Browse HepaGam B HepaGam B Home Patients and Families Healthcare Professionals Plasma Safety Common Questions HepaGam B Canadian Product Monograph and Canadian Package Insert

HepaGam B is the only hepatitis B immune globulin (HBIG) available in Canada for the prevention of hepatitis B recurrence following liver transplantation.

Health Canada granted a Notice of Compliance with Conditions (NOC/c) to HepaGam B, for the prevention of hepatitis B recurrence following liver transplantation in adult patients with hepatitis B.

Health Canada has issued a conditional marketing authorization under the Notice of Compliance with Conditions policy to reflect the promising nature of the clinical evidence in patients with this serious disease, and the need for further follow up to verify the clinical benefit.

This NOC/c is based on an interim analysis of an ongoing Phase III clinical study examining the effectiveness of HepaGam B in hepatitis B surface antigen positive / hepatitis B ‘e’ antigen negative liver transplant patients. This open-label study compares the efficacy of HepaGam B during the first year following transplant to data from untreated retrospective control patients meeting similar entry criteria.

• For the HepaGam B treated patients, 1/14 (7.1 %) evaluable patients exhibited hepatitis B recurrence (hepatitis B surface antigen positive) compared to 12/14 (85.7%) of historical control patients.
• These results provide promising clinical evidence that HepaGam B is efficacious in preventing hepatitis B recurrence.

A systematic review of the clinical trial literature and meta-analysis supports the efficacy of hepatitis B immune globulin (HBIG) prophylaxis in the prevention of hepatitis B recurrence following liver transplantation.

Patients should be advised about the conditional nature of the marketing authorization for HepaGam B.

HepaGam B is used in the prevention of hepatitis B recurrence following liver transplantation, in adult patients with Hepatitis B who have no or low levels of HBV replication ^1,2. The efficacy of HepaGam B in conjunction with antivirals such as Lamivudine will be assessed in a Phase III confirmatory study. For more information, see: Product Monograph

HBIG products provide passive immunization to HBV and significantly decrease HBV recurrence and increase graft and patient survival following liver transplantation in hepatitis B surface antigen positive patients ^{1, 3, 4}.

The clinical effectiveness of HBIG prophylaxis in the prevention of HBV recurrence following liver transplantation is dependent on the dose, length of administration and the viral replication status of the patient at the time of transplant ^{1, 3, 4}.

Hepatitis B immune globulin is most effective when administered in high doses (to achieve anti-HBs levels greater than 500 mIU/mL), over long time periods (greater than 6 months) ². A Cangene meta-analysis of the literature data showed that patients treated with long-term high-dose HBIG had a HBV recurrence rate of 15%, compared to a 40% recurrence rate in subjects treated with long-term, low-dose HBIG. Short-term immunoprophylaxis with HBIG may delay HBV recurrence, but the overall rate of re-infection is similar to untreated patients ⁵. Therefore, it is important that treatment be continued long-term.

The absence of HBV replication at the time of liver transplant is associated with an increase in the effectiveness of HBIG. As a result, HepaGam B is recommended in patients who have no or low levels of viral replication at the time of liver transplantation.

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 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.

True hypersensitivity reactions are rare. These reactions can occur in very rare cases of IgA deficiency or hypersensitivity to human globulin. 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 physician should discuss the risks and benefits of this product with the patient, before prescribing or administering to the patient.

Immune globulin administration may impair the efficacy of live attenuated virus vaccines such as measles, rubella, mumps and varicella ^6-9. Persons requiring vaccination with these vaccines while receiving HepaGam B should be tested for titers of antibodies against the said vaccine 3 months after vaccination and if titers are insufficient to afford protection should be revaccinated. There are no available data on concomitant use of HepaGam B and other medications.

Antibodies present in HepaGam B may interfere with some serological tests (see PRODUCT MONOGRAPH, Drug-Laboratory Interactions).

The maltose contained in HepaGam B 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.

The most common expected adverse drug reactions for intravenous immune globulins like HepaGam B are chills, fever, headaches, vomiting, allergic reactions, nausea, arthralgia and moderate low back pain ^1,2,6. 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. In studies with healthy volunteers, only 1 adverse drug reaction of nausea was been reported in the 70 adult subjects who received an intramuscular administration of HepaGam B.

Although no anaphylactic reactions have been reported following HepaGam B administration, anaphylactic reactions have been reported following the administration of intravenous immune globulin (human) products on rare occasions ¹⁰.

For the prevention of hepatitis B recurrence following liver transplantation in adult patients with hepatitis B, HepaGam B, should be administered intravenously to attain serum anti-HBs levels greater than 500 mIU/mL as described below ^{1, 2}.

These dosing recommendations are based on a systematic review of the clinical trial literature and meta-analysis undertaken by Cangene Corporation (see PRODUCT MONOGRAPH, PART II: SCIENTIFIC INFORMATION - CLINICAL TRIALS). This report found that hepatitis B Immune globulin (HBIG) prophylaxis was most effective when administered in high doses (to achieve anti-HBs levels of greater than 500 mIU/mL) over longer time periods (greater than 6 months). The recommended dosing schedule described below is designed to achieve anti-HBs levels of greater than 500 mIU/mL. This regimen is based on that published in Terrault et al., 19963 and reviewed by Shouval & Samuel, 20003. This regimen is currently being evaluated in a Phase III clinical trial. Recommendations for dose adjustments are based on McGory et al., 199611, using a similar dosing regimen.

Each dose of HepaGam B should be administered as an intravenous dose of 35 mL (10,920 IU anti-HBs). The first dose should be administered concurrently with the grafting of the transplanted liver (the anhepatic phase) with subsequent daily dosing from Day 1 through Day 7 post-operatively, followed by biweekly dosing from Day 14 up to 3 months, and thereafter from Month 4 onwards once every month.

Anti-HBs levels should be measured after the first week of treatment, to allow for initial adjustment of dosage (see PRODUCT MONOGRAPH, PART I: HEALTH PROFESSIONAL INFORMATION – DOSAGE AND ADMINISTRATION).

HepaGam B should be prepared for IV administration under aseptic conditions. DO NOT SHAKE VIAL; AVOID FOAMING (see PRODUCT MONOGRAPH, Administration).

• HepaGam B should be administered as provided through a separate IV line using an Intravenous administration set containing an in-line filter and a constant infusion pump.
• 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 or there is concern about the speed of infusion.

A carton containing a 1 mL single dose (> 312 IU), filled in a 3 mL glass vial with a plastic flip off seal and a package insert.

A carton containing a 5 mL single dose (> 1560 IU) filled in a 6 mL glass vial with a plastic flip off seal and a package insert.

For product inquiries, please contact Cangene Corporation at 1 877-CANGENE (226-4363).

For medical inquiries regarding, please contact Cangene Corporation medical affairs at 1-800-768-2304.

Please contact your hospital blood bank, The Canadian Blood Services or Héma-Québec to receive HepaGam B.

1. HepaGam B Product Monograph, Cangene Corporation, May 29, 2007. 
2. Roche B, Samuel D. Liver transplantation for hepatitis B virus-replated liver disease: Indications, prevention of recurrence and results. J Hepatol 2003; 39:S181-9.
3. Unpublished data on file.
4. Terrault NA, Zhou S, Combs C, Hahn JA, Lake JR, Roberts JP et al. Prophylaxis in liver transplant recipients using a fixed dosing schedule of hepatitis B immunoglobulin. Hepatology 1996; 24(6):1327 33.
5. Tchervenkov JI, Metrakos P, Deschenes M, Alpert E, Tector AJ, Cantarovich M et al. Decreasing viral load pretransplant and passive immunoprophylaxis with hepatitis B immunoglobulin posttransplant prevents hepatitis B virus recurrence after liver transplantation: an 8 year single center experience. Transplant Proc 2001; 33(1 2):1514 5.
6. 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.
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. Miura M, Katada Y, Ishihara J. Time interval of measles vaccination in patients with Kawasaki disease treated with additional intravenous immune globulin. Eur J Pediatr 2004;163(1):25 9.
9. Ruderman JW, Barka N, Peter JB, Stiehm ER. Antibody response to MMR vaccination in children who received IVIG as neonates.Am J Dis Child 1991;145(4):425 6.
10. Canadian Immunization guide. Health Canada, Sixth edition, 2002.
11. Ellis EF and Henney CS. Adverse reactions following administration of human gamma globulin. J Allerg 1969; 43:45 54.
12. McGory RW, Ishitani MB, Oliveira WM, Stevenson WC, McCullough CS, Dickson RC et al. Improved outcome of orthotopic liver transplantation for chronic hepatitis B cirrhosis with aggressive passive immunization. Transplantation 1996; 61(9):1358-1364.