Human Rabies Immunoglobulin

Usage

• Human Rabies Immunoglobulin (HRIG) is prescribed for post-exposure prophylaxis of rabies infection in individuals who have been exposed to the rabies virus through bites, scratches, or other contact with potentially infected animals. It is crucial in providing passive immunity immediately after exposure.
• Pharmacological Classification: Immunoglobulin, Biological Product, Immunizing Agent.
• Mechanism of Action: HRIG provides passive immunity by delivering preformed rabies antibodies that neutralize the rabies virus before it can establish infection in nerve tissue. This is crucial in the critical period immediately following exposure, providing protection until the body’s active immune response, stimulated by rabies vaccine, can develop.

Alternate Names

• Rabies Immune Globulin (RIG)
• Human Rabies Antiserum
• Brand Names:
  • HyperRAB® S/D
  • Imogam Rabies-HT
  • KEDRAB®
  • KamRAB™

How It Works

• Pharmacodynamics: HRIG provides immediate passive immunity by directly neutralizing the rabies virus at the site of exposure. This prevents the virus from spreading to the central nervous system. The antibodies bind to the rabies virus, preventing it from entering nerve cells.
• Pharmacokinetics:
  • Absorption: HRIG is administered intramuscularly (IM) and locally infiltrated at the wound site, providing rapid access to the circulation and the area of potential viral entry.
  • Distribution: The immunoglobulin distributes throughout the extracellular fluid.
  • Metabolism: As a protein, it undergoes proteolytic degradation throughout the body.
  • Elimination: Primarily through proteolysis, with a half-life of approximately 21 days (although this varies somewhat between products).
• Mode of Action: Neutralization of the rabies virus through antibody binding. The specific mechanism involves the binding of antibodies in the HRIG preparation to the rabies virus glycoprotein, thereby blocking viral entry into host cells.
• Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: HRIG’s mechanism is direct neutralization of rabies virus rather than interaction with cellular receptors, enzymes, or neurotransmitters.
• Elimination Pathways: HRIG is eliminated by proteolytic degradation like other endogenous immunoglobulins, not renal or hepatic pathways or CYP enzyme metabolism.

Dosage

Standard Dosage

Adults: 20 IU/kg of body weight, administered as a single dose. As much of the dose as possible should be infiltrated around the wound site. Any remaining volume should be injected intramuscularly at a distant anatomical site from the vaccine administration.

Children: 20 IU/kg of body weight, administered as a single dose. Follow the same administration guidelines as adults. Pediatric safety considerations emphasize careful infiltration around the wound, particularly in small children, to avoid compartment syndrome. Do not exceed the recommended dose.

Special Cases:

• Elderly Patients: Same as standard adult dosage. Careful consideration should be given to potential comorbidities and any concurrent medications.
• Patients with Renal Impairment: No dose adjustment required.
• Patients with Hepatic Dysfunction: No dose adjustment required.
• Patients with Comorbid Conditions: While no specific adjustments are mandated based on most comorbid conditions, clinical judgment should guide dosing in patients with bleeding disorders, thrombocytopenia, or conditions affecting immune response.

Clinical Use Cases

The dosage of HRIG is consistent across clinical settings following rabies exposure. The dose is independent of specific situations like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations like cardiac arrest. HRIG use is solely determined by rabies exposure and prior rabies vaccination status.

Dosage Adjustments

No dose adjustments are routinely made for factors like renal/hepatic dysfunction, metabolic disorders, or genetic polymorphisms. It is crucial to administer the correct 20 IU/kg dose but avoid exceeding this due to potential interference with the rabies vaccine’s efficacy.

Side Effects

Common Side Effects

• Local reactions at the injection site (pain, swelling, redness, induration)
• Mild fever
• Headache
• Myalgia
• Nausea

Rare but Serious Side Effects

• Anaphylaxis (rare)
• Serum sickness (rare)

Long-Term Effects

Generally, no long-term adverse effects are associated with HRIG administration, as it is a single dose treatment.

Adverse Drug Reactions (ADR)

Anaphylaxis, although rare, requires immediate medical attention. Symptoms can include hives, difficulty breathing, swelling of the face, and a drop in blood pressure.

Contraindications

There are no absolute contraindications to HRIG administration following a potential rabies exposure due to the near-100% fatality rate of the disease. However, caution is advised for individuals with a history of hypersensitivity reactions to human immunoglobulin preparations or IgA deficiency with anti-IgA antibodies.

Drug Interactions

• HRIG can interfere with the immune response to live attenuated virus vaccines (e.g., measles, mumps, rubella, varicella, rotavirus), delaying their administration for 3 months after HRIG use.
• Immunosuppressants and other medications affecting the immune system can theoretically reduce the efficacy of the rabies vaccine given concurrently with HRIG.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: Category C (US FDA). Due to the severity of rabies, the benefits generally outweigh the risks. Data on potential fetal risks is limited. HRIG should be used during pregnancy only when clearly needed after potential rabies exposure.
• HRIG’s excretion in breast milk and its potential effects on neonates are not fully understood. However, due to the severity of rabies, it should not be withheld from breastfeeding mothers if indicated following exposure.

Drug Profile Summary

• Mechanism of Action: Provides passive immunity against rabies virus.
• Side Effects: Local reactions at the injection site, mild fever, headache. Rarely: anaphylaxis.
• Contraindications: No absolute contraindications. Use caution in individuals with a history of immunoglobulin hypersensitivity or IgA deficiency with anti-IgA antibodies.
• Drug Interactions: Live attenuated virus vaccines.
• Pregnancy & Breastfeeding: Use only if clearly needed.
• Dosage: 20 IU/kg as a single dose, infiltrated around the wound and IM at a distant site.
• Monitoring Parameters: Observe for signs of hypersensitivity reactions. Monitor for adequate response to rabies vaccine with antibody titers if needed.

Popular Combinations

HRIG is always used in conjunction with a rabies vaccine for post-exposure prophylaxis in previously unvaccinated individuals.

Precautions

• General Precautions: Screen for prior immunoglobulin hypersensitivity and IgA deficiency. Ensure the needle is not in a blood vessel during administration.
• Specific Populations: Refer to pregnancy and breastfeeding section. Exercise caution in children to avoid compartment syndrome in small extremities during infiltration.
• Lifestyle Considerations: No specific lifestyle considerations apply.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Human Rabies Immunoglobulin?

A: The recommended dosage is 20 IU/kg body weight as a single dose.

Q2: How is HRIG administered?

A: Infiltrate as much as possible into and around the wound, and administer any remaining amount IM at a site distant from the rabies vaccine injection.

Q3: Can HRIG be given to pregnant or breastfeeding women?

A: Yes, if indicated for post-exposure prophylaxis, as the benefits generally outweigh the risks.

Q4: What are the common side effects of HRIG?

A: Pain and swelling at the injection site, mild fever, headache, myalgia, nausea.

Q5: Are there any contraindications to HRIG administration?

A: No absolute contraindications due to the severity of rabies. Caution advised for individuals with a history of immunoglobulin hypersensitivity reactions.

Q6: Can HRIG interfere with other vaccines?

A: Yes, it can interfere with the immune response to live attenuated virus vaccines. These vaccines should be delayed for 3 months after HRIG administration.

Q7: Is HRIG always given with rabies vaccine?

A: Yes, for post-exposure prophylaxis in previously unvaccinated individuals. Previously vaccinated individuals with documented adequate titers require only booster doses of rabies vaccine.

Q8: How long does the protection from HRIG last?

A: HRIG provides immediate but transient passive immunity. The rabies vaccine, given concurrently, stimulates the body’s active immune response, providing lasting protection.

Q9: What should be done if an allergic reaction occurs after HRIG administration?

A: Anaphylaxis is a rare but serious adverse reaction to HRIG. It requires immediate medical attention, usually with epinephrine and other supportive measures.

Q10: What is the role of wound cleansing in rabies post-exposure prophylaxis?

A: Thorough wound cleansing with soap and water or povidone-iodine is crucial as the first step in rabies post-exposure prophylaxis. It helps to reduce the viral load before HRIG and rabies vaccine are administered.