) and acellular pertussis vaccine adsorbed onto aluminum adjuvants.^{152 182 187 192 193} Used to stimulate active immunity to diphtheria, tetanus, and pertussis.^{111 152 182 187 192 193 195 196 205} Commercially available as diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed (DTaP; Daptacel, Infanrix, Tripedia)^{152 182 187} and tetanus toxoid and reduced diphtheria toxoid and acellular pertussis vaccine adsorbed (Tdap; Adacel, Boostrix).^{192 193} Antigen potency varies depending on the manufacturer.^{152 182 187 192 193} DTaP also commercially available in a fixed-combination vaccine that contains diphtheria, tetanus, pertussis, and poliovirus antigens (DTaP-IPV; Kinrix),²²³ in a fixed-combination vaccine that contains diphtheria, tetanus, pertussis, hepatitis B, and poliovirus antigens (DTaP-HepB-IPV; Pediarix),¹⁰⁹ in a combination vaccine that contains diphtheria, tetanus, pertussis, and Haemophilus influenza type b (Hib) antigens (DTaP/Hib; TriHIBit),^{152 164} and in a combination vaccine that contains diphtheria, tetanus, pertussis, poliovirus, and Hib antigens (DTaP-IPV/Hib; Pentacel).²²⁴ Although no longer available in the US, diphtheria and tetanus toxoids and whole-cell pertussis vaccine adsorbed (DTP, also referred to as DTwP) may still be used in other countries.^{100 198}

Uses for Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed, Tetanus Toxoid and Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed

Prevention of Diphtheria, Tetanus, and Pertussis

Diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed (DTaP) and tetanus toxoid and reduced diphtheria toxoid and acellular pertussis vaccine adsorbed (Tdap) are used to stimulate active immunity to diphtheria, tetanus, and pertussis.^{100 148 152 182 187 192 193}

Diphtheria is caused by toxigenic strains of Corynebacterium diphtheriae or, rarely, toxigenic strains of C. ulcerans.^{100 111 132 195 196 198 205 228} The overall case-fatality rate for diphtheria is 5–10% with higher death rates (up to 20%) among individuals <5 years of age and >40 years of age.¹⁹⁸ Diphtheria is uncommon in the US, but toxigenic strains of Corynebacterium continue to circulate in areas of the US where the disease previously was endemic.^{100 111 198 228} Diphtheria continues to circulate worldwide and is endemic in Albania, Russia, and countries of the former Soviet Union and in many countries in Africa, Latin America, Asia/South Pacific, and the Middle East.^{100 111 198} Before widespread immunization against diphtheria was initiated in the 1940s, there were approximately 100,000–200,000 cases of diphtheria and 13,000–15,000 diphtheria-related deaths each year in the US.¹⁹⁸ Most cases of diphtheria occur in individuals who are unvaccinated or incompletely vaccinated against the disease.^{100 111 198}

Tetanus is a potentially fatal disease caused by a neurotoxic exotoxin (tetanospasmin) produced by Clostridium tetani.^{100 132 198} C. tetani spores are ubiquitous in the environment worldwide and found in soil and in animal (e.g., horses, sheep, cattle, dogs, cats, rats, guinea pigs, chickens) and human intestinal tracts.^{100 111 132 195 198} The spores can contaminate open wounds, especially puncture wounds or those with devitalized tissue; anaerobic wound conditions allow the spores to germinate and produce exotoxins that disseminate through the blood and lymphatic system.^{100 195 198} Neonatal tetanus (tetanus neonatorum) occurs in infants born under nonsterile conditions to women inadequately vaccinated against tetanus; infection usually involves a contaminated umbilical stump and occurs because infant does not have passively acquired maternal antibodies against tetanus.^{100 111 132 195 198 205} 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.^{100 195 198 132} Tetanus occurs worldwide, almost exclusively in individuals who are unvaccinated or inadequately vaccinated against the disease.¹⁰⁰ An average of 31 cases was reported each year in the US from 2000 through 2007 (case fatality rate 10%);¹⁹⁸ a low of 20 cases was reported in 2003.¹⁹⁸ Most cases of tetanus in the US occur following acute injuries or wounds (puncture wounds, lacerations, abrasions)^{198 199} and usually occur in adults ≥40 years of age; however, an increase in the disease has been reported recently in younger adults (e.g., heroin abusers).^{198 199}

Pertussis (whooping cough) is an acute respiratory tract infection caused by Bordetella pertussis.^{100 197 198 201 205} During 2000–2006, there were 103,940 cases of pertussis reported in the US (average 14,849 cases each year) and 156 pertussis-related deaths.²⁰⁵ However, it has been suggested that pertussis infection and reinfection are underrecognized among adults and adolescents and that the pertussis burden may be substantially greater; approximately 600,000 cases are estimated to occur annually among adults.²⁰⁵ The risk for severe pertussis and death is highest among infants <12 months of age (especially during the first few months of life until they have received 1 or 2 doses of DTaP);^{100 205} 93% of pertussis-related deaths occur in this age group, usually in unvaccinated infants.²⁰⁵ B. pertussis infections in adults and adolescents may be asymptomatic or range from mild to severe.²⁰⁵ Outbreaks involving adolescents have occurred in various settings (e.g., middle and high schools, residence facilities for disabled individuals, entire communities).²⁰¹ Data from 2000-2006 indicate that 27% of reported pertussis cases occurred in individuals 15–39 years of age and household contact with these individuals appears to be the source of infection for most cases occurring in young infants.²⁰⁵

The appropriate vaccine containing diphtheria, tetanus, and pertussis antigens is selected based on age and whether primary or booster immunization is indicated.^{100 148 152 182 187 192 193 205}

DTaP (Daptacel, Infanrix, Tripedia) is used for primary and booster immunization in children 6 weeks through 6 years of age.^{100 148 149 152 182 187}

Tdap is used for booster immunization in adolescents and adults 10 through 64 years of age (Boostrix) or in adolescents and adults 11 through 64 years of age (Adacel).^{192 193 195 196} Although safety and efficacy of Tdap have not been established for primary immunization,^{192 193} USPHS Advisory Committee on Immunization Practices (ACIP) states that a single dose of Tdap (Adacel, Boostrix) should be included in the immunization series when adolescents and adults 11 through 64 years of age require primary immunization† against diphtheria and tetanus, unless the pertussis antigens are contraindicated.^{195 196} The goal of this strategy is to reduce morbidity associated with pertussis in adults.^{195 196}

ACIP, AAP, and American Academy of Family Physicians (AAFP) recommend that all individuals be immunized against diphtheria, tetanus, and pertussis.^{100 112 184} Use of a combination vaccine generally is preferred over separate injections of equivalent component vaccines;^{112 227} 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.^{112 227} Therefore, a fixed-combination preparation containing antigens for all 3 diseases is preferred for primary and booster immunization in children 6 weeks through 6 years of age unless a component is contraindicated or should not be used.^{100 112 134 184} Diphtheria and tetanus toxoids adsorbed (DT) should be used for primary or booster immunization in this age group only when there is a contraindication to the pertussis antigens contained in DTaP.^{100 112 134 184}

Tetanus and diphtheria toxoids adsorbed (Td) usually is the preparation of choice for primary and booster immunization against diphtheria and tetanus in individuals ≥7 years of age.^{100 112} However, to reduce morbidity associated with pertussis in adults, ACIP, AAP, and AAFP recommend that a single dose of Tdap (Adacel, Boostrix) be used in place of a required primary or booster dose of Td in all individuals 11 through 64 years of age, unless the pertussis antigens are contraindicated.^{195 196} Any individual in this age group who previously received a single dose of Tdap should then receive Td for all subsequent primary or booster doses.^{195 196}

For internationally adopted children whose immune status is uncertain, vaccinations can be repeated or serologic tests performed to confirm immunity.¹³⁴ For DTaP, ACIP states that the simplest approach is to revaccinate according to the US recommended immunization schedule; if a severe local reaction occurs, perform serologic testing for specific IgG antibody to tetanus and diphtheria toxoids to determine whether additional doses are necessary.¹³⁴ If child's records indicate they received ≥3 doses of DTaP (or DTP; no longer commercially available in the US), perform serologic tests; if protective antitoxin antibody levels are present, recorded doses are considered valid and vaccination series should be completed as age-appropriate.¹³⁴ Alternatively, give a single booster dose of DTaP followed by serologic testing 1 month later; if protective levels are present, the recorded doses are considered valid.¹³⁴ If antibody concentrations are indeterminate after the booster dose, give the complete vaccination series.¹³⁴

DTaP or Tdap may be indicated in conjunction with passive immunization with tetanus immune globulin (TIG) for postexposure prophylaxis in individuals with tetanus-prone wounds who are inadequately immunized against tetanus or whose tetanus immunization history is uncertain.^{100 111 195 196 198 201} (See Postexposure Prophylaxis of Tetanus under Uses.)

DTaP and Tdap are not indicated for treatment of diphtheria, tetanus, or pertussis.^{100 192 198 201}

Because diphtheria and tetanus infections do not necessarily confer immunity, initiate or complete primary immunization against diphtheria and tetanus at the time of recovery from these infections in any previously unvaccinated or incompletely vaccinated individual.^{100 198 201} In addition, although well documented pertussis is likely to confer short-term immunity against the disease, protection wanes over time (waning may begin as early as 5–7 years after infection) and initiation or completion of active immunization is indicated at the time of recovery.^{100 195 196 201 205}

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 series in those receiving primary immunization with Infanrix (DTaP) and/or Pediarix (DTaP-HepB-IPV).²²³

When there are no contraindications to any of the individual components, the commercially available fixed-combination vaccine containing diphtheria, tetanus, pertussis, hepatitis B virus (HBV), and poliovirus antigens (DTaP-HepB-IPV; Pediarix) can be used as a 3-dose series in children 6 weeks through 6 years of age born to HBsAg-negative women.^{109 208} ACIP states this fixed-combination vaccine also may be used to complete the HBV vaccine series in infants 6 months through 6 years of age born to HBsAg-positive women†.²⁰⁸ Pediarix should not be used for the initial dose of hepatitis B vaccine that is indicated in neonates.¹⁰⁰ For 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 series.^{100 109} Pediarix also 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;¹⁰⁹ data not available regarding the safety and efficacy of Pediarix used following ≥1 dose of a DTaP vaccine from a different manufacturer.¹⁰⁹ Children who have received a 3-dose series of Pediarix should complete the DTaP and IPV series according to the recommended childhood immunization schedule.^{100 109} 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.¹⁰⁹

The commercially available 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.^{100 224} For prevention of diphtheria, tetanus, and pertussis, children who receive the 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 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 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

When a fourth dose of DTaP and a fourth dose of Hib vaccine are indicated in a child 15 through 18 months of age, a kit (DTaP/Hib; TriHIBit) containing both DTaP (Tripedia) and Hib polysaccharide conjugate (tetanus toxoid conjugate) vaccine (ActHIB) may be used.¹⁷⁴ ActHIB in the kit is reconstituted with Tripedia.¹⁶⁴ (See Dosage and Administration.) Extemporaneous vaccine combinations should not be prepared using other commercially available DTaP and Hib vaccines.^{100 110 148 149}

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

Travelers who are unvaccinated or incompletely vaccinated against diphtheria, tetanus, and pertussis should receive the remaining recommended doses prior to travel.¹³²

Tetanus, diphtheria, and pertussis occur worldwide; the incidence of pertussis is highest in young children in developing countries and other countries where routine immunization against pertussis is not widely practiced.¹³² CDC, AAP, and others recommend that travelers be adequately immunized against diphtheria, tetanus, and pertussis before leaving the US.^{100 121 132}

Optimum protection against diphtheria and tetanus is achieved with a primary series of 3 doses of age-appropriate preparation containing diphtheria and tetanus toxoids adsorbed.^{132 132} Those with an uncertain history of vaccination should be considered unvaccinated and should receive the full 3-dose primary immunization series.^{132 201} A booster dose of Td should be administered prior to travel if ≥10 years have elapsed since primary immunization or the last booster dose.¹³² A dose of Tdap (Adacel, Boostrix) can be substituted for a booster dose of Td in any adolescent or adult 11 through 64 years of age who has not previously received a dose of Tdap.^{195 201} (See Dosage and Administration.)

If necessary to complete the vaccination series before departure, adults, adolescents, and children can receive an accelerated immunization schedule using the age-appropriate minimum intervals between doses.^{100 121 132} (See Dosage under Dosage and Administration.)

Any individual wounded while traveling who received their most recent dose of a tetanus toxoid-containing preparation >5 years previously may require a dose for postexposure prophylaxis of tetanus, depending on the nature of the wound.¹³² (See Postexposure Prophylaxis of Tetanus under Uses.)

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.^{100 111 195 196 198 201}

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).^{100 111 195 196 198 201}

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.^{100 111 132 198} Tetanus also has been associated with apparently clean, superficial wounds, surgical procedures, insect bites, animal bites, dental infections, chronic sores and infections, and IV drug abuse.^{132 198}

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).^{100 111}

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

A dose of Tdap is preferred to a dose of Td in adolescents and adults 11 through64 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.

Td is used in adults, adolescents, and children ≥7 years of age. For children 6 weeks through 6 years of age, DTaP usually is indicated, but DT can be used if pertussis antigens are contraindicated. Monovalent tetanus toxoid adsorbed generally is used only when preparations containing tetanus and diphtheria antigens and preparations containing tetanus, diphtheria, and pertussis antigens are contraindicated or unavailable.

If only 3 doses of tetanus toxoid fluid (no longer commercially available in the US) have been received previously, a fourth dose should be given 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. 1991; 40(RR-10):1-28, MMWR Recomm Rep. 2006; 55(RR-3):1-43, and MMWR Recomm Rep. 2006; 55(RR-17):1-37.

Table 1. Summary Guide to Tetanus Prophylaxis in Routine Wound Management111195196

Previous Doses of Tetanus Toxoid Adsorbed Received	Clean, Minor Wounds	All Other Wounds
	Tdap or Td	TIG	Tdap or Td	TIG
Unknown or <3	Yes	No	Yes	Yes
≥3	No	No	No	No

Any individual whose tetanus vaccination status is unknown or uncertain should be considered to have had no previous doses of tetanus toxoid adsorbed.^{111 195 196}

ACIP, AAP, and AAFP recommend that a single dose of Tdap (Adacel, Boostrix) be used in place of a dose of Td for postexposure prophylaxis in individuals 11 through 64 years of age who have not previously received a dose of Tdap and received their last dose of Td ≥5 years earlier.^{112 195 196 201 205} Any individual in this age group who previously received a single dose of Tdap should receive Td for postexposure prophylaxis.^{112 195 196 201}

Anti-infectives are 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.^{100 111}

Postexposure Prophylaxis of Diphtheria

Postexposure vaccination in household and other close contacts of an individual with culture-confirmed or suspected diphtheria.^{100 111 198}

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 (a single IM dose of penicillin G benzathine or oral erythromycin given for 7–10 days).^{100 111 198 228} Take samples for cultures prior to giving the anti-infective and continue to observe individual for 7 days for evidence of disease.^{111 198 228}

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.^{100 111 198} Close contacts who previously completed the primary vaccination series should receive a booster dose of an age-appropriate preparation containing diphtheria toxoid adsorbed if it has been ≥5 years since their last booster dose.^{100 111 198}

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,^{100 111 198} 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 the CDC at 404-639-8257 from 8:00 a.m. to 4:30 p.m. EST Monday–Friday or the CDC Director's Emergency Operation Center (DEOC) at 770-488-7100 after hours, on weekends, and holidays.^{198 204 228}

Postexposure Prophylaxis of Pertussis

Postexposure vaccination in household and other close contacts of an individual with pertussis.^{100 111 195 196 201}

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).^{100 111 198 206}

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.^{100 111 198} Those who received their third dose of DTaP ≥6 months before the exposure should receive a fourth dose.¹⁰⁰

Safety and efficacy of Tdap administered following pertussis exposure in individuals 10 through 64 years of age have not been evaluated, but a booster dose of Tdap is not contraindicated in those who have not previously received a dose.¹⁹⁸ ACIP and AAP state that individuals 11 through 18 years of age 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) can receive a dose of Tdap if they have not previously received a dose.^{100 195 196 201}

Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed, Tetanus Toxoid and Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed Dosage and Administration

Administration

DTaP and Tdap

Administer by deep IM injection.^{152 182 187 192 193}

Do not administer IV, intradermally, or sub-Q.^{152 182 187 192 193}

To ensure a uniform suspension of antigens, shake vigorously prior to withdrawing a dose.^{152 182 187 192 193} DTaP and Tdap occur as turbid, white suspensions after shaking.^{152 182 187 192 193} Discard if vaccine cannot be resuspended.^{182 187 192 193}

Do not mix with any other vaccine or solution.^{182 187 193}

DTaP: Administer IM into anterolateral muscles of the thigh or deltoid muscle of the arm.^{134 152 182 187} Use anterolateral thigh in infants.^{134 187} In young children, use the deltoid muscle if muscle mass is adequate; alternatively, use the anterolateral thigh.¹³⁴

Tdap: Administer IM into deltoid muscle of the upper arm.^{192 193}

Avoid administering into the gluteal area or areas where there may be a major nerve trunk.^{152 182 192}

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, the thickness of adipose tissue and muscle at the injection site, and the injection technique.¹³⁴

Although some experts state that aspiration (i.e., pulling back on the syringe plunger after needle insertion and before injection) can be performed to ensure that a blood vessel has not been entered, ACIP states this procedure is not required because large blood vessels are not present at recommended IM injection sites.¹³⁴

Syncope may occur following vaccination (usually in adolescents and young adults).^{134 205} Observe vaccinee for approximately 15 minutes after vaccine dose is administered; if syncope occurs, observe patient until symptoms resolve.^{134 205}

DTaP or Tdap may be given simultaneously with TIG (using different syringes and different injection sites) for postexposure prophylaxis of tetanus when passive immunization is considered necessary in addition to active immunization with a vaccine containing tetanus toxoid adsorbed.^{100 111 134 152 182 192 193 195 196} (See Postexposure Prophylaxis of Tetanus under Uses.)

May be given simultaneously with other age-appropriate vaccines during the same health-care visit (using different syringes and different injection sites).^{100 111 112 134 195 196 201} (See Interactions.)

When multiple vaccines are administered during a single health-care visit, each vaccine should be given 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 If multiple vaccines must be given into a single limb, the deltoid muscle may be used in older children and adults, but the anterolateral thigh is preferred in infants and younger children.¹³⁴

Combination Vaccines Containing DTaP and Other Antigens

Administer DTaP-IPV (Kinrix), DTaP-HepB-IPV (Pediarix), DTaP-IPV/Hib (Pentacel), and DTaP/Hib (TriHIBit) by IM injection.^{109 164 223 224}

Do not administer these combination vaccines sub-Q, IV, or intradermally.^{109 164 223 224}

Shake vaccine well immediately prior to administration to provide a uniform, turbid, white suspension.^{109 164 223 224} Discard vaccine if it contains particulates, appears discolored, or cannot be resuspended with thorough agitation.^{109 164 223 224}

Do not mix Kinrix, Pediarix, or any component of Pentacel or TriHIBit with any other vaccine or solution.^{109 152 223 224}

Depending on patient age, administer by IM injection into the deltoid muscle or anterolateral thigh.^{109 134 164 223 224} In children ≥3 years of age, IM injections should be made into the deltoid muscle if muscle mass is adequate; alternatively, the anterolateral thigh can be used.^{109 134 224} In children ≤2 years of age, the preferred site for IM injection is the anterolateral aspect of the thigh.^{109 134 224}

Vaccines generally should not be administered into buttock muscle in children because of the potential for injection-associated injury to sciatic nerve.¹³⁴

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, the thickness of adipose tissue and muscle at the injection site, and the injection technique.¹³⁴ Consider anatomic variability, especially in the deltoid muscle, and use clinical judgment to avoid inadvertent underpenetration or overpenetration of muscle.¹³⁴

Reconstitution (DTaP-IPV/Hib; Pentacel)

DTaP-IPV/Hib (Pentacel) is commercially available as a kit containing single-dose vials of a 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 a single-dose vial of lyophilized ActHIB vaccine by adding the entire contents of a single-dose vial of the DTaP-IPV vaccine according to manufacturer's instructions to provide a combined preparation containing diphtheria, tetanus, pertussis, IPV, and Hib antigens.²²⁴ Shake thoroughly until a cloudy, uniform suspension is obtained.²²⁴

Administer DTaP-IPV/Hib (Pentacel) immediately after reconstitution.²²⁴

Reconstitution (TriHIBit)

When kit containing both DTaP (Tripedia) and Hib vaccine (ActHIB) is used, reconstitute single-dose vial of lyophilized ActHIB vaccine by adding 0.6 mL of the Tripedia vaccine according to manufacturer's instructions to provide a combined preparation containing antigens to diphtheria, tetanus, pertussis, and Hib (DTaP/Hib).¹⁶⁴ Agitate thoroughly.¹⁶⁴ Administer immediately (within 30 minutes) after reconstitution.¹⁶⁴

Dosage

DTaP (Daptacel, Infanrix, Tripedia) is used only in children 6 weeks through 6 years of age.^{100 148 149 152 182 187}

Tdap (Boostrix) is used only in adolescents and adults 10 through 64 years of age.^{193 195 196}

Tdap (Adacel) is used only in adolescents and adults 11 through 64 years of age.^{192 195 196}

DTaP-IPV (Kinrix) is used only in children 4 years through 6 years of age.²²³

DTaP-HepB-IPV (Pediarix) is used only in children 6 weeks through 6 years of age.¹⁰⁹

DTaP-IPV/Hib (Pentacel) is used only in children 6 weeks through 4 years of age.²²⁴

TriHIBit kit containing both DTaP (Tripedia) and Hib vaccine (ActHIB) is used only when both a fourth dose of DTaP and a fourth dose of Hib vaccine both are indicated in a child 15 through 18 months of age.¹⁶⁴

Only limited data exist regarding safety, efficacy, or immunogenicity of different DTaP vaccines administered interchangeably in the primary or booster immunization series.^{100 127 134 149 183 190} ACIP recommends that the same DTaP preparation used for the initial dose be used to complete the primary and booster immunization series whenever possible.^{127 134 149 183} However, if the health-care provider does not know or have available the particular DTaP vaccine used previously in a child, any of the commercially available DTaP vaccines may be used to complete the immunization series.^{100 127 149 183} 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.¹⁸³

Medically stable preterm and low birthweight infants generally should be vaccinated at the usual chronologic age using usual dosage.²⁰⁷ (See Pediatric Precautions under Cautions.)

Interruption of the recommended 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.^{111 112 192 193 198}

If an accelerated immunization schedule is necessary in infants and children 6 weeks through 6 years of age (e.g., for catch-up immunization, immunization prior to travel), minimum intervals between first, second, and third doses of DTaP are 4 weeks; minimum intervals between third, fourth, and fifth doses are 6 months.^{112 121}

In adolescents and adults 11 through 64 years of age, an interval of at least 5 years usually is recommended between Tdap (Adacel, Boostrix) and the last dose of any vaccine containing diphtheria, tetanus, or pertussis antigens,^{192 195 196 205} although an interval as short as 2 years may be used when indicated to provide protection against pertussis (e.g., health-care personnel in direction patient contact, adolescents or adults in close contact with infants <12 months of age).^{195 196 205}

Pediatric Patients

Prevention of Diphtheria, Tetanus, and Pertussis

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