HYPERHEP B

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Injectable Administration
-Do not administer hepatitis B immune globulin, HBIG in the same syringe or inject at the same site as hepatitis B virus vaccine. Hepatitis B immune globulin may be given at the same time as the hepatitis B vaccine, as long as a different site is utilized.
-Use a separate vial of hepatitis B immune globulin, sterile syringe, and needle for each person receiving HBIG.
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Do not use if particulate matter is present or if the product is not clear to opalescent (Nabi-HB and HepaGamB) or colorless to pale yellow (HyperHEP B S/D). Do not shake HepaGam B vials to avoid foaming.
Intramuscular Administration
-Promptly use the product after the vial has been entered; use Nabi-HB within 6 hours of vial entry. No preservatives are in the single-dose vials; discard any unused product in a vial that has been entered.
-The anterolateral thigh is the preferred site for IM injection in neonates (5/8 inch needle), infants (1 inch needle), and children 1-2 years of age (1-1 and 1/4 inch needle). For children >= 3 years and adolescents, the deltoid is the preferred site (5/8 inch to 1 inch needle). Consider the volume to be administered when deciding on the injection site. If the buttock is used due to the volume to be injected, avoid the central region to minimize the possibility of involvement with the sciatic nerve; inject into the upper, outer quadrant of the gluteus maximus, and direct the needle anterior (i.e., not inferior or perpendicular to the skin).
-Aspiration before injection (i.e., pulling back on the syringe plunger after needle insertion but before injection) is not necessary because no large blood vessels are present at the recommended injection sites, and a process that includes aspiration might be more painful for infants. However, the manufacturer of HyperHEP B S/D advises to draw back on the plunger of the syringe before injection in order to be certain that the needle is not in a blood vessel, as the product is not to be administered intravenously because of the potential for serious reactions.

An injection site reaction including pain, tenderness, and erythema may occur with intramuscular administration of hepatitis B immune globulin, HBIG. Of 50 adults who got Nabi-HB, 12% had erythema and 4% had an ache at the injection site.

A newborn born to a hepatitis B virus carrier developed anaphylaxis after hepatitis B immune globulin, HBIG (HyperHEP S/D) IM administration 6 hours after birth. Specifically, the neonate developed hypotension and an erythematous rash (unspecified) 7 minutes after HBIG receipt. The rash began at the scalp and face and invaded the entire body in about 5 minutes. The rash began to fade in about 15 minutes and blood pressure and blood gases normalized after 30 minutes; intravenous dexamethasone and diphenhydramine, as well as ventilatory support were administered. Urticaria, angioedema, and severe allergic reactions such as anaphylactic shock could occur after HBIG administration, as anaphylactoid reactions have been reported after the injection of human immune globulin preparations. Have epinephrine available in the event of a severe allergic reaction.

Of 50 adults who received hepatitis B immune globulin, HBIG by intramuscular injection, 2% had arthralgia, 10% had myalgia, 14% had headache, 4% had nausea, 2% had vomiting, 6% had malaise, 2% had ecchymosis, 4% had increased alkaline phosphatase, 2% had elevated hepatic enzymes (AST), 2% had decreased white blood cell count, and 2% had increased serum creatinine. All reactions were at least probably related to HBIG, and most were mild in nature.

Hepatitis B immune globulin, HBIG is made from human plasma and, thus, may contain infectious agents such as viruses and theoretically the Creutzfeldt-Jakob Disease (CJD) agent that can cause disease. Screening plasma donors for prior exposure to certain viruses, testing for the presence of viruses, and inactivating and/or reducing viruses has reduced the risk of transmission of infectious agents. The manufacturing processes are designed to reduce the risk of transmitting viral infection; the manufacturing process for HBIG includes an effective step for inactivating known enveloped viruses such as HBV, HCV, and HIV. Despite these measures, HBIG can still potentially transmit disease, and the possibility that unknown infectious agents may be present exists. No evidence exists that HBV, HCV, or HIV has ever been transmitted by HBIG commercially available in the United States. Individuals who receive infusions of blood or plasma products may develop signs and/or symptoms of some viral infections, particularly hepatitis C. Report all infections possibly to have been transmitted by HBIG to the manufacturer. Discuss the risks and benefits of HBIG with the patient before prescribing or administering it to the patient.

The maltose contained in the hepatitis B immune globulin, HBIG product HepaGam B can interfere with some types of blood glucose monitoring systems. For example, blood glucose testing systems based on the glucose dehydrogenase pyrroloquinequinone (GDH-PQQ) method can result in falsely elevated glucose readings. Inaccurate hyperglycemia results may lead to life-threatening hypoglycemia because of inappropriate administration of insulin. Falsely elevated glucose readings could also mask true cases of hypoglycemia. Measurement of blood glucose must be done with a glucose-specific method if a patient takes a parenteral product that contains maltose. Read the product information of the blood glucose testing system including the information about the test strips to determine if the system is appropriate for use with maltose-containing parenteral products. If any uncertainty exists, contact the manufacturer of the testing system.

The hepatitis B immune globulin, HBIG preparations HepaGam B and Nabi-HB are contraindicated for use by patients with known severe, potentially life-threatening reactions to human globulin such as anaphylactic or severe systemic reactions. Cautiously administer HyperHEP B S/D to patients with a history of systemic allergic reactions after human immune globulin preparation receipt. HepaGam B is contraindicated for use by patients with IgA deficiency and antibodies against IgA and a history of a hypersensitivity reaction. Patients with IgA deficiency have the potential to develop antibodies against IgA and, thus, anaphylactic reactions to HBIG. Patients with known antibodies to IgA may have a greater risk of severe hypersensitivity and anaphylactic reactions. Unless contraindicated, weigh the potential benefit of HBIG receipt against the potential for hypersensitivity reactions. If HBIG is administered, have epinephrine available.

Avoid intravenous administration of Hepatitis B immune globulin, HBIG because of the potential for serious reactions. Hepatitis B immune globulin, HBIG for postexposure prophylaxis is only administered intramuscularly.

Intramuscular injections of hepatitis B immune globulin, HBIG can cause injury at the injection site and should be used cautiously in patients with thrombocytopenia or coagulopathy (e.g., hemophilia). Only administer HBIG to patients who have severe thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections if the expected benefits of HBIG outweigh the risks.

The manufacturers advise deferral of live virus vaccination until approximately 3 months after hepatitis B immune globulin, HBIG administration. However, the Advisory Committee on Immunization Practices states that Ty21a typhoid; yellow fever; live, attenuated influenza vaccine; zoster; and rotavirus vaccines may be administered at any time before, concurrent with, or after administration of HBIG. For all other live vaccines, do not administer simultaneously with HBIG, as HBIG may interfere with live virus vaccines. If simultaneous administration of measles-containing vaccine or varicella-containing vaccine (except zoster) is unavoidable, administer the products at different sites and revaccinate or test for seroconversion after recommended interval of at least 3 months between HBIG administration and any measles or varicella-containing vaccine except the zoster vaccine. After live virus vaccination, wait at least 2 weeks before HBIG administration. If the interval between administration of a live vaccine vaccines and subsequent administration of HBIG is < 14 days, repeat vaccination after 3 months unless serologic testing indicates a protective antibody response. Administering inactivated vaccines and toxoids either simultaneously with or at any interval before or after receipt of an antibody-containing product should not substantially impair development of a protective antibody response. Administer the inactivated vaccine or toxoid and HBIG at different sites using the standard recommended doses.

Close attention to the blood glucose testing systems is needed for patients with diabetes mellitus, hyperglycemia, or hypoglycemia who receive the hepatitis B immune globulin, HBIG product HepaGam B. The maltose contained in HepaGam B can interfere with some types of blood glucose monitoring systems. For example, blood glucose testing systems based on the glucose dehydrogenase pyrroloquinequinone (GDH-PQQ) method can result in falsely elevated glucose readings. Inaccurate hyperglycemia readings may lead to life-threatening hypoglycemia because of inappropriate administration of insulin. Falsely elevated glucose readings could also mask true cases of hypoglycemia. Measurement of blood glucose must be done with a glucose-specific method if a patient takes a parenteral product that contains maltose. Read the product information of the blood glucose testing system including the information about the test strips to determine if the system is appropriate for use with maltose-containing parenteral products. If any uncertainty exists, contact the manufacturer of the testing system.

Description: Hepatitis B immune globulin, HBIG is a sterile solution of immune globulins against hepatitis B surface antigen (HBsAg) that provides passive immunity to patients exposed to the hepatitis B virus (HBV) such as through exposure to HBsAg-positive blood, sexual contact with HBsAg-positive people, household exposure to patients with acute HBV infection, and birth from a HBsAg-positive mother. Administration of hepatitis B vaccine and HBIG within 12-24 hours after birth with subsequent completion of a 3-dose vaccine series is 85-95% effective in preventing acute and chronic HBV infection in infants born to women who are positive for both HBsAg and hepatitis B e antigen (HBeAg). As a comparison, administration of hepatitis B vaccine in a 3- or 4-dose schedule without HBIG beginning < 12 hours after birth prevents 70-95% of perinatal HBV infections. A systematic review and meta-analysis reported that HBIG, alone or combined with hepatitis B vaccine, reduced the risk of perinatal transmission of hepatitis B to infants of mothers who are HBsAg-positive and HBeAg-positive. Infants born to HBsAg-positive and HBeAg-negative mothers who receive hepatitis B vaccine and HBIG within 12-24 hours after birth with subsequent completion of a 3-dose vaccine series should have the same high degree of protection as infants born to women who are both HBsAg- and HBeAg-positive. In all post-exposure cases, combined treatment with HBIG and hepatitis B vaccine provides short and long-term protection against HBV and is less costly than multiple doses of HBIG. HBIG does not appear to suppress the active immunity induced by the hepatitis B vaccination. Hepatitis B immune globulin, HBIG is FDA approved for certain pediatric patients as young as neonates.

For post-exposure hepatitis B prophylaxis:
-after percutaneous (e.g., bite, needlestick) or mucosal exposure to HBsAg-positive blood or body fluids that contain blood among patients who are unvaccinated, incompletely vaccinated, or vaccine non-responders:
NOTE: Receipt of HBIG is not recommended for pediatric patients who are vaccinated, incompletely vaccinated, or unvaccinated against HBV after exposure to an unknown HBsAg status source. Unvaccinated or incompletely vaccinated patients are recommended to get the hepatitis B vaccine series.
Intramuscular dosage:
Infants, Children, and Adolescents: 0.06 mL/kg/dose IM as soon as possible after exposure (preferably less than 24 hours after exposure but no later than 7 days after exposure) plus hepatitis B vaccination series initiation or completion at a different site.
-perinatal exposure:
Intramuscular dosage:
Neonates born to HBsAg-positive mothers and neonates less than 2 kg* born to mothers with unknown HBsAg status: 0.5 mL IM for 1 dose after physiologic stabilization of the infant and preferably within 12 hours of birth plus hepatitis B vaccination series initiation at a different site. If needed, test mother for HBsAg status.
Neonates at least 2 kg born to mothers with unknown HBsAg status*: 0.5 mL IM for 1 dose if evidence is suggestive of maternal HBV infection (e.g., presence of HBV DNA, HBeAg-positive, or mother known to be chronically infected with HBV). Otherwise, immediately test the mother for HBsAg status, and if the mother is HBsAg-positive, administer 0.5 mL IM for 1 dose as soon as possible but no later than 7 days after birth. Also, initiate the hepatitis B vaccination series within 12 hours of birth.
-sexual exposure to HBsAg-positive persons among patients who are unvaccinated, incompletely vaccinated, or vaccine nonresponders:
NOTE: Receipt of HBIG is not recommended for pediatric patients either vaccinated, incompletely vaccinated, or unvaccinated against HBV after exposure to an unknown HBsAg status source. Unvaccinated or incompletely vaccinated patients are recommended to get the hepatitis B vaccine series.
Intramuscular dosage:
Children and Adolescents: 0.06 mL/kg/dose IM as soon as possible after exposure (preferably less than 24 hours after exposure but no later than 14 days after exposure or if sexual contact will continue) plus hepatitis B vaccination series initiation or completion at a different site.
-household exposure to persons with acute HBV infection:
NOTE: The recommendations of the Advisory Committee on Immunization Practices for pediatric patients does not include information about the use of HBIG for household exposures. All pediatric patients are recommended to receive a hepatitis B vaccine series starting at birth.
Intramuscular dosage:
Children and Adolescents who have an identifiable blood exposure to the index patient such as through sharing toothbrushes or razors: 0.06 mL/kg/dose IM for 1 dose as soon as possible after exposure (preferably less than 24 hours after exposure but no later than 14 days after exposure) plus hepatitis B vaccination series initiation or completion at a different site.
Neonates and Infants whose primary caregiver has acute HBV infection: 0.5 mL IM for 1 dose as soon as possible after exposure plus hepatitis B vaccination series initiation or completion at a different site.

Maximum Dosage Limits:
-Neonates
0.5 ml/dose IM.
-Infants
0.06 ml/kg/dose IM for HBsAg-positive blood exposure and 0.5 ml/dose IM for acute HBV infection in mother or primary caregiver.
-Children
0.06 ml/kg/dose IM.
-Adolescents
0.06 ml/kg/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.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: The antibodies to the hepatitis B surface antigen (HBsAg) in hepatitis B immune globulin, HBIG provide passive immunization for individuals exposed to the hepatitis B virus, as evidenced by a reduction in the attack rate of hepatitis B after its use.

Pharmacokinetics: Hepatitis B Immune Globulin, HBIG is administered intramuscularly (IM). After IM administration of Nabi-HB to adults, the half-life was 23.1 +/- 5.5 days. After a 0.06 ml/kg/dose IM of HepaGam B to adults, the mean half-life was 22-25 days.

Standard doses of HBIG provide passively acquired antibodies to the hepatitis B surface antigen and, thus, temporary protection (i.e., 3-6 months).


-Route-Specific Pharmacokinetics
Intramuscular Route
After IM administration of Nabi-HB to adults, the maximum concentration occurred at 6.5 +/- 4.3 days. After a 0.06 ml/kg/dose IM of HepaGam B to adults, the maximum concentration occurred within 4-5 days.