VAQTA

General Administration Information
For storage information, see the specific product information within the How Supplied section.
-Inform the parent, guardian, or responsible adult of the benefits and risks of the vaccine. Provide the Vaccine Information Statements from the manufacturer to the parent or guardian before each immunization. This action is required by the National Childhood Vaccine Injury Act of 1986.
-Record the manufacturer, lot number, administration date, and the name and address of the person administering the vaccine in the patient's permanent record. These actions are required by the National Childhood Vaccine Injury Act of 1986.

Route-Specific Administration

Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intramuscular Administration
-Use vaccine as supplied; reconstitution is not necessary.
-Shake vigorously just prior to administration. With through agitation, Harvix is a homogenous, turbid white suspension, and Vaqta is a slightly opaque, white suspension. If the vaccine cannot be resuspended or the appearance is not as described, discard it.
-Do not mix with any other vaccine.
-Storage of unopened vials:-Manufacturer recommendations: Store refrigerated at 2-8 degrees C (36 to 46 degrees F); do not freeze.
-Off-label storage information: According to a 2007 published article, storage of Havrix (GlaxoSmithKline) at room temperature for up to 72 hours is acceptable, and Vaqta (Merck) can be stored at 37 degrees C (98.6 degrees F) for up to 12 months. Other sources suggest that Havrix (GlaxoSmithKline) may maintain stability for up to 3 weeks at 37 degrees C. NOTE: Because changes in vaccine formulation can affect stability and effectiveness, confirmation of acceptable duration of storage at room temperature directly from the manufacturer for the specific vaccine being administered is recommended.


Intramuscular (IM) Injection
-For vials, use a sterile syringe and needle to withdraw suspension from vial. For prefilled syringes, attach a sterile needle.-For children 1-2 years, a needle at least 1 inch long is preferred for administration into the thigh; a 5/8 inch needle is sufficient for administration into the deltoid if the skin is stretched flat and the needle is inserted at a 90 degree angle.
-For children >= 3 years, the needle size required for deltoid injection ranges from 5/8- to 1-inch.

-Inject into the anterolateral aspect of the mid-thigh (for children 12-23 months of age) or the deltoid muscle of the upper arm (usually suitable for older children). Do NOT administer in the gluteal muscle; gluteal administration has resulted in lower hepatitis A seroconversion.
-When concomitant administration of other vaccines or immunoglobulin is required, they should be given with different syringes and at different injection sites.

Report all adverse reactions to the Vaccine Adverse Event Reporting System (VAERS), as well as to the manufacturer. The toll-free number for VAERS is 1-800-822-7967. Educate the responsible adult(s) to promptly report any adverse reaction after vaccine administration to a health care provider.

Most adverse reactions to hepatitis A vaccine, inactivated that have been reported are mild in nature, last 24 hours or less, and are self-limiting. The most frequently reported adverse reaction was an injection site reaction, manifested as induration, redness, swelling, pain, or tenderness. Among children and adolescents who received the vaccine in clinical studies, 3.4% to 30.3% had injection site pain or tenderness; the incidence of pain was lower in older children and adolescents (3.4% in 2 to 18 years vs. 30.3% in 15 to 24 months). Less than 0.5% of patients experienced severe soreness. Erythema occurred in 0.8% to 23.9% of children and adolescents, while injection site warmth was noted in up to 1.7% of patients. Swelling after injection occurred in up to 10.2% of patients. Across studies of pediatric and adult patients, induration was reported in up to 10% of patients, and hematoma formation was reported in less than 1% of patients. Bruising of the injection site, as well as pruritus and rash around the site (less than 1%), have been observed.

Fever may occur after hepatitis A vaccine, inactivated receipt. After Havrix administration, 2.7-3.3% had fever >= 100.6 degrees F, and 0.4-1.1% had fever >= 102.4 degrees F. After Vaqta administration, 8.2-12.4% had fever > 98.6 degrees F within 2 weeks of administration, and 2.1-3.8% had fever > 101 degrees F. Across different age groups, fever occurred in 16.4% of children who received Vaqta during clinical trials. Other general systemic adverse effects include irritability, which varied greatly among children 12-24 months of age (2.8-33.3%, resulting in grade 3 irritability or inconsolable crying in 0.3-1.5%). Other generalized systemic reactions reported among adult or pediatric populations include fatigue (1-10%), malaise (1-10%), lymphadenopathy (< 1%), chills (1.3%), arthralgia (< 1%), and myalgia (<= 5%). Increases in creatine phosphokinase, muscle stiffness, vasculitis, and hyperhidrosis have been noted.

Gastrointestinal adverse reactions to hepatitis A vaccine, inactivated reported specifically among children and adolescents include anorexia (18.3-20.5%), abdominal pain (1.1-1.2%), and diarrhea (3.8-4.6%). Additional reactions reported across multiple clinical studies in adult or pediatric populations include nausea (1-10%), vomiting (< 1%), constipation (1-9.9%), and dysgeusia (< 1%). Hepatitis and jaundice have been observed during post-marketing surveillance.

Adverse neurological reactions to hepatitis A vaccine, inactivated observed during clinical trials among adolescents and children include headache with an incidence of < 9%, and drowsiness (20.8-22.3%). Across multiple patient populations, insomnia occurred in < 10% of patients; vertigo, photophobia, and hypertonia occurred in < 1%. Post-marketing, dizziness, encephalopathy, Guillain-Barre syndrome, hypoesthesia, multiple sclerosis, myelitis, peripheral neuropathy, cerebellar ataxia, encephalitis, and paresthesias have been noted. Four seizures have been reported among children 2, 4, and 27 days after the first vaccine dose of the series, and 12 days after a booster dose.

Systemic allergic reactions, including angioedema, anaphylactoid reactions, angioedema, erythema multiforme, and serum sickness-like syndrome have occurred with hepatitis A vaccine, inactivated during post-marketing use. Bronchial constriction, dyspnea, and respiratory distress have been reported on the day of vaccine receipt. Asthma, wheezing, rash (unspecified), generalized erythema, urticaria, pruritus, ocular irritation, ocular pruritus, and dermatitis have occurred in < 1% of children, adolescents, and adults. Vesicular rash, morbilliform rash, or a rash with measles, rubella, or varicella characteristics have occurred in 1-9.9% of patients. Have appropriate medical treatment and supervision available to manage possible anaphylactic reactions after vaccine administration. Diaper dermatitis occurred in 1.1-2.4% of children 12-23 months of age who received the vaccine.

Post-marketing, syncope has been noted with the hepatitis A vaccine, inactivated. Syncope can be accompanied by transient neurological signs such as visual disturbance, paresthesia, and tonic-clonic limb movements. Have procedures in place to avoid falling injury and to restore cerebral perfusion after syncope.

Thrombocytopenia has been reported post-marketing with the hepatitis A vaccine, inactivated. The frequency of occurrence or causal relationship to the vaccine of post-marketing events cannot be reliably determined because events are reported voluntarily from a population of uncertain size.

Temporal relationships between hepatitis A vaccine, inactivated and infective events have occurred. In clinical trials involving children and adolescents, upper respiratory infection, rhinorrhea, and pharyngitis were observed in 2.3-5.2%, 2-6.2%, and 0-1.2% of patients, respectively. Reactions reported in 1-9.9% of patients within 2 weeks of vaccine receipt in any study when the vaccine was given alone or concomitantly with other vaccines include otitis media, nasopharyngitis, viral infections, streptococcal pharyngitis, laryngotracheobronchitis, viral exanthema, viral gastroenteritis, roseola, cough, and respiratory or nasal congestion.

Prior to administration, inform the parent, guardian, or responsible adult of the benefits and risks of the vaccine, and provide the Vaccine Information Statement, accessible at the Centers for Disease Control and Prevention (CDC) website. These actions are required by the National Childhood Vaccine Injury Act of 1986. If a dose of hepatitis A vaccine, inactivated has been previously given, question the parent or guardian about previous adverse reactions that may preclude further administration. Report all adverse reactions to the Vaccine Adverse Event Reporting System (VAERS), as well as the manufacturer. The toll-free number for VAERS is 1-800-822-7967. Educate the responsible adult(s) to promptly report any adverse reaction after vaccine administration to a health care provider.

Hepatitis A vaccine, inactivated is contraindicated in patients who have had a severe allergic reaction (e.g., anaphylaxis) temporally associated with a previous dose of this vaccine or hypersensitivity to any of its components. Use of this vaccine is contraindicated in patients with a neomycin hypersensitivity; the vaccines contain a residual amount of neomycin from the manufacturing process. Patients who develop symptoms suggestive of hypersensitivity should not receive further injections of the vaccine. Further, patients with latex hypersensitivity may not be appropriate candidates for vaccination with Vaqta as the syringe plunger and tip caps of prefilled syringes and the vial stopper contain dry natural latex rubber that may cause allergic reactions. Have epinephrine 1 mg/mL injection and other agents used in the treatment of severe anaphylaxis immediately available in the event of a serious allergic reaction to the vaccine.

Hepatitis A vaccine, inactivated is indicated for intramuscular administration and, thus, should be given cautiously to persons receiving anticoagulant therapy. Also, patients with thrombocytopenia, coagulopathy (e.g., hemophilia), other bleeding disorders, or vitamin K deficiency should be monitored closely for bleeding at the IM injection site. Steps to avoid hematoma formation are recommended.

The decision to administer or to delay vaccination with the hepatitis A vaccine, inactivated because of current or recent febrile illness depends on the severity of symptoms and on the etiology of the disease. The Advisory Committee on Immunization Practices recommends that vaccinations be delayed during the course of a moderate or severe acute febrile illness and administered after the acute phase of illness has resolved, unless the patient is at immediate risk of hepatitis A infection. Use caution when administering the vaccine to patients with severely compromised cardiopulmonary status. All vaccines can be administered to persons with minor illnesses such as diarrhea, mild upper-respiratory infection with or without low-grade fever, or other low-grade febrile illness. Persons with moderate or severe febrile illness should be vaccinated as soon as they have recovered from the acute phase of the illness.

Patients with immunosuppression may respond to hepatitis A vaccine, inactivated with lower antibody titers than non-immunosuppressed patients. Immunosuppressed persons may include patients with human immunodeficiency virus (HIV) infection; severe combined immunodeficiency (SCID); hypogammaglobulinemia; agammaglobulinemia; altered immune states due to generalized neoplastic disease; or an immune system compromised by radiation therapy or drug therapy (e.g., chemotherapy or corticosteroid therapy with greater than physiologic doses). Short-term (less than 2 weeks) corticosteroid therapy or intra-articular, bursal, or tendon injections with corticosteroids should not be immunosuppressive. Patients vaccinated with hepatitis A vaccine, inactivated within 2 weeks before starting immunosuppressive therapy or while receiving immunosuppressive therapy should be considered unvaccinated and should be revaccinated at least 3 months after therapy is discontinued if immune competence has been restored. Lower antibody titers are particularly a concern in patients with human immunodeficiency virus (HIV) infection, as the CD4 count at the time of vaccination (especially CD4 less than 200 cells/mm3) has been associated with reduced development of anti-HAV IgG antibodies; however, data suggest that patients will respond to vaccination after immunologic reconstitution with highly active antiretroviral therapy. Hepatitis A vaccine using a standard dose and schedule has been shown to be immunogenic for children with HIV infection. In 1 study, 32 HIV-infected children with a mean CD4 count of 1,483 cells/mm3 (range, 572 to 2,717) had protective antibody concentrations (greater than 20 milli-international units/mL) after a booster dose, which was given 6 months after the first dose. The guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV recommend vaccinating patients with a CD4 count less than 200 cells/mm3 if they have ongoing risks for hepatitis A. For HIV patients without risk factors, waiting to vaccinate until CD4 count is 200 cells/mm3 or higher is an option. Assess the antibody response (total or anti-HAV IgG) to the hepatitis A vaccine, inactivated 1 to 2 months after completing the series. If negative, revaccinate, preferably after the CD4 count is 200 cells/mm3 or higher.

Hepatitis A vaccine, inactivated is only indicated for intramuscular administration; do not give via intravenous administration, subcutaneous administration, or intradermal administration. Incorrect administration may result in inadequate immunity.

Patients with chronic hepatic disease may have a lower antibody response to hepatitis A vaccine, inactivated. During immunogenicity studies in adults, subjects with various forms of chronic hepatic disease had lower geometric mean antibody titers 1 month following dose 1 of the vaccine (ranging from 478 milli-international units/ml for chronic hepatitis C patients to 1245 milli-international units/ml in healthy patients). One month after a booster dose given 6 months after dose 1, seroconversion rates were similar among groups. The relationship between these data and the duration of protective immunity is unknown.

Description: Hepatitis A vaccine, inactivated is used to confer immunity against hepatitis A and is universally recommended for primary immunization for children 12-23 months of age. The vaccine may also be used in children and adolescents desiring immunity, prior to expected exposure to the hepatitis A virus, or for postexposure prophylaxis as an alternative to immune globulin. Hepatitis A vaccine is not effective in the prevention of other forms of hepatitis such as hepatitis B, hepatitis C, or hepatitis E. There are currently two different products available; both require the administration of a series of at least two doses, although substantial protection is afforded by the initial (i.e., primary) dose. Hepatitis A vaccines are FDA approved for use in pediatric patients as young as children >= 1 year of age.

General Dosing Information
-Primary immunization with hepatitis A vaccine is universally recommended for all pediatric patients; routine vaccination can be administered to children as young as 12 months of age. Children who are not vaccinated by age 2 years can be vaccinated at subsequent visits.
-Vaccinate patients traveling to, living in, or relocating to an area of high endemic risk. Information regarding specific locales may be found through the CDC or a local public health agency.
-Hepatitis A vaccination is recommended for patients with chronic liver disease, patients 1 year and older infected with HIV, and all previously unvaccinated persons who anticipate close personal contact (e.g., household contact or regular babysitting) with an international adoptee from a country of high or intermediate endemicity during the first 60 days after arrival of the adoptee in the United States. Ideally, administer the first dose at least 2 weeks before the arrival of the adoptee.
-In healthy children and adolescents, use of the hepatitis A vaccine for postexposure prophylaxis is preferred over immune globulin due to advantages of long-term protection and easier administration. Do not use the combination hepatitis A/hepatitis B vaccine, as no data are available; the combination vaccine contains half the hepatitis A antigen that is contained in the single-antigen hepatitis vaccine.
-Different brands of hepatitis A vaccines are interchangeable.

For hepatitis A prophylaxis:
-for primary immunization:
Intramuscular dosage:
Children and Adolescents: 0.5 mL IM ideally given at 12 to 23 months of age followed by a 0.5 mL booster dose at least 6 months after the first dose. Complete the Havrix series 6 to 12 months apart or Vaqta series 6 to 18 months apart. Catch-up vaccination may occur in patients 2 years and older, with doses separated by 6 to 18 months.
-for postexposure hepatitis A prophylaxis*:
Intramuscular dosage:
Children and Adolescents who have not previously received the hepatitis A vaccine: 0.5 mL IM as soon as possible after exposure. Efficacy when administered more than 2 weeks after exposure is not established. A second dose is not necessary for postexposure prophylaxis; however, a 0.5 mL booster dose can be administered at least 6 months after the first dose to complete the series. Complete the Havrix series 6 to 12 months apart or Vaqta series 6 to 18 months apart.
-for patients traveling to regions that have high or intermediate hepatitis A endemicity*:
Intramuscular dosage:
Infants 6 to 11 months: 0.5 mL IM before departure; revaccinate with 2 doses, separated by 6 to 18 months, between 12 to 23 months of age.
Children and Adolescents: 0.5 mL IM at any time before departure; ideally, administer as soon as travel is considered. Administer a 0.5 mL booster at least 6 months after the first dose to complete the series. Complete the Havrix series 6 to 12 months apart or Vaqta series 6 to 18 months apart.

Maximum Dosage Limits:
-Neonates
Safety and efficacy have not been established.
-Infants
Infants 5 months and younger: Safety and efficacy have not been established.
Infants 6 to 11 months: 0.5 mL mL/dose IM is recommended by ACIP for international travel; not FDA-approved.
-Children
0.5 mL/dose IM.
-Adolescents
0.5 mL/dose IM.

Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed. However, consult current immunization schedules for recommended vaccines for use in young dialysis patients; the ACIP states that all routine vaccinations are likely effective in patients with chronic renal disease.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Injection of hepatitis A vaccine produces antibodies that confer protection against hepatitis A infection. Stimulation of specific antibodies takes place without producing any disease symptoms. During the course of natural infection with the hepatitis A virus, the initial antibody response is predominantly of the IgM class. This response lasts for several months, but during convalescence, antibodies of the IgG class become dominant. Patients with anti-HAV of the IgG class are immune to reinfection.

Pharmacokinetics: Hepatitis A vaccine, inactivated is administered intramuscularly. The distribution, metabolism, and excretion of the vaccine have not been well defined. The absolute lower limit of antibodies against the virus (anti-HAV) necessary to confer immunity is not defined. Some investigators have postulated a minimum protective antibody concentration at 10 milli-international units/ml. However, concentrations of > 20 and more recently, > 33 milli-international units/ml of anti-HAV antibodies were recognized as the definition of seroconversion in clinical trials of Havrix, whereas concentrations > 10 milli-international units/ml were used in clinical trials of Vaqta. The exact timing of antibody appearance is not known; however, in a sample of vaccinees aged 2-18 years, 97-100% had protective antibodies 1 month after the first dose, and 100% had protective concentrations 1 month after a booster dose. IgG anti-HAV remains detectable for the person's lifetime. To maintain the highest antibody titers a booster dose is recommended between 6 and 18 months after the initial dose.


-Special Populations
Pediatrics
Children 11-25 months of age
Immunogenicity to the hepatitis A vaccine (Havrix, 0.5 ml/dose) was similar among children 11-13 months of age, children 15-18 months of age, and children 23-25 months of age who received 2 doses of the vaccine 6 months apart. One month after the second dose, the geometric mean titer was 1461 milli-international units/ml for children 11-13 months of age at the time of the first dose, 1635 milli-international units/ml for children 15-18 months of age at the time of the first dose, and 1911 milli-international units/ml for children 23-25 months of age at the time of the first dose. Vaccination response rates were 99-100%.

Children 2-12 years and Adolescents
Seroconversion was examined in children and adolescents (n = 314) immunized with 2 doses of hepatitis A vaccine (Havrix, 0.5 ml/dose) 6 months apart. Two weeks following the initial dose, seroconversion occurred in 91.6-96.1% of patients. One month after the initial dose, seroconversion occurred in 96.8-100% of patients (geometric mean titers = 194-305 milli-international units/ml). Following 2 doses, 100% of patients converted (geometric mean titers = 2495-3644 milli-international units/ml). Combined data from 11 randomized trials ( n > 2000) indicated that hepatitis A vaccine, inactivated (Vaqta) is highly immunogenic. Among patients who received a 0.5 ml dose, 97% were seropositive 1 month after the first dose and 100% after the second dose when given 6 months apart, with geometric mean titers of 43 milli-international units/ml and 10,007 milli-international units/ml, respectively.