Drugs Details

Drugs Info of HepaGam B, HepaGam B NovaPlus, Hyperhep B, Nabi-HB
Drugs Details
  • Drugs Type  : Multum
  • Date : 30th Jan 2015 03:32 am
  • Brand Name : HepaGam B, HepaGam B NovaPlus, Hyperhep B, Nabi-HB
  • Generic Name : hepatitis B immune globulin (Pronunciation: HEP a TYE tis B im MYOON GLOB yoo lin)
Descriptions

HepaGam B, Hepatitis B Immune Globulin Intravenous (Human), is a solvent/detergent- treated sterile solution of purified gamma globulin containing anti-HBs. It is prepared from plasma donated by healthy, screened donors with high titers of anti-HBs that is purified by an anion- exchange column chromatography manufacturing method9,10. HepaGam B (hepatitis b immune globulin human) is formulated as a 5% (50 mg/mL) protein solution with 10% maltose and 0.03% polysorbate 80 at pH 5.6. It is available in 1 mL and 5 mL single dose vials. The product appears as a clear to opalescent liquid. It contains no preservatives and is intended for single use. HepaGam B (hepatitis b immune globulin human) may be administered intravenously or intramuscularly dependent upon indication [see INDICATIONS]. The source plasma used in the manufacture of this product was tested by FDA licensed Nucleic Acid testing (NAT) for HIV-1 and HCV and found to be negative. An investigational NAT for HBV was performed on all Source Plasma used, and found to be negative; however, the significance of a negative result has not been established. Plasma also has been tested by in-process NAT for hepatitis A virus (HAV) and parvovirus B19 (B19) via minipool testing and the limit for B19 in the manufacturing pool is set not to exceed 104 IU of B19 DNA per mL.

The manufacturing process contains two steps implemented specifically for virus clearance. The solvent and detergent step (using tri-n-butyl phosphate and Triton X-100) is effective in the inactivation of enveloped viruses, such as hepatitis B, hepatitis C and HIV11. Virus filtration, using a Planova 20N virus filter, is effective for the removal of viruses based on their size, including some non-enveloped viruses12. These two viral clearance steps are designed to increase product safety by reducing the risk of transmission of enveloped and non-enveloped viruses. In addition to these two specific steps, the process step of anion-exchange chromatography was identified as contributing to the overall viral clearance capacity for small non-enveloped viruses.

The inactivation and reduction of known enveloped and non-enveloped model viruses were validated in laboratory studies as summarized in Table 5. The viruses employed for spiking studies were selected to represent those viruses that are potential contaminants in the product, and to represent a wide range of physiochemical properties in order to challenge the manufacturing process's ability for viral clearance in general.

Table 5 - Virus Reduction Values Obtained Through Validation Studies8

Enveloped Enveloped Non-Enveloped
Genome RNA DNA RNA DNA
Virus HIV-1 BVDV PRV HAV EMC MMV PPV
Family retro flavi herpes picorna parvo
Size (nm) 80-100 50-70 120-200 25-30 30 20-25 18-24
Anion Exchange Chromatography (partitioning) Not evaluated 2.3 n.e. 3.4 n.e.
20N Filtration (size exclusion) ≥ 4.7 ≥ 3.5 ≥ 5.6 a n.e. 4.8 n.e. 4.1
Solvent/Detergent (inactivation) ≥ 4.7 ≥ 7.3 ≥ 5.5 Not evaluated
Total Reduction (log10) ≥ 9.4 ≥ 10.8 ≥ 11.1 2.3 4.8 3.4 4.1
Abbreviations:
HIV-1: human immunodeficiency virus-1; relevant virus for human immunodeficiency virus-1 and model for HIV-2
BVDV: bovine viral diarrhea virus; model virus for hepatitis C virus (HCV) and West Nile virus (WNV)
PRV: pseudorabies virus; model for large enveloped DNA viruses, including herpes
HAV: human hepatitis A virus; relevant virus for HAV and model for small non-enveloped viruses in general
EMC: encephalomyocarditis virus; model for HAV and for small non- enveloped viruses in general
MMV: murine minute virus; model for human parvovirus B19 and for small non-enveloped viruses in general
PPV: porcine parvovirus; model for human parvovirus B19 and for small non- enveloped viruses in general n.e.: not evaluated
a The PRV was retained by the 0.1 µm pre-filter during the virus validation. Since manufacturing employs a 0.1 µm pre-filter before the 20N filter, the claim of ≥ 5.6 reduction is considered applicable.

The product potency is expressed in international units (IU) by comparison to the World Health Organization (WHO) standard Hepatitis B Immune Globulin. Each vial contains greater than 312 IU/mL. The measured potency of each lot is stamped on the vial label [see Dosage Forms and Strengths].

What are the possible side effects of hepatitis B immune globulin (HepaGam B, HepaGam B NovaPlus, Hyperhep B, Nabi-HB)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

  • increased blood pressure (severe headache, blurred vision, trouble concentrating, chest pain, numbness, seizure);
  • left-sided stomach pain; or
  • nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or...

Read All Potential Side Effects and See Pictures of HepaGam B »

What are the precautions when taking hepatitis b immune globulin (human) (HepaGam B)?

See also Warning section.

Before receiving hepatitis B immune globulin, tell your doctor or pharmacist if you are allergic to it; or to other immune globulin products; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: bleeding/blood clotting problems, a certain immune system problem (immunoglobulin A deficiency).

This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

This medication is made from human...

Read All Potential Precautions of HepaGam B »

REFERENCES

What are the possible side effects of hepatitis B immune globulin (HepaGam B, HepaGam B NovaPlus, Hyperhep B, Nabi-HB)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

  • increased blood pressure (severe headache, blurred vision, trouble concentrating, chest pain, numbness, seizure);
  • left-sided stomach pain; or
  • nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or...

Read All Potential Side Effects and See Pictures of HepaGam B »

What are the precautions when taking hepatitis b immune globulin (human) (HepaGam B)?

See also Warning section.

Before receiving hepatitis B immune globulin, tell your doctor or pharmacist if you are allergic to it; or to other immune globulin products; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: bleeding/blood clotting problems, a certain immune system problem (immunoglobulin A deficiency).

This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

This medication is made from human...

Read All Potential Precautions of HepaGam B »

9. Bowman JM, et al. WinRho: Rh immune globulin prepared by ion exchange for intravenous use. Canadian Med Assoc J 1980; 123:1121-5.

What are the possible side effects of hepatitis B immune globulin (HepaGam B, HepaGam B NovaPlus, Hyperhep B, Nabi-HB)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

  • increased blood pressure (severe headache, blurred vision, trouble concentrating, chest pain, numbness, seizure);
  • left-sided stomach pain; or
  • nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or...

Read All Potential Side Effects and See Pictures of HepaGam B »

What are the precautions when taking hepatitis b immune globulin (human) (HepaGam B)?

See also Warning section.

Before receiving hepatitis B immune globulin, tell your doctor or pharmacist if you are allergic to it; or to other immune globulin products; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: bleeding/blood clotting problems, a certain immune system problem (immunoglobulin A deficiency).

This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

This medication is made from human...

Read All Potential Precautions of HepaGam B »

10. Friesen AD, et al. Column ion-exchange preparation and characterization of an Rh immune globulin (WinRho) for intravenous use. Journal Appl Biochem 1981; 3:164- 75.

What are the possible side effects of hepatitis B immune globulin (HepaGam B, HepaGam B NovaPlus, Hyperhep B, Nabi-HB)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

  • increased blood pressure (severe headache, blurred vision, trouble concentrating, chest pain, numbness, seizure);
  • left-sided stomach pain; or
  • nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or...

Read All Potential Side Effects and See Pictures of HepaGam B »

What are the precautions when taking hepatitis b immune globulin (human) (HepaGam B)?

See also Warning section.

Before receiving hepatitis B immune globulin, tell your doctor or pharmacist if you are allergic to it; or to other immune globulin products; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: bleeding/blood clotting problems, a certain immune system problem (immunoglobulin A deficiency).

This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

This medication is made from human...

Read All Potential Precautions of HepaGam B »

11. Horowitz B. Investigations into the application of tri(n-butyl)phosphate /detergent mixtures to blood derivatives. Morgenthaler J (ed): Virus Inactivation in Plasma Products, Curr Stud Hematol Blood Transfus 1989; 56:83-96.

What are the possible side effects of hepatitis B immune globulin (HepaGam B, HepaGam B NovaPlus, Hyperhep B, Nabi-HB)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

  • increased blood pressure (severe headache, blurred vision, trouble concentrating, chest pain, numbness, seizure);
  • left-sided stomach pain; or
  • nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or...

Read All Potential Side Effects and See Pictures of HepaGam B »

What are the precautions when taking hepatitis b immune globulin (human) (HepaGam B)?

See also Warning section.

Before receiving hepatitis B immune globulin, tell your doctor or pharmacist if you are allergic to it; or to other immune globulin products; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: bleeding/blood clotting problems, a certain immune system problem (immunoglobulin A deficiency).

This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

This medication is made from human...

Read All Potential Precautions of HepaGam B »

12. Burnouf T. Value of virus filtration as method for improving the safety of plasma products. Vox Sang 1996; 70:235-6.

What are the possible side effects of hepatitis B immune globulin (HepaGam B, HepaGam B NovaPlus, Hyperhep B, Nabi-HB)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

  • increased blood pressure (severe headache, blurred vision, trouble concentrating, chest pain, numbness, seizure);
  • left-sided stomach pain; or
  • nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or...

Read All Potential Side Effects and See Pictures of HepaGam B »

What are the precautions when taking hepatitis b immune globulin (human) (HepaGam B)?

See also Warning section.

Before receiving hepatitis B immune globulin, tell your doctor or pharmacist if you are allergic to it; or to other immune globulin products; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: bleeding/blood clotting problems, a certain immune system problem (immunoglobulin A deficiency).

This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

This medication is made from human...

Read All Potential Precautions of HepaGam B »


This monograph has been modified to include the generic and brand name in many instances.

Indications

Prevention of Hepatitis B recurrence following liver transplantation

HepaGam B™, Hepatitis B Immune Globulin Intravenous (Human), is indicated for the prevention of hepatitis B recurrence following liver transplantation, in HBsAg-positive liver transplant patients.

HepaGam B (hepatitis b immune globulin (human)) should be administered intravenously for this indication.

Postexposure Prophylaxis

HepaGam B (hepatitis b immune globulin (human)) is indicated for the treatment of acute exposure to blood containing HBsAg, perinatal exposure of infants born to HBsAg-positive mothers, sexual exposure to HBsAg-positive persons and household exposure to persons with acute HBV infection in the following settings:

Acute Exposure to Blood Containing HBsAg

Following either parenteral exposure (needlestick, bite, sharps), direct mucous membrane contact (accidental splash), or oral ingestion (pipetting accident), involving HBsAg-positive materials such as blood, plasma or serum.1-2

Perinatal Exposure of Infants Born to HBsAg-positive Mothers

Infants born to mothers positive for HBsAg with or without HBeAg.1

Sexual Exposure to HBsAg-positive Persons

Sexual partners of HBsAg-positive persons.1-2

Household Exposure to Persons with Acute HBV Infection

Infants less than 12 months old whose mother or primary caregiver is positive for HBsAg. Other household contacts with an identifiable blood exposure to the index patient.

HepaGam B (hepatitis b immune globulin (human)) is indicated for intramuscular use only for these post-exposure prophylaxis indications.

Dosage Administration

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration; if these are seen, vials should not be used. During preparation, do not shake vials; avoid foaming.

Any vial of HepaGam B (hepatitis b immune globulin (human)) that has been entered should be used promptly. Do not reuse or save for future use. This product contains no preservative; therefore, partially used vials should be discarded immediately.

Prevention of Hepatitis B recurrence following liver transplantation

For the prevention of hepatitis B recurrence following liver transplantation in HBsAg positive liver transplant patients, HepaGam B (hepatitis b immune globulin (human)) is administered intravenously according to a set dosing regimen designed to attain serum levels of antibodies to hepatitis B surface antigen (anti-HBs) greater than 500 IU/L3

Based upon the HepaGam B (hepatitis b immune globulin (human)) clinical trial, patients should receive 20,000 lU/dose [see Clinical Trials in Liver Transplant Patients]. The volume of each 20,000 IU dose should be calculated from the measured potency of the particular lot of HepaGam B™ (Hepatitis B Immune Globulin Intravenous [Human]) as stamped on the vial label. The first dose should be administered concurrently with the grafting of the transplanted liver (the anhepatic phase) with subsequent dosing as recommended in Table 1.

Table 1 - HepaGam B (hepatitis b immune globulin (human)) Dosing Regimen

Anhepatic Phase Week 1
Post-Operative
Weeks 2-12 Post-Operative Month 4 Onwards
First dose Daily from day 1-7 Every 2 weeks from day 14 Monthly

* Each dose should contain 20,000 IU calculated from the measured potency as stamped on the vial label [see Dosage Forms and Strengths].

HepaGam B (hepatitis b immune globulin (human)) dose adjustments may be required in patients who fail to reach anti-HBs levels of 500 IU/L within the first week post-liver transplantation.4 Patients who have surgical bleeding or abdominal fluid drainage (> 500 mL) or patients who undergo plasmapheresis are particularly susceptible to extensive loss of circulated anti-HBs. In these cases, the dosing regimen should be increased to a half-dose (10,000 IU calculated from the measured potency as stamped on the vial label) intravenously every 6 hours until the target anti-HBs is reached.

Hepatitis B Immune Globulin (HBIG) products are most effective in patients with no or low levels of HBV replication at the time of transplantation.5

Regular monitoring of serum HBsAg and levels of anti-HBs antibody should be performed pre-infusion to track treatment response and allow for treatment adjustment.

HepaGam B (hepatitis b immune globulin (human)) should be prepared for intravenous administration under aseptic conditions. HepaGam B (hepatitis b immune globulin (human)) should be administered through a separate intravenous line using an intravenous administration set via infusion pump.

The rate of administration should be set at 2 mL per minute.

The rate of infusion should be decreased to 1 mL per minute or slower if the patient develops discomfort, infusion-related adverse events or there is concern about the speed of infusion.

Postexposure Prophlyaxis

For postexposure prophylaxis indications, HepaGam B (hepatitis b immune globulin (human)) must be administered intramuscularly only as directed below.

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

HepaGam B (hepatitis b immune globulin (human)) may be administered at the same time (but at a different site), or up to one month preceding hepatitis B vaccination without impairing the active immune response to Hepatitis B Vaccine.1-2

Acute Exposure to Blood Containing HBsAg

Table 2 summarizes prophylaxis for percutaneous (needlestick, bite, sharps), ocular, or mucous membrane exposure to blood according to the source of exposure and vaccination status of the exposed person. For greatest effectiveness, passive prophylaxis with HepaGam B (hepatitis b immune globulin (human)) should be given as soon as possible after exposure, as its value after seven days following exposure is unclear.1-2 An injection of 0.06 mL/kg of body weight should be administered intramuscularly as soon as possible after exposure, and within 24 hours if possible. Consult the Hepatitis B Vaccine package insert for dosage information regarding the vaccine.

For persons who refuse Hepatitis B Vaccine or are known non-responders to vaccine, a second dose of HepaGam B™ (Hepatitis B Immune Globulin Intravenous [Human]) should be given one month after the first dose.2

Table 2 - Recommendations for Hepatitis B Prophylaxis Following Percutaneous or Permucosal Exposure1,2

Source Exposed Person
Unvaccinated Vaccinated
HBsAg-positive 1. Hepatitis B Immune Globulin Intravenous (Human) (HBIGIV) x 1 immediately*
2. Initiate HB vaccine series†
1. Test exposed person for anti-HBs
2. If inadequate antibody‡, Hepatitis B Immune Globulin Intravenous (Human) x1 immediately plus either HB vaccine booster dose, or a second dose of HBIGIV*, 1 month later*
Known Source -High Risk for HBsAg-positive 1. Initiate HB vaccine series
2. Test source of HBsAg. If positive, Hepatitis B immune Globulin Intravenous (Human) (HBIGIV) x 1
1. Test source for HBsAg only if exposed is vaccine nonresponder; if source is HBsAg-positive, give Hepatitis B Immune Globulin Intravenous (Human) x 1 immediately plus eithei HB vaccine booster dose, or a second dose of HBIGIV*, 1 month later§
Known Source -Low Risk for HBsAg-positive Initiate HB vaccine series Nothing required
Unknown Source Initiate HB vaccine series Nothing required
*Hepatitis B Immune Globulin Intravenous (Human) dose of 0.06 mL/kg i.m.
† See manufacturers' recommendation for appropriate dose.
‡ Less than 10 mlU/mL anti-HBs by radioimmunoassay, negative by enzyme immunoassay.
§ Two doses of Hepatitis B Immune Globulin Intravenous (Human) is preferred if no response after at least four doses of vaccine.
Prophylaxis of Infants Born to Mothers who are Positive for HBsAg with or without HBeAg

Table 3 contains the recommended schedule of Hepatitis B prophylaxis for infants born to mothers that are either known to be positive for HBsAg or have not been screened. Infants born to mothers known to be HBsAg-positive should receive 0.5 mL HepaGam B (hepatitis b immune globulin (human)) after physiologic stabilization of the infant and preferably within 12 hours of birth. The Hepatitis B Vaccine series should be initiated simultaneously, if not contraindicated, with the first dose of the vaccine given concurrently with the HepaGam B (hepatitis b immune globulin (human)) , but at a different site. Subsequent doses of the vaccine should be administered in accordance with the recommendations of the manufacturer. Women admitted for delivery, who were not screened for HBsAg during the prenatal period, should be tested. While test results are pending, the newborn infant should receive Hepatitis B Vaccine within 12 hours of birth (see manufacturers' recommendations for dose). If the mother is later found to be HBsAg-positive, the infant should receive 0.5 mL HepaGam B (hepatitis b immune globulin (human)) as soon as possible and within seven days of birth; however, the efficacy of HepaGam B (hepatitis b immune globulin (human)) administered after 48 hours of age is not known.6 Testing for HBsAg and anti-HBs is recommended at 12-15 months of age. If HBsAg is not detectable and anti-HBs is present, the child has been protected.1

Table 3 - Recommended Schedule of Hepatitis B Immune-prophylaxis to Prevent Perinatal Transmission of Hepatitis B Virus Infection1

Age of Infant
Administer Infant born to mother known to be HBsAg-positive Infant born to mother not screened for HBsAg
First Vaccination* Hepatitis B Immune Globulin Intravenous (Human)† Birth (within 12 hours)
Birth (within 12 hours)
Birth (within 12 hours) If mother is found to be HBsAg-positive, administer dose to infant as soon as possible, not later than 1 week after birth
Second Vaccination* 1 month 1-2 months
Third Vaccination* 6 months‡ 6 months‡
* See manufacturers' recommendations for appropriate dose,
† 0.5 mL administered i.m. at a site different from that used for the vaccine,
‡ See ACIP recommendation.1
Sexual Exposure to HBsAg-positive Persons

All susceptible persons whose sexual partners have acute hepatitis B infection should receive a single dose of HepaGam B™ (Hepatitis B Immune Globulin Intravenous [Human]) (0.06 mL/kg) and should begin the Hepatitis B Vaccine series, if not contraindicated, within 14 days of the last sexual contact or if sexual contact with the infected person will continue. Administering the vaccine with HepaGam B (hepatitis b immune globulin (human)) may improve the efficacy of post exposure treatment. The vaccine has the added advantage of conferring long-lasting protection.1-2

Household Exposure to Persons with Acute HBV Infection

Prophylaxis of an infant less than 12 months of age with 0.5 mL HepaGam B (hepatitis b immune globulin (human)) and Hepatitis B Vaccine is indicated if the mother or primary caregiver has acute HBV infection. Prophylaxis of other household contacts of persons with acute HBV infection is not indicated unless they had an identifiable blood exposure to the index patient, such as by sharing toothbrushes or razors. Such exposures should be treated like sexual exposures. If the index patient becomes an HBV carrier, all household contacts should receive Hepatitis B Vaccine.1-2

How Supplied

Dosage Forms and Strength

HepaGam B, Hepatitis B Immune Globulin Intravenous (Human), is a sterile solution of purified gamma globulin (5% or 50 mg/mL) containing anti-HBs. Each vial contains greater than 312 lU/mL of anti-HBs and is supplied in a carton containing a 1.0 mL single use vial or a carton containing a 5.0 mL single use vial. The measured potency of each lot is stamped on the vial label.

To ensure that the label claim of >312 lU/mL is maintained over the product shelf life, a higher potency of 550 lU/mL is targeted at the time of manufacture. As with other specific immune globulin products, this higher target potency is a manufacturing requirement to account for variability in the potency assay and changes in potency over time. The potency assay has a relative standard deviation (RSD) of approximately 10%. Based on statistical assessment of manufactured lots with a target potency of 550 lU/mL, the actual potency test result may vary from approximately 400 to 700 lU/mL (3x RSD). The measured potency is provided on the container label. Due to the inherent variability of the potency assay, dosing for the prevention of hepatitis B recurrence following liver transplantation should be calculated from the measured potency of the particular lot of HepaGam B as stamped on the vial label [See DOSAGE AND ADMINISTRATION].

Storage and Handling

HepaGam B (Hepatitis B Immune Globulin Intravenous [Human]) is supplied as:

NDC Number: Contents:
60492-0052-1
60492-0052-2
a carton containing a 1.0 mL single dose vial (>312 lU/mL; measured potency of each lot is stamped on the vial label) and a package insert.
NDC Number: Contents:
60492-0051-1
60492-0051-2
a carton containing a 5.0 mL single dose vial (>312 IU/mL: measured potency of each lot is stamped on the vial label) and a package insert.

Store at 36 to 46 °F (2 to 8 °C). Do not freeze. Do not use after expiration date. Use within 6 hours after the vial has been entered.

REFERENCES

1. CDC. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States. Recommendations of the Advisory Committee on Immunization Practices (ACIP). Part 1: Immunization of infants, children, and adolescents. MMWR2005; 54(RR-16): 1-32.

2. CDC. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States. Recommendations of the Advisory Committee on Immunization Practices (ACIP). Part 2: Immunization of adults. MMWR 2006; 55(RR-16): 1-33.

5. Samuel D, Muller R, Alexander G, Fassati L. Ducot B, Benhamou JP et al. Liver transplantation in European patients with the hepatitis B surface antigen. N Engl J Med 1993: 329(25):1842-1847.

6. Beasley RP et al.: Efficacy of hepatitis B immune globulin for the prevention of perinatal transmission of the hepatitis B virus carrier state: Final report of a randomized double-blind, placebo-controlled trial. Hepatology 1983; 3:135-41.

Distributed by: Apotex Corp Weston, FL 33326. Manufactured by: Cangene Corporation Winnipeg, Canada R3T 5Y3. April 2007.


This monograph has been modified to include the generic and brand name in many instances.

Side Effects

Overall Adverse Reaction Profile

The most common expected adverse drug reactions for intravenous immune globulins like HepaGam B (hepatitis b immune globulin (human)) are chills, fever, headaches, vomiting, allergic reactions, nausea, arthralgia and moderate low back pain.7-8 In a clinical trial in liver transplant patients, 2 adverse drug reactions of tremor and hypotension were reported in 2 of 14 patients who received intravenous infusions of HepaGam B.8 In studies with healthy volunteers, only 1 adverse drug reaction of nausea was reported in the 70 adult subjects who received an intramuscular administration of HepaGam B (hepatitis b immune globulin (human)) .8

Although no anaphylactic reactions have been reported following HepaGam B (hepatitis b immune globulin (human)) administration, anaphylactic reactions have been reported following the administration of other immune globulin products on rare occasions [see WARNINGS AND PRECAUTIONS].

Adverse Reactions in Clinical Trials

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Hepatitis B-Related Liver Transplantation

In an ongoing clinical trial, only 2 adverse drug reactions occurred following the 313 (<1%) HepaGam B (hepatitis b immune globulin (human)) infusions in 14 liver transplant patients. A listing of all adverse events (including those assessed as unrelated to study drug) occurring in >10% of patients are summarized in Table 4 below. These adverse events were reported in an interim analysis from a one-year Phase 3 clinical trial examining HepaGam B (hepatitis b immune globulin (human)) for the prevention of hepatitis B recurrence following liver transplantation. This study utilized the recommended dosing regimen outlined in Table 1 [See DOSAGE AND ADMINISTRATION]. The 2 attributed adverse drug reactions of tremor and hypotension were reported in 2 patients. All reactions were associated with a single HepaGam B (hepatitis b immune globulin (human)) infusion during the first week post-transplant. All reactions resolved on the same day and did not recur with subsequent HepaGam B (hepatitis b immune globulin (human)) infusions.

Table 4 - Adverse Events (AEs) Occurring in >10% of Liver Transplant Patients

Adverse Event by system organ class Number of AEs
(in number of patients) N=14
Blood and lymphatic systems disorder
- Splenomegaly 8(6)
Eye disorders
- Presbyopia 2(2)
Gastrointestinal disorders  
-Aphthous stomatitis 3(3)
- Diarrhoea 10(8)
- Dyspepsia 5(5)
- Gingival Hyperplasia 3(3)
General disorders  
- Fatigue 6(6)
- Oedema peripheral 3(2)
- Pyrexia 3(3)
Hepatobiliary disorders
- Hepatobiliary disease 3(3)
Immune system disorders
- Liver transplant rejection 7(5)
Infections and infestations
- Diarrhea Infectious 2(2)
- Pneumonia 2(2)
- Sepsis 3(2)
Metabolism and nutrition disorders
- Hyperglycaemia 4(4)
Musculoskeletal
- Back pain 2(2)
Nervous system disorders
- Amnesia 2(2)
- Essential Tremor 6(2)
- Headache 15(9)
Psychiatric disorders
- Agitation 2(2)
Renal and urinary disorders
- Nocturia 2(2)
Respiratory thoracic and mediastinal
- Pleural effusion 3(3)
Skin and subcutaneous tissue disorders
- Pruritus 3(3)
- Rash 2(2)
Vascular disorders
- Hypertension 8(7)
- Hypotension 2(2)
Healthy Volunteer Studies

Seventy healthy male and female volunteers received a single dose of HepaGam B™ (Hepatitis B Immune Globulin Intravenous [Human]) intramuscularly in clinical trials.8 Seventeen (17) subjects reported 30 adverse events following administration of HepaGam B (hepatitis b immune globulin (human)) . The most frequently reported adverse events included 4 subjects (6%) who experienced headache. 7 subjects (10%) who had cold symptoms or flu and 2 subjects (3%) who experienced lightheadeness/ fainted. The majority of events were reported as mild and were not related to study drug. One adverse event, an episode of nausea, was considered to be drug related. There were no serious adverse events reported. A similar number of subjects in the comparator groups reported adverse events.

Postmarketing Experience

As of April 2007, there have been no postmarketing adverse events reported for HepaGam B (hepatitis b immune globulin (human)) administered i.m.

Read the HepaGam B (hepatitis b immune globulin (human)) Side Effects Center for a complete guide to possible side effects

Interactions

Live Attenuated Virus Vaccines

Immune globulin administration may impair the efficacy of live attenuated virus vaccines such as measles, rubella, mumps and varicella.1,2,7 Vaccination with live virus vaccines should be deferred until approximately three months after administration of HepaGam B, Hepatitis B Immune Globulin Intravenous (Human). Persons who received HepaGam B (hepatitis b immune globulin (human)) less than 14 days after live virus vaccination should be revaccinated 3 months after the administration of the immune globulin, unless serologic test results indicate that antibodies were produced.1-2

There are no available data on drug interactions of HepaGam B (hepatitis b immune globulin (human)) with other medications.

Drug-Laboratory Interactions: Serological Testing

Antibodies present in HepaGam B (hepatitis b immune globulin (human)) may interfere with some serological tests. After administration of immune globulins like HepaGam B (hepatitis b immune globulin (human)) , a transitory increase of passively transferred antibodies in the patient's blood may result in misleading positive results in serological testing (e.g. Coombs' test).

Drug-Laboratory Interactions: Blood Glucose Testing

HepaGam B™ (Hepatitis B Immune Globulin Intravenous [Human]) contains maltose which can interfere with certain types of blood glucose monitoring systems, [see WARNINGS AND PRECAUTIONS] Only testing systems that are glucose-specific should be used in patients receiving HepaGam B. This interference can result in falsely elevated glucose readings that can lead to untreated hypoglycemia or to inappropriate insulin administration, resulting in life-threatening hypoglycemia.

The product information of the blood glucose testing system, including that of the test strips, should be carefully reviewed 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 to determine if the system is appropriate for use with maltose-containing parenteral products.

REFERENCES

1. CDC. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States. Recommendations of the Advisory Committee on Immunization Practices (ACIP). Part 1: Immunization of infants, children, and adolescents. MMWR2005; 54(RR-16): 1-32.

2. CDC. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States. Recommendations of the Advisory Committee on Immunization Practices (ACIP). Part 2: Immunization of adults. MMWR 2006; 55(RR-16): 1-33.

7. Committee for Proprietary Medicinal Products (CPMP). Core SPC for human plasma derived hepatitis-B immunoglobulin for intravenous use (CPMP/BPWG/4027/02). London, UK: The European Agency for the Evaluation of Medicinal Products. 2003.

8. Unpublished data on file.


This monograph has been modified to include the generic and brand name in many instances.

Warnings

Included as part of the PRECAUTIONS section.

Precautions

General

HepaGam B is made from human plasma. Products made from human plasma may contain infectious agents, such as viruses and theoretically, the Creutzfeldt-Jakob disease agent. The risk that such products can transmit an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and by inactivating and/or removing certain viruses. The HepaGam B (hepatitis b immune globulin (human)) manufacturing process includes a solvent/detergent treatment step (using tri-n-butyl phosphate and Triton X-100) that is effective in inactivating known enveloped viruses such as HBV, HCV, and HIV. HepaGam B (hepatitis b immune globulin (human)) is filtered using a Planova 20N Virus Filter that is effective in reducing the levels of some enveloped and non-enveloped viruses. These two processes are designed to increase product safety. Despite these measures, such products can still potentially transmit disease. There is also the possibility that unknown infectious agents may be present in such products. ALL infections thought by a physician to have been transmitted by this product should be reported by the physician or other healthcare provider to Cangene Corporation at 1-877-CANGENE (226-4363). The physician should discuss the risks and benefits of this product with the patient.

Anaphylactic Precautions

Although allergic reactions have not been reported following HepaGam B administration [see ADVERSE REACTIONS], the product should be administered only in a setting where appropriate equipment and personnel trained in the management of acute anaphylaxis are available. If hypotension or anaphylaxis occurs, the administration of HepaGam B (hepatitis b immune globulin (human)) should be discontinued immediately and supportive care given as needed.

Interference with Blood Glucose Testing

The maltose contained in HepaGam B (hepatitis b immune globulin (human)) can interfere with some types of blood glucose monitoring systems, i.e., those based on the glucose dehydrogenase pyrroloquinequinone (GDH-PQQ) method. This can result in falsely elevated glucose readings and, consequently, in the inappropriate administration of insulin, resulting in life-threatening hypoglycemia. Cases of true hypoglycemia may go untreated if the hypoglycemic state is masked by falsely elevated results.

Monitoring: Serum anti-HBs Antibody Levels

Liver transplant patients should be monitored regularly for serum anti-HBs antibody levels using a quantitative assay [See DOSAGE AND ADMINISTRATION].

Infusion Reactions

Certain adverse drug reactions may be related to the rate of infusion. The recommended infusion rate given under DOSAGE AND ADMINISTRATION must be closely followed. Patients must be closely monitored and carefully observed for any symptoms throughout the infusion period and immediately following an infusion.

Coagulation Disorders

For postexposure prophylaxis indications, HepaGam B™ (Hepatitis B Immune Globulin Intravenous [Human]) must be administered intramuscularly only. In patients who have severe thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections, HepaGam B (hepatitis b immune globulin (human)) should be given only if the expected benefits outweigh the potential risks.

Nonclinical Toxicology

Nonclinical pharmacology studies have not been performed with Hepatitis B Immune Globulin Intravenous (Human) as there is broad experience in humans with intravenous and intramuscular administration of immune globulin products. Since the product is of human origin, immunogenicity is expected when administered to animals.

Toxicology studies have not been performed with Hepatitis B Immune Globulin Intravenous (Human) because the product has been formulated with ingredients that are know to be non-toxic at the levels at which they are present in the final product.

Use in Specific Populations

Pregnancy Category C

Animal reproduction studies have not been conducted with HepaGam B (hepatitis b immune globulin (human)) . It is also not known whether HepaGam B (hepatitis b immune globulin (human)) can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. HepaGam B (hepatitis b immune globulin (human)) should be given to a pregnant woman only if clearly indicated.

Nursing Mothers

It is not known whether HepaGam B is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when HepaGam B (hepatitis b immune globulin (human)) is administered to a nursing mother.


This monograph has been modified to include the generic and brand name in many instances.

OverDose

Consequences of an overdose are not known. Although no data are available, clinical experience reported with other intravenously administered human immune globulin preparations suggests that doses above 1 g immune globulin/kg body weight are tolerated. For intramuscular administration of HepaGam B (hepatitis b immune globulin (human)) , the only manifestations of overdose would be pain and tenderness at the injection site.

ContrainDications

Individuals known to have anaphylactic or severe systematic reactions associated with the parenteral administration of human globulin preparations should not receive HepaGam B (hepatitis b immune globulin (human)) , (Hepatitis B Immune Globulin Intravenous [Human]), or any other human immune globulin. HepaGam B (hepatitis b immune globulin (human)) contains less than 40 micro-grams/mL of IgA. Individuals who are deficient in IgA may have the potential to develop IgA antibodies and have an anaphylactoid reaction. The physician must weigh the potential benefit of treatment with HepaGam B (hepatitis b immune globulin (human)) against the potential for hypersensitivity reactions.

For postexposure prophylaxis indications, HepaGam B (hepatitis b immune globulin (human)) must be administered intramuscularly only. In patients who have severe thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections, HepaGam B (hepatitis b immune globulin (human)) should be given only if the expected benefits outweigh the potential risks.


This monograph has been modified to include the generic and brand name in many instances.

Clinical Pharamacology

Mechanism of Action

HBIGIV products provide passive immunization for individuals exposed to the hepatitis B virus, by binding to the surface antigen and reducing the rate of hepatitis B infection.13-16

Hepatitis B virus reinfection following liver transplantation is the consequence of exposure of the new liver graft to hepatitis B virus. Reinfection may occur immediately at the time of liver reperfusion due to circulating virus or later from virus retained in extrahepatic sites.

The mechanism whereby hepatitis B Immune globulin (HBIG) protects the transplanted liver against HBV reinfection is not well understood. HBIG may protect naive hepatocytes against infection through blockage of a putative HBV receptor.17 Alternatively, HBIG may neutralize circulating virions through immune precipitation and immune complex formation or may trigger an antibody-dependent cell-mediated cytotoxicity response resulting in target cell lysis.17-18 In addition, HBIG has been reported to bind to hepatocytes and interact with HBsAg within cells.19 Regardless of the mechanism, there is evidence of a dose-dependent response to HBIG treatment.5-8

Postexposure Prophylaxis.

Clinical studies conducted prior to 1983 with hepatitis B immune globulins similar to HepaGam B™ (Hepatitis B Immune Globulin Intravenous [Human]) demonstrated the advantage of simultaneous administration of hepatitis B vaccine and Hepatitis B Immune Globulin (Human), by the i.m. route. The Centers for Disease Control and Prevention Advisory Committee on Immunization Practices (ACIP) advises that the combination prophylaxis be provided following certain instances of hepatitis B exposure.1-2 Recommendations on post-exposure prophylaxis are based on available efficacy data, primarily from studies in neonates.1-2 Cases of hepatitis B are rarely seen following exposure to HBV in persons with pre-existing anti-HBs antibodies.

Infants born to HBsAg-positive mothers are at risk of being infected with HBV and becoming chronic carriers.' The risk is especially great if the mother is also HBeAg-positive.1 For an infant with perinatal exposure to an HBsAg-positive and HBeAg-positive mother, a regimen combining one dose of Hepatitis B Immune Globulin (Human) at birth with the hepatitis B vaccine series started soon after birth has been shown to be 85-98% effective in preventing development of the HBV carrier state.1-2 Regimens involving either multiple doses of Hepatitis B Immune Globulin (Human) alone or the vaccine series alone have a 70-75% efficacy, while a single dose of Hepatitis B Immune Globulin (Human) alone has 50% efficacy.1-2

Since infants have close contact with primary caregivers and have a higher risk of becoming HBV carriers after acute HBV infection, prophylaxis of an infant less than 12 months of age with Hepatitis B Immune Globulin (Human) and Hepatitis B Vaccine is indicated if the mother or primary caregiver has acute HBV infection.1

Sexual partners of HBsAg-positive persons are at increased risk of acquiring HBV infection. A single dose of Hepatitis B immune Globulin (Human) is 75% effective if administered within two weeks of the last sexual exposure to a person with acute hepatitis B.12

HBV infection is a well-recognized risk to health-care personnel (HCP). The risk of HBV infection is primarily related to the degree of contact with blood in the work place and also to the hepatitis B e antigen (HBeAg) status of the source person. In studies of HCP who sustained injuries from needles contaminated with blood containing HBV, the risk of developing clinical hepatitis if the blood was hepatitis B surface antigen (HBsAg) and HBeAg-positive was 22%-31%; the risk of developing serologic evidence of HBV infection was 37%-62%. In comparison, the risk of developing clinical hepatitis from needles contaminated with HBsAg-positive, HBeAg-negative blood is 1 %-6%, and the risk of developing serological evidence of HBV infection is 23%-37%.20 The current recommendations of the Advisory Committee on Immunization Practices12, recommends postexposure prophylaxis with hepatitis B immune globulin and/or hepatitis B vaccine series for any susceptible, unvaccinated person who sustains an occupational blood or body fluid exposure.

The pharmacokinetic profile of HepaGam B (hepatitis b immune globulin (human)) has been evaluated in two clinical trials [see Clinical Studies].

The comparative bioavailability of HepaGam B™ (Hepatitis B Immune Globulin Intravenous [Human]) and another commercially available hepatitis B immunoglobulin product indicates that HepaGam B (hepatitis b immune globulin (human)) has similar efficacy.

Clinical Studies

Clinical Trials in Liver Transplant Patients

A clinical trial examining the effectiveness of HepaGam B (hepatitis b immune globulin (human)) in the prevention of hepatitis B recurrence following liver transplantation is currently ongoing. The study is a multi-center, open-labeled, superiority study involving HBsAg-positive/HBeAg-negative liver transplant patients. The study included two arms, an active treatment group of patients enrolled to receive the described dosing regimen of HepaGam B (hepatitis b immune globulin (human)) starting during transplant and continuing over the course of a year, and a retrospective untreated control group of historical patients with data gathered by chart review.

An interim report of this study evaluated the data from 30 liver transplant patients, 16 HepaGam B (hepatitis b immune globulin (human)) patients who have completed the study and 14 retrospective untreated control patients. The patients in both groups were HBsAg-positive/ HBeAg-negative liver transplant patients who met similar entry criteria, had similar medical history and had similar status at transplant based on MELD and/or ChildPugh-Turcotte scores.

In the active treatment group, HepaGam B (hepatitis b immune globulin (human)) doses of 35 mL started during transplant according to the regimen identified in Table 1 [see DOSING AND ADMINISTRATION]. As a result of the targeted potency of 550 lU/mL at the time of manufacture [see Dosage Forms and Strengths], the 35 mL doses of HepaGam B (hepatitis b immune globulin (human)) used in this study actually contained between 17,000 and 23,000 IU anti-HBs. These 35 mL doses consistently yielded anti-HBs trough levels > 500 IU/L (99% of all anti-HBs levels were > 500 IU/L; see Figure 1).

Figure 1: Frequency Histogram of Trough anti-HBs Levels more than 30 days after Transplant

Frequency Histogram of Trough anti-HBs Levels more than 30 days after Transplant - illustration

Values below the target trough were only observed in the 2 patients with HBV recurrence who had anti-HBs levels <150 IU/L at the time of seroconversion.

For the efficacy endpoint of the proportion of patients with HBV recurrence (HBsAg positive and/or HBeAg positive after 4 weeks post-OLT), a significant treatment effect was observed. As summarized in Table 6, HBV recurrence was seen in 2/15 or 13% of HepaGam B™ (Hepatitis B Immune Globulin Intravenous [Human]) patients compared to 12/14 or 86% of retrospective untreated control patients (see Table 6). One of the 16 HepaGam B (hepatitis b immune globulin (human)) patients died 2 weeks post-transplant was excluded from all efficacy analyses, but was included for safety analyses. The death was not HBV or study drug related.

Table 6 - Interim Results of Study HB-005 for the Prevention of Hepatitis B Recurrence Following Liver Transplantation

  HepaGam B Retrospective Untreated Control P-value
(Fisher's Exact Test)
HBV Recurrence Proportion, % (95% confidence interval) 13.3
(1.7 -40.5)
85.7
(57.2 -98.2)
< 0.001

The conclusion that HepaGam B (hepatitis b immune globulin (human)) monotherapy post-OLT is effective at preventing HBV recurrence post-OLT is further supported by the secondary endpoints of time to recurrence, survival, anti-HBs levels and biochemical markers of liver inflammation. Time to recurrence for the HepaGam B (hepatitis b immune globulin (human)) treatment group was 358 days for two HBV recurrent patients. In comparison, the retrospective untreated control patients had a median time to recurrence of 88 days with a 95% confidence interval of 47 to 125 days. Survival calculations showed that 93% (14/15) of patients in the active treatment group survived for at least 1-year post-OLT compared to 43% (6/14) retrospective control patients. One patient in the active treatment group died 266 days post-OLT. The median time to death for the retrospective control patients was 339 days calculated using the product limit method. The endpoints for HBV recurrence were supported by an observed drop in anti-HBs levels and elevated liver function tests at the time of recurrence.

HepaGam B (hepatitis b immune globulin (human)) is recommended in patients who have no or low levels of viral replication at the time of liver transplantation. The clinical trial evaluating HepaGam B (hepatitis b immune globulin (human)) in liver transplant patients selected patients with no or low replication status only. HepaGam B (hepatitis b immune globulin (human)) therapy has not been evaluated in combination with antiviral therapy post-transplantation.

Comparative Bioavailability Studies

The pharmacokinetic profile of HepaGam B (hepatitis b immune globulin (human)) after intramuscular injection of 0.06 mL/kg in two 84-day pharmacokinetics studies8,70 volunteers were administered HepaGam B (hepatitis b immune globulin (human)) . The mean peak concentrations (Cmax) in both studies were comparable and occurred within 4-5 days of administration. Both studies demonstrated mean elimination half-lives (t½) following i.m. administration of 22 to 25 days. The mean clearance rate was 0.21 to 0.24 L/day and the volume of distribution was approximately 7.5 L. Thus, HepaGam B (hepatitis b immune globulin (human)) demonstrates pharmacokinetic parameters similar to those reported by Scheiermann and Kuwert.21

The maximum concentration of anti-HBs achieved by HepaGam B (hepatitis b immune globulin (human)) was consistent with that of two other licensed Hepatitis B Immune Globulin (Human) products when compared in the two pharmacokinetic trials.8 Comparability of pharmacokinetics between HepaGam B (hepatitis b immune globulin (human)) and a commercially available hepatitis B immune globulin product administered i.m. indicates that similar efficacy of HepaGam B (hepatitis b immune globulin (human)) should be inferred.

REFERENCES

1. CDC. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States. Recommendations of the Advisory Committee on Immunization Practices (ACIP). Part 1: Immunization of infants, children, and adolescents. MMWR2005; 54(RR-16): 1-32.

2. CDC. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States. Recommendations of the Advisory Committee on Immunization Practices (ACIP). Part 2: Immunization of adults. MMWR 2006; 55(RR-16): 1-33.

5. Samuel D, Muller R, Alexander G, Fassati L. Ducot B, Benhamou JP et al. Liver transplantation in European patients with the hepatitis B surface antigen. N Engl J Med 1993: 329(25):1842-1847.

6. Beasley RP et al.: Efficacy of hepatitis B immune globulin for the prevention of perinatal transmission of the hepatitis B virus carrier state: Final report of a randomized double-blind, placebo-controlled trial. Hepatology 1983; 3:135-41.

7. Committee for Proprietary Medicinal Products (CPMP). Core SPC for human plasma derived hepatitis-B immunoglobulin for intravenous use (CPMP/BPWG/4027/02). London, UK: The European Agency for the Evaluation of Medicinal Products. 2003.

8. Unpublished data on file.

12. Burnouf T. Value of virus filtration as method for improving the safety of plasma products. Vox Sang 1996; 70:235-6.

13. Grady GF, LeeVA. Hepatitis B immune globulin - prevention of hepatitis from accidental exposure among medical personnel. N Engl J Med 1975; 293:1067-70.

14.Seeff LB, et al. Type B hepatitis after needlestick exposure: Prevention with hepatitis B immune globulin. Ann Int Med 1978: 88: 285-93.

15. Krugman S, Giles JP. Viral hepatitis, type B (MS-2-strain). Further observations on natural history and prevention. N Engl J Med 1973; 288:755-60.

16. Hoofnagle JH, et al. Passive-active immunity from hepatitis B immune globulin. Ann Int Med 1979;91:813-8.

17.Shouval D, Samuel D. Hepatitis B immune globulin to prevent hepatitis B virus graft reinfection following liver transplantation: a concise review. Hepatology 2000: 32(6):1189-1195.

18. Sawyer RG, McGory RW, Gaffey MJ, McCullough CC, Shephard BL, Houlgrave CW et al. Improved clinical outcomes with liver transplantation for hepatitis B-induced chronic liver failure using passive immunization. Ann Surg 1998; 227(6): 841-50.

19.Schilling R, Ijaz S, Davidoff M, Lee JY Locarnini S, Williams R, Naoumov NV. Endocytosis of hepatitis B immune globulin into hepatocytes inhibits the secretion of hepatitis B virus surface antigen and virions. J Virol 2003;77(16): 8882-92.

20.CDC. Updated U.S. Public Health Service Guidelines for the management of occupational exposures to HBV, HCV, and HIV and recommendations for postexposure prophylaxis. MMWR 2001; 50(RR-11): 1-42.

21 .Scheiermann N, Kuwert EK. Uptake and elimination of hepatitis B immunoglobulins after intramuscular application in man. Dev Biol Standard 1983; 54:347-55.


This monograph has been modified to include the generic and brand name in many instances.

Patient Information

Patients should be informed that HepaGam B™ (hepatitis b immune globulin (human)) (Hepatitis B Immune Globulin Intravenous [Human]) is prepared from human plasma. Products made from human plasma may contain infectious agents such as viruses that can cause disease. The risk that such products will transmit an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and by inactivating and/or removing certain viruses during manufacturing. Despite these measures, such products can still potentially transmit disease. There is also the possibility that unknown infectious agents may be present in such products.

Individuals known to have severe, potentially life-threatening reaction to human globulin should not receive HepaGam B (hepatitis b immune globulin (human)) or any other immune globulin products. Individuals who are deficient in IgA may have the potential for developing IgA antibodies and have severe potentially life threatening allergic reactions. In case of allergic or anaphylactic reaction, the infusion should be stopped immediately. In case of shock, the current medical standards for treatment of shock should be observed.

The maltose contained in HepaGam B (hepatitis b immune globulin (human)) can interfere with some types of blood glucose monitoring systems. Only testing systems that are glucose-specific should be used in patients receiving HepaGam B (hepatitis b immune globulin (human)) . This inference can result in falsely elevated glucose readings that can lead to untreated hypoglycemia or to inappropriate insulin administration, resulting in life-threatening hypoglycemia.


This monograph has been modified to include the generic and brand name in many instances.

Consumer Overview Uses

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

 

HEPATITIS B IMMUNE GLOBULIN - INJECTION

 

(hep-a-TYE-tis bee i-MYUN-GLOB-yoo-lin)

 

COMMON BRAND NAME(S): Hepagam B, Hyperhep B S-D, Nabi-HB

 

WARNING: This medication may rarely cause serious blood clots (such as pulmonary embolism, stroke, heart attack, deep vein thrombosis). You may be at increased risk for blood clots if you are an older adult, are severely dehydrated, have a catheter in a vein close to your heart for administering medications, or have a history of blood clots, heart/blood vessel disease, heart failure, stroke, or if you are immobile (such as very long plane flights or bedridden). If you use estrogen-containing products, these may also increase your risk. Before using this medication, discuss the risks and benefits and if you have any of these conditions, report them to your doctor or pharmacist.

Being adequately hydrated before and after receiving this medication may help reduce your risk of blood clots. If you are receiving this medication into a vein, the risk may also be decreased by infusing this medication more slowly or by using a less concentrated form of this medication if available.

Get medical help right away if any of these side effects occur: shortness of breath/rapid breathing, chest/jaw/left arm pain, unusual sweating, sudden dizziness/fainting, pain/swelling/warmth in the arm/leg, sudden/severe headache, slurred speech, weakness on one side of the body, sudden vision changes, or confusion.

 

USES: This medication is used to prevent a certain serious virus infection (hepatitis B) in people who have been exposed to this virus under certain conditions (such as direct contact with blood or body fluids containing this virus). Certain brands of this medication may also be given after a liver transplant to prevent return of hepatitis B infection in people with previous infection. Ask your doctor or pharmacist if you have questions about your particular brand. This medication is made from healthy human blood that has high levels of certain defensive substances (antibodies) that help fight hepatitis B.

 

HOW TO USE: If this medication is given for prevention of hepatitis B after direct exposure to the virus, it is given by injection into a muscle by a healthcare professional. It is best to receive this medication as soon as possible after exposure. If you wait too long after being exposed, the medication may not be effective. Your doctor may also recommend vaccination after receiving this medication. Talk with your doctor about the best treatment for you.

If this medication is given after a liver transplant to prevent return of hepatitis B infection, it is given by injection into a vein by a healthcare professional. For this use, it should be given on a regular schedule. To help you remember, mark your calendar with an appointment reminder.

The dosage and schedule of injections is based on your medical condition, weight, and response to treatment.

Consumer Overview Side Effect

SIDE EFFECTS: See also Warning section.

Redness, pain, or tenderness at the injection site may occur. Nausea, vomiting, fever, chills, dizziness, headache, or back/joint pain may also occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist promptly.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

 

Read the HepaGam B (hepatitis b immune globulin (human)) Side Effects Center for a complete guide to possible side effects

Learn More »

PRECAUTIONS: See also Warning section.

Before receiving hepatitis B immune globulin, tell your doctor or pharmacist if you are allergic to it; or to other immune globulin products; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: bleeding/blood clotting problems, a certain immune system problem (immunoglobulin A deficiency).

This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

This medication is made from human blood. Even though the blood is carefully tested, and this medication goes through a special manufacturing process, there is an extremely small chance that you may get infections (such as hepatitis A) from the medication. Consult your doctor or pharmacist for more information.

Some immune globulin products are made with maltose. This substance can cause false high blood sugar levels when your blood sugar is normal or even low. If you have diabetes, check with your doctor or pharmacist whether the product you are using contains maltose and whether your blood sugar testing supplies will work with this product. Rarely, serious problems have occurred when too much insulin was given because of false high sugar readings or when low blood sugar went untreated.

Tell your doctor of any recent or planned immunizations/vaccinations. This medication may prevent a good response to certain live viral vaccines (such as measles, mumps, rubella, varicella). If you have recently received any of these vaccines, your doctor may have you tested for a response or have you vaccinated again later. If you plan on getting any of these vaccines, your doctor will instruct you about the best time to receive them so you get a good response.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding.

Consumer Overview Missed Dose

DRUG INTERACTIONS: See also Warning section.

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

This medication may interfere with certain tests (including certain blood sugar tests, Coomb's test), possibly causing false test results. The blood sugar interference can lead to serious (possibly fatal) consequences. Tell all laboratory personnel and all your doctors and pharmacists that you use this medication, and which type of blood sugar testing strips you use.

 

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

 

NOTES: If you are receiving this medication on a regular schedule, laboratory and/or medical tests (such as levels of antibody in the blood) may be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

 

MISSED DOSE: For the best possible benefit, it is important to receive each scheduled dose of this medication as directed. If you miss a dose, contact your doctor immediately to establish a new dosing schedule.

 

STORAGE: Not applicable. This medication is given in a hospital or doctor's office and will not be stored at home.

 

Information last revised June 2013. Copyright(c) 2013 First Databank, Inc.

Patient Detailed Side Effect

Brand Names: HepaGam B, HepaGam B NovaPlus, Hyperhep B, Nabi-HB

Generic Name: hepatitis B immune globulin (Pronunciation: HEP a TYE tis B im MYOON GLOB yoo lin)

  • What is hepatitis B immune globulin (HepaGam B)?
  • What are the possible side effects of hepatitis B immune globulin (HepaGam B)?
  • What is the most important information I should know about hepatitis B immune globulin (HepaGam B)?
  • What should I discuss with my health care provider before receiving hepatitis B immune globulin (HepaGam B)?
  • How is hepatitis B immune globulin given (HepaGam B)?
  • What happens if I miss a dose (HepaGam B)?
  • What happens if I overdose (HepaGam B)?
  • What should I avoid while receiving hepatitis B immune globulin (HepaGam B)?
  • What other drugs will affect hepatitis B immune globulin (HepaGam B)?
  • Where can I get more information?

What is hepatitis B immune globulin (HepaGam B)?

Hepatitis B immune globulin is made from human plasma containing proteins that protect against the type B form of hepatitis (inflammation of the liver).

Hepatitis B immune globulin is used to prevent hepatitis B in people receiving a liver transplant, and in babies born to mothers infected with hepatitis B. It is also used to prevent hepatitis B in people who have been exposed to contaminated blood products, or through household or sexual contact with an infected person.

Hepatitis B immune globulin is not a vaccine. Therefore it will not provide long-term protection from hepatitis B. For long-term protection you must receive a hepatitis B vaccine such as Engerix-B, Recombivax HB, or Twinrix.

Hepatitis B immune globulin may also be used for other purposes not listed in this medication guide.

What are the possible side effects of hepatitis B immune globulin (HepaGam B)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

  • increased blood pressure (severe headache, blurred vision, trouble concentrating, chest pain, numbness, seizure);
  • left-sided stomach pain; or
  • nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Less serious side effects may include:

  • upset stomach, diarrhea;
  • tremors or shaking;
  • joint or back pain;
  • fever, chills;
  • headache; or
  • tired feeling.

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

Read the HepaGam B (hepatitis b immune globulin (human)) Side Effects Center for a complete guide to possible side effects

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What is the most important information I should know about hepatitis B immune globulin (HepaGam B)?

Hepatitis B immune globulin is not a vaccine. Therefore it will not provide long-term protection from hepatitis B. For long-term protection you must receive a hepatitis B vaccine such as Engerix-B, Recombivax HB, or Twinrix.

You should not receive this medication if you are allergic to human globulins, or if you have an immunoglobulin A deficiency. Hepatitis B immune globulin should not be injected into your muscle if you have a bleeding or blood clotting disorder such as hemophilia.

Hepatitis B immune globulin is made from human plasma (part of the blood) and may contain viruses and other infectious agents that can cause disease. Although donated human plasma is screened, tested, and treated to reduce the risk of it containing anything that could cause disease, there is still a small possibility it could transmit disease. Talk with your doctor about the risks and benefits of using this medication.

To be sure this medication is helping your condition, your blood will need to be tested often. This will help your doctor determine how long to treat you with hepatitis B immune globulin. Your liver function will also need to be tested. Do not miss any scheduled visits to your doctor.

Do not receive a "live" vaccine while you are being treated with hepatitis B immune globulin, and for at least 3 months after your treatment ends. The live vaccine may not work as well during this time, and may not fully protect you from disease.

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Patient Detailed How Take

What should I discuss with my health care provider before receiving hepatitis B immune globulin (HepaGam B)?

You should not receive this medication if you are allergic to human globulins, or if you have an immunoglobulin A deficiency. Hepatitis B immune globulin should not be injected into your muscle if you have a bleeding or blood clotting disorder such as hemophilia.

Hepatitis B immune globulin is made from human plasma (part of the blood) and may contain viruses and other infectious agents that can cause disease. Although donated human plasma is screened, tested, and treated to reduce the risk of it containing anything that could cause disease, there is still a small possibility it could transmit disease. Talk with your doctor about the risks and benefits of using this medication.

FDA pregnancy category C. This medication may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether hepatitis B immune globulin passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How is hepatitis B immune globulin given (HepaGam B)?

Hepatitis B immune globulin is given as an injection into a muscle or through a needle placed into a vein. Your doctor, nurse, or other healthcare provider will give you this injection.

Hepatitis B immune globulin is given to liver transplant patients as part of the transplant procedure, and then for several weeks or months afterward. The medication is usually given to transplant patients as an IV (injected into a vein) every day for 7 days, then every 2 weeks for the next 11 weeks, followed by monthly injections from then on.

To be sure this medication is helping your condition, your blood will need to be tested often. This will help your doctor determine how long to treat you with hepatitis B immune globulin after your transplant. Your liver function will also need to be tested. Do not miss any scheduled visits to your doctor.

To protect against hepatitis B after exposure to the disease, this medication is usually given as soon as possible after exposure to an infected person. A booster medication is then given 24 hours later.

Babies born to mothers infected with hepatitis B should receive this medication within 12 hours of birth, or when the newborn is otherwise medically stable.

For people who have had sexual contact with someone infected with hepatitis B, this medication should be given within 14 days after the last contact. The medication may also be given at any time if contact with the infected person will continue.

Any infant whose parent or caregiver is infected with hepatitis B should receive this medication.

This medication can cause you to have unusual results with certain medical tests, including some blood glucose tests. Tell any doctor who treats you that you are receiving hepatitis B immune globulin.

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Patient Detailed Avoid Taking

What happens if I miss a dose (HepaGam B)?

Call your doctor for instructions if you miss a dose, or if you miss an appointment to have your injection given.

What happens if I overdose (HepaGam B)?

An overdose of this medication is not expected to produce life-threatening side effects. Overdose symptoms may include pain or tenderness where the injection was given.

What should I avoid while receiving hepatitis B immune globulin (HepaGam B)?

Do not receive a "live" vaccine while you are being treated with hepatitis B immune globulin, and for at least 3 months after your treatment ends. The live vaccine may not work as well during this time, and may not fully protect you from disease.

What other drugs will affect hepatitis B immune globulin (HepaGam B)?

There may be other drugs that can interact with hepatitis B immune globulin. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

Where can I get more information?

Your doctor or pharmacist may have information about this medication written for health professionals that you may read. You may also find additional information from your local health department or the Centers for Disease Control and Prevention.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

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