Introduction

Fixed-combination preparations containing tetanus and diphtheria toxins (toxoids) adsorbed onto aluminum adjuvant. Used to stimulate active immunity to diphtheria and tetanus. Commercially available as diphtheria and tetanus toxoids adsorbed (DT) and tetanus and diphtheria toxoids adsorbed (Td). DT contains higher dose of diphtheria toxoid than Td.

Uses for Diphtheria and Tetanus Toxoids

Prevention of Diphtheria and Tetanus

DT: Prevention of diphtheria and tetanus in infants and children 6 weeks through 6 years of age. Use only when diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed (DTaP) cannot be used (i.e., when pertussis antigens contraindicated or should not be used).

Td: Prevention of diphtheria and tetanus in adults, adolescents, and children ≥7 years of age.

Diphtheria is caused by toxigenic strains of Corynebacterium diphtheriae or, rarely, C. ulcerans. Overall case-fatality rate is 5–10%; higher death rates (up to 20%) among individuals <5 years of age and >40 years of age. Diphtheria uncommon in US, but C. diphtheriae continues to circulate in US areas where the disease previously was endemic. Reported worldwide, particularly in tropical countries; endemic in many countries in Asia, the South Pacific, the Middle East, and Eastern Europe and in Haiti and Dominican Republic. Consult CDC Travelers' Health website ([Web]) for information regarding where diphtheria is endemic. 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 the US. Most diphtheria cases occur in individuals unvaccinated or incompletely vaccinated against the disease.

Tetanus is a potentially fatal disease caused by a neurotoxic exotoxin (tetanospasmin) produced by Clostridium tetani. 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). 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. 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. Obstetric tetanus occurs within 6 weeks after delivery or termination of pregnancy because of contaminated wounds or abrasions or unclean deliveries or abortions. Generalized tetanus is characterized by rigidity and convulsive muscle spasms that usually involve the jaw (lockjaw) and neck and then become generalized. Tetanus occurs worldwide; reported most frequently in densely populated regions in hot, damp climates with soil rich in organic matter. 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. Average of 29 cases reported each year in US from 2001 through 2008 (case fatality rate 13%). Most US cases occur following an acute wound, usually a puncture or contaminated, infected, or devitalized wound. Almost all reported cases occur in individuals unvaccinated or inadequately vaccinated against the disease.

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.

Combination preparation containing antigens for all 3 diseases (DTaP) preferred for primary and booster immunization against these diseases in infants and children 6 weeks through 6 years of age, unless pertussis antigens contraindicated or should not be used. Use DT for primary or booster immunization against diphtheria and tetanus only when DTaP cannot be used.

Td usually preparation of choice for primary and booster immunization against diphtheria and tetanus in individuals ≥7 years of age. However, to reduce morbidity associated with pertussis, ACIP, AAP, and others recommend that a single dose of tetanus toxoid and reduced diphtheria toxoid and acellular pertussis vaccine adsorbed (Tdap) be used in place of a required primary or booster dose of Td in all individuals ≥7 years of age who have not previously received Tdap, unless pertussis antigens contraindicated or should not be used. Use Td for subsequent primary or booster doses.

Combined active immunization with a preparation containing tetanus toxoid adsorbed and passive immunization with tetanus immune globulin (TIG) is used to prevent tetanus in individuals with tetanus-prone wounds who are inadequately vaccinated against tetanus or whose tetanus vaccination status is uncertain. (See Postexposure Prophylaxis of Tetanus under Uses.)

DT and Td not indicated for treatment of diphtheria or tetanus.

Because diphtheria and tetanus infections may not confer immunity against the diseases, initiate or complete primary immunization against diphtheria and tetanus at the time of recovery in any previously unvaccinated or incompletely vaccinated individual.

Preexposure Vaccination Against Tetanus and Diphtheria in High-risk Groups

Pregnant women should be adequately immunized against tetanus and diphtheria; protection against these diseases is conferred to their infants through transplacental transfer of maternal antibody.

Ideally, complete primary immunization and administer appropriate booster doses prior to pregnancy. To ensure protection (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).

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). In addition, to ensure protection against pertussis, these experts recommend give a dose of Tdap during each pregnancy, regardless of prior vaccination history. (See Pregnancy under Cautions.)

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

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. 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; use Td for subsequent booster doses.

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

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

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 the usual age-appropriate catch-up vaccination schedule. 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. When indicated to provide protection against pertussis before travel, Tdap may be administered regardless of interval since last dose of Td.

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. (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.

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). Take samples for cultures prior to giving the anti-infective and continue to observe individual for 7 days for evidence of disease.

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. Contacts who previously completed the primary vaccination series should receive an immediate booster dose of an age-appropriate preparation containing diphtheria toxoid adsorbed if it has been >5 years since their last booster dose.

Diphtheria antitoxin (equine) (available in the US only from CDC under an investigational new drug [IND] protocol) is no longer routinely recommended for postexposure prophylaxis of diphtheria in contacts, but may be recommended in exceptional circumstances for postexposure prophylaxis in individuals with known or suspected exposure to toxigenic Corynebacterium. 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 CDC Emergency Operations Center at 770-488-7100 after hours, on weekends, and holidays.

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 unknown or uncertain.

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).

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. 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.

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).

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.

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.

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. Those who previously received a single dose of Tdap should receive Td for postexposure prophylaxis.

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.

Diphtheria and Tetanus Toxoids Dosage and Administration

Administration

IM Administration

DT or Td: Administer only by IM injection.

Do not administer IV, sub-Q, or intradermally.

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.

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

Avoid injection into gluteal area or areas where there may be a major nerve trunk. 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.

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

Do not dilute. Do not mix with any other vaccine or solution.

Syncope (vasovagal or vasodepressor reaction; fainting) may occur following vaccination; may be accompanied by transient neurologic signs (e.g., visual disturbance, paresthesia, tonic-clonic limb movements). Occurs most frequently in adolescents and young adults. Have procedures in place to avoid falling injury and restore cerebral perfusion following syncope. Syncope and secondary injuries may be averted if vaccinees sit or lie down during and for 15 minutes after vaccination. If syncope occurs, observe patient until symptoms resolve.

When passive immunization with TIG is indicated in addition to active immunization with a preparation containing tetanus toxoid adsorbed for postexposure prophylaxis of tetanus, DT or Td may be given simultaneously with TIG using different syringes and different injection sites. (See Postexposure Prophylaxis of Tetanus under Uses.)

May be given simultaneously with other age-appropriate vaccines. (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. Separate injection sites by at least 1 inch (if anatomically feasible) to allow appropriate attribution of any local adverse effects that may occur.

Dosage

Dosing schedule (i.e., number of doses) and specific preparation for primary and/or booster immunization (i.e., DT, Td) varies depending on age. Follow age-appropriate recommendations for specific preparation used.

To ensure optimal protection, give complete primary vaccination series and recommended booster doses. Interruptions resulting in intervals between doses longer than recommended do not interfere with the final immunity achieved; there is no need to give additional doses or start the vaccination series over.

Pediatric Patients

Prevention of Diphtheria and Tetanus

Infants and Children 6 Weeks Through 6 Years of Age (DT)

Each dose is 0.5 mL.

Primary immunization consists of a series of 4 doses with or without a fifth (booster) dose.

ACIP, AAP, and others recommend that first 3 doses be given 4–8 weeks apart (usually at 2, 4, and 6 months of age) and fourth dose given approximately 6–12 months after third dose (usually at 15–18 months of age). Fourth dose may be given as early as 12 months of age, provided at least 6 months have elapsed since third dose.

At 4 through 6 years of age (usually just prior to entry into kindergarten or elementary school), give fifth (booster) dose to those who completed the primary series before their fourth birthday. Fifth dose not necessary if last dose of primary series was given at ≥4 years of age.

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 after first dose and give fourth and fifth dose at 6-month intervals after third dose. Fifth dose not necessary if fourth dose was given at ≥4 years of age.

Previously Unvaccinated Children 7 through 10 Years of Age (Td)

Each dose is 0.5 mL.

Primary immunization consists of a series of 3 doses; give second dose 4–8 weeks after first dose and give third dose 6–12 months after second dose.

ACIP and others state that preferred primary immunization schedule for catch-up vaccination in previously unvaccinated children 7 through 10 years of age is a single dose of Tdap (unless pertussis antigens contraindicated or should not be used) followed by a dose of Td given 1–2 months after Tdap and a second dose of Td given at least 6–12 months after first Td dose. Alternatively, substitute Tdap for any 1 of the Td doses. Do not give these children a Tdap booster dose at 11 through 12 years of age.

Previously Unvaccinated Adolescents 11 through 18 years (Td)

Each dose is 0.5 mL.

Primary immunization consists of a series of 3 doses; give second dose 4–8 weeks after first dose and give third dose 6–12 months after second dose.

ACIP and others state that preferred primary immunization schedule for catch-up vaccination in previously unvaccinated adolescents 11 through 18 years of age is a single dose of Tdap (unless pertussis antigens contraindicated or should not be used) followed by a dose of Td given at least 4 weeks after Tdap and a second dose of Td given 6–12 months after first Td dose. Alternatively, substitute Tdap for any 1 of the Td doses.

Booster Doses in Adolescents 11 through 18 Years of Age (Td)

Booster dose is 0.5 mL.

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 (DT, Td, DTaP, DTP [not commercially available in US]) receive a booster dose of a preparation containing diphtheria and tetanus toxoids at 11 through 12 years of age.

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. If Tdap unavailable or administered previously, use Td.

Postexposure Prophylaxis of Diphtheria

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

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 and complete the primary vaccination series.

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.

Used as an adjunct to anti-infective postexposure prophylaxis. (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. (See Postexposure Prophylaxis of Tetanus under Uses.)

Wound care is an essential part of postexposure prophylaxis of tetanus and is necessary regardless of vaccination status. Clean and debride wounds properly, especially if dirt or necrotic tissue are present; remove all necrotic tissue and foreign material.

Children 7 through 10 Years of Age (Td)

Emergency booster dose is 0.5 mL.

Individuals who previously received <3 doses of a tetanus-toxoid-containing preparation or whose vaccination status is unknown: Give emergency booster dose of Td as soon as possible if injury and possible exposure to tetanus occurs.

Individuals who previously received ≥3 doses of a tetanus toxoid-containing preparation: Give emergency booster dose of Td 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 a tetanus toxoid-containing preparation. If injury extensive (moderately or very tetanus prone), give emergency booster dose of Td if >5 years have elapsed since primary immunization against tetanus or last booster dose.

Adolescents 11 through 18 Years of Age (Td)

Emergency booster dose is 0.5 mL.

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.

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

Use single dose of Tdap (instead of Td) if individual has not previously received Tdap. If Tdap not available or administered previously, use Td.

Adults

Prevention of Diphtheria and Tetanus

Primary Immunization in Adults ≥19 Years of Age (Td)

Each dose is 0.5 mL.

Primary immunization in previously unvaccinated adults or those with an uncertain vaccination history consists of a series of 3 doses. Give second dose 4–8 weeks after first dose and give third dose 6–12 months after second dose.

Previously unvaccinated adults ≥19 years of age (including those ≥65 years of age): 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 at 6–12 months after first Td dose. Alternatively, substitute Tdap for any 1 of the Td doses. If Tdap not available or administered previously, use Td.

Booster Doses in Adults ≥19 Years of Age (Td)

Booster dose is 0.5 mL.

After primary immunization, give routine booster dose of Td every 10 years. In addition, in the event of injury and possible exposure to tetanus, emergency booster dose of Td may be indicated. (See Postexposure Prophylaxis of Tetanus under Dosage and Administration.)

Adults ≥19 years of age (including those ≥65 years of age) who have not previously received a dose of Tdap: Unless pertussis antigens contraindicated or should not be used, ACIP and others state substitute a single dose of Tdap (instead of Td). Thereafter, give routine booster dose of Td every 10 years.

Postexposure Prophylaxis of Diphtheria

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

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 and complete the primary vaccination series.

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.

Used as an adjunct to anti-infective postexposure prophylaxis. (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. (See Postexposure Prophylaxis of Tetanus under Uses.)

Wound care is an essential part of postexposure prophylaxis of tetanus. Wound care is necessary regardless of vaccination status. Clean and debride wounds properly, especially if dirt or necrotic tissue are present; remove all necrotic tissue and foreign material.

Adults ≥19 Years of Age (Td)

Emergency booster dose is 0.5 mL.

Individuals who previously received <3 doses of a tetanus-toxoid-containing preparation or whose vaccination status is unknown: Give emergency booster dose of Td as soon as possible if an injury and possible exposure to tetanus occurs.

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

Adults ≥19 years of age (including those ≥65 years of age) who have not previously received a dose of Tdap: ACIP and other state substitute a single dose of Tdap (instead of Td). If Tdap not available or administered previously, use Td.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations.

Contraindications

• Severe allergic reaction (e.g., anaphylaxis) after previous dose of DT or Td, any vaccine component, or any preparation containing diphtheria or tetanus toxoids (See Hypersensitivity Reactions under Cautions.)

Warnings/Precautions

Warnings

Frequent Booster Doses

Administer booster doses only when indicated. Booster doses given more frequently than recommended are associated with an increased incidence and severity of adverse effects.

Administer routine booster doses once every 10 years. Emergency booster dose not usually indicated unless at least 5 years have elapsed since last dose. If booster dose is given sooner than 10 years after previous dose, do not give next routine booster dose for 10 years. (See Dosage and Administration.)

Guillain-Barré Syndrome and Other Neurologic Disorders

Guillain-Barré syndrome (GBS) reported in temporal association with tetanus toxoid.

A review by the Institute of Medicine (IOM) found evidence of a causal relationship between tetanus toxoid and brachial neuritis and GBS. 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.

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. Some manufacturers state base decision to administer a preparation containing tetanus toxoid adsorbed to an individual with a history of GBS within 6 weeks after receiving a prior dose on careful consideration of potential benefits and possible risks.

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. ACIP does not consider brachial neuritis a precaution or contraindication for further doses.

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 antigens. Deaths have been reported.

Prior to use, review patient’s health status and history regarding possible sensitivity or any adverse events after previous doses; take all precautions known for preventing allergic or any other adverse effects.

Some manufacturers suggest that if further doses are being considered (e.g., for tetanus postexposure prophylaxis) in an individual with a history of severe allergic reaction to a previous dose, consider consultation with an allergist. Although skin testing has been suggested to help determine whether additional doses of a tetanus toxoid-containing preparation can be used in an individuals who developed a systemic reaction to the toxoid, utility of skin testing has been questioned since mild, nonspecific skin-test reactivity to tetanus toxoid commonly occurs, particularly when the preparation is used undiluted.

Epinephrine and other appropriate agents and equipment should be available for immediate use in case an anaphylactic reaction occurs.

Arthus-type Hypersensitivity Reactions

Arthus-type hypersensitivity reactions to tetanus toxoid reported, most frequently in those who have received a large number of booster doses of preparations containing diphtheria and tetanus toxoids.

Reaction is an extensive local inflammatory reaction (vasculitis) that generally begins 2–12 hours after a dose. There may be severe pain, swelling, induration, edema, hemorrhage, and necrosis. In some cases, painful swelling may extend from the shoulder to the elbow.

Arthus reactions usually resolve without sequelae.

Individuals who have Arthus-type hypersensitivity reactions or a temperature >39.4°C following a dose of a tetanus toxoid-containing preparation usually have high serum tetanus antitoxin levels and generally should not receive doses more frequently than every 10 years, even if postexposure prophylaxis against tetanus is indicated.

Latex Sensitivity

Some packaging components of Td (Tenivac) single-dose syringes (i.e., tip caps) contain dry natural latex.

Some individuals may be hypersensitive to natural latex proteins. Take appropriate precautions if this preparation administered to individuals with history of latex sensitivity.

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 the benefits of vaccination outweigh the risk of a potential allergic reaction. Contact-type allergy is the most common type of latex sensitivity.

General Precautions

Individuals with Altered Immunocompetence

If administered to individuals immunosuppressed as the result of disease or immunosuppressive therapy, consider possibility that the immune response to the vaccine and efficacy may be reduced in these individuals. (See Specific Drugs under Interactions.)

Recommendations regarding use of tetanus and diphtheria toxoids in HIV-infected individuals are the same as those for individuals who are not HIV-infected. However, immunization may be less effective in HIV-infected individuals than in immunocompetent individuals.

Thimerosal Precautions

Although there is no convincing evidence that the low concentrations of thimerosal (a mercury-containing preservative) contained in some vaccines is harmful to vaccine recipients, efforts to eliminate or reduce the thimerosal content in vaccines is recommended as a prudent measure to reduce mercury exposure in infants and children and part of an overall strategy to reduce mercury exposures from all sources, including food and drugs.

It was suggested that thimerosal in vaccines theoretically could have adverse effects in vaccine recipients; however, there is no conclusive evidence that the low levels of thimerosal contained in vaccines cause harm in vaccine recipients.

Td (manufactured by MassBiologics) is formulated without preservatives, but contains trace amounts of thimerosal from the manufacturing process (≤0.3 mcg of mercury per 0.5-mL dose). FDA states that trace amounts of thimerosal from the manufacturing process are not considered clinically important.

DT and Td (Tenivac) do not contain thimerosal or any other preservatives.

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.

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).

Limitations of Vaccine Effectiveness

May not protect all individuals from diphtheria and tetanus.

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

Duration of Immunity

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

Following primary immunization, duration of protection against tetanus is approximately 10 years. 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. Antitoxin response induced by tetanus toxoid adsorbed has longer duration than that induced by tetanus toxoid fluid (no longer commercially available in US).

Pre- and Postvaccination Serologic Testing

Routine prevaccination serologic testing not recommended.

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

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. 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.

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.

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

Do not administer DT or Td that has been mishandled or has not been stored at recommended temperature.

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

Specific Populations

Pregnancy

Category C.

Because of risks associated with tetanus and diphtheria infection, ACIP, AAP, and AAFP state pregnancy not considered a contraindication for preparations containing diphtheria and tetanus antigens.

Ideally, complete primary immunization against tetanus and diphtheria prior to pregnancy. Although there is no evidence that the toxoids are teratogenic, waiting until second or third trimester of pregnancy (and before 36 weeks of gestation) to administer Td is recommended.

Although Td generally preferred preparation for primary immunization against diphtheria and tetanus during pregnancy, 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. In addition, to ensure protection against pertussis, these experts recommend a dose of Tdap during each pregnancy, regardless of woman's prior vaccination history. To maximize maternal antibody response and passive antibody transfer to infant, optimal timing for Tdap dose is between 27 and 36 weeks of gestation.

Pregnant women who were previously vaccinated but received most recent dose of a preparation containing tetanus and diphtheria antigens ≥10 years ago should receive a booster dose of a preparation containing tetanus and diphtheria toxoids adsorbed during second or third trimester of pregnancy (and before 36 weeks of gestation). 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). Use Tdap (instead of Td) for the booster dose; preferably give Tdap during third trimester (optimally between 27 and 36 weeks of gestation).

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

Lactation

Not known whether diphtheria or tetanus toxoids absorbed are distributed into milk. Manufacturers recommend caution in nursing women.

ACIP states breastfeeding is not considered a contraindication for Td.

Pediatric Use

DT: Safety and efficacy not established in infants <6 weeks of age or in children ≥7 years of age.

Td: Safety and efficacy not established in children <7 years of age.

DT contains a higher dose of diphtheria toxoid (25 Lf units) than Td (2 Lf units). Because individuals ≥7 years of age have an increased incidence of adverse reactions to preparations containing >2 Lf units of diphtheria toxoid, DT should not be used in individuals ≥7 years of age.

Apnea reported following IM administration of vaccines in some infants born prematurely. 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.

Geriatric Use

DT: Not indicated in adults, including geriatric adults.

Td: Proportion of adults ≥65 years of age with seroprotective antibody levels after single dose of Td (Tenivac) in clinical study was marginally lower for tetanus and lower for diphtheria compared with younger individuals; rate of solicited adverse events generally similar to that in younger adults.

Common Adverse Effects

Mild to moderate local reactions at injection site, including erythema, warmth, edema, tenderness, induration, urticaria, and rash; a nodule may be palpable at the injection site. Mild systemic reactions, including fatigue or malaise, fever, chills, headache, drowsiness, fretfulness, hypotension, nausea, diarrhea, vomiting, anorexia, generalized body ache, myalgia, arthralgia.

Administration

IM Administration

DT or Td: Administer only by IM injection.

Do not administer IV, sub-Q, or intradermally.

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.

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

Avoid injection into gluteal area or areas where there may be a major nerve trunk. 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.

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

Do not dilute. Do not mix with any other vaccine or solution.

Syncope (vasovagal or vasodepressor reaction; fainting) may occur following vaccination; may be accompanied by transient neurologic signs (e.g., visual disturbance, paresthesia, tonic-clonic limb movements). Occurs most frequently in adolescents and young adults. Have procedures in place to avoid falling injury and restore cerebral perfusion following syncope. Syncope and secondary injuries may be averted if vaccinees sit or lie down during and for 15 minutes after vaccination. If syncope occurs, observe patient until symptoms resolve.

When passive immunization with TIG is indicated in addition to active immunization with a preparation containing tetanus toxoid adsorbed for postexposure prophylaxis of tetanus, DT or Td may be given simultaneously with TIG using different syringes and different injection sites. (See Postexposure Prophylaxis of Tetanus under Uses.)

May be given simultaneously with other age-appropriate vaccines. (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. Separate injection sites by at least 1 inch (if anatomically feasible) to allow appropriate attribution of any local adverse effects that may occur.

Dosage

Dosing schedule (i.e., number of doses) and specific preparation for primary and/or booster immunization (i.e., DT, Td) varies depending on age. Follow age-appropriate recommendations for specific preparation used.

To ensure optimal protection, give complete primary vaccination series and recommended booster doses. Interruptions resulting in intervals between doses longer than recommended do not interfere with the final immunity achieved; there is no need to give additional doses or start the vaccination series over.

Pediatric Patients

Prevention of Diphtheria and Tetanus

Infants and Children 6 Weeks Through 6 Years of Age (DT)

Each dose is 0.5 mL.

Primary immunization consists of a series of 4 doses with or without a fifth (booster) dose.

ACIP, AAP, and others recommend that first 3 doses be given 4–8 weeks apart (usually at 2, 4, and 6 months of age) and fourth dose given approximately 6–12 months after third dose (usually at 15–18 months of age). Fourth dose may be given as early as 12 months of age, provided at least 6 months have elapsed since third dose.

At 4 through 6 years of age (usually just prior to entry into kindergarten or elementary school), give fifth (booster) dose to those who completed the primary series before their fourth birthday. Fifth dose not necessary if last dose of primary series was given at ≥4 years of age.

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 after first dose and give fourth and fifth dose at 6-month intervals after third dose. Fifth dose not necessary if fourth dose was given at ≥4 years of age.

Previously Unvaccinated Children 7 through 10 Years of Age (Td)

Each dose is 0.5 mL.

Primary immunization consists of a series of 3 doses; give second dose 4–8 weeks after first dose and give third dose 6–12 months after second dose.

ACIP and others state that preferred primary immunization schedule for catch-up vaccination in previously unvaccinated children 7 through 10 years of age is a single dose of Tdap (unless pertussis antigens contraindicated or should not be used) followed by a dose of Td given 1–2 months after Tdap and a second dose of Td given at least 6–12 months after first Td dose. Alternatively, substitute Tdap for any 1 of the Td doses. Do not give these children a Tdap booster dose at 11 through 12 years of age.

Previously Unvaccinated Adolescents 11 through 18 years (Td)

Each dose is 0.5 mL.

Primary immunization consists of a series of 3 doses; give second dose 4–8 weeks after first dose and give third dose 6–12 months after second dose.

ACIP and others state that preferred primary immunization schedule for catch-up vaccination in previously unvaccinated adolescents 11 through 18 years of age is a single dose of Tdap (unless pertussis antigens contraindicated or should not be used) followed by a dose of Td given at least 4 weeks after Tdap and a second dose of Td given 6–12 months after first Td dose. Alternatively, substitute Tdap for any 1 of the Td doses.

Booster Doses in Adolescents 11 through 18 Years of Age (Td)

Booster dose is 0.5 mL.

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 (DT, Td, DTaP, DTP [not commercially available in US]) receive a booster dose of a preparation containing diphtheria and tetanus toxoids at 11 through 12 years of age.

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. If Tdap unavailable or administered previously, use Td.

Postexposure Prophylaxis of Diphtheria

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

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 and complete the primary vaccination series.

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.

Used as an adjunct to anti-infective postexposure prophylaxis. (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. (See Postexposure Prophylaxis of Tetanus under Uses.)

Wound care is an essential part of postexposure prophylaxis of tetanus and is necessary regardless of vaccination status. Clean and debride wounds properly, especially if dirt or necrotic tissue are present; remove all necrotic tissue and foreign material.

Children 7 through 10 Years of Age (Td)

Emergency booster dose is 0.5 mL.

Individuals who previously received <3 doses of a tetanus-toxoid-containing preparation or whose vaccination status is unknown: Give emergency booster dose of Td as soon as possible if injury and possible exposure to tetanus occurs.

Individuals who previously received ≥3 doses of a tetanus toxoid-containing preparation: Give emergency booster dose of Td 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 a tetanus toxoid-containing preparation. If injury extensive (moderately or very tetanus prone), give emergency booster dose of Td if >5 years have elapsed since primary immunization against tetanus or last booster dose.

Adolescents 11 through 18 Years of Age (Td)

Emergency booster dose is 0.5 mL.

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.

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

Use single dose of Tdap (instead of Td) if individual has not previously received Tdap. If Tdap not available or administered previously, use Td.

Adults

Prevention of Diphtheria and Tetanus

Primary Immunization in Adults ≥19 Years of Age (Td)

Each dose is 0.5 mL.

Primary immunization in previously unvaccinated adults or those with an uncertain vaccination history consists of a series of 3 doses. Give second dose 4–8 weeks after first dose and give third dose 6–12 months after second dose.

Previously unvaccinated adults ≥19 years of age (including those ≥65 years of age): 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 at 6–12 months after first Td dose. Alternatively, substitute Tdap for any 1 of the Td doses. If Tdap not available or administered previously, use Td.

Booster Doses in Adults ≥19 Years of Age (Td)

Booster dose is 0.5 mL.

After primary immunization, give routine booster dose of Td every 10 years. In addition, in the event of injury and possible exposure to tetanus, emergency booster dose of Td may be indicated. (See Postexposure Prophylaxis of Tetanus under Dosage and Administration.)

Adults ≥19 years of age (including those ≥65 years of age) who have not previously received a dose of Tdap: Unless pertussis antigens contraindicated or should not be used, ACIP and others state substitute a single dose of Tdap (instead of Td). Thereafter, give routine booster dose of Td every 10 years.

Postexposure Prophylaxis of Diphtheria

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

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 and complete the primary vaccination series.

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.

Used as an adjunct to anti-infective postexposure prophylaxis. (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. (See Postexposure Prophylaxis of Tetanus under Uses.)

Wound care is an essential part of postexposure prophylaxis of tetanus. Wound care is necessary regardless of vaccination status. Clean and debride wounds properly, especially if dirt or necrotic tissue are present; remove all necrotic tissue and foreign material.

Adults ≥19 Years of Age (Td)

Emergency booster dose is 0.5 mL.

Individuals who previously received <3 doses of a tetanus-toxoid-containing preparation or whose vaccination status is unknown: Give emergency booster dose of Td as soon as possible if an injury and possible exposure to tetanus occurs.

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

Adults ≥19 years of age (including those ≥65 years of age) who have not previously received a dose of Tdap: ACIP and other state substitute a single dose of Tdap (instead of Td). If Tdap not available or administered previously, use Td.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations.

Other Vaccines

Although specific data not available regarding concurrent administration of DT or Td with all other available vaccines, primary immunization against diphtheria and tetanus can be integrated with primary immunization against pertussis, Haemophilus influenzae type b (Hib), hepatitis A, hepatitis B, influenza, measles, mumps, rubella, meningococcal disease, pneumococcal disease, poliomyelitis, rotavirus, and varicella. However, each parenteral vaccine should be administered using a different syringe and different injection site.

DT or Td may be administered simultaneously with or at any interval before or after live viral vaccines, including measles, mumps, and rubella vaccine (MMR). In addition, DT or Td may be administered simultaneously with or at any interval before or after inactivated vaccines, including Hib vaccine, hepatitis B vaccine (HepB), and poliovirus vaccine inactivated (IPV).

Specific Drugs