Professional Information
Hepatitis A Virus Vaccine Inactivated and Hepatitis B Virus Vaccine Recombinant (Systemic)
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VA CLASSIFICATION
Primary: IM100
Commonly used brand name(s): Twinrix.
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).
Category:
Immunizing agent (active) —
Indications
General considerations
Hepatitis A
Hepatitis A virus (HAV) is highly contagious and the predominant mode of transmission is person to person via the fecal-oral route. Infection is acquired by contaminated water or food, infected food handlers, after breakdown in usual sanitary conditions or after floods or natural disasters, by ingesting uncooked or undercooked shellfish (oysters, clams, mussels) from contaminated waters, during travel to areas of the world with poor hygienic conditions, among institutionalized children and adults, in day care centers, and by parenteral transmission, either by blood transfusions or by sharing needles with infected people.{01}
Hepatitis B
The hepatitis B virus (HBV) occurs throughout the world with highly variable prevalences. A human reservoir of persistently infected persons is present in nearly all communities of the world. In the United States, the primary means of transmission are parenteral drug abuse, unprotected sexual activity, occupationally acquired infection, or travelers returning from high prevalence countries.{01}
After a person has been exposed to HBV, there is no definitive treatment for acute infection. Those who develop antibodies to HBsAg after active infection are protected against subsequent infection.{01}
Accepted
Hepatitis A and Hepatitis B virus infection (prophylaxis)—Hepatitis A inactivated and hepatitis B recombinant combination vaccine is indicated for preexposure immunization against disease caused by hepatitis A virus (HAV) and infection by all known subtypes of hepatitis B virus in persons 18 years of age or older.{01}
—Unless otherwise contraindicated, hepatitis A and hepatitis B combination vaccine is indicated in persons 18 years of age or older who are at increased risk of infection due to behavior or occupational factors. Examples of groups identified as being at increased risk of infection include: • International travelers; persons from areas of low endemicity who travel to areas of intermediate or high endemicity are at risk for acquiring hepatitis A. These areas include, but are not limited to, Africa, the Caribbean, Central America, eastern Europe, the Middle East, South America (temperate and tropical), south and southeast Asia (except Japan), southern Europe, and the former Soviet Union .{01}
• Military personnel identified as being at increased risk for HBV, including military recruits.{01}
• People living in, or relocating to, areas of higher HAV endemicity and who have risk factors for HBV.{01}
• Persons engaging in high-risk sexual activity, such as sexually active homosexual and bisexual males.{01}
• Users of illicit injectable drugs.{01}
• Persons at risk through their work, such as laboratory workers who handle live hepatitis A and hepatitis B virus, police and other personnel who render first aid or medical assistance, and workers who come in contact with feces or sewage.{01}
• Employees of child day-care centers and correctional facilities, residents of drug and alcohol treatment centers, and patients and staff in hemodialysis units.{01}
• Patients who frequently receive blood products, including those people who have clotting-factor disorders, such as hemophiliacs and other recipients of therapeutic blood products.{01}
• Persons with chronic liver disease, including those with alcoholic cirrhosis, chronic hepatitis C, autoimmune hepatitis, and primary biliary cirrhosis.{01}
• Healthcare personnel who give first aid or emergency medical assistance.{01}
• People who are at increased risk for HBV infection and who are close contacts of patients with acute or relapsing hepatitis A and individuals who are at increased risk for HAV infection and who are close contacts of those with hepatitis B infections either acute or chronic.{01}
Unaccepted
Hepatitis A and hepatitis B vaccine will not give protection from hepatitis caused by agents such as hepatitis C virus, hepatitis E virus, or other pathogens that infect the liver{01}.
Pharmacology/Pharmacokinetics
Physicochemical characteristics:
Source—
Hepatitis A vaccine inactivated is a sterile suspension of inactivated hepatitis A virus (strain HM175) grown in MRC-5 cells and combined with purified surface antigen of the hepatitis B virus.{01}
Hepatitis B recombinant vaccines are produced from Saccharomyces cerevisiae cells, which carry the gene for the hepatitis B surface antigen (HBsAg) in synthetic media that contain inorganic salts, amino acids, dextrose, and vitamins. Yeast-derived protein constitutes no more than 5% of the final product. Bulk preparations of each antigen are adsorbed separately onto aluminum salts and then pooled during formulation.{01}
Protective effect—
Clinical studies were analyzed following administration of three doses of the hepatitis A and hepatitis B combination vaccine in healthy adults and it was shown to be safe and immunogenic. Immunogenicity studies have shown that 93.8%, 98.8%, and 99.9% of patients developed protective antibodies against HAV, and 30.8%, 78.2%, and 98.5% of patients developed protective antibodies against HBV after 1, 2, and 3 doses, respectively{01}.
Time to protective effect
Protective antibodies against HAV were detected in 99.9% of patients, and protective antibodies against HBV were detected in 98.5% of patients one month after completion of the three dose series{01}.
Duration of protective effect
The duration of protective effect by the combination vaccine is at least 4 years, as demonstrated by clinical studies{01}.
Precautions to Consider
Pregnancy/Reproduction
Pregnancy—
Studies have not been done in humans . It is unknown whether the combination of hepatitis A and hepatitis B vaccine can cause fetal harm or can affect reproductive capacity. It should be used in pregnant women only if the benefit outweighs the risk.{01}
Studies have not been done in animals.{01}
Note: Healthcare providers are encouraged to register pregnant women who received hepatitis A and hepatitis B vaccine in the SmithKline Beecham Pharmaceuticals vaccination registry by calling 1–800–366–8900 extension 5231.{01}
FDA Pregnancy Category C.{01}
Breast-feeding
It is not known whether the vaccine is distributed into human breast milk. However, many drugs are distributed into human breast milk, caution should be used when administering to nursing women.{01}
Pediatrics
No information is available on the relationship of age to the effects of the combination hepatitis A and hepatitis B vaccine in the pediatric population. Safety and efficacy have not been established in patients under the age of 18 years.{01}
Geriatrics
Appropriate studies on the relationship of age to the effects of the combination hepatitis A and hepatitis B vaccine in the geriatric population have not been performed. However, no specific geriatric problems have been documented to date.{01}
Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):
» Anticoagulants{01} (caution is recommended because bleeding may occur following intramuscular administration of the hepatitis A inactivated and hepatitis B recombinant combination vaccine{01})
Immunosuppressive therapy (because normal defense mechanisms are suppressed, the patient's antibody response to hepatitis A inactivated and hepatitis B recombinant combination vaccine may not be as expected{01})
Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).
Except under special circumstances, this medication should not be used when the following medical problem exists:
» Hypersensitivity to any component of the vaccine (there have been rare reports of anaphylaxis/anaphylactoid reactions following the use of hepatitis A vaccine inactivated ; therefore, persons experiencing hypersensitivity reactions after a dose of hepatitis A vaccine inactivated or hepatitis B vaccine recombinant should not receive further doses of the combination hepatitis A and hepatitis B vaccine{01})
Risk-benefit should be considered when the following medical problems exist
Allergy to yeast (the manufacturing procedures used to make this vaccine result in a product that contains no more than 5% yeast protein{01})
» Bleeding disorders{01} or
» Thrombocytopenia{01} (caution is recommended because bleeding may occur following intramuscular administration of the hepatitis A inactivated and hepatitis B recombinant combination vaccine{01})
Hepatitis A, current infection{01} or
Hepatitis B, current infection{01} (hepatitis A inactivated and hepatitis B recombinant combination vaccine will not prevent infection in patients who have unrecognized hepatitis A or hepatitis B at the time of vaccination{01})
Illness, moderate or severe, with or without fever (administration of the vaccine should be delayed, except when withholding the vaccine entails a greater risk to the patient than a possible superimposed reaction to the vaccine{01})
Immune deficiency conditions ( because normal defense mechanisms are suppressed, the patient's antibody response to hepatitis A inactivated and hepatitis B recombinant combination vaccine may not be as expected{01})
Side/Adverse Effects
Note: Results from two clinical studies indicated no relationship between Hepatitis B vaccine and the development of multiple sclerosis and that vaccination with hepatitis B does not appear to increase the short-term risk of multiple sclerosis relapse.{01}
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Those indicating need for medical attention
Incidence rare
Anaphylactic reaction (difficulty in breathing or swallowing; hives; itching, especially of feet or hands; reddening of skin, especially around ears ; swelling of eyes, face, or inside of nose; unusual tiredness or weakness, sudden and severe)—seen only with hepatitis A vaccine inactivated{01}
Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent (> 10%)
Soreness at injection site {01}
Incidence less frequent (1 to 10%)
Induration at injection site {01}(hardening or thickening of skin at injection site)
upper respiratory tract infection (cough; fever; sneezing; sore throat){01}
Incidence rare (less than 1%)
Abdominal pain {01}
anorexia (loss of appetite ; weight loss){01}
arthralgia (pain, swelling, or redness in joints; difficulty in moving){01}
back pain {01}
dizziness {01}
erythema ( redness of skin; unusually warm skin){01}
flushing (feeling of warmth ; redness of the face, neck, arms and occasionally upper chest){01}
injection site reactions, including ecchymoses {01}(bruising ; large, flat, blue or purplish patches in the skin), itching, redness, or swelling at injection site {01}
influenza-like symptoms (nausea; vomiting){01}
insomnia (sleeplessness; trouble sleeping){01}
irritability and agitation {01}
migraine ( severe headache){01}
myalgia {01}(muscle pain)
paresthesia (tingling, burning, or prickly sensations){01}
petechiae {01}(small, red or purple spots on skin)
rash {01}
respiratory tract illness ( headache; sore throat; runny nose; fever){01}
somnolence (sleepiness; unusual drowsiness){01}
syncope ( fainting or lightheadedness when getting up from a lying or sitting position; unusually fast heartbeat; palpitations){01}
sweating {01}
urticaria {01}(hives or skin rash; itching)
vertigo {01}(feeling of constant movement of self or surroundings; sensation of spinning)
weakness {01}
Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Hepatitis A Virus Vaccine Inactivated and Hepatitis B Virus Vaccine Recombinant (Systemic) .
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):
Before receiving this vaccine
» Conditions affecting use, especially:
Hypersensitivity to hepatitis A vaccine inactivated, hepatitis B vaccine recombinant, or any of their components
Other medications, especially anticoagulants
Other medical problems, especially bleeding disorders or thrombocytopenia
Proper use of this vaccine
» Proper dosing
Side/adverse effects
Signs of potential side effects, especially anaphylactic reaction
General Dosing Information
Before the injection of any vaccine, the health care professional should take all reasonable precautions to prevent allergic or other adverse reactions.{01} The patient's history should be reviewed for possible vaccine sensitivity, previous vaccine related adverse reactions, and to determine that there is no contraindication to the vaccine being given.{01}
Hepatitis A vaccine inactivated and hepatitis B vaccine recombinant is administered by intramuscular injection in the deltoid region.{01} It should not be administered in the gluteal region because a suboptimal response may result.{01} It also should not be injected intravenously, intradermally, or subcutaneously.{01}
As with any vaccine, vaccination may not protect 100% of the recipients. As hepatitis D (caused by the delta virus) does not occur in the absence of the hepatitis B infection, it can be expected that prevention of hepatitis D infection will occur with vaccination with the combination hepatitis A and B vaccine.{01}
Epinephrine injection and other appropriate agents used for the control of immediate allergic reactions must be immediately available should an acute anaphylactic reaction occur.{01}
Patients should be informed of the importance of adhering to the immunization schedule. As with any vaccine it is important to question the patient concerning the occurrence of symptoms/signs after a previous dose of the same vaccine. If any suspected adverse events have occurred, the Vaccine Adverse Events Reporting System (VAERS) should be notified. The number for forms and information is 1–800–822–7967.{01}
Parenteral Dosage Forms
HEPATITIS A VIRUS VACCINE INACTIVATED AND HEPATITIS B VIRUS VACCINE RECOMBINANT INJECTABLE SUSPENSION
Usual Adult Dose
Hepatitis A and Hepatitis B (prophylaxis)
Intramuscular, into the deltoid muscle, 1 mL (720 enzyme linked immunosorbant assay [ELISA] units of inactivated hepatitis A virus and 20 mcg of hepatitis B surface antigen) for a total of three doses on a 0-, 1- and 6-month schedule.{01}
Usual Pediatric Dose
Safety and efficacy have not been established.{01}
Usual Geriatric Dose
See Usual adult dose.
{01}
Strength(s) usually available
U.S.—
Not less than 720 enzyme linked immunosorbent assay (ELISA) units of inactivated hepatitis A virus and 20 mcg of recombinant HBsAg protein per mL (Rx) [Twinrix (aluminum phosphate) (aluminum hydroxide) (amino acids) (2–phenoxyethanol 5 mg [as a preservative]) (sodium chloride) (phosphate buffer ) (polysorbate 20) (water for injection) (formalin [not more than 0.1 mg] ) (thimerosal [<1 mcg of mercury] ) (residual MRC-5 cellular proteins [not more than 2.5 mcg]) (neomycin sulfate [not more than 20 nanograms per dose])]{01}
Packaging and storage:
Store refrigerated between 2 and 8 °C (36 and 46 °F). Protect from freezing.{01}
Preparation of dosage form:
The vaccine should be used as supplied, and should not be diluted. The full recommended dose of the vaccine should be used. The vial should be shaken well immediately before withdrawal of the dose. In addition, thorough agitation at the time of administration is necessary to maintain suspension of the vaccine. After agitation, the vaccine is a slightly opaque, white suspension. The vaccine should be discarded if the suspension does not appear homogenous. Any vaccine remaining in the vial should be discarded.{01}
Auxiliary labeling:
• Refrigerate. Do not freeze; discard if freezing occurs.{01}
• Shake well.{01}
Developed: 08/22/2001
References
- Product Information: Twinrix®, hepatitis A inactivated and hepatitis B recombinant vaccine. SmithKline Beecham, Philadelphia, PA, (PI revised 5/2001) reviewed 7/2001.
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