Hepatitis A and Hepatitis B Recombinant Vaccine
(hep a TYE tis aye & hep a TYE tis bee ree KOM be nant vak SEEN)
- Engerix-B and Havrix
- Havrix and Engerix-B
- Hepatitis A
- Hepatitis B
- Hepatitis B and Hepatitis A Vaccine
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, suspension [preservative free]:
Twinrix: Hepatitis A virus antigen 720 ELISA units and hepatitis B surface antigen 20 mcg per mL (1 mL) [contains aluminum, yeast protein, and trace amounts of neomycin; may contain natural rubber/natural latex in prefilled syringe]
Brand Names: U.S.
- Vaccine, Inactivated (Viral)
Hepatitis A vaccine, an inactivated virus vaccine, offers active immunization against hepatitis A virus infection at an effective immune response rate in up to 99% of subjects.
Recombinant hepatitis B vaccine is a noninfectious subunit viral vaccine. The vaccine is derived from hepatitis B surface antigen (HBsAg) produced through recombinant DNA techniques from yeast cells. The portion of the hepatitis B gene which codes for HBsAg is cloned into yeast which is then cultured to produce hepatitis B vaccine.
In immunocompetent people, Twinrix provides active immunization against hepatitis A virus infection (at an effective immune response rate >99% of subjects) and against hepatitis B virus infection (at an effective immune response rate of 93% to 97%) 30 days after completion of the 3-dose series. This is comparable to using hepatitis A vaccine and hepatitis B vaccine concomitantly.
Onset of Action
Seroconversion for antibodies against HAV and HBV were detected 1 month after completion of the 3-dose series.
Duration of Action
HAV and HBV seropositivity have been observed for 15 years in adults and for 10 years in children (Diaz-Mitoma 2008, Van Herck 2007).
Use: Labeled Indications
Hepatitis A and B diseases prevention:
Twinrix: Active immunization of persons 18 years and older (US labeling) or 19 years and older (Canadian labeling) against disease caused by hepatitis A virus and hepatitis B virus (all known subtypes)
Canadian labeling: Additional uses (not in US labeling): Approved for active immunization of children and adolescents ages 1 to 15 years.
Twinrix Junior [Canadian product]: Active immunization of children and adolescents ages 1 to 18 years against disease caused by hepatitis A virus and hepatitis B virus (all known subtypes).
Limitations of use: Hepatitis A/hepatitis B vaccine cannot be used for postexposure prophylaxis.
Severe allergic reaction (eg, anaphylaxis) after a previous dose of any hepatitis A–containing or hepatitis B–containing vaccine, or any component of the formulation, including yeast and neomycin.
Canadian labeling: Additional contraindications (not in US labeling): Severe febrile illness.
Primary immunization: IM:
US labeling: 1 mL given on a 0-, 1-, and 6-month schedule for a total of 3 doses
Accelerated regimen: 1 mL on day 0, day 7, and days 21 to 30, followed by a booster at 12 months for a total of 4 doses
Canadian labeling: Adults ≥19 years (Twinrix): 1 mL given on a 0-, 1-, and 6-month schedule for a total of 3 doses
Accelerated regimen: 1 mL on day 0, day 7, and day 21, followed by a booster at 12 months for a total of 4 doses
Refer to adult dosing.
Primary immunization: Canadian labeling: IM:
Children and Adolescents:
Twinrix Junior: Ages 1 to 18 years: 0.5 mL given on a 0-, 1-, and 6-month schedule for a total of 3 doses
Twinrix: Ages 1 to 15 years: 1 mL given on elected date followed by second dose (1 mL) 6 to 12 months later for a total of 2 doses
Dosing: Renal Impairment
There are no dosage adjustments provided in the manufacturer’s labeling.
Dosing: Hepatic Impairment
There are no dosage adjustments provided in the manufacturer’s labeling.
IM: Shake well prior to use. Do not dilute prior to administration. Discard if the suspension is discolored or does not appear homogenous after shaking or if there are cracks in the vial or syringe. Administer IM in the deltoid region; do not administer in the gluteal region (may give suboptimal response). Administer in the anterolateral thigh in infants (Canadian labeling). Do not administer IV, intradermally, or SubQ (US labeling). To prevent syncope-related injuries, adolescents and adults should be vaccinated while seated or lying down (NCIRD/ACIP 2011). US law requires that the date of administration, the vaccine manufacturer, lot number of vaccine, and the administering-person's name, title, and address be entered into the patient's permanent medical record.
For patients at risk of hemorrhage following IM injection, the vaccine should be administered IM if, in the opinion of the physician familiar with the patient's bleeding risk, the vaccine can be administered by this route with reasonable safety. If the patient receives antihemophilia or other similar therapy, IM vaccination can be scheduled shortly after such therapy is administered. A fine needle (23 gauge or smaller) should be used for the vaccination and firm pressure applied to the site (without rubbing) for at least 2 minutes. The patient should be instructed concerning the risk of hematoma from the injection. Patients on anticoagulant therapy should be considered to have the same bleeding risks and treated as those with clotting factor disorders (NCIRD/ACIP 2011). Although subcutaneous administration is not recommended in US labeling (antibody response may be suboptimal), the Canadian product labeling suggests that subcutaneous administration may be used in patients at risk for hemorrhage (including those with thrombocytopenia).
Do not mix with other vaccines or injections. Separate needles and syringes should be used for each injection.
Store in refrigerator at 2°C to 8°C (36°F to 46°F); do not freeze (discard if frozen).
There are no known significant interactions.
In the U.S., all serious adverse reactions must be reported to the U.S. Department of Health and Human Services (DHHS) Vaccine Adverse Event Reporting System (VAERS) 1-800-822-7967 or online at https://vaers.hhs.gov/esub/index. In Canada, adverse reactions may be reported to local provincial/territorial health agencies or to the Vaccine Safety Section at Public Health Agency of Canada (1-866-844-0018).
Incidence of adverse effects of the combination product were similar to those occurring after administration of hepatitis A vaccine and hepatitis B vaccine alone. (Incidence reported is not versus placebo.)
Central nervous system: Headache (13% to 22%), fatigue (11% to 14%)
Local: Injection site reaction: Soreness (35% to 41%), redness (8% to 11%)
1% to 10%:
Central nervous system: Fever (2% to 4%)
Gastrointestinal: Diarrhea (4% to 6%), nausea (2% to 4%), vomiting (≤1%)
Local: Injection site reaction: Swelling (4% to 6%), induration
Respiratory: Upper respiratory tract infection
<1% (Limited to important or life-threatening): Abdominal pain, anorexia, diaphoresis, dizziness, erythema, flu-like syndrome, insomnia, migraine, paresthesia, petechiae, rash, respiratory tract illness, somnolence, syncope, urticaria, vertigo
Children (as reported in Canadian labeling):
>10%: Local: Injection site pain/redness
1% to 10%:
Central nervous system: Fever (≥37.5°C), drowsiness, fatigue, headache, irritability, malaise
Gastrointestinal: Appetite decreased, diarrhea, nausea, vomiting
Local: Injection site edema
<1% (Limited to important or life-threatening): Dizziness, hypotension, influenza-like illness, lymphadenopathy, paresthesia, pruritus, rash, urticaria
Postmarketing and/or case reports: See individual agents.
Concerns related to adverse effects:
• Anaphylactoid/hypersensitivity reactions: Immediate treatment (including epinephrine 1 mg/mL) for anaphylactoid and/or hypersensitivity reactions should be available during vaccine use (NCIRD/ACIP 2011).
• Syncope: Syncope has been reported with use of injectable vaccines and may result in serious secondary injury (eg, skull fracture, cerebral hemorrhage); typically reported in adolescents and young adults and within 15 minutes after vaccination. Procedures should be in place to avoid injuries from falling and to restore cerebral perfusion if syncope occurs (NCIRD/ACIP 2011).
• Acute illness: The decision to administer or delay vaccination because of current or recent febrile illness depends on the severity of symptoms and the etiology of the disease. Consider deferring administration in patients with moderate or severe acute illness (with or without fever) unless they are at immediate risk of hepatitis A or hepatitis B infection; vaccination should not be delayed for patients with mild acute illness (with or without fever) (NCIRD/ACIP 2011).
• Bleeding disorders: Use with caution in patients with bleeding disorders (including thrombocytopenia) and/or patients on anticoagulant therapy; bleeding/hematoma may occur from IM administration; if the patient receives antihemophilia or other similar therapy, IM injection can be scheduled shortly after such therapy is administered (NCIRD/ACIP 2011). Canadian product labeling recommends subcutaneous administration for patients with thrombocytopenia or at risk for hemorrhage; however, antibody response may be suboptimal.
Concurrent drug therapy issues:
• Vaccines: In order to maximize vaccination rates, the ACIP recommends simultaneous administration (ie, >1 vaccine on the same day at different anatomic sites) of all age-appropriate vaccines (live or inactivated) for which a person is eligible at a single clinic visit, unless contraindications exist. The use of combination vaccines is generally preferred over separate injections, taking into consideration provider assessment, patient preference, and potential adverse events. When using combination vaccines, the minimum age for administration is the oldest minimum age for any individual component; the minimum interval between dosing is the greatest minimum interval between any individual components. The ACIP prefers each dose of a specific vaccine in a series come from the same manufacturer when possible (NCIRD/ACIP 2011).
• Altered immunocompetence: Use with caution in severely immunocompromised patients (eg, patients receiving chemo/radiation therapy or other immunosuppressive therapy [including high-dose corticosteroids]); may have a reduced response to vaccination. In general, household and close contacts of persons with altered immunocompetence may receive all age-appropriate vaccines (IDSA [Rubin 2014]; NCIRD/ACIP 2011); inactivated vaccines should be administered ≥2 weeks prior to planned immunosuppression when feasible (IDSA [Rubin 2014]).
• Elderly: Patients >60 years may have lower response rates to hepatitis B vaccine.
• Hemodialysis: Use with caution in patients undergoing hemodialysis; may not obtain adequate antibody titers following primary immunization.
Dosage form specific issues:
• Latex: Packaging may contain natural latex rubber.
• Yeast, neomycin, aluminum: May contain aluminum, yeast, and trace amounts of neomycin.
• Effective immunity: Vaccination may not result in effective immunity in all patients. Response depends upon multiple factors (eg, type of vaccine, age of patient) and is improved by administering the vaccine at the recommended dose, route, and interval. Vaccines may not be effective if administered during periods of altered immune competence (NCIRD/ACIP 2011). Due to the long incubation periods for hepatitis, unrecognized hepatitis A or B infection may be present; immunization may not prevent infection in these patients.
Monitor for syncope for 15 minutes following administration (NCIRD/ACIP 2011). If seizure-like activity associated with syncope occurs, maintain patient in supine or Trendelenburg position to reestablish adequate cerebral perfusion.
Pregnancy Risk Factor
Animal reproduction studies have not been conducted with this combination. Inactivated vaccines have not been shown to cause increased risks to the fetus (NCIRD/ACIP 2011).
• Discuss specific use of vaccine and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience injection site pain or irritation, headache, or loss of strength or energy. Have patient report immediately to prescriber severe dizziness, passing out, burning or numbness feeling, abnormal movements, or vision changes (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.
More about hepatitis a adult vaccine/hepatitis b adult vaccine
- Other brands: Twinrix