HepaGam B [Hepatitis B Immune Globulin (Human) Injection] - Theoretical Risk of Thrombotic Events with Intravenous Administration and Related Labeling Update - Notice to Hospitals

Starting date:

June 11, 2012

Posting date:

June 14, 2012

Type of communication:

Notice to Hospitals

Subcategory:

Biologic/vaccine

Source of recall:

Health Canada

Audience:

Healthcare Professionals

Identification number:

RA-14805

This is duplicated text of a letter from Cangene Corporation.
Contact the company for a copy of any references, attachments or enclosures.

Notice about Health Canada advisories

Notice to Hospitals - Health Canada Endorsed Important Safety Information on HepaGam B [Hepatitis B Immune Globulin (Human) Injection]

June 11, 2012

Dear Healthcare Professional:

Please distribute to relevant departments (Surgery; Blood Banks; Departments of Transfusion Medicine; Internal Medicine; Anaesthesia; Intensive Care; Pharmacy, and other professional staff/departments involved with IVIGs and post this Notice in your institution).

Subject: Theoretical Risk of Thrombotic Events with Intravenous HepaGam B^® [Hepatitis B Immune Globulin (Human) Injection] and Related Labeling Update

Cangene Corporation, in cooperation with the Health Canada, would like to inform you of planned changes to the Canadian Product Monograph for HepaGam B^®, including pertinent precautions regarding thrombotic events.

• There is a theoretical risk for the arterial and venous thrombosis at the intravenous doses of HepaGam B^® for the liver transplantation indication.
• Such a risk may exist because an in-house analysis detected measurable levels of procoagulant (factor XIa) activity in HepaGam B^®. The significance of these levels is being evaluated.
• Patients should be informed of signs and symptoms of thrombotic events.
• Caution should be used when administering immune globulins, including HepaGam B^®, to patients with risk factors for thrombotic events.

Indications for HepaGam B^®

HepaGam B^® is authorized for hepatitis B post-exposure prophylaxis including the treatment of acute exposure to blood containing, perinatal exposure of infants born to HBsAg-positive mothers, sexual exposure to HBsAg positive persons and household exposure to persons with acute HBV infection. HepaGam B^® is administered intramuscularly for post-exposure prophylaxis.

HepaGam B^® is also indicated for the prevention of hepatitis B recurrence following liver transplantation. HepaGam B^® should be administered intravenously for this indication.^*

^* It should be noted that the liver transplant indication has been issued a marketing authorization with conditions, pending the results of confirmatory studies to verify clinical benefit.

Additional Information on Possible Thrombotic Risks

The detection of procoagulant activity in HepaGam B^® was the result of a comprehensive review of all immune globulins manufactured by Cangene, and the significance of these findings is being evaluated. Changes to the manufacturing process for HepaGam B^® are planned to minimize the occurrence of procoagulant activity.

There have been post-marketing and literature reports of serious thrombotic adverse events associated with the administration of intravenous and subcutaneous immune globulin products (IVIG, SCIG) in a wide range of patient populations.^{Footnote 1, Footnote 2} Recently, coagulation factors, including activated factor XI, have been identified in IVIG batches associated with thrombotic events.^{Footnote 3, Footnote 4} Measurable levels of procoagulant (factor XIa) activity have been detected in HepaGam B^®.

There have been no post-marketing safety reports of thrombotic adverse events attributed to intravenous administration of HepaGam B^®. However, HepaGam B^® presents a theoretical risk for arterial and venous thrombosis at the intravenous doses for the liver transplantation indication. In the Canadian Product Monograph, the maximum daily dose of HepaGam B^® corresponds to 70 mL (20,000 IU) as a result of dose adjustments. In contrast, post-exposure prophylaxis doses are over 10 times lower (0.06 mL/kg bodyweight) and are administered intramuscularly.

Patients at risk include those with a history of atherosclerosis, cardiovascular risk factors, impaired cardiac output, coagulation disorders, prolonged periods of immobilization, advanced age and/or known/suspected hyperviscosity from any cause, including dehydration.

Risk Management Measures

Physicians and patients should take available precautions to minimize risk in all patients receiving HepaGam B^®, including administering HepaGam B^® at the minimum rate of infusion practicable. Physicians should consider baseline assessment of blood viscosity in patients at risk for hyperviscosity including those with cryoglobulins, fasting chylomicronemia/markedly high triacylglycerols (triglycerides), or monoclonal gammopathies.

Physicians should inform patients of the symptoms of a thrombotic event, including shortness of breath, pain and swelling of a limb, focal neurological deficits, chest pain, and other manifestations of thrombotic and embolic events. Patients should also be informed what to do if these symptoms occur.

Based on this information, the Warnings and Precautions section of the current Canadian Product Monograph for HepaGam B^® will be updated to include pertinent precautions regarding thrombotic events.

Managing marketed health product-related adverse reactions depends on health care professionals and consumers reporting them. Reporting rates determined on the basis of spontaneously reported post-marketing adverse reactions are generally presumed to underestimate the risks associated with health product treatments. Any case of serious thrombotic event or other serious or unexpected adverse reactions in patients receiving HepaGam B^® should be reported to Cangene Corporation or Health Canada.

Please report any adverse events you encounter with Cangene product to Cangene Corporation Pharmacovigilance at 1-800-768-2304. Please provide the lot number(s) of products associated with reported adverse events, whenever possible.

Cangene Corporation
155 Innovation Drive, Winnipeg, MB
Canada, R3T 5Y3
Tel: 204-275-4509
Fax: 204-275-4330
Cell: 204-295-2935 (24 hour access)
Toll free number (for USA and Canada) 800-768-2304 (24 hour access)
E-mail: pharmacovigilance@cangene.com

To correct your mailing address or fax number, contact Cangene Corporation.

To report suspected adverse reactions to these or other health products, please contact Health Canada's Canada Vigilance Program toll-free at 1-866-234-2345, or visit the MedEffect™ Canada Web site for information on how to report.

The Reporting Forms, postage paid labels, and Guidelines can be found on the MedEffect™ Canada Web site in the Adverse Reaction Reporting section. The Reporting Form is also in the Canadian Compendium of Pharmaceuticals and Specialties.

For other health product inquiries related to this communication, please contact Health Canada at:
Marketed Health Products Directorate
E-mail: mhpd_dpsc.public@hc-sc.gc.ca
Telephone: 613-954-6522
Fax: 613-952-7738

More information regarding HepaGam B and this communication can be found on the Cangene website and on the MedEffect™ Canada website.

original signed by

Pam Bobbette
Director of Quality
Cangene Corporation