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Hepatitis A and Hepatitis B Recombinant Vaccine

Medically reviewed by Drugs.com. Last updated on Jul 14, 2020.

Pronunciation

(hep a TYE tis aye & hep a TYE tis bee ree KOM be nant vak SEEN)

Index Terms

  • Engerix-B and Havrix
  • Havrix and Engerix-B
  • HepA
  • HepA-HepB
  • Hepatitis A
  • Hepatitis B
  • Hepatitis B and Hepatitis A Vaccine
  • HepB

Dosage Forms

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, formaldehyde, yeast protein, and trace amounts of neomycin; may contain natural rubber/natural latex in prefilled syringe]

Brand Names: U.S.

  • Twinrix

Pharmacologic Category

  • Vaccine
  • Vaccine, Inactivated (Viral)

Pharmacology

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.

Contraindications

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.

Dosing: Adult

Note: Immunization during coronavirus disease 2019 (COVID-19) pandemic: Routine vaccination should not be delayed because of the COVID-19 pandemic (CDC 2020; WHO 2020). In general, simultaneous administration of all vaccines for which a patient is eligible (according to current immunization schedules/guidelines) is recommended (ACIP [Ezeanolue 2020]). However, vaccination of patients with suspected or confirmed COVID-19 infection (regardless of symptoms) should be postponed to avoid exposure to health care personnel and other patients (CDC 2020). Additional information is available from the CDC, the American Academy of Pediatrics, and the Immunization Action Coalition.

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

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Immunization during coronavirus disease 2019 (COVID-19) pandemic: Routine vaccination should not be delayed because of the COVID-19 pandemic (CDC 2020; WHO 2020). In general, simultaneous administration of all vaccines for which a patient is eligible (according to current immunization schedules/guidelines) is recommended (ACIP [Ezeanolue 2020]). However, vaccination of patients with suspected or confirmed COVID-19 infection (regardless of symptoms) should be postponed to avoid exposure to health care personnel and other patients (CDC 2020). Additional information is available from the CDC, the American Academy of Pediatrics, and the Immunization Action Coalition.

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

Administration

IM: Resuspend vaccine prior to use by shaking vigorously for at least 15 to 30 seconds until a uniform hazy white appearance occurs. Discard if the suspension is discolored, clear, or does not appear homogenous after shaking. Administer IM in the deltoid region; do not administer in the gluteal region (may give suboptimal response). Do not administer IV, intradermally, or SubQ (US labeling). Do not mix with other vaccines or injections; separate needles and syringes should be used for each injection. To prevent syncope-related injuries, patients should be vaccinated while seated or lying down (ACIP [Ezeanolue 2020]). US law requires that the date of administration, the vaccine manufacturer, lot number of vaccine, Vaccine Information Statement (VIS) edition date and date it was provided, and the administering person's name, title, and address be recorded.

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 (ACIP [Ezeanolue 2020]). 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).

Storage

Store in refrigerator at 2°C to 8°C (36°F to 46°F); do not freeze (discard if frozen).

Drug Interactions

There are no known significant interactions.

Test Interactions

Following vaccination, hepatitis B surface antigen (HBsAg), a component of the vaccine, has been transiently detected in blood samples. Therefore, serum HBsAg detection may not have diagnostic value within 28 days after receipt of hepatitis B vaccine.

Adverse Reactions

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.) Also see individual agents.

>10%:

Central nervous system: Headache (13% to 22%), fatigue (11% to 14%)

Local: Local soreness/soreness at injection site (35% to 41%), erythema at injection site (8% to 11%)

1% to 10%:

Dermatologic: Skin sclerosis (at injection site)

Gastrointestinal: Diarrhea (4% to 6%), nausea (2% to 4%), vomiting (≤1%)

Local: Local swelling (at injection site: 4% to 6%)

Respiratory: Upper respiratory tract infection

Miscellaneous: Fever (2% to 4%)

<1%, postmarketing, and/or case reports: Abdominal pain, abnormal hepatic function tests, agitation, alopecia, anaphylactoid reaction, anaphylaxis, angioedema, anorexia, arthralgia, arthritis, back pain, Bell’s palsy, brain disease, bronchospasm, bruise, bruising at injection site, chills, conjunctivitis, diaphoresis, dizziness, drowsiness, dyspepsia, dyspnea (including asthma-like symptoms), eczema, encephalitis, erythema, erythema multiforme, erythema nodosum, flu-like symptoms, flushing, Guillain-Barre syndrome, hepatitis, herpes zoster, hyperhidrosis, hypersensitivity reaction, hypoesthesia, immune thrombocytopenia, injection site pruritus, injection site reaction (burning sensation at injection site, pain at injection site), insomnia, irritability, jaundice, lichen planus, malaise, meningitis, migraine, multiple sclerosis, myalgia, myasthenia, myelitis, neuropathy, neuritis, optic neuritis, otalgia, palpitations, paralysis, paresis, paresthesia, petechiae, respiratory tract disease, seizure, serum sickness-like reaction (days to weeks after vaccination), skin rash, syncope, tachycardia, thrombocytopenia, tinnitus, transverse myelitis, urticaria, vasculitis, vertigo, visual disturbance, weakness

Warnings/Precautions

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 (ACIP [Ezeanolue 2020]).

• Shoulder injury related to vaccine administration: Vaccine administration that is too high on the upper arm may cause shoulder injury (eg, shoulder bursitis or tendinitis) resulting in shoulder pain and reduced range of motion following injection. Use proper injection technique for vaccines administered in the deltoid muscle (eg, injecting in the central, thickest part of the muscle) to reduce the risk of shoulder injury related to vaccine administration (Cross 2016; Foster 2013).

• 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 (ACIP [Ezeanolue 2020]).

Disease-related concerns:

• 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. Defer 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) (ACIP [Ezeanolue 2020]).

• Bleeding disorders: Use with caution in patients with bleeding disorders (including thrombocytopenia); 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 (ACIP [Ezeanolue 2020]). 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:

• Anticoagulant therapy: Use with caution in patients receiving anticoagulant therapy; bleeding/hematoma may occur from IM administration (ACIP [Ezeanolue 2020]).

• 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; however, vaccination should not be deferred because a specific brand name is unavailable (ACIP [Ezeanolue 2020]).

Special populations:

• Altered immunocompetence: Consider deferring immunization during periods of severe immunosuppression (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. Inactivated vaccines should be administered ≥2 weeks prior to planned immunosuppression when feasible; inactivated vaccines administered during chemotherapy should be readministered after immune competence is regained (ACIP [Ezeanolue 2020]; 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.

Other warnings/precautions:

• Appropriate use: Use of this vaccine for specific medical and/or other indications (eg, immunocompromising conditions, hepatic or kidney disease, diabetes) is also addressed in the annual ACIP Recommended Immunization Schedules (refer to CDC schedule for detailed information). Specific recommendations for vaccination in immunocompromised patients with asplenia, cancer, HIV infection, cerebrospinal fluid leaks, cochlear implants, hematopoietic stem cell transplant (prior to or after), sickle cell disease, solid organ transplant (prior to or after), or those receiving immunosuppressive therapy for chronic conditions as well as contacts of immunocompromised patients are available from the IDSA (Rubin 2014).

• 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 (ACIP [Ezeanolue 2020]). 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.

Monitoring Parameters

Monitor for syncope for 15 minutes following administration (ACIP [Ezeanolue 2020]). If seizure-like activity associated with syncope occurs, maintain patient in supine or Trendelenburg position to reestablish adequate cerebral perfusion.

Pregnancy Considerations

Based on data collected from a pregnancy registry between 2001 and 2015, an increased risk of major birth defects or miscarriage was not observed following maternal use of hepatitis A and hepatitis B vaccine.

Inactivated vaccines have not been shown to cause increased risks to the fetus (ACIP [Ezeanolue 2020]). Refer to current immunization schedule for vaccinating pregnant females.

Patient Education

What is this drug used for?

• It is used to prevent hepatitis A infection.

• It is used to prevent hepatitis B infection.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Injection site pain or irritation

• Headache

• Loss of strength or energy

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Severe dizziness

• Passing out

• Burning or numbness feeling

• Abnormal movements

• Vision changes

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.