TZIELD (teplizumab) and the Risk of Viral Reactivation

Serious and life-threatening cases of viral reactivation, including Epstein–Barr virus (EBV) and cytomegalovirus (CMV), have been reported with TZIELD.

Audience

Healthcare professionals including pediatric and adult endocrinologists, diabetologists, internal medicine practitioners, infectious-disease specialists, pediatricians, general practitioners, nurse practitioners, hospital and community pharmacists, and diabetic centre nurses.

Key messages

• Serious and life-threatening cases of viral reactivation, including Epstein–Barr virus (EBV) and cytomegalovirus (CMV), have been reported with TZIELD.
• Patients who are immunocompromised are at increased risk of viral reactivation.
• TZIELD is now contraindicated in patients with an active viral infection (including EBV or CMV), any active serious infection, or who are immunocompromised.
• Healthcare professionals are advised to follow the recommendations for EBV and CMV screening and monitoring, and TZIELD discontinuation in the event of confirmed infection or prolonged severe lymphopenia (see the Information for healthcare professionals section).
• The Canadian Product Monograph for TZIELD has been updated to include this safety information.

Background

TZIELD is a CD3-directed monoclonal antibody indicated to delay the onset of Stage 3 type 1 diabetes in adult and pediatric patients 8 years of age and older with Stage 2 type 1 diabetes.

As an immunomodulatory agent, TZIELD affects lymphocyte populations, which may increase the risk of serious infections, including viral reactivation. Individuals who are immunocompromised are at increased risk.

Serious and life-threatening cases of viral reactivation, including EBV and CMV, have been reported with TZIELD in the post-market setting. Most cases occurred within 2 months following the last infusion. Some of the cases occurred in patients who continued TZIELD treatment despite persistent, severe lymphopenia.

Cases of EBV-associated lymphoproliferative disorder may occur in individuals treated with TZIELD receiving concomitant immunosuppressive therapy and/or with conditions associated with immunologic impairment. 

Information for consumers

TZIELD is used to delay the onset of Stage 3 type 1 diabetes in adults and children 8 years of age and older who have Stage 2 type 1 diabetes. In Stage 3, the body cannot make enough insulin on its own, and insulin injections may be needed.

TZIELD works by slowing down the autoimmune response involved in type 1 diabetes. Because TZIELD affects the immune system, certain infections may occur or become active again during or after treatment.

Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are common viruses that may stay inactive in the body after an initial infection. TZIELD may cause these viruses to become active again which, especially in people with a weakened immune system, can become serious and potentially life-threatening. These infections may occur during treatment with TZIELD or up to 2 months after the last dose.

Patients should:

• Tell their healthcare professional right away if they develop symptoms of infection, such as fever, swollen glands, or fatigue during or after TZIELD treatment.
• Not stop their TZIELD treatment without consulting their healthcare professional.
• Speak to their healthcare professional if they have any questions or concerns about this information.

Information for healthcare professionals

Healthcare professionals are advised that: 

• TZIELD is now contraindicated in patients who have an active viral infection (including EBV or CMV), any active serious infection, or who are immunocompromised.
• Prior to initiating treatment with TZIELD, patients should be evaluated for active EBV and CMV infection, with an undetectable viral load confirmed (e.g., polymerase chain reaction testing), in addition to existing pre-treatment laboratory evaluations.
• Patients should be monitored for signs and symptoms of infection (including viral reactivation) during TZIELD treatment and for at least 2 months following the last infusion. Lymphocyte counts should continue to be monitored throughout the treatment period.
• If EBV or CMV infection is suspected, then TZIELD should be paused, and prompt and complete diagnostic testing should be performed, including verification of viral load. If EBV or CMV infection is confirmed, then TZIELD should be permanently discontinued, and appropriate treatment should be initiated.
• Consistent with existing discontinuation criteria, TZIELD should also be permanently discontinued if prolonged severe lymphopenia (<0.5 X 10⁹ lymphocytes/L lasting 1 week or longer) or any serious infection develops.

Action taken by Health Canada

Health Canada, in collaboration with sanofi-aventis Canada Inc., has updated the Canadian Product Monograph for TZIELD to include this new safety information.

Health Canada is communicating this important safety information to healthcare professionals and Canadians via the Recalls and Safety Alerts Database on the Healthy Canadians Web Site. This communication will be further distributed through the MedEffect™ e-Notice email notification system.

Report health or safety concerns

Managing marketed health product-related side effects depends on healthcare professionals and consumers reporting them. Any case of viral reactivation (including EBV or CMV) or other serious or unexpected side effects in patients receiving TZIELD should be reported to sanofi-aventis Canada Inc. or Health Canada.

sanofi-aventis Canada Inc.
1755 Steeles Avenue West 
Toronto, ON, M2R 3T4
Toll free: 1-800-265-7927

E-mail: SanofiMedInfoCA@sanofi.com

To correct your mailing address or fax number, contact sanofi-aventis Canada Inc.

You can report any suspected adverse reactions associated with the use of health products to Health Canada by:

• Calling toll-free at 1-866-234-2345; or
• Visiting MedEffect Canada's Web page on Adverse Reaction Reporting (http://www.hc-sc.gc.ca/dhp-mps/medeff/report-declaration/index-eng.php) for information on how to report online, by mail or by fax.

For other health product inquiries related to this communication, contact Health Canada at:

Biologic and Radiopharmaceutical Drugs Directorate 
E-mail: brdd.dgo.enquiries@hc-sc.gc.ca

Original signed by

Maneesh Puri
Country Medical Head, Autoimmune T1D, sanofi-aventis Canada Inc.