Havrix (Vaccine)

HAVRIX™

SmithKline Beecham

Hepatitis A Vaccine (Inactivated)

Active Immunization Agent against infection by Hepatitis A virus

Action And Clinical Pharmacology: Hepatitis A vaccine (inactivated) confers immunity against hepatitis A virus (HAV) infection by inducing the production of specific anti-HAV antibodies.

In clinical studies involving subjects of 18 to 50 years of age, specific humoral antibodies against HAV were detected in more than 88% of vaccinees at day 15 and 99% at month 1 following administration of a single dose of Havrix 1440.

In clinical studies involving subjects of 1 to 18 years of age, specific humoral antibodies against HAV were detected in more than 93% of vaccinees at day 15 and 99% of vaccinees 1 month following administration of Havrix 720 Junior.

Results of a hepatitis A outbreak control program showed a substantial drop in symptomatic cases in 4 930 vaccinees within 3 weeks of receiving 1 dose of hepatitis A vaccine. In villages where more than 70% of estimated susceptible individuals were vaccinated, a dramatic drop in the number of symptomatic cases of disease was observed within 8 weeks of vaccination.

The mean titre of anti-HAV antibodies induced by hepatitis A vaccine (inactivated) is at least 3 times higher than the maximum observed after passive immunization using immune globulin (human). In a randomly selected subset of subjects, vaccine-induced anti-HAV antibodies were shown to be qualitatively indistinguishable from immune globulin (human) anti-HAV antibodies.

To obtain long-term immunity a booster dose is recommended at any time between 6 and 12 months after primary vaccination, to induce long term antibody titres.

Primates exposed to the virulent heterologous hepatitis A strain were vaccinated 2 days after exposure. This post exposure vaccination resulted in total protection of the animals.

Indications And Clinical Uses: For active immunization against HAV infection in subjects at risk of exposure to HAV.

Hepatitis A vaccine (inactivated) will not prevent hepatitis infection caused by other agents such as hepatitis B virus, hepatitis C virus, hepatitis E virus or other pathogens known to infect the liver.

In areas of low and intermediate prevalence of hepatitis A, immunization is particularly recommended in subjects who are, or will be, at increased risk of infection such as: Travelers: Persons traveling to areas where the prevalence of hepatitis A is high. These areas include Africa, Asia, the Mediterranean basin, the Middle East, Central and South America.

Armed Forces: Armed Forces personnel who travel to higher endemicity areas or to areas where hygiene is poor have an increased risk of HAV infection. Active immunization is indicated for these individuals.

Persons for whom Hepatitis A is an Occupational Hazard: These include employees in day-care centres, nursing, medical and paramedical personnel in hospitals and institutions, especially gastroenterology and pediatric units, sewage workers, and food handlers, among others.

Persons for whom There is an Increased Risk of Transmission of Hepatitis A: e.g., homosexuals, persons with multiple sexual partners, abusers of injectable drugs, hemophiliac patients.

Contacts of Infected Persons: Since virus shedding of infected persons may occur for a prolonged period, active immunization of close contacts is recommended.

Specific Population Groups known to have Higher Incidence of Hepatitis A: e.g., North American Indians, Inuits, recognized community-wide HAV epidemics.

Subjects with chronic liver disease or who are at risk of developing chronic liver disease (e.g., HB and HC chronic carriers and alcohol abusers): Hepatitis A tends to compromise the outcome of chronic liver disease.

In areas of intermediate to high prevalence of hepatitis A (e.g., Africa, Asia, the Mediterranean basin, the Middle East, Central and South America) susceptible individuals may be considered for active immunization.

Contra-Indications: Hepatitis A vaccine (inactivated) should not be administered to subjects with known hypersensitivity to any component of the vaccine preparation, or to subjects having shown signs of hypersensitivity after previous administration.

As with other vaccines, the administration of hepatitis A vaccine (inactivated) should be postponed in subjects with severe febrile illness. The presence of a minor infection however, is not a contraindication.

Precautions: General: As with other injectable vaccines, appropriate medication (e.g., epinephrine) should be readily available for immediate use in case of anaphylaxis or anaphylactoid reactions following administration of the vaccine. For this reason, the vaccinee should remain under medical supervision for 30 minutes after immunization.

Hepatitis A vaccine (inactivated) should be administered with caution to subjects with thrombocytopenia or a bleeding disorder since bleeding may occur following an i.m. administration to these subjects.

It is possible that subjects may be in the incubation period of a hepatitis A infection at the time of immunization. It is not known whether hepatitis A vaccine (inactivated) will prevent hepatitis A in such cases.

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.

Pregnancy: The effect on fetal development has not been assessed. However, as with all inactivated viral vaccines, the risks to the fetus are considered to be negligible. Hepatitis A vaccine (inactivated) should be used during pregnancy only when clearly needed.

Lactation: It is unknown whether hepatitis A vaccine (inactivated) is excreted in breast milk. Therefore, caution should be exercised if it is to be administered to breast-feeding women.

Patients with Special Diseases and Conditions: As with other vaccines, hemodialysis patients and subjects with an impaired immune system may not obtain adequate antibody titres after the primary immunization course. Such patients may require administration of additional doses of hepatitis A vaccine (inactivated). However, no specific dosing recommendations can be made at this time.

Drug Interactions: The concomitant administration of hepatitis A vaccine (inactivated) and immune globulin (human) does not influence the seroconversion rate, but may result in a relatively lower anti-HAV antibody titre than when the vaccine is given alone. Hepatitis A vaccine (inactivated) and immune globulin (human) should be administered at separate injection sites.

Since hepatitis A vaccine (inactivated) is an inactivated vaccine, its concomitant use with other inactivated vaccines is unlikely to result in interference with immune responses. When concomitant administration of other vaccines is considered necessary, the vaccines must be given with different syringes and at different injection sites.

Clinical experiences with the concomitant administration of hepatitis A vaccine (inactivated) and the recombinant hepatitis B virus vaccine, have been satisfactory. No interference in the respective immune responses to both antigens has been observed.

Concomitant administration of typhoid, yellow fever, cholera (injectable) or tetanus vaccine does not interfere with hepatitis A vaccine (inactivated) immune response.

Hepatitis A vaccine (inactivated) must not be mixed with other vaccines.

Adverse Reactions: Hepatitis A vaccine (inactivated) is well tolerated. In controlled clinical studies, signs and symptoms were monitored in all subjects for 4 days following administration of the vaccine. A checklist was used for this purpose. The vaccinees were also requested to report any clinical events occurring during the study period.

The frequency of solicited adverse events was lower following the booster dose of hepatitis A vaccine (inactivated). Most events reported were considered by the subjects as “mild” and did not last for more than 24 hours. The frequency of solicited adverse events reported following administration is not different from the frequency of solicited adverse events reported following the administration of other aluminum adsorbed purified antigen vaccines.

Of the local solicited adverse events the most frequently reported was injection site soreness (less than 0.5% reported as severe) which resolved spontaneously. Other local solicited reactions reported were mild redness and swelling, with a frequency varying betweeen 4 and 7% of all vaccinations.

The systemic adverse events reported by vaccinees were essentially mild, did not last for more than 24 hours and included headache, malaise, fatigue, fever, nausea, and loss of appetite. These events were reported with a frequency varying between 1 and 12.8% of vaccinations.

The nature of the signs and symptoms observed in children is similar to that of adults, however, these have been reported less frequently.

As with other vaccines, rare events, such as anaphylaxis, have been observed in temporal association with the administration of the vaccine (see Precautions).

Dosage And Administration: Primary Immunization: Adults 19 years and over: A single dose of Havrix 1440 is used for primary immunization.

Children and adolescents: 1 year up to and including 18 years: A single dose of Havrix 720 Junior is used for primary immunization. If a pediatric vial is not available, a pediatric dose of 0.5 mL may be withdrawn from the Havrix 1440 vial.

Booster Dose: A booster dose is recommended at any time between 6 and 12 months after a single dose of Havrix 1440 or Havrix 720 Junior in order to ensure long-term protection.

Concomitant Administration with Immune Globulin (Human): Concomitant administration of hepatitis A vaccine (inactivated) and immune globulin (human) may be considered when a subject is at risk of being exposed to hepatitis A before adequate anti-HAV antibody titres can be reached.

Method of Administration: Hepatitis A vaccine (inactivated) should be injected i.m. in the deltoid region in adults and children, and in the anterolateral part of the thigh in children up to 2 years of age. The vaccine should not be administered i.m. in the gluteal region or s.c./intradermally since administration by these routes may result in a less than optimal anti-HAV antibody response.

As with all parenterals, vaccine products should be inspected visually for any foreign particulate matter or discoloration prior to administration. Before use of hepatitis A vaccine (inactivated), the vial/syringe should be well shaken to obtain a slightly opaque, white suspension. Discard if the contents of the vial/syringe appear otherwise.

The vaccine must be used as supplied.

Hepatitis A vaccine (inactivated) should never be administered i.v.

Availability And Storage: Each mL of sterile suspension contains: formaldehyde-inactivated hepatitis A virus (HM175 hepatitis A virus strain) adsorbed onto 0.5 mg of aluminum in the form of aluminum hydroxide. The viral antigen content is determined by an Elisa test. Each dose is standardized to ensure a viral antigen content of not less than: Havrix 720 Junior: 720 Elisa Units of viral antigen in a 0.5 mL dose volume. Havrix 1440: 1440 Elisa Units of viral antigen in a 1 mL dose volume. Nonmedicinal ingredients: aluminum hydroxide, amino acids for injection, disodium phosphate, monopotassium phosphate, neomycin sulfate (less than 10 ng), polysorbate 20, potassium chloride, sodium chloride and water for injection.

Havrix meets the World Health Organization requirement for biological substances including those for final vaccine residual bovine serum albumin. Havrix 720 Junior: single dose prefilled syringes of 0.5 mL, packages of 1. Havrix 1440: single dose vials and prefilled syringes of 1 mL, packages of 1.

The vaccine should not be used beyond the expiry date stamped on the vial or syringe. Store at 2 to 8°C. Do not freeze; discard if vaccine has been frozen. Stability studies of Havrix show that the potency of unopened vaccine is not significantly affected after exposure at 37°C for up to 3 weeks. However, this is not a storage recommendation.

HAVRIX™ SmithKline Beecham Hepatitis A Vaccine (Inactivated) Active Immunization Agent against infection by Hepatitis A virus

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