Timing of the Third Hepatitis B Vaccine Dose
The third dose of hepatitis B vaccine must be administered at least 16 weeks after the first dose AND at least 8 weeks after the second dose, with the final dose not given before 24 weeks of age in infants. 1
Minimum Interval Requirements
The Advisory Committee on Immunization Practices establishes clear minimum intervals for hepatitis B vaccination that must be followed 1:
- Between dose 1 and dose 2: Minimum 4 weeks 1
- Between dose 2 and dose 3: Minimum 8 weeks 1
- Between dose 1 and dose 3: Minimum 16 weeks 1
For infants specifically, the final dose cannot be administered before 24 weeks of age (approximately 6 months), regardless of when earlier doses were given. 1
Grace Period Rule
Vaccine doses administered up to 4 days before the minimum interval are considered valid and do not need to be repeated 1. This "4-day grace period" provides flexibility in scheduling while maintaining immunologic effectiveness.
Important exception: For the accelerated Twinrix schedule (0,7,21-30 days, and 12 months), the 4-day grace period does NOT apply to the first three doses, though it does apply to standard hepatitis B vaccine schedules 1.
Standard Vaccination Schedules
The typical recommended schedules are 1:
- Infants born to HBsAg-negative mothers: Birth (or by 2 months), 1-2 months, and 6 months 1
- Infants born to HBsAg-positive mothers: Birth (within 12 hours with HBIG), 1-2 months, and 6 months 1, 2
- Adults: 0,1, and 6 months for traditional vaccines OR 0 and 1 month for Heplisav-B 3
Interrupted Schedules
If the vaccination series is interrupted, do not restart the series—simply continue where you left off. 1 The third dose should be administered as soon as possible while respecting the minimum intervals outlined above 1.
Common Pitfalls to Avoid
- Do not administer the third dose before 16 weeks from the first dose, even if 8 weeks have passed since the second dose 1
- Do not give the final infant dose before 24 weeks of age, as this may compromise long-term immunity 1
- Do not restart the series if interrupted—inadequate doses or those given too early should be repeated, but properly timed doses count toward the series 1
- Doses given more than 4 days before the minimum interval must be repeated 1