RECOMBIVAX HB®

MSD

Hepatitis B Vaccine (Recombinant)

Vaccine

Pharmacology: Hepatitis B vaccine (recombinant) is a noninfectious subunit viral vaccine derived from hepatitis B surface antigen (HBsAg) produced in yeast cells. A portion of the hepatitis B virus gene, coding for HBsAg, was cloned into yeast and the vaccine for hepatitis B was produced from cultures of this recombinant yeast strain according to methods developed by MSD.

The antigen is harvested and purified from fermentation cultures of a recombinant strain of the yeast Saccharomyces cerevisiae containing the gene for the adw subtype of HBsAg. The HBsAg protein is released from the yeast cells by cell disruption and purified by a series of physical and chemical methods including butyl agarose chromatography. The vaccine produced has been shown to be equivalent to the plasma vaccine in terms of animal potency (mouse, monkey, and chimpanzee) and protective efficacy (chimpanzee).

The vaccine against hepatitis B, prepared from recombinant yeast cultures, is free of association with human blood or blood products and therefore the diseases potentially transmitted by blood and blood products.

Indications: For immunization against infection caused by all known subtypes of hepatitis B virus.

It will not prevent hepatitis caused by other agents, such as hepatitis A virus, non-A, non-B hepatitis viruses, or other viruses known to infect the liver.

Vaccination is recommended in persons of all ages, especially those who are or will be at increased risk of infection with hepatitis B virus.

The incidence of infection is known to vary greatly in different geographic areas and in different populations throughout the world. Vaccination strategy should vary accordingly.

Areas with high prevalence: In these areas, most of the population are at risk of acquiring hepatitis B, often at a young age. Therefore, vaccination should be targeted to: infants born to HBsAg-positive mothers; infants and children; susceptible adults.

Areas with low prevalence: In these areas vaccination may be limited to those who are in groups identified as being at increased risk of infection. The following categories might be identified in low-prevalence areas:

Infants born to HBsAg-positive mothers.

Health Care Personnel: Dentists and oral surgeons. Physicians and surgeons. Nurses. Paramedical personnel and custodial staff who may be exposed to the virus via blood or other patient specimens. Dental hygienists and dental nurses. Laboratory personnel handling blood, blood products and other patient specimens. Dental, medical and nursing students.

Selected Patients and Patient Contacts: Patients and staff in hemodialysis units and hematology/oncology units. Patients requiring frequent and/or large volume blood transfusions or clotting factor concentrates (e.g., persons with hemophilia, thalassemia). Patients (residents) and staff of institutions for the mentally handicapped. Classroom contacts of deinstitutionalized mentally handicapped persons who have persistent hepatitis B antigenemia and who show aggressive behavior. Household and other intimate contacts of persons with persistent hepatitis B antigenemia.

Military Personnel Identified as Being at increased Risk.

Morticians and Embalmers.

Blood Bank and Plasma Fractionation Workers.

Persons at Increased Risk of the Disease Due to Their Sexual Practices such as: Persons who repeatedly contract sexually transmitted diseases. Homosexually active males. Female prostitutes.

Prisoners.

Users of Illicit Injectable Drugs.

Contraindications: Hypersensitivity to any component of the vaccine.

Warnings: Because of the long incubation period for hepatitis B, it is possible for unrecognized infection to be present at the time hepatitis B vaccine (recombinant) is given. It may not prevent hepatitis B in such patients.

Patients who develop symptoms suggestive of hypersensitivity after an injection should not receive further injections (see Contraindications).

Precautions: General: Persons with immunodeficiency or those receiving immunosuppressive therapy require larger vaccine doses and respond less well than healthy individuals. As with any parenteral vaccine, epinephrine should be available for immediate use should an anaphylactoid reaction occur.

Any serious active infection is reason for delaying use of hepatitis B vaccine (recombinant), except when, in the opinion of the physician, withholding the vaccine entails a greater risk.

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

Lactation: Data not available.

Adverse Effects: Hepatitis B vaccine (recombinant) is generally well tolerated. No serious adverse reactions attributable to vaccination were reported during the course of clinical trials involving its administration to over 1 000 individuals. The frequency of complaints was somewhat lower following the second and third vaccine doses compared with the first dose. As with any vaccine, there is the possibility that broad use of the vaccine could reveal rare adverse reactions not observed in clinical trials.

In a group of studies 3 258 doses of vaccine were administered to 1 252 healthy adults. Vaccine recipients were monitored for 5 days after each dose, and the following side effects were reported:

Local Reactions in Injection Site: injection site reactions, consisting principally of local pain, soreness and tenderness and including pruritus, erythema, ecchymoses, swelling, warmth and nodule formation (16.7%).

Body as a Whole: fatigue/asthenia 4.2%; malaise 1.2%; fever (³37.8°C) 3.2%; sweating 0.5%; chills 0.2%; flushing 0.2%; aching 0.4%; sensation of warmth 0.4%.

Integumentary: pruritus 0.3%, rash 0.2%, urticaria 0.1%.

Digestive: nausea 1.8%, diarrhea 1.1%, vomiting 0.3%, abdominal pains/cramps 0.3%, dyspepsia 0.2%, diminished appetite 0.1%.

Musculoskeletal: myalgia 0.4%, arthralgia 0.5%, back pain 0.2%, neck pain 0.2%, shoulder pain 0.2%, neck stiffness 0.2%.

Nervous: headache 4.1%, lightheadedness 0.3%, vertigo/dizziness 0.5%, paresthesia 0.1%.

Respiratory: pharyngitis 1.2%, rhinitis 0.8%, cough 0.2%, upper respiratory infection (NOS) 1.0%, influenza (NOS) 0.3%.

Special Senses: earache 0.2%.

Dosage: The deltoid muscle is the preferred site for i.m. injection in adults. Data suggest that injections given in the buttocks frequently are given into fatty tissue instead of into muscle. Such injections may result in lower seroconversion rate than is expected. The anterolateral thigh is the recommended site for i.m. injection in infants and children.

I.M.: Do not inject i.v. or intradermally.

Hepatitis B vaccine (recombinant) is for i.m. injection. It may, however, be administered s.c. to persons at risk of hemorrhage following i.m. injections. However, when other aluminum-adsorbed vaccines have been administered s.c., an increased incidence of local reactions including s.c. nodules has been observed. Therefore, s.c. administration should be used only in persons (e.g., hemophiliacs) at risk of hemorrhage following i.m. injections.

Shake well before withdrawal and use. Thorough agitation at the time of administration is necessary to maintain suspension of the vaccine. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. After thorough agitation, hepatitis B vaccine (recombinant) is a slightly opaque, white suspension.

The immunization regimen consists of 3 doses of vaccine given according to the following schedule: 1st dose: at elected date; 2nd dose: 1 month later; 3rd dose: 6 months after the first dose.

The volume of vaccine to be given on each occasion is shown in Table I.

Recombivax HB Dialysis Formulation: Recombivax HB dialysis formulation (40 µg/mL) is intended only for adult predialysis/dialysis patients.

The recommended vaccination regimen for predialysis/dialysis patients is shown in Table II.

Dosage for Infants Born to HBsAg-Positive Mothers: Infants born to HBsAg-positive mothers are at high risk of becoming chronic carriers of hepatitis B virus and of developing the chronic sequelae of hepatitis B virus infection. Well-controlled studies have shown that administration of three 0.5 mL doses of hepatitis B immune globulin starting at birth is 75% effective in preventing establishment of the chronic carrier state in these infants during the first year of life. Protection is transient and the effectiveness of the hepatitis B immune globulin declines thereafter. Results from clinical studies indicate that administration of one 0.5 mL dose of hepatitis B immune globulin at birth and three 5 µg (0.5 mL) doses of hepatitis B vaccine (recombinant), the first dose given within 1 week after birth, was 96% effective in preventing establishment of the chronic carrier state in infants born to HBsAg- and HBeAg-positive mothers. Testing for HBsAg and anti-HBs is recommended at 12 to 15 months to monitor the final success or failure of therapy. If HBsAg is not detectable, and anti-HBs is present, the child has been protected.

The recommended dosage for infants born to HBsAg-positive mothers is shown in Table III.

Acute Exposure to Blood Containing HBsAg: There are no prospective studies directly testing the efficacy of a combination of hepatitis B immune globulin and hepatitis B vaccine (recombinant) in preventing clinical hepatitis B following percutaneous, ocular or mucous membrane exposure to hepatitis B virus. However, recent studies have established the relative efficacies of immune globulins and/or hepatitis B vaccine in various exposure situations. Since most persons with such exposures (e.g., health care workers) are candidates for the hepatitis B vaccine and since combined hepatitis B immune globulin plus vaccine is more efficacious than hepatitis B immune globulin alone in perinatal exposures, the following guidelines are recommended for persons who have been exposed to hepatitis B virus such as through (1) percutaneous (needlestick), ocular, mucous membrane exposure to blood known or presumed to contain HBsAg, (2) human bites by known or presumed HBsAg carriers, that penetrate the skin, or (3) following intimate sexual contact with known or presumed HBsAg carriers: Hepatitis B immune globulin (0.06 mL/kg) should be given as soon as possible after exposure and within 24 hours if possible. Hepatitis B vaccine 1.0 mL (10 µg/1.0 mL) should be given i.m. within 7 days of exposure and second and third doses given 1 and 6 months, respectively, after the first dose.

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

For Syringe Use Only: Withdraw the recommended dose from the vial using a sterile needle and syringe free of preservatives, antiseptics, and detergents.

Supplied: Adults: Each 1 mL dose of sterile, suspension contains: hepatitis B surface antigen 10 µg/vial. Formulated in an alum adjuvant, and thimerosal (mercury derivative) 1:20 000 added as a preservative. Single dose vials of 1 mL; 3 dose vials of 3 mL.

Children: Each 0.5 mL dose of sterile suspension contains: hepatitis B antigen 5 µg/vial. Formulated in an alum adjuvant, and thimerosal (mercury derivative) 1:20 000 added as a preservative. Single dose vials of 0.5 mL.

Dialysis Formulation: Each single dose vial for adult predialysis and dialysis patients contains: hepatitis B antigen 40 µg. Single dose vials of 1 mL.

Store unopened and opened vials at 2 to 8°C. Storage above or below the recommended temperature may reduce potency. Do not freeze because freezing destroys potency.

The vaccine is used directly as supplied. No dilution or reconstitution is necessary. Thimerosal (mercury derivative) in 1:20 000 dilution is present in the vaccine as a preservative. Do not use vaccine after the expiration date.