ZYDELIG (idelalisib) - Increased Risk of Fatal and Serious Infections

Starting date:
May 3, 2016
Posting date:
May 3, 2016
Type of communication:
Dear Healthcare Professional Letter
Subcategory:
Drugs
Source of recall:
Health Canada
Issue:
Important Safety Information
Audience:
Healthcare Professionals, General Public
Identification number:
RA-58118

Audience

Healthcare professionals working in the following settings: Hematology, Medical Oncology, Oncology Pharmacy

Key messages

  • Decreased overall survival and an increased risk of serious adverse events (mostly infections) were observed in patients receiving ZYDELIG compared to the control groups in clinical trials.
  • These trials evaluated the addition of ZYDELIG to standard therapies for first line treatment of chronic lymphocytic leukemia (CLL) and early line treatment of relapsed indolent non-Hodgkin’s lymphoma (iNHL).
  • ZYDELIG should not be used for first line treatment of CLL.
  • The Canadian Product Monograph for ZYDELIG will be updated to reflect this new information.

         

Issue

Decreased overall survival and increased rate of serious adverse events have been observed in patients receiving ZYDELIG compared to the control groups in Phase 3 studies evaluating the addition of ZYDELIG to standard therapies for first line treatment of CLL and early lines of relapsed iNHL. The majority of events were infections, which included sepsis and pneumonia.

Products affected

ZYDELIG 150 and 100 mg tablets.

Background information

ZYDELIG is approved in combination with rituximab for the treatment of patients with relapsed CLL. In addition, ZYDELIG is approved with conditions as a monotherapy for the treatment of patients with follicular lymphoma who have received at least two prior systemic regimens and are refractory to both rituximab and an alkylating agent.

Increased rates of serious adverse events and deaths, generally due to infections, were observed during a review of three ongoing Phase 3 studies in patients receiving ZYDELIG for first line treatment of CLL and early lines of treatment of relapsed iNHL. Infectious events included (but were not limited to) sepsis, febrile neutropenia, and opportunistic infections such as Pneumocystis carinii/jirovecii pneumonia (PCP/PJP) and cytomegalovirus (CMV).

Gilead is stopping all ongoing ZYDELIG clinical trials for first-line treatment of CLL and early line treatment of iNHL and amending the clinical trial documentation for all ongoing studies to reflect the new safety information where risk mitigation measures have already been implemented.

Who is affected

Information for consumers

ZYDELIG contains idelalisib, which belongs to a group of medicines called antineoplastic agents. It affects the growth of cancerous white blood cells, causing them to die. ZYDELIG is used in combination with rituximab (another anti-cancer drug) for the treatment of chronic lymphocytic leukemia (CLL), a type of blood cancer, in patients who were previously treated for their cancer. ZYDELIG is also used alone for the treatment of follicular lymphoma (a type of blood cancer) in patients who were previously treated at least twice and did not respond to either rituximab or an alkylating agent.

Based on the results of the clinical trials mentioned, the use of ZYDELIG is not supported for first line treatment of CLL. Patients and caregivers should contact their healthcare professionals to discuss what this new information means to them. Do not stop taking the drug until you talk to a healthcare professional.

Information for health care professionals

ZYDELIG should not be used for first line treatment of CLL.

For patients taking ZYDELIG, healthcare professionals should:

  • Counsel patients about the increased risk of serious and/or fatal infections
  • Administer prophylaxis for PCP/PJP to all patients throughout ZYDELIG treatment. Monitor patients for CMV and permanently discontinue ZYDELIG in patients with evidence of infection or viremia (positive polymerase chain reaction (PCR) or antigen test)
  • Monitor blood counts in all patients at least every 2 weeks for the first 6 months of treatment with ZYDELIG, and at least weekly in patients while absolute neutrophil count is less than 1.0 x 109/L.

This information is based on currently available data and recommendations may change.

Action taken by Health Canada

Health Canada is working with Gilead Sciences Canada, Inc. to update the ZYDELIG Product Monograph based on this new information. Health Canada is also communicating this important safety information to health care professionals and to the public through its Healthy Canadians Web site and MedEffectTM e-Notice.

Report health or safety concerns

Managing marketed health product-related side effects depends on healthcare professionals and consumers reporting them. Adverse events including any case of serious infections and/or fatal infections in patients receiving ZYDELIG should be reported to Gilead Sciences Canada, Inc. or Health Canada.

Gilead Sciences Canada, Inc.
6711 Mississauga Road, Suite 600
Mississauga, ON, L5N 2W3
www.gilead.ca
Toll free: 1-866-207-4267
E-mail: CA-SafetyMailbox@gilead.com

To correct your mailing address or fax number, contact Gilead Sciences 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 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:
Marketed Health Products Directorate
E-mail: mhpd_dpsc@hc-sc.gc.ca
Telephone: 613-954-6522
Fax: 613-952-7738

Please refer to the accompanying Product Monograph for a complete description of the risk profile for ZYDELIG.

Contact Gilead Medical Information at 1-866-207-4267 if you have additional questions. This information is being sent in agreement with Health Canada.

Sincerely,

Original signed by

John McHutchison, MD
Executive Vice President, Clinical Research
Gilead Sciences, Inc.

For more information

The manufacturer advised Health Canada of the risk associated with this health product. Health Canada supports the actions taken by the manufacturer and as such a risk assessment was not required and a Summary Safety Review was not prepared.