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]
Pharmacology
Mechanism of Action
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.
Pharmacokinetics/Pharmacodynamics
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.
Dosage and Administration
Dosing: Adult
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
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 [Kroger 2017]). 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 (ACIP [Kroger 2017]). 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 [Kroger 2017]).
- 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 [Kroger 2017]).
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 [Kroger 2017]).
- 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 [Kroger 2017]). 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 [Kroger 2017]).
- 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 [Kroger 2017]).
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 [Kroger 2017]; 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 [Kroger 2017]). 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 [Kroger 2017]). If seizure-like activity associated with syncope occurs, maintain patient in supine or Trendelenburg position to reestablish adequate cerebral perfusion.
Pregnancy
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 [Kroger 2017]). 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.
Frequently reported side effects of this drug
- Injection site pain or irritation
- Headache
- Loss of strength or energy
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Severe dizziness
- Passing out
- Burning or numbness feeling
- Abnormal movements
- Vision changes
- Signs of a significant reaction like 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. 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 brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
