I gave Engerix B (hepatitis B vaccine) by mistake as the second dose of Twinrix (combined hepatitis A and B vaccine); how should I complete the hepatitis A and B vaccination series?

Managing an Inadvertent Engerix-B Dose as Second Dose of Twinrix Series

Count the Engerix-B dose as a valid second dose and complete the series with a third dose of Twinrix at the appropriate interval, ensuring the patient receives adequate hepatitis A protection. 1

Understanding the Error and Its Implications

When Engerix-B (monovalent hepatitis B vaccine) is mistakenly given as the second dose of a Twinrix series, the patient has received:

• Dose 1 (Twinrix): 720 EL.U. hepatitis A antigen + 20 µg hepatitis B antigen 2
• Dose 2 (Engerix-B): 20 µg hepatitis B antigen only (no hepatitis A component) 1

The critical issue is that the patient missed the second hepatitis A dose but received appropriate hepatitis B antigen. 1

Recommended Completion Strategy

Continue the series without restarting—the hepatitis B component is on track, but hepatitis A protection requires attention. 1

Step 1: Count the Engerix-B as Valid Dose #2 for Hepatitis B

• The CDC explicitly states that mixing hepatitis B vaccine manufacturers does not compromise immunogenicity, and doses from different manufacturers are considered valid. 1
• The Engerix-B dose (20 µg) provides the same hepatitis B antigen content as the Twinrix dose, so hepatitis B protection proceeds normally. 1
• Do not restart the series—interrupted schedules should always be continued from where they left off. 1

Step 2: Complete with Third Dose of Twinrix

• Administer the third dose of Twinrix at least 8 weeks after the Engerix-B dose (dose 2) and at least 16 weeks after the first Twinrix dose (dose 1). 1
• The standard schedule would place this at month 6 from the initial dose, which satisfies both minimum interval requirements. 1
• This third Twinrix dose will provide the second hepatitis A antigen exposure (720 EL.U.) and the third hepatitis B antigen exposure (20 µg). 2

Step 3: Consider Additional Hepatitis A Dose

After completing the modified Twinrix series, administer one additional dose of monovalent hepatitis A vaccine (Havrix or Vaqta) 6 months after the third Twinrix dose to ensure robust hepatitis A immunity. 3

Rationale:

• The patient will have received only two hepatitis A antigen exposures (first Twinrix + third Twinrix) instead of the standard three. 2, 3
• While two doses of hepatitis A vaccine provide substantial protection (approximately 95% after dose 1, virtually 100% after dose 2), the standard recommendation is a two-dose series at 0 and 6–12 months for monovalent vaccines. 3
• Adding a fourth dose (monovalent hepatitis A) ensures the patient achieves the same hepatitis A protection as someone who completed a standard two-dose hepatitis A series. 3

Complete Corrected Schedule

Timing	Vaccine Given	Hepatitis A Doses	Hepatitis B Doses
Month 0	Twinrix (dose 1)	1	1
Month 1	Engerix-B (dose 2)	1	2
Month 6	Twinrix (dose 3)	2	3
Month 12	Havrix or Vaqta	3	3

1, 2, 3

Alternative Simplified Approach (If Additional Dose Not Feasible)

If administering a fourth dose is impractical, the patient will still have adequate protection against both viruses with the modified three-dose series (Twinrix → Engerix-B → Twinrix). 1, 4

• Hepatitis B: Three doses of 20 µg each provides >90% seroprotection in adults under 40 years. 1, 5
• Hepatitis A: Two doses of 720 EL.U. each (from the two Twinrix doses) provides approximately 95–100% seroprotection. 3, 4

However, this approach deviates from standard schedules and may not provide optimal long-term hepatitis A immunity, particularly if the patient is at ongoing risk. 3

Critical Timing Rules

• Minimum interval between doses 2 and 3: 8 weeks 1
• Minimum interval between doses 1 and 3: 16 weeks 1
• Grace period: Doses given ≤4 days before the minimum interval are valid 1
• No maximum interval: Delays do not require restarting the series 1

Common Pitfalls to Avoid

• Never restart the series—this wastes doses and delays protection. 1, 5
• Do not give the third dose before 16 weeks from the first dose, even if 8 weeks have passed since the second dose. 1
• Do not assume two hepatitis A doses are equivalent to three—while protection is high, the standard recommendation for Twinrix is three doses for optimal immunity. 2, 3
• Do not use Twinrix solely for hepatitis B when hepatitis A is not indicated—but in this case, the patient already started Twinrix, so completing with Twinrix is appropriate. 3, 5
• Document the error clearly in the patient's record to ensure future providers understand the modified schedule. 5

Post-Vaccination Considerations

• Serologic testing is not routinely recommended for immunocompetent adults after completing the series. 1
• Consider testing if the patient is immunocompromised, on hemodialysis, or has other risk factors for vaccine non-response. 1
• Counsel the patient that they have received adequate hepatitis B protection but may benefit from the additional hepatitis A dose for optimal immunity. 3