Vaqta (Hepatitis A Vaccine)

VAQTA®

MSD

Hepatitis A Vaccine (Purified Inactivated)

Vaccine

Action And Clinical Pharmacology: Hepatitis A vaccine, purified inactivated is an inactivated whole virus vaccine which has been shown to induce antibody to hepatitis A virus protein.

Disease Epidemiology: Hepatitis A virus is one of several hepatitis viruses that cause a systemic infection with pathology in the liver. The incubation period ranges from approximately 20 to 50 days. While the course of the disease is generally benign and does not result in chronic hepatitis, infection with hepatitis A virus remains an important cause of morbidity and occasional fulminant hepatitis and death.

Hepatitis A is transmitted most often by the fecal-oral route, with infection occurring primarily within private households, daycare centers, neonatal intensive care units, and chronic-care hospitals. Common-source outbreaks due to contaminated food and water supplies have occurred following consumption of certain foods such as raw shellfish, and uncooked foods prepared by an infected food-handler or otherwise contaminated prior to ingestion (salads, sandwiches, frozen raspberries, etc). Bloodborne transmission, while uncommon, is possible via blood transfusion, contaminated blood products, or from needles shared with an infected viremic individual. Sexual transmission has also been reported.

The disease burden due to hepatitis A in the U.S. has been estimated to be approximately 75 800 cases of clinical hepatitis each year, resulting in 11 400 hospitalizations, and 80 deaths due to fulminant hepatitis. Worldwide, it has been estimated that 1.4 million cases occur annually. The clinical manifestations of hepatitis A infection often pass unrecognized in children 2 years of age whereas overt hepatitis develops in the majority of infected older children and adults. Symptoms and signs of hepatitis A infection are similar to those associated with other types of viral hepatitis and include anorexia, nausea, fever/chills, jaundice, dark urine, light-colored stools, abdominal pain, malaise, and fatigue.

Clinical Evaluation: Clinical trials conducted worldwide with several formulations of the vaccine in 9 181 healthy individuals ranging from 2 to 85 years of age have demonstrated that Vaqta is highly immunogenic and generally well tolerated.

Protection from hepatitis A disease has been shown to be related to the presence of antibody; an anamnestic antibody response occurs in healthy individuals with a history of infection who are subsequently re-exposed to hepatitis A virus. Similarly, protection after vaccination with hepatitis A vaccine (purified inactivated) was associated with the onset of seroconversion with an anamnestic antibody response following booster vaccination with hepatitis A vaccine (purified inactivated).

Clinical Studies: In combined clinical studies, 97% of 1 214 children and adolescents 2 to 17 years of age seroconverted (³10 mIU/mL of hepatitis A antibody, measured by a modification of the Havab radioimmunoassay [RIA]) within 4 weeks after a single approximately 25 U i.m. dose of hepatitis A vaccine (purified inactivated). Similarly, 95% of 1 428 adults ³18 years of age seroconverted within 4 weeks after a single approximately 50 U i.m. dose of hepatitis A vaccine (purified inactivated). Immune memory was later demonstrated by an anamnestic antibody response in individuals who received a booster dose.

While a study evaluating hepatitis A vaccine (purified inactivated) alone in a postexposure setting has not been conducted, the concurrent use of hepatitis A vaccine (purified inactivated) (approximately 50 U) and immune globulin (IG, 0.06 mL/kg) was evaluated in a clinical study involving healthy adults 18 to 39 years of age. Table I provides seroconversion rates at 4 and 24 weeks after the first dose in each treatment group and at 1 month after a booster dose of hepatitis A vaccine (purified inactivated) (administered at 24 weeks).

A very high degree of protection has been demonstrated after a single dose of hepatitis A vaccine (purified inactivated) in children and adolescents. The protective efficacy, immunogenicity, and safety of hepatitis A vaccine (purified inactivated) were evaluated in a randomized, double-blind placebo-controlled study involving 1 037 susceptible healthy children and adolescents 2 to 16 years of age in a U.S. community with recurrent outbreaks of hepatitis A (The Monroe Efficacy Study). Each child received a single i.m. dose of hepatitis A vaccine (purified inactivated) (approximately 25 U) or placebo. Among those individuals who were initially seronegative (by modified HAVAB), seroconversion was achieved in >99% of vaccine recipients within 4 weeks after vaccination. The onset of seroconversion following a single dose of hepatitis A vaccine (purified inactivated) was shown to parallel the onset of protection against clinical hepatitis A disease. Because of the long incubation period of the disease (approximately 20 to 50 days), analysis of protective efficacy was based on cases of hepatitis A occurring ³50 days after vaccination in order to exclude any children incubating the infection before vaccination. In subjects who were initially seronegative, the protective efficacy of a single dose of hepatitis A vaccine (purified inactivated) was observed to be 100% with 25 cases of clinical hepatitis A occurring in the placebo group and none in the vaccine group (p
The total duration of the protective effect of hepatitis A vaccine (purified inactivated) in healthy vaccinees is unknown at present. However, seropositivity was shown to persist up to 18 months after a single approximately 25 U dose in most children and adolescents who participated in The Monroe Efficacy Study. In adults, seropositivity has been shown to persist up to 6 months after a single approximately 50 U dose (studies ongoing). Studies are ongoing to evaluate longer-term persistence and the need, if any, for additional booster doses. Persistence of immunologic memory was demonstrated with an anamnestic antibody response to a booster dose of approximately 25 U given 6 to 18 months after the primary dose in children and adolescents, and to a booster dose of approximately 50 U given 6 months after the primary dose to adults. In the absence of study data on antibody persistence for vaccine recipients over several decades, an extrapolation from a kinetic model of antibody decay was used to estimate the duration of antibody. Extrapolation of observed antibody titers from year 2 to 3 in 118 children and adults, most of whom had received 3 injections of 6, 13 or 25 U vaccine, suggests that detectable levels of antibody may persist after the booster dose for many years. The median duration based on this extrapolation was calculated to be 21 years [95% CI= (14 to 27 years)].

Indications And Clinical Uses: For vaccination against infection caused by hepatitis A virus.

Hepatitis A vaccine (purified inactivated) is indicated for active pre-exposure prophylaxis against disease caused by hepatitis A virus. Vaccination is recommended in children 2 years of age and older, adolescents, and adults who are at risk of contracting or spreading infection or who are at risk of life-threatening disease if infected, including but not limited to: A. Travelers to endemic or outbreak areas.

B. Frequently affected communities: members residing in any community with 1 or more recorded outbreaks within the last 5 years.

C. Daycare: Children and staff of daycare centers as well as their parents, siblings and other contacts.

D. Military personnel prior to departure for endemic or outbreak areas.

E. Persons for whom Hepatitis A is an occupational hazard: healthcare workers; staff and residents of orphanages, chronic care hospitals and mental healthcare facilities; sewage workers.

F. Hemophiliacs and other recipients of therapeutic blood products.

G. Food handlers.

H. Consumers of high-risk foods: e.g., raw shellfish.

I. Persons at increased risk of the disease due to their sexual practices: homosexually-active males; persons who repeatedly contract sexually transmitted diseases.

J. Users of illicit injectable drugs.

Hepatitis A vaccine (purified inactivated) will not prevent hepatitis caused by infectious agents other than hepatitis A virus.

Revaccination: see Dosage.

Contra-Indications: Hypersensitivity to any component of the vaccine. tag_WarningWarnings

Manufacturers’ Warnings In Clinical States: If hepatitis A vaccine (purified inactivated) is used in individuals with malignancies or those receiving immunosuppressive therapy or who are otherwise immunocompromised, the expected immune response may not be obtained.

Hepatitis A vaccine (purified inactivated) is not recommended for use in infants younger than 2 years of age since data on use in this age group are not currently available.

Precautions: General: Individuals who develop symptoms suggestive of hypersensitivity after an injection of hepatitis A vaccine (purified inactivated) should not receive further injections of the vaccine (see Contraindications).

As with any vaccine, adequate treatment provisions, including epinephrine, should be available for immediate use should an anaphylactic or anaphylactoid reaction occur.

Since there is a possibility that the vaccine may contain trace amounts of neomycin, the possibility of an allergic reaction in individuals sensitive to this substance should be kept in mind when considering the use of this vaccine (see Supplied).

As with any vaccine, vaccination with hepatitis A vaccine (purified inactivated) may not result in a protective response in all susceptible vaccinees.

Any acute infection or febrile illness is reason for delaying use of hepatitis A vaccine (purified inactivated) except when, in the opinion of the physician, withholding the vaccine entails a greater risk.

Hepatitis A vaccine (purified inactivated) will not prevent hepatitis caused by infectious agents other than hepatitis A virus. Because of the long incubation period (approximately 20 to 50 days) for hepatitis A, it is possible for unrecognized hepatitis A infection to be present at the time the vaccine is given. The vaccine may not prevent hepatitis A in such individuals.

Children: Hepatitis A vaccine (purified inactivated) has been shown to be generally well-tolerated and highly immunogenic in individuals 2 to 17 years of age. See Dosage for the recommended dosage schedule.

Safety and effectiveness in infants below 2 years of age have not been established.

Pregnancy: Animal reproduction studies have not been conducted with hepatitis A vaccine (purified inactivated). It is also not known whether hepatitis A vaccine (purified inactivated) can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Hepatitis A vaccine (purified inactivated) should be given to a pregnant woman only if clearly needed.

Lactation: It is not known whether hepatitis A vaccine (purified inactivated) is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when hepatitis A vaccine (purified inactivated) is administered to a woman who is breast-feeding.

Carcinogenesis, Mutagenesis, Reproduction: Hepatitis A vaccine (purified inactivated) has not been evaluated for its carcinogenic or mutagenic potential, or its potential to impair fertility.

Drug Interactions: Other Vaccines: Data are not yet available to recommend concurrent use with other vaccines.

Immune Globulin: For individuals requiring either postexposure prophylaxis or combined immediate and longer-term protection (e.g., travelers departing on short notice to endemic areas), hepatitis A vaccine (purified inactivated) may be administered concomitantly with IG using separate sites and syringes.

Adverse Reactions: No serious vaccine-related adverse experiences were observed during clinical trials.

In The Monroe Efficacy Study, 1 037 healthy children and adolescents 2 to 16 years of age received either a primary dose of approximately 25 U of hepatitis A vaccine and a booster 6, 12 or 18 months later, or placebo. Subjects were observed during a 5-day period for fever and local complaints and during a 14-day period for systemic complaints. Injection-site complaints, generally mild and transient, were the most frequently reported complaints. Table II summarizes the local and systemic complaints (³1%) reported in this study, without regard to causality. There were no significant differences in the rates of any complaint between vaccine and placebo recipients after dose 1.

Children/Adolescents 2 to 17 years of age: In combined clinical trials (including Monroe Efficacy Study participants) involving 2 595 healthy children and adolescents who received one or more approximately 25 U doses of hepatitis A vaccine, fever and local complaints were observed during a 5-day period following vaccination and systemic complaints during a 14-day period following vaccination. Injection-site complaints, generally mild and transient, were the most frequently reported complaints. Table III lists the complaints (³1%) reported, without regard to causality, in decreasing order of frequency within each body system.

Laboratory Findings: Very few laboratory abnormalities were reported and included isolated reports of elevated liver function tests, eosinophilia, and increased urine protein.

Adults 18 years of age and older: In combined clinical trials involving 1 529 healthy adults who received 1 or more approximately 50 U doses of hepatitis A vaccine, fever and local complaints were observed during a 5-day period following vaccination and systemic complaints during a 14-day period following vaccination. Injection-site complaints, generally mild and transient, were the most frequently reported complaints. Table IV lists the complaints (³1%) reported, without regard to causality, in decreasing order of frequency within each body system.

Dosage And Administration: For i.m. use only. The deltoid muscle is the preferred site for injection.

Do not inject i.v., intradermally, or s.c.

The vaccination series consists of 1 primary dose and 1 booster dose given according to the following schedule:

Children/Adolescent: Individuals 2 to 17 years of age should receive a single 0.5 mL (approximately 25 U) dose of vaccine at elected date and a booster dose of 0.5 mL (approximately 25 U) 6 to 18 months later.

Adults: Adults 18 years of age and older should receive a single 1.0 mL (approximately 50 U) dose of vaccine at an elected date and a booster dose of 1.0 mL (approximately 50 U) 6 months later.

Known or Presumed Exposure to Hepatitis A Virus, Travel to Endemic Areas, and Use With Immune Globulin: Hepatitis A vaccine (purified inactivated) may be administered concomitantly with IG using separate sites and syringes. The vaccination regimen for hepatitis A vaccine (purified inactivated) should be followed as stated above. Consult the manufacturers’ Product Monograph for the appropriate dosage of IG. A booster dose of hepatitis A vaccine (purified inactivated) should be administered at the appropriate time as outlined above (see Pharmacology, Clinical Studies and Precautions, Drug Interactions).

The vaccine should be used as supplied; no reconstitution is necessary.

Shake well before withdrawal and use. Thorough agitation is necessary to maintain suspension of the vaccine.

Parenteral drug products should be inspected visually for extraneous particulate matter and discoloration prior to administration whenever solution and container permit. After thorough agitation, hepatitis A vaccine (purified inactivated) is a slightly opaque, white suspension.

It is important to use a separate, sterile syringe and needle for each individual to prevent transmission of infectious agents from one person to another.

Availability And Storage: 0.5 mL: Each sterile, i.m. injection, 0.5 mL pediatric/adolescent suspension dose, contains: approximately 25 U of hepatitis A virus protein. Nonmedicinal ingredients: aluminum hydroxide, sodium borate and sodium chloride. Single use vials, packages of 1. Single use prefilled syringes, packages of 1.

1 mL: Each sterile, i.m. injection, 1 mL adult suspension dose, contains: approximately 50 U of hepatitis A virus protein. Nonmedicinal ingredients: aluminum hydroxide, sodium borate and sodium chloride. Single use vials, packages of 1 and 5. Single use prefilled syringes, packages of 1 and 5.

Vaqta is a highly purified inactivated whole virus vaccine derived from hepatitis A virus grown in cell culture in human MRC-5 diploid fibroblasts. It contains inactivated virus of a strain which was originally derived by further serial passage of a proven attenuated strain. The virus is grown, harvested, purified by a combination of physical and high performance liquid chromatographic techniques, formalin inactivated, and then adsorbed onto aluminum hydroxide. One mL of the vaccine contains approximately 50 U of hepatitis A antigen, equivalent to approximately 50 ng of virus protein per mL which is highly purified and is formulated without a preservative. Within the limits of current assay variability, the 50 U dose contains less than 0.1 g of nonviral protein, less than 4 106g of DNA, less than 104g of bovine albumin, less than 0.8 g of formaldehyde and a trace of neomycin B sulfate (0.002 g). Other process chemical residuals are less than 10 parts per billion (ppb).

Store vaccine at 2 to 8°C. Do not freeze since freezing destroys potency. Stability studies with Vaqta show that the potency of unopened vaccine is not significantly affected after exposure at 37°C for up to 6 months. This is not, however, a storage recommendation.

VAQTA® MSD Hepatitis A Vaccine (Purified Inactivated) Vaccine

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