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Tenivac

Generic Name: Diphtheria and Tetanus Toxoids Adsorbed, Tetanus and Diphtheria Toxoids Adsorbed
Class: Toxoids
ATC Class: J07AF01
VA Class: IM105

Introduction

Fixed-combination preparations containing tetanus and diphtheria toxins (toxoids) adsorbed onto aluminum adjuvant.100 112 113 114 Used to stimulate active immunity to diphtheria and tetanus.100 112 113 114 Commercially available as diphtheria and tetanus toxoids adsorbed (DT) and tetanus and diphtheria toxoids adsorbed (Td).112 113 114 DT contains higher dose of diphtheria toxoid than Td.112 113 114

Uses for Tenivac

Prevention of Diphtheria and Tetanus

DT: Prevention of diphtheria and tetanus in infants and children 6 weeks through 6 years of age.100 114 199 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).100 105 114 199

Td: Prevention of diphtheria and tetanus in adults, adolescents, and children ≥7 years of age.112 113 199 199

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.166 229 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 () 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 the US.166 Most diphtheria cases occur in individuals unvaccinated or incompletely vaccinated against the disease.100 105 166

Tetanus is a potentially fatal disease caused by a neurotoxic exotoxin (tetanospasmin) produced by Clostridium tetani.105 113 114 115 166 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.105 115 166 195 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

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.100 105 195 196 199 200 201 205

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.100 105 166 199 Use DT for primary or booster immunization against diphtheria and tetanus only when DTaP cannot be used.100 105 114 166 199

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 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.105 195 196 199 200 201 205 234 235 236 237 238 Use Td for subsequent primary or booster doses.105 195 196 199 200 201 205 236

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.100 105 112 113 166 195 196 205 (See Postexposure Prophylaxis of Tetanus under Uses.)

DT and Td not indicated for treatment of diphtheria or tetanus.113 114

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.100 105 166

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.100 105 195 205

Ideally, complete primary immunization and administer appropriate booster doses prior to pregnancy.100 105 195 205 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).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.)

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 and tetanus 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 the 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 dose of Td.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 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.100 105 166

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,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 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.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 unknown or uncertain.100 105 112 113 195 196 201 205

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).100 105 112 113 166 195 196 201 205

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.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.

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.

Table 1. Summary Guide to Tetanus Prophylaxis in Routine Wound Management195196237

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.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.195 196 201 205 237 Those who previously received a single dose of 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

Tenivac Dosage and Administration

Administration

IM Administration

DT or Td: Administer only by IM injection.112 113 114

Do not administer IV, sub-Q, or intradermally.112 113

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.112 113 114 134 In infants and children 6 weeks to 2 years of age, anterolateral thigh is preferred;134 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

Avoid injection into gluteal area or areas where there may be a major nerve trunk.112 113 114 134 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

Shake vial or syringe well immediately prior to use.112 113 114 Should appear as a uniform, white, cloudy suspension;112 113 114 discard if it contains particulate matter, is discolored, or cannot be resuspended.112 113 114

Do not dilute.112 113 114 Do not mix with any other vaccine or solution.112 113 114

Syncope (vasovagal or vasodepressor reaction; fainting) may occur following vaccination;114 134 may be accompanied by transient neurologic signs (e.g., visual disturbance, paresthesia, tonic-clonic limb movements).134 Occurs most frequently in adolescents and young adults.134 Have procedures in place to avoid falling injury and restore cerebral perfusion following syncope.134 Syncope and secondary injuries may be averted if vaccinees sit or lie down during and for 15 minutes after vaccination.134 If syncope occurs, observe patient until symptoms resolve.134

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.100 105 112 134 195 196 205 (See Postexposure Prophylaxis of Tetanus under Uses.)

May be given simultaneously with other age-appropriate vaccines.100 105 134 199 201 (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

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.100 112 113 114 199 200 Follow age-appropriate recommendations for specific preparation used.112 113 114 199 200

To ensure optimal protection, give complete primary vaccination series and recommended booster doses.113 114 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.100 134 166

Pediatric Patients

Prevention of Diphtheria and Tetanus
Infants and Children 6 Weeks Through 6 Years of Age (DT)
IM

Each dose is 0.5 mL.114

Primary immunization consists of a series of 4 doses with or without a fifth (booster) dose.100 105 114 199

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).100 105 199 Fourth dose may be given as early as 12 months of age, provided at least 6 months have elapsed since 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 completed the primary series before their fourth birthday.100 105 114 199 Fifth dose not necessary if last dose of primary series was given at ≥4 years of age.100 105 199

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.199 Fifth dose not necessary if fourth dose was given at ≥4 years of age.199

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

Each dose is 0.5 mL.112 113

Primary immunization consists of a series of 3 doses;113 199 give second dose 4–8 weeks after first dose and give third dose 6–12 months after second dose.112 113 196 199

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.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 (Td)
IM

Each dose is 0.5 mL.112 113

Primary immunization consists of a series of 3 doses;113 196 199 give second dose 4–8 weeks after first dose and give third dose 6–12 months after second dose.112 113 196 199

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.196 199 Alternatively, substitute Tdap for any 1 of the Td doses.196

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

Booster dose is 0.5 mL.100 105 112 113 196 201

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.100 105 196 199 201

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.195 199 201 If Tdap unavailable or administered previously, use Td.195

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 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.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.100 105 112 113 166 196 201 (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.100 105 Clean and debride wounds properly, especially if dirt or necrotic tissue are present; remove all necrotic tissue and foreign material.105

Children 7 through 10 Years of Age (Td)
IM

Emergency booster dose is 0.5 mL.100 105 112 113

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.100 105 113 166

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.100 113 166 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.100 113 166

Adolescents 11 through 18 Years of Age (Td)
IM

Emergency booster dose is 0.5 mL.100 105 112 113

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.100 105 113 166 196

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.100 113 166 196 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.100 113 166 196

Use single dose of Tdap (instead of Td) if individual has not previously received Tdap.105 166 196 237 If Tdap not available or administered previously, use Td.105 166 196 237

Adults

Prevention of Diphtheria and Tetanus
Primary Immunization in Adults ≥19 Years of Age (Td)
IM

Each dose is 0.5 mL.112 113

Primary immunization in previously unvaccinated adults or those with an uncertain vaccination history consists of a series of 3 doses.100 112 113 195 Give second dose 4–8 weeks after first dose and give third dose 6–12 months after second dose.100 112 113 195 200

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.195 200 Alternatively, substitute Tdap for any 1 of the Td doses.195 200 If Tdap not available or administered previously, use Td.195 200

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

Booster dose is 0.5 mL.100 112 195

After primary immunization, give routine booster dose of Td every 10 years.100 112 195 200 In addition, in the event of injury and possible exposure to tetanus, emergency booster dose of Td may be indicated.100 112 166 195 (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).195 200 236 237 Thereafter, give routine booster dose of Td every 10 years.195 200 237

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 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.100 105 166

Used as an adjunct to anti-infective postexposure prophylaxis.100 166 (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.100 105 112 113 166 195 205 (See Postexposure Prophylaxis of Tetanus under Uses.)

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

Adults ≥19 Years of Age (Td)
IM

Emergency booster dose is 0.5 mL.100 112 113

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.100 113 166

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.100 113 166 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.100 113 166

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).195 200 237 If Tdap not available or administered previously, use Td.196 201 237

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations.

Cautions for Tenivac

Contraindications

  • Severe allergic reaction (e.g., anaphylaxis) after previous dose of DT or Td, any vaccine component, or any preparation containing diphtheria or tetanus toxoids112 113 114 (See Hypersensitivity Reactions under Cautions.)

Warnings/Precautions

Warnings

Frequent Booster Doses

Administer booster doses only when indicated.100 112 113 Booster doses given more frequently than recommended are associated with an increased incidence and severity of adverse effects.100 112 113 195

Administer routine booster doses once every 10 years.112 113 Emergency booster dose not usually indicated unless at least 5 years have elapsed since last dose.113 If booster dose is given sooner than 10 years after previous dose, do not give next routine booster dose for 10 years.113 (See Dosage and Administration.)

Guillain-Barré Syndrome and Other Neurologic Disorders

Guillain-Barré syndrome (GBS) reported in temporal association with tetanus toxoid.113

A review by the Institute of Medicine (IOM) found evidence of a causal relationship between tetanus toxoid and brachial neuritis and GBS.112 113 114 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 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.112 113

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

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.100 112 113 114 117 118 Deaths have been reported.113

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.112 113 114

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.112 113 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.100

Epinephrine and other appropriate agents and equipment should be available for immediate use in case an anaphylactic reaction occurs.112 113 114

Arthus-type Hypersensitivity Reactions

Arthus-type hypersensitivity reactions to tetanus toxoid reported,100 112 195 196 201 most frequently in those who have received a large number of booster doses of preparations containing diphtheria and tetanus toxoids.166

Reaction is an extensive local inflammatory reaction (vasculitis) that generally begins 2–12 hours after a dose.166 195 196 201 There may be severe pain, swelling, induration, edema, hemorrhage, and necrosis.166 195 201 In some cases, painful swelling may extend from the shoulder to the elbow.166

Arthus reactions usually resolve without sequelae.195 196

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.100 113 195 196

Latex Sensitivity

Some packaging components of Td (Tenivac) single-dose syringes (i.e., tip caps) contain dry natural latex.113

Some individuals may be hypersensitive to natural latex proteins.137 138 139 Take appropriate precautions if this preparation administered to individuals with history of latex sensitivity.137 138 139

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.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 the immune response to the vaccine and efficacy may be reduced in these individuals.112 113 114 134 (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.105 155 156 However, immunization may be less effective in HIV-infected individuals than in immunocompetent individuals.105

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,131 134 147 148 151 153 154 157 158 216 217 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.127 128 129 131 134

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.131 134 147 148 151 153 154 157 158 216 217

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).112 FDA states that trace amounts of thimerosal from the manufacturing process are not considered clinically important.104

DT and Td (Tenivac) do not contain thimerosal or any other preservatives.113 114

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.100 134

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).100 134

Limitations of Vaccine Effectiveness

May not protect all individuals from diphtheria and tetanus.112 113 114

Optimum protection against diphtheria and tetanus achieved with a primary series of 3 doses of preparations containing diphtheria and tetanus toxoids adsorbed.100 166

Duration of Immunity

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

Following primary immunization, duration of protection against tetanus is approximately 10 years.105 166 Although some individuals may be protected for life, antitoxin levels decrease over time and only approach minimal protective level in most individuals 10 years after last dose.166 Antitoxin response induced by tetanus toxoid adsorbed has longer duration than that induced by tetanus toxoid fluid (no longer commercially available in US).166

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 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

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 DT or Td that has been mishandled or has not been stored at recommended temperature.134

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

Specific Populations

Pregnancy

Category C.112 113

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.100 105 195 196 201 205

Ideally, complete primary immunization against tetanus and diphtheria prior to pregnancy.100 105 195 205 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.100 105 201 205

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 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).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 of 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

Lactation

Not known whether diphtheria or tetanus toxoids absorbed are distributed into milk.112 113 Manufacturers recommend caution in nursing women.112 113

ACIP states breastfeeding is not considered a contraindication for Td.205

Pediatric Use

DT: Safety and efficacy not established in infants <6 weeks of age or in children ≥7 years of age.114

Td: Safety and efficacy not established in children <7 years of age.112 113

DT contains a higher dose of diphtheria toxoid (25 Lf units) than Td (2 Lf units).112 113 114 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.113 114

Apnea reported following IM administration of vaccines in some infants born prematurely.114 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.114

Geriatric Use

DT: Not indicated in adults, including geriatric adults.114

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;113 rate of solicited adverse events generally similar to that in younger adults.113

Common Adverse Effects

Mild to moderate local reactions at injection site, including erythema,100 112 113 114 warmth,112 114 edema,112 114 tenderness,112 113 induration,100 112 113 114 urticaria,112 114 and rash;112 114 a nodule may be palpable at the injection site.100 113 Mild systemic reactions, including fatigue or malaise,112 113 114 195 fever,100 112 113 114 chills,195 headache,112 113 195 drowsiness,100 fretfulness,100 hypotension,114 nausea,112 114 195 diarrhea,195 vomiting,195 anorexia,100 generalized body ache,195 myalgia,112 arthralgia.100 112 195

Interactions for Tenivac

Other Vaccines

Although specific data not available regarding concurrent administration of DT or Td with all other available vaccines,113 114 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.100 105 199 However, each parenteral vaccine should be administered using a different syringe and different injection site.100 105 199

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).105 134 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).134

Specific Drugs

Drug

Interaction

Comments

Diphtheria antitoxin (equine) (available in the US only from CDC under an investigational new drug [IND] protocol)

Although specific studies are not available, diphtheria antitoxin (equine) is unlikely to impair the immune response to diphtheria toxoid adsorbed100

May be administered simultaneously using different syringes and different injection sites100

Hib vaccine

May be administered simultaneously with (using different syringes and injection sites) or at any time before or after Hib vaccine100 105 199

Immune globulin (immune globulin IM [IGIM], immune globulin IV [IGIV]) or specific hyperimmune globulin (hepatitis B immune globulin [HBIG], rabies immune globulin [RIG], tetanus immune globulin [TIG], varicella zoster immune globulin [VZIG])

May be administered simultaneously with (using different syringes and injection sites) or at any time before or after immune globulin or specific hyperimmune globulin134

For postexposure prophylaxis in wound management, active immunization against tetanus (if indicated) with DT or Td should be initiated at the same time as passive immunization with TIG; however, TIG and the toxoid should be given at separate sites using different syringes100 112 113 114 195 196

Immunosuppressive agents (e.g., alkylating agents, antimetabolites, corticosteroids, radiation)

Individuals receiving immunosuppressive agents may have a diminished immunologic response to diphtheria and tetanus toxoids adsorbed112 113 114

There is some evidence that children receiving immunosuppressive therapy, including those with malignancies receiving maintenance chemotherapy, may have adequate antibody responses to diphtheria and tetanus toxoids adsorbed105 103

Short-term (<2 weeks), low- to moderate-dose systemic corticosteroid therapy; long-term, alternate-day, systemic corticosteroid therapy using low to moderate doses of short-acting drugs; topical corticosteroid therapy (e.g., nasal, cutaneous, ophthalmic); or intra-articular, bursal, or tendon injections with corticosteroids should not be immunosuppressive in usual dosages100 134

Measles, mumps, and rubella vaccine (MMR)

DT and MMR have been administered simultaneously without a decrease in immune response or increase in adverse effects100 105 199

May be administered simultaneously with (using different syringes and different injection sites) or at any interval before or after MMR105 134

Meningococcal vaccine

MCV4 (Menactra): Td has been administered concomitantly with Menactra without reduced antibody response or increased adverse effects;142 201 although clinical importance unclear, antibody responses to certain meningococcal antigens were higher when Menactra was administered concomitantly with Td compared with administration 1 month after Td;142 201 no effect on antibody responses to tetanus and diphtheria antigens142

Td may be administered simultaneously with (using different syringes and different injection sites) or at any interval before or after meningococcal vaccine (Menactra, Menveo, Menomune)134 196 201

Poliovirus vaccine

DT and poliovirus vaccine live oral (OPV; not commercially available in US) have been administered simultaneously without a decrease in immune response or increase in adverse effects100 105 199

May be administered simultaneously with poliovirus vaccine inactivated (IPV) using different syringes and different injection sites105 134

Stability

Storage

Parenteral

Injectable Suspension, for IM use

2–8°C.112 113 114 Do not freeze; discard if freezing occurs.112 113 114

Actions

  • DT and Td are sterile suspensions prepared by mixing suitable quantities of diphtheria and tetanus toxoids that have been formaldehyde-treated, purified, and adsorbed onto an aluminum adjuvant.112 113 114

  • Antigen content of the toxoids is expressed in terms of flocculation units (Lf).112 113 114 Each 0.5 mL of DT contains 25 Lf units of diphtheria toxoid and 5 Lf units of tetanus toxoid.114 Each 0.5 mL of Td contains 2 Lf units of diphtheria toxoid and, depending on the manufacturer, 2 or 5 Lf units of tetanus toxoid.112 113

  • DT and Td stimulate active immunity to diphtheria and tetanus by inducing production of specific neutralizing antitoxin antibodies.105 112 113 114

  • A complete primary immunization series with the age-appropriate preparation is needed to induce optimum levels of antitoxin that provide protection.100 166

  • Diphtheria toxoid component provides protection only against the exotoxin elucidated by C. diphtheriae.113 114 Immunization does not prevent or eliminate colonization or carriage of C. diphtheriae in pharynx, nose, or skin.100

  • Protective levels of diphtheria antitoxin (defined as ≥0.1 international units/mL)113 114 166 195 196 attained in >95% of individuals after primary vaccination series.114 166 Antitoxin levels may persist for 10 years.166

  • Protective levels of tetanus antitoxin (defined as ≥0.1 international units/mL using enzyme-linked immunoabsorbent assay [ELISA])195 196 attained in almost 100% of individuals after the primary vaccination series.166 Antitoxin levels persist for approximately 10 years.100 113 166 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

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 ).112 113 114 226

  • Advise patient and/or patient’s parent or guardian of the risks and benefits of vaccination with tetanus and diphtheria toxoids.112 113 114

  • Importance of receiving the complete primary immunization series and recommended booster doses to ensure highest level of protection against tetanus and diphtheria.100 112 113 114

  • Advise patient that the toxoids may not provide protection in all vaccinees.113 114

  • Advise patient they should not receive tetanus and diphtheria toxoids if they have had a life-threatening allergic reaction to a previous dose.113 114

  • Importance of contacting clinicians if a severe or unusual adverse reaction occurs following a dose.112 113 114 Clinicians or individuals can report any adverse reactions that occur following vaccination to Vaccine Adverse Event Reporting System (VAERS) at 800-822-7967 or .112 113 114

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.112 113 114

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.112 113 114

  • Importance of informing patients of other important precautionary information.112 113 114 (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.

Diphtheria and Tetanus Toxoids Adsorbed (DT)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injectable suspension, for IM use

Diphtheria Toxoid 25 Lf units and Tetanus Toxoid 5 Lf units per 0.5 mL

Diphtheria and Tetanus Toxoids Adsorbed

Sanofi Pasteur

Tetanus and Diphtheria Toxoids Adsorbed (Td)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injectable suspension, for IM use

Tetanus Toxoid 2 Lf units and Diphtheria Toxoid 2 Lf units per 0.5 mL

Tetanus and Diphtheria Toxoids Adsorbed

MassBiologics

Tetanus Toxoid 5 Lf units and Diphtheria Toxoid 2 Lf units per 0.5 mL

Tenivac

Sanofi Pasteur

AHFS DI Essentials. © Copyright, 2016, American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814. Review Date: September 06, 2016.

References

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

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112. MassBiologics. Tetanus and diphtheria toxoids adsorbed suspension for intramuscular injection prescribing information. Boston, MA; 2014 Jul.

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