Tetanus Immune Globulin

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

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.

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

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

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

Single dose of 250 units.104

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

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

Adults

Single dose of 250 units.100 101 104

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.

Contraindications

• Manufacturer states none known.104

Warnings/Precautions

Warnings

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

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

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

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

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

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

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

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

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

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

Storage

Parenteral

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

Does not contain thimerosal or any other preservatives.104

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.

Applies to tetanus immune globulin: intramuscular solution

Along with its needed effects, tetanus immune globulin may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking tetanus immune globulin:

• Difficulty in breathing or swallowing
• hives
• itching, especially of soles or palms
• reddening of skin, especially around ears
• swelling of eyes, face, or inside of nose
• unusual tiredness or weakness, sudden and severe

Applies to tetanus immune globulin: intramuscular solution

Local

Local side effects have included soreness, pain, and tenderness at the injection site.[Ref]

Renal

Renal side effects have included rare cases of nephrotic syndrome.[Ref]

Hypersensitivity

Hypersensitivity reactions have included rare cases of angioneurotic edema and anaphylactic shock.[Ref]

Other

Other side effects have included slight temperature elevation.[Ref]

Some side effects of tetanus immune globulin may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.