Rabies Immunoglobulin

Approved Indications

• Post-exposure prophylaxis (PEP) of rabies in individuals exposed or potentially exposed to rabies virus and who have not been previously vaccinated:
• Category III exposures: Transdermal bites or scratches, licks on broken skin, exposure to bat bites or mucous membranes
• Category II exposures in high-risk regions (off-label use in some protocols)

Clinically Accepted Off-Label Uses

• Delayed administration in late-presenting bite victims (up to 7 days after starting vaccine if RIG was not previously given)
• Use in previously immunized individuals exposed again after long intervals (case-by-case basis in immunocompromised hosts)

General Dosing

• Human Rabies Immunoglobulin (HRIG):
• 20 IU/kg body weight (single dose)
• Equine Rabies Immunoglobulin (ERIG):
• 40 IU/kg body weight (single dose)

Note: Dose is calculated based on body weight, regardless of the number or size of wounds.

Route & Technique

• Infiltrate as much of the calculated dose as possible into and around the wound site(s)
• Any remaining volume should be injected intramuscularly at a site distant from the rabies vaccine administration site (e.g., anterolateral thigh or gluteal muscle)

Timing

• Administer on Day 0 of PEP, with the first dose of rabies vaccine
• Do not exceed the calculated dose to avoid neutralizing the vaccine
• RIG is not recommended after Day 7 of starting vaccine, as active antibody production has begun

Pediatrics, Elderly, and Special Populations

• Use same IU/kg dose as adults
• Carefully calculate total volume to avoid under- or overdosing
• In small children, dilute with normal saline to infiltrate all wounds adequately

Renal/Hepatic Impairment

• No dose adjustment needed

Rabies Immunoglobulin provides passive immunization by supplying preformed neutralizing antibodies against rabies virus. These antibodies bind to and inactivate the virus at the site of inoculation, preventing its entry into peripheral nerves and central nervous system. This temporary immunity protects the individual until their immune system generates an active response from the rabies vaccine. The combination of local RIG infiltration and systemic vaccination provides immediate and long-term protection against rabies, a nearly universally fatal disease if untreated.

• Onset of Action: Immediate neutralizing activity upon administration
• Peak Activity: Detectable antibody levels within hours
• Duration: Protective antibodies persist for ~21 days
• Distribution: Limited to extracellular space, mainly at infiltration site and IM injection area
• Metabolism: Broken down like other immunoglobulins by reticuloendothelial system
• Elimination: No active excretion; slowly degraded in tissues over time

• Pregnancy:
• No formal FDA category (not classified under old system)
• Considered safe during pregnancy as benefits far outweigh theoretical risks
• No known teratogenic effects
• Lactation:
• Safe to use while breastfeeding
• No known excretion into breast milk
• No adverse effects reported in infants

RIG should never be withheld due to pregnancy or lactation if indicated.

• Primary Class: Passive Immunizing Agent
• Subclass: Rabies-Specific Immune Globulin
• Type:
• HRIG – purified immunoglobulin G (IgG) from human plasma
• ERIG – F(ab')2 fragments from equine (horse) serum

• Absolute Contraindications:
• Known hypersensitivity to human or equine immunoglobulins
• Prior complete rabies vaccination (RIG not indicated in previously vaccinated persons)
• Relative Caution:
• History of anaphylaxis to blood products (for HRIG)
• Horse allergy (for ERIG)

• Do not inject RIG into the same muscle or site as the rabies vaccine
• Do not exceed the recommended dose, as high antibody levels may interfere with vaccine-induced immunity
• Monitor patients with a history of allergic reactions closely, especially for ERIG (risk of serum sickness or anaphylaxis)
• Ensure full infiltration of all wounds, especially in multiple or deep bites
• Use caution in patients with bleeding disorders when injecting intramuscularly

Common Adverse Effects

• Local reactions: Pain, tenderness, swelling at injection site
• Systemic: Fever, malaise, headache, dizziness

Serious/Rare Adverse Effects

• Hypersensitivity reactions:
• Urticaria, angioedema, bronchospasm (more common with ERIG)
• Anaphylaxis (very rare; ERIG > HRIG)
• Serum sickness (delayed hypersensitivity, especially with equine product)

HRIG has a significantly lower rate of allergic reactions compared to ERIG.

• Rabies Vaccine:
• Administer at a separate site to prevent interference with vaccine response
• Live Vaccines (e.g., MMR, varicella):
• If RIG is given, delay live vaccines for ≥3 months due to potential interference with immune response
• Immunosuppressive drugs:
• May blunt response to rabies vaccine; still administer RIG and full vaccine course
• Alcohol:
• No known interaction
• Enzyme Systems:
• Not metabolized via CYP450 pathways; no significant enzyme-mediated interactions

• WHO (2023):
• Endorses RIG use only in Category III exposures
• Recommends HRIG or ERIG for passive immunization when available
• Bites on head, face, neck, fingers, or genitals are high-risk and require urgent RIG use
• CDC Guidelines (2022):
• RIG should be given only once, on Day 0
• Emphasis on full infiltration into wounds, including multiple sites
• Stresses that RIG should not delay vaccine initiation
• EMA/FDA:
• Reaffirmed safety profile of HRIG in pregnancy
• Encouraged development of monoclonal antibodies as future RIG alternatives

• Temperature:
• Store at 2°C to 8°C (36°F to 46°F); do not freeze
• Light:
• Protect from direct light
• Handling:
• Shake gently before use if in suspension
• Discard unused portion of opened vials
• Inspect for discoloration or particulates before use