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Tetanus Immune Globulin

Class: Serums
ATC Class: J07AM52
VA Class: IM500
Brands: HyperTET S/D

Introduction

Specific immune globulin (hyperimmune globulin).104 106 Tetanus immune globulin (TIG) contains tetanus antitoxin and is used to provide temporary passive immunity to tetanus.104 106 110 111 TIG commercially available in the US is prepared from plasma of donors immunized with tetanus toxoid.104 Other tetanus antitoxin preparations (e.g., equine tetanus antitoxin) may be available in other countries.101

Uses for Tetanus Immune Globulin

Postexposure Prophylaxis of Tetanus

Postexposure prophylaxis of tetanus in individuals with tetanus-prone wounds who have previously received <3 doses of a preparation containing tetanus toxoid adsorbed or whose tetanus vaccination status is uncertain.100 101 103 104 110 112 113 115

TIG provides temporary passive immunity against tetanus.100 104 110 It is not a substitute for active immunization with a preparation containing tetanus toxoid adsorbed and is not a substitute for adequate medical and surgical care of contaminated or potentially contaminated wounds.100 101 (See General under Dosage and Administration.)

Tetanus is a potentially fatal disease caused by a neurotoxic exotoxin produced by Clostridium tetani (tetanospasmin).101 110 111 C. tetani spores are ubiquitous in the environment and are found in soil and in animal (e.g., horses, sheep, cattle, dogs, cats, rats, guinea pigs, chickens) and human intestinal tracts.100 101 110 111 The spores can contaminate open wounds, especially puncture wounds or those with devitalized tissue; anaerobic wound conditions allow the spores to germinate and produce exotoxins that disseminate through the blood and lymphatic system.101 110 Neonatal tetanus occurs in infants born under nonsterile conditions to women inadequately vaccinated against tetanus; infection usually involves a contaminated umbilical stump and occurs because infant does not have passively acquired maternal antibodies against tetanus.100 101 110 111 115 Obstetric tetanus occurs within 6 weeks after delivery or termination of pregnancy because of contaminated wounds or abrasions or unclean deliveries or abortions.115 Generalized tetanus is characterized by rigidity and convulsive muscle spasms that usually involve the jaw (lockjaw) and neck and then become generalized.101 110 111 Tetanus occurs worldwide, almost exclusively in individuals who are unvaccinated or inadequately vaccinated against the disease.101 111 An average of 31 cases reported each year in the US from 2000 through 2007 (case fatality rate 10%);110 20 cases reported in 2003.110 Most cases of tetanus in the US occur following acute injuries or wounds (puncture wounds, lacerations, abrasions) and usually occur in adults ≥40 years of age; however, an increase in the disease has been reported in younger adults (e.g., heroin abusers).110 116

Tetanus-prone wounds include wounds contaminated with dirt, feces, soil, or saliva; puncture wounds; avulsions; and wounds resulting from crushing, burns, or frostbite.100 101 103 110 111 Tetanus also has been associated with apparently clean, superficial wounds, surgical procedures, insect bites, animal bites, dental infections, chronic sores and infections, and IV drug abuse.110 111 Tetanus is not transmitted person-to-person.110 111

TIG is not necessary for tetanus postexposure prophylaxis in patients with clean, minor wounds (regardless of their immunization status) or for patients with tetanus-prone wounds who have previously received ≥3 doses of a preparation containing tetanus toxoid adsorbed.100 101 103

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).100 101 110 112 113 115 See Table 1 for ACIP guidelines regarding tetanus postexposure prophylaxis.100 112 113

Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed (Tdap). A dose of Tdap is preferred to a dose of Td in adolescents and adults 11 through 64 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.

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

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

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

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

Adapted from the Recommendations of the Immunization Practices Advisory Committee (ACIP) on prevention of diphtheria, tetanus, and pertussis published in MMWR Recomm Rep. 1991; 40(RR-10):1-28, MMWR Recomm Rep. 2006; 55(RR-3):1-43, and MMWR Recomm Rep. 2006; 55(RR-17):1-37.

Table 1. Summary Guide to Tetanus Prophylaxis in Routine Wound Management100112113

 

Clean, Minor Wounds

All Other Wounds

Previous Doses of Tetanus Toxoid Adsorbed Received

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.100 104 112 113 115

Anti-infectives are not indicated for tetanus postexposure prophylaxis.100 110

Treatment of Tetanus

Treatment of tetanus.101 104 110 111 115 Used in conjunction with an anti-infective active against C. tetani (e.g., metronidazole, penicillin G) and with sedatives and muscle relaxants as needed.101 111 115

Treatment of neonatal tetanus in conjunction with an anti-infective active against C. tetani (e.g., penicillin G).108 109

Evidence of effectiveness of TIG in the treatment of active tetanus infection is limited and optimum dosage not established.101 104 Although TIG can neutralize unbound exotoxin, it does not affect toxin already bound to nerve endings.110

Recovery from tetanus does not result in naturally-acquired tetanus immunity.100 104 110 111 As soon as possible, initiate or complete active immunization against tetanus using a preparation containing tetanus toxoid adsorbed.100 104 110 111

Tetanus Immune Globulin Dosage and Administration

General

  • Wound care is an essential part of postexposure prophylaxis or treatment of tetanus.100 101 104 110 111 Wound care is necessary regardless of vaccination status.100 101 104 110 Clean and debride wounds properly, especially if dirt or necrotic tissue is present; remove all necrotic tissue and foreign material.101 110

  • For treatment of tetanus, an anti-infective active against C. tetani (e.g., metronidazole or penicillin G given for 10–14 days) may be indicated in addition to TIG.101 Control tetanic muscle spasms as indicated.101 111 (See Treatment of Tetanus under Uses.)

Administration

IM Administration

Administer by deep IM injection.104

Do not administer IV101 104 or intrathecally.101 (See Administration Precautions under Cautions.)

Some clinicians recommend that part of the TIG dose be infiltrated locally around wound;101 110 efficacy of this approach not proven.101

IM injections of TIG preferably should be made into the anterolateral aspect of the thigh or deltoid muscle.104 Because of the risk of injury to the sciatic nerve, the gluteal muscle should not be used as an injection site.104

Although the manufacturer recommends that aspiration (i.e., pulling back on the syringe plunger after needle insertion and before injection) be performed to ensure that a blood vessel has not been entered,104 ACIP and AAP state this procedure is not required because large blood vessels are not present at recommended IM injection sites.101 106

Do not administer TIG in the same syringe or at the same injection site as tetanus toxoid adsorbed.100 101 104 106 115 (See Specific Drugs under Interactions.)

Do not mix with other immune globulins, vaccines, or solutions.101 104

Dosage

Pediatric Patients

Postexposure Prophylaxis of Tetanus
Children <7 Years of Age
IM

Single dose of 4 units/kg.104 Consider using adult dosage (single dose of 250 units) regardless of child’s size since theoretically the amount of toxin produced by C. tetani in a child’s body would be the same as that produced in an adult’s body.104

Children ≥7 Years of Age
IM

Single dose of 250 units.104

Treatment of Tetanus
Children
IM

3000–6000 units usually recommended.101 110 Optimum dosage not established;101 104 adjust dosage according to severity of infection.104

Some clinicians suggest that a portion of the TIG dose be infiltrated locally around the wound,101 110 although efficacy of this approach has not been established.101

Neonatal Tetanus
IM

500 units has been administered in conjunction with anti-infective therapy (e.g., 10-day regimen of penicillin G).108 109

Adults

Postexposure Prophylaxis of Tetanus
IM

Single dose of 250 units.100 101 104

Treatment of Tetanus
IM

3000–6000 units usually recommended.101 110 Optimum dosage not established;101 104 adjust dosage according to severity of infection.104

Some clinicians suggest that a portion of the TIG dose be infiltrated locally around the wound,101 110 although efficacy of this approach has not been established.101

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations.

Cautions for Tetanus Immune Globulin

Contraindications

  • Manufacturer states none known.104

Warnings/Precautions

Warnings

Risk of Transmissible Agents in Plasma-derived Preparations

Because TIG is prepared from pooled human plasma, it may carry a risk of transmitting infectious agents, including the causative agents of viral hepatitis and HIV infection, and theoretically may carry a risk of transmitting the causative agent of Creutzfeldt-Jakob disease (CJD) or variant CJD (vCJD).104 107

Improved donor screening, viral-inactivation procedures (e.g., solvent/detergent treatment), and/or filtration procedures have reduced, but not completely eliminated, risk of pathogen transmission with plasma-derived preparations.104

The manufacturing process for TIG includes certain chemical (solvent/detergent) treatment procedures and/or heat-treatment procedures to reduce viral infectious potential.104

Because no purification method has been shown to be totally effective in removing the risk of viral infectivity from plasma-derived preparations and because new blood-borne viruses or other disease agents may emerge which may not be inactivated by the manufacturing process or the chemical (solvent/detergent) treatment procedures currently used, administer TIG only when a benefit is expected.104

Any infection believed to have been transmitted by TIG should be reported to the manufacturer at 800-520-2807.104

Sensitivity Reactions

Hypersensitivity Reactions

Sensitization to repeated injections of human immune globulin occurs rarely.104

Angioedema, nephrotic syndrome, and anaphylactic shock reported rarely.104

Use caution in individuals who have exhibited previous systemic allergic reactions to immune globulin.104

Skin testing (i.e., intradermal injection of concentrated IgG solutions) is unreliable since localized areas of inflammation may occur as the result of localized tissue irritation and can be misinterpreted as a positive allergy reaction.104

Epinephrine and other appropriate agents should be readily available in case anaphylaxis or other serious allergic reaction occurs.104

General Precautions

Individuals with Altered Immunocompetence

Recommendations regarding use of TIG in individuals with altered immunocompetence are the same as those for individuals who are not immunocompromised.105

ACIP states that recommendations concerning use of TIG in patients with altered immunocompetence, including HIV-infected individuals or those severely immunocompromised because of congenital immunodeficiency, leukemia, lymphoma, aplastic anemia, generalized malignancy, or therapy with alkylating agents, antimetabolites, radiation, or corticosteroids, are the same as those for patients who are not immunocompromised.105

AAP states that TIG should be used in the management of tetanus prone wounds in all HIV-infected individuals, regardless of their tetanus immunization history.101

Administration Precautions

Do not administer TIG in the same syringe or at the same injection site as tetanus toxoid adsorbed.100 101 104 106 (See Specific Drugs under Interactions.)

Avoid inadvertent IV administration of TIG; serious systemic reactions (e.g., precipitous decrease in BP, anaphylaxis-like reaction) have occurred following inadvertent IV administration of immune globulin intended for IM administration.104

Individuals with Bleeding Disorders

Because bleeding may occur following IM administration in individuals with thrombocytopenia or a bleeding disorder (e.g., hemophilia) or in those receiving anticoagulant therapy, use in such individuals only if benefits outweigh risks.104 106

ACIP states that IM injections can be used in individuals who have bleeding disorders or are receiving anticoagulant therapy if a clinician familiar with the patient's bleeding risk determines that the injection can be administered with reasonable safety.106 In these cases, use a fine needle (23 gauge) to administer the dose and apply firm pressure to the injection site (without rubbing) for ≥2 minutes.106 If patient is receiving antihemophilia therapy, administer the IM dose shortly after a scheduled dose of such therapy.106

Advise individual and/or their family about the risk of hematoma from IM injections.106

Duration of Immunity

TIG provides only short-term protection against tetanus.104 110

As soon as possible, initiate or complete active immunization against tetanus using a preparation containing tetanus toxoid adsorbed.100 110

Specific Populations

Pregnancy

Category C.104

Use during pregnancy only when clearly needed.104

ACIP states that pregnancy is not generally considered a contraindication to use of TIG for treatment or postexposure prophylaxis of tetanus.103 115

Pediatric Use

Safety and efficacy not established in children.104

AAP recommends that postexposure prophylaxis (including use of TIG) in children follow the same guidelines as those in adults.101

Geriatric Use

Information not available regarding differences in efficacy and safety between geriatric and younger individuals.

Common Adverse Effects

Slight soreness at site of injection, low-grade fever.104

Interactions for Tetanus Immune Globulin

Inactivated Vaccines and Toxoids

Immune globulins, including TIG, are not expected to have a clinically important effect on the immune response to inactivated vaccines or toxoids; inactivated vaccines, recombinant vaccines, polysaccharide vaccines, and toxoids may be administered simultaneously with (using different syringes and different injection sites) or at any interval before or after administration of TIG.106

Live Vaccines

Antibodies present in immune globulins, including TIG, may interfere with the immune response to certain live virus vaccines (e.g., measles, mumps, and rubella virus vaccine live [MMR], rotavirus vaccine live oral, varicella virus vaccine live).101 104 106 (See Specific Drugs under Interactions.) There is no evidence that immune globulin preparations interfere with the immune response to yellow fever virus vaccine live, typhoid vaccine live oral, influenza virus vaccine live intranasal, or poliovirus vaccine live oral (OPV; no longer commercially available in the US).106

Specific Drugs

Drug

Interaction

Comments

Influenza vaccine

Intranasal live influenza vaccine: No evidence that immune globulin preparations interfere with the immune response to the vaccine106

Parenteral inactivated influenza vaccine: Interference with the immune response to this inactivated vaccine is not expected106

Intranasal live influenza vaccine or parenteral inactivated influenza vaccine may be given simultaneously with or at any interval before or after TIG106

Measles, mumps, and rubella vaccine (MMR)

Immune globulin preparations, including TIG, may interfere with the immune response to measles and rubella antigens contained in MMR; the effect of TIG on the immune response to mumps antigen in the vaccine is unknown106

MMR should not be administered simultaneously with or within 3 months before or after TIG104 106

If TIG is administered <14 days after MMR, revaccination is necessary at least 3 months after the TIG dose, unless serologic testing indicates that there was an adequate antibody response to all 3 antigens contained in MMR106

Rotavirus vaccine

TIG may interfere with the immune response to rotavirus vaccine106

Safety and efficacy data not available regarding use of rotavirus vaccine in infants who have received an immune globulin within 42 days114

Rotavirus vaccine may be administered simultaneously with or at any time before or after blood or antibody-containing preparations117 118

Tetanus toxoid adsorbed

Active immunization against tetanus should be initiated at the same time as passive immunization with TIG; however, TIG and preparations containing tetanus toxoid adsorbed should be given at separate sites using different syringes101 104 112 113 115

Typhoid vaccine

Oral live typhoid vaccine (Vivotif): No evidence that immune globulin preparations interfere with the immune response to the vaccine106

Parenteral inactivated typhoid vaccine (Typhim Vi): Specific studies evaluating concomitant use with immune globulins not available; interaction not expected since this is an inactivated vaccine106

Oral live typhoid vaccine (Vivotif): May be given simultaneously with or at any time before or after TIG106

Parenteral inactivated vaccines may be given simultaneously with TIG (using different syringes and injection sites) or at any time before or after TIG106

Varicella vaccine

Immune globulin preparations, including TIG, may interfere with the immune response to varicella vaccine live106

Varicella vaccine live should not be administered simultaneously with or within 3 months before or after TIG106

If TIG is administered <14 days after varicella vaccine live, revaccination is necessary at least 3 months after the TIG dose, unless serologic testing indicates that there was an adequate antibody response to the vaccine106

Yellow fever vaccine

No evidence that immune globulin preparations interfere with the immune response to yellow fever virus vaccine live106

Yellow fever vaccine may be given simultaneously with TIG (using different syringes and injection sites) or at any time before or after TIG106

Tetanus Immune Globulin Pharmacokinetics

Elimination

Half-life

Approximately 28 days.a

Stability

Storage

Parenteral

Injection, for IM Use

2–8°C.104 Do not freeze; if freezing occurs, discard TIG.104

Does not contain thimerosal or any other preservatives.104

Actions

  • TIG is a sterile, concentrated, nonpyrogenic solution of immunoglobulins prepared by cold alcohol fractionation from plasma of adults immunized with tetanus toxoid.104

  • TIG contains 15–18% protein.104 It is standardized against US Standard Antitoxin and US Control Tetanus Toxin to contain ≥250 tetanus antitoxin units per dose.104

  • Used to provide temporary passive immunity to tetanus.100 101 104 110 112 113 115

  • Tetanus antitoxin antibodies in TIG neutralize exotoxin produced by C. tetani, the causative organism of tetanus.104 115 TIG can only neutralize unbound exotoxin, it does not affect toxin already bound to nerve endings.110

  • Tetanus incubation period is usually 8–10 days (range 3–21 days) following infection of a wound.101 110 111 Symptoms of neonatal tetanus usually occur during the first 2 weeks of life.101 110

Advice to Patients

  • Advise patient and/or patient's parent or guardian of the risks and benefits of TIG.104

  • Advise patient and/or patient's parent or guardian that TIG is only one component of a postexposure regimen used to prevent tetanus in unvaccinated or incompletely vaccinated individuals with a tetanus-prone wound.104 Importance of completing active immunization with a preparation containing tetanus toxoid adsorbed as soon as possible.101 104 110

  • Importance of informing clinicians if any adverse reactions (e.g., hypersensitivity reactions) occur.104

  • Advise patient and/or patient's parent or guardian that HyperTET S/D is prepared from pooled human plasma.104 Although improved donor screening and viral-inactivating and purification procedures used in manufacture of plasma-derived preparations have reduced the risk of pathogen transmission, TIG is a potential vehicle for transmission of human viruses, including the causative agents of viral hepatitis and HIV infection, and theoretically may carry a risk of transmitting the causative agent of CJD or vCJD.104

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.104

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breastfeed.104

  • Importance of informing patients of other important precautionary information. (See Cautions.) 104

Preparations

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

Tetanus Immune Globulin

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IM use

≥250 units

HyperTET S/D (solvent/detergent treated)

Talecris

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions September 1, 2010. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

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

References

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

100. Centers for Disease Control. Diphtheria, tetanus, and pertussis: recommendations for vaccine use and other preventive measures: Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR Recomm Rep. 1991; 40(RR-10):1-28.

101. American Academy of Pediatrics. Red Book: 2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009.

102. Abrutyn E, Berlin JA. Intrathecal therapy in tetanus: a meta-analysis. JAMA. 1991;266:2262-7.

103. Centers for Disease Control. Update on adult immunization: recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR Recomm Rep. 1991; 40(RR-12):18,49,70,87.

104. Talecris Biotherapeutics. HyperTET S/D (tetanus immune globulin [human]) solvent/detergent treated prescribing information. Research Triangle Park, NC; 2008 May.

105. Centers for Disease Control and Prevention. Recommendations of the Advisory Committee on Immunization Practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence. MMWR Recomm Rep. 1993; 42(RR-4):1-18.

106. Centers for Disease Control and Prevention. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006; 55(RR-15):1-48.

107. US Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research (CBER). Guidance for industry. Revised preventive measures to reduce the possible risk of transmission of Creutzfeldt-Jakob disease (CJD) and variant Creutzfeldt-Jakob disease (vCJD) by blood and blood products. May 2010. From FDA website.

108. Craig AS, Reed GW, Mohon RT et al. Neonatal tetanus in the United States: a sentinel event in the foreign-born. Pediatr Infect Dis J. 1997; 16:955-9. [PubMed 9380471]

109. Centers for Disease Control and Prevention. Neonatal tetanus—Montana, 1998. MMWR Morb Mortal Wkly Rep. 1998; 47:928-30. [IDIS 414319] [PubMed 9822366]

110. Centers for Disease Control and Prevention. Epidemiology and prevention of vaccine-preventable diseases. 11th ed. Washington, DC: Public Health Foundation; 2009.

111. Centers for Disease Control and Prevention. Health information for international travel, 2010. Atlanta, GA: US Department of Health and Human Services; 2010. Updates available from CDC website.

112. Kretsinger K, Broder KR, Cortese MM et al. Preventing tetanus, diphtheria, and pertussis among adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine recommendations of the Advisory Committee on Immunization Practices (ACIP) and recommendation of ACIP, supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC), for use of Tdap among health-care personnel. MMWR Recomm Rep. 2006; 55:1-37.

113. Broder KR, Cortese MM, Iskander JK et al. Preventing tetanus, diphtheria, and pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006; 55:1-34.

114. Merck & Co. RotaTeq (rotavirus vaccine, live, oral, pentavalent) prescribing information. Whitehouse Station, NJ; 2009 Dec.

115. Murphy TV, Slade BA, Broder KR et al. Prevention of pertussis, tetanus, and diphtheria among pregnant and postpartum women and their infants recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2008; 57:1-51. [PubMed 18509304]

116. Pascual FB, McGinley EL, Zanardi LR et al. Tetanus surveillance--United States, 1998--2000. MMWR Surveill Summ. 2003; 52:1-8. [PubMed 12825541]

117. Cortese MM, Parashar UD, Centers for Disease Control and Prevention (CDC). Prevention of rotavirus gastroenteritis among infants and children: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2009; 58:1-25.

118. Committee on Infectious Diseases, American Academy of Pediatrics. Prevention of rotavirus disease: updated guidelines for use of rotavirus vaccine. Pediatrics. 2009; 123:1412-20. [PubMed 19332437]

a. AHFS drug information 2010. McEvoy GK, ed. Tetanus immune globulin. Bethesda, MD: American Society of Health-System Pharmacists; 2010:3343-5.

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