Should a patient who has received rituximab (rituximab) and been bitten by a dog receive only rabies vaccination or also rabies immunoglobulin (Immunoglobulin)?

Rabies Post-Exposure Prophylaxis in Rituximab-Treated Patients

Direct Recommendation

A patient who has received rituximab within the past 6 months and been bitten by a dog should receive BOTH rabies vaccination AND rabies immunoglobulin (RIG), using a 5-dose vaccine schedule rather than the standard 4-dose regimen. 1, 2

Rationale for Combined Therapy

Why Immunoglobulin is Essential

• Rituximab profoundly impairs humoral immunity for up to 6 months after treatment, depleting B cells and reducing vaccine responses. 1

• Rabies immunoglobulin provides immediate passive antibody protection during the critical first 7 days before vaccine-induced antibodies develop—a period when rituximab-treated patients may fail to mount adequate responses. 1, 2

• The EULAR guidelines explicitly recommend administering tetanus immunoglobulin to rituximab patients with contaminated wounds within 6 months of treatment due to reduced vaccine responses; this same principle applies to rabies exposure, which is universally fatal without proper prophylaxis. 1

Vaccination Schedule Modification

• Immunosuppressed patients require the extended 5-dose vaccine schedule (days 0,3,7,14, and 28) rather than the standard 4-dose regimen used for immunocompetent individuals. 2, 3

• Rituximab-induced immunosuppression persists for approximately 6 months, with adequate vaccine responses documented only at 6 months post-treatment, but responses in the 1-6 month window remain uncertain. 1

Specific Treatment Protocol

Immediate Wound Management

• Thoroughly wash and flush the wound for 15 minutes with soap and copious water. 1, 4

• Apply povidone-iodine solution or similar virucidal agent to the wound site. 4

• Avoid suturing when possible to prevent deeper viral inoculation. 3

• Administer tetanus prophylaxis as indicated. 1

Rabies Immunoglobulin Administration

• Administer human rabies immunoglobulin (HRIG) at 20 IU/kg body weight as soon as possible. 1, 2, 4

• Infiltrate up to half the HRIG dose thoroughly around and into the wound(s) if anatomically feasible; inject the remainder intramuscularly in the gluteal area. 1, 4

• HRIG must be given only once, at the beginning of prophylaxis, and can be administered up to day 7 if not given initially. 1, 2

• Never administer HRIG in the same syringe or anatomical site as the vaccine. 1, 2

Vaccine Administration

• Administer 1.0 mL rabies vaccine (HDCV or PCECV) intramuscularly on days 0,3,7,14, and 28. 2

• Inject in the deltoid area for adults and older children; the anterolateral thigh is acceptable for younger children. 1, 2

• Never use the gluteal area, as this results in significantly lower neutralizing antibody titers. 1, 4

Critical Timing Considerations

• Begin treatment immediately after exposure, regardless of time interval—this is a medical urgency. 2, 3

• Even delayed treatment is indicated, as rabies incubation periods exceeding 1 year have been documented. 2, 3

• If HRIG was not given initially, it can still be administered through day 7 after the first vaccine dose; beyond day 7, it is not indicated. 1, 5

Common Pitfalls to Avoid

• Do not use the standard 4-dose vaccine schedule recommended for immunocompetent patients—rituximab recipients require the full 5-dose regimen. 2

• Do not omit HRIG based on prior rabies vaccination history—rituximab's immunosuppressive effects override the benefits of previous vaccination. 1, 2

• Do not administer the full HRIG dose systemically—wound infiltration is critical for local viral neutralization. 1, 4

• Do not delay treatment to observe the dog—initiate prophylaxis immediately while arranging for 10-day animal observation if feasible. 3

Monitoring Considerations

• Consider serologic testing to confirm adequate antibody response given the patient's immunosuppressed state. 1, 3

• Rituximab is associated with hypogammaglobulinemia and increased infectious complications, with severe infections increasing from 17.2% to 21.7% post-treatment. 6

• Monitor for adverse reactions to HRIG, though these are rare (0.183% in one large series) and typically mild and transient. 7

Evidence Quality Note

The recommendation for combined therapy is based on extrapolation from high-quality EULAR guidelines for tetanus prophylaxis in rituximab patients 1, combined with established CDC/WHO rabies prophylaxis protocols 1, 2 and specific guidance for immunosuppressed patients 2, 3. While no studies directly address rabies prophylaxis in rituximab-treated patients, the biological rationale is compelling given rituximab's profound and prolonged B-cell depletion and the universally fatal nature of rabies without adequate prophylaxis.