What are the potential drug interactions with tetanus toxoid (TT)?

Drug Interactions with Tetanus Toxoid

Tetanus toxoid has minimal clinically significant drug interactions, but certain immunosuppressive medications can reduce vaccine immunogenicity, and concurrent administration with tetanus immune globulin (TIG) requires specific technique to avoid interference. 1

Key Drug Interactions Affecting Vaccine Response

Immunosuppressive Medications

Disease-modifying antirheumatic drugs (DMARDs) variably affect tetanus vaccine immunogenicity:

• Rituximab causes the most significant reduction in vaccine response, though the degree varies between studies—one study showed 73% achieved protective antibody titers versus 96-100% in controls, while another found similar rates of 4-fold antibody rise (39.1% vs 42.3%) 1
• TNF-inhibitors (infliximab, etanercept, adalimumab) produce modestly lower antibody titers but generally maintain protective levels 1
• Abatacept shows approximately 10% lower rates of protective antibody development when vaccine is given 2 weeks after dosing; delaying vaccination to 8 weeks after abatacept improves response rates to near-normal levels 1
• JAK-inhibitors demonstrate modest impairment in immunogenicity 1
• IL-6, IL-17, and IL-12/23 inhibitors do not impair tetanus vaccine immunogenicity 1
• Methotrexate and belimumab do not significantly interfere with protective antibody development 1, 2

Concurrent Passive Immunization

When tetanus toxoid and TIG are given together, specific administration technique is critical:

• Use separate syringes and separate anatomical sites to prevent interference with active immunization 1, 2
• Adsorbed tetanus toxoid is mandatory when given with TIG—plain (fluid) tetanus toxoid shows significant antibody suppression when co-administered with antitoxin 3, 4
• Human tetanus immune globulin (TIG) does not interfere with adsorbed tetanus toxoid response, unlike animal-derived antitoxin which causes 10-15 day delay in active immunity 4
• High doses of TIG (400 units) can suppress immunity induction following the first dose of adsorbed toxoid 3

Conjugate Vaccine Interactions

Tetanus toxoid used as a carrier protein in conjugate vaccines can cause immune interactions:

• Co-administration of multiple tetanus toxoid (TT) conjugate vaccines produces immune enhancement (higher antibody levels) 5
• Large amounts of TT carrier protein may cause carrier-induced epitopic suppression, affecting responses to meningococcal or pneumococcal polysaccharides 5
• CRM197 (diphtheria toxoid variant) conjugates can induce bystander interference when given with diphtheria-tetanus-acellular pertussis vaccines, reducing responses to Haemophilus influenzae type b vaccine conjugated to TT 5

Contraindications and Precautions

Absolute Contraindications

• History of neurologic reaction (encephalopathy, Guillain-Barré syndrome within 6 weeks) after previous dose 1
• Severe hypersensitivity reaction (anaphylaxis, generalized urticaria) after previous dose 1

Relative Precautions

• Arthus-type hypersensitivity reactions after previous dose—defer vaccination until at least 10 years have elapsed, even for emergency doses 1
• Temperature ≥105°F (≥40.5°C) within 48 hours after previous dose 1
• Guillain-Barré syndrome history—while extremely rare (risk lower than expected by chance), vaccination decision should weigh benefits versus recurrence risk 1
• Moderate or severe acute illness with or without fever—defer routine vaccination 1

Conditions NOT Contraindications

Common misconceptions that should not prevent tetanus vaccination:

• Pregnancy (though deferring to second trimester is reasonable precaution) 1
• Minor illness such as mild upper respiratory infection 1
• Breastfeeding 1
• Immunosuppression in lupus or other rheumatic diseases—tetanus toxoid is safe and ~90% achieve protective response 2
• Family history of convulsions or CNS disorders 1
• Local reactions alone from previous doses 1

Critical Clinical Pearls

• For patients on rituximab requiring urgent tetanus protection within 24 weeks of dosing, use passive immunization with TIG instead of active vaccination 2
• Persons with Arthus reactions typically have very high serum tetanus antitoxin levels and should not receive boosters more frequently than every 10 years 1
• Prophylactic acetaminophen (15 mg/kg every 4 hours for 24 hours) should be given to children with seizure history to reduce post-vaccination fever risk 1, 6
• If anaphylaxis is suspected from previous dose, intradermal skin testing with appropriately diluted tetanus toxoid can guide decision-making—94 of 95 patients with reported anaphylactic symptoms tolerated subsequent vaccination 1