What is the maximum dose of Human Rabies Immunoglobulin (HRIG)?

Maximum Dose of Human Rabies Immunoglobulin (HRIG)

The maximum dose of Human Rabies Immunoglobulin (HRIG) is 20 IU/kg body weight, which should not be exceeded as higher doses may suppress active antibody production in response to the rabies vaccine. 1

HRIG Dosing Guidelines

• The recommended dose of 20 IU/kg (0.133 mL/kg) body weight is applicable to all age groups, including children and infants 1
• This dose should be administered only once at the beginning of post-exposure prophylaxis
• If not administered when vaccination begins (day 0), HRIG can be given up to and including day 7 of the post-exposure prophylaxis series 1
• Beyond the seventh day, HRIG is not indicated because an antibody response to the cell culture vaccine is presumed to have occurred 1

Administration Technique

The proper administration technique for HRIG is critical for effectiveness:

1. If anatomically feasible, thoroughly infiltrate the full dose of HRIG in the area around and into the wounds 1
2. Any remaining volume should be injected intramuscularly at a site distant from vaccine administration 1
3. HRIG should never be administered in the same syringe or in the same anatomical site as the first vaccine dose 1

Rationale for Dose Limitation

The 20 IU/kg dose should not be exceeded because:

• Higher doses may partially suppress active production of antibodies in response to the vaccine 1
• This could potentially reduce the effectiveness of the overall post-exposure prophylaxis regimen

Common Pitfalls in HRIG Administration

• Failure to infiltrate wounds properly with HRIG is associated with rare failures of post-exposure prophylaxis 1
• Administering HRIG in the same anatomical site as the vaccine can interfere with vaccine effectiveness
• Delaying HRIG administration beyond 7 days after starting vaccination is not recommended as it provides no additional benefit

Special Considerations

• For previously vaccinated individuals (those who have received complete pre-exposure or post-exposure prophylaxis with cell culture vaccines), HRIG is not indicated 1
• These individuals should receive only the vaccine component of post-exposure prophylaxis
• Immunocompromised patients may require special consideration and antibody titer monitoring after vaccination 1

Research Developments

While the standard dose remains 20 IU/kg, some research suggests that lower doses might be effective:

• In vitro and animal studies have shown that much lower doses of HRIG (as low as 0.025 IU) may provide adequate neutralization of rabies virus 2
• However, these findings have not been validated in human clinical trials and should not change current clinical practice

The 20 IU/kg dose of HRIG remains the gold standard for post-exposure prophylaxis in previously unvaccinated individuals, as recommended by the Advisory Committee on Immunization Practices (ACIP).