What is the appropriate management if the second dose of the post‑exposure rabies vaccine (intramuscular schedule days 0, 3, 7, 14, 28) is missed?

Management of Missed Second Dose in Rabies Post-Exposure Prophylaxis

If the second dose (day 3) of the rabies vaccine series is missed, continue the vaccination schedule from where you left off without restarting the entire series—administer the missed dose as soon as possible and maintain the same intervals for the remaining doses. 1

Core Principle: Never Restart the Series

• The CDC explicitly states that most interruptions in the vaccine schedule do not require reinitiation of the entire series. 1
• Delays of a few days for individual doses are unimportant and do not compromise protection. 2, 1
• The effect of longer lapses (weeks or more) is not fully characterized, but the series should still be continued rather than restarted. 2

Practical Management Algorithm

Step 1: Administer the Missed Dose Immediately

• Give the second dose (originally scheduled for day 3) as soon as the patient presents, regardless of how much time has elapsed. 1
• This becomes the new "day 3" for scheduling purposes. 1

Step 2: Complete the Remaining Doses

• Administer the third dose 4 days after the second dose (maintaining the day 3→7 interval). 1
• Administer the fourth dose 7 days after the third dose (maintaining the day 7→14 interval). 1
• For example: If the patient received day 0 on schedule but missed day 3 and presents on day 10, give the second dose immediately (day 10), third dose on day 14, and fourth dose on day 21. 1

Step 3: Assess HRIG Status

• If HRIG was not given on day 0, it can still be administered up to and including day 7 after the first vaccine dose. 2, 3
• Beyond day 7, do NOT administer HRIG because vaccine-induced antibodies are presumed to have developed, and additional passive antibody may suppress the active immune response. 2, 1

Special Populations Requiring Modified Approach

Immunocompromised Patients

• These patients require a 5-dose regimen (days 0,3,7,14, and 28) plus HRIG at 20 IU/kg on day 0, even if previously vaccinated. 2, 3
• Mandatory serologic testing is required 1-2 weeks after the final dose to confirm adequate antibody response (≥0.5 IU/mL by RFFIT). 2, 1, 3
• If a dose is missed, continue the series with the same intervals and obtain antibody titers after completion. 1

Previously Vaccinated Individuals

• These patients need only 2 doses total (days 0 and 3) and should NOT receive HRIG. 2, 1
• If the second dose is missed, give it as soon as possible—no additional doses are needed. 1

When to Consider Serologic Testing

• Routine antibody testing is unnecessary in immunocompetent individuals completing the 4-dose regimen. 3
• Consider serologic testing 7-14 days after the final dose if: 1, 3
  • The patient is immunocompromised
  • There are substantial deviations from the schedule (lapses of weeks)
  • There are concerns about vaccine potency or administration technique
• Acceptable antibody response is defined as complete neutralization of challenge virus at ≥1:5 dilution by RFFIT. 1

Reassuring Evidence on Incomplete Series

• Over 1,000 persons annually in the United States receive only 3 or 4 doses with no documented cases of rabies developing, even when >30% had confirmed exposure to rabid animals. 2, 1
• No case of human rabies in the United States has been attributed to receiving fewer than the complete vaccine course when modern cell-culture vaccines are used. 2, 1
• Virus-neutralizing antibodies peak by approximately day 14-28 after starting vaccination, meaning protective immunity is established well before completion of the series. 3

Critical Pitfalls to Avoid

• Never restart the entire series—this wastes vaccine, delays protection, and increases costs without improving outcomes. 1
• Never give HRIG after day 7—it may suppress the active antibody response that has already begun. 2, 1
• Never give HRIG to previously vaccinated persons—it inhibits the anamnestic (memory) immune response. 2, 1
• Never administer vaccine in the gluteal area—this produces inadequate antibody response and is associated with vaccine failure. 2, 3