Summary Safety Review - Zydelig (idelalisib) - Assessing the potential risk of serious infections

Review decision

A Summary Safety Review complements other safety related information to help Canadians make informed decisions about their use of health products. Each summary outlines what was assessed in Health Canada’s review, what was found and what action was taken by Health Canada, if any.


Issued: 2017-03-03

Product

Zydelig (idelalisib)

Potential Safety Issue

Serious infections

Key Messages

  • Zydelig is authorized for sale in Canada to treat 2 types of blood cancer: relapsed chronic lymphocytic leukemia, and follicular lymphoma in patients who have received at least two other types of treatment that no longer work for them.
  • Health Canada reviewed the risk of serious infections with Zydelig because of clinical trial reports of an increased rate of serious infections (sometimes leading to death) amongst those treated with Zydelig, compared to patients who were not. These clinical trials were testing new uses of Zydelig: earlier treatment and different drug combinations than currently authorized by Health Canada.
  • Health Canada's review of the available information concluded there was a risk of serious infections (sometimes leading to death) associated with Zydelig use. As such, the product information was updated to warn about the increased risk of infections.

Overview

Health Canada reviewed the risk of serious infections with Zydelig because of clinical trial reports of increased rates of serious infections (sometimes leading to death) amongst those treated with Zydelig, compared to those who were not.

In March 2016, Health Canada reported that clinical trials involving Zydelig, in Canada and internationally, were being stopped due to serious side effects. In May 2016, Health Canada reported that serious side effects seen in clinical trials included infections with Pneumocystis jirovecii pneumonia (PJP) and cytomegalovirus (CMV). These clinical trials were testing new uses of Zydelig: earlier treatment and different drug combinations than authorized by Health Canada.

Use in Canada

  • Zydelig is a prescription drug authorized for sale in Canada to treat 2 types of blood cancers: relapsed chronic lymphocytic leukemia and follicular lymphoma. Zydelig belongs to a group of medicines called antineoplastic agents that acts by changing the growth of cancerous white blood cells, causing them to die. The drug is used together with rituximab (another anti-cancer drug) for the treatment of chronic lymphocytic leukemia, a type of blood cancer, in patients previously treated with other drugs. Zydelig is also used alone for the treatment of follicular lymphoma, a type of blood cancer, in patients who have received at least two other types of treatment that no longer work for them.
  • Idelalisib has been marketed in Canada since April 2015 under the brand name Zydelig. It is available as a tablet that is taken by mouth.

Safety Review Findings

  • At the time of the review, Health Canada had received a total of 23 Canadian reports of death associated with Zydelig use (6 from clinical trials and 17 from after being on the market). In these reports, there was 1 death reported with a PJP infection, and none with CMV infection. These reports did not provide strong evidence that Zydelig alone was the cause of death, since the disease itself or other patient risk factors may also be associated with these infections. These cases all occurred in patients with other risk factors for PJP.
  • A search of the scientific literature found cases describing serious infections in patients treated with Zydelig.
  • Patients with chronic lymphocytic leukemia and follicular lymphoma are at an increased risk of infections such as PJP and CMV due to the disease itself as well as possible complications linked with disease treatments.

Conclusions and actions

  • Health Canada's review of the available information concluded there was a risk of serious infections, which may lead to death, associated with Zydelig use.
  • The Canadian product information was updated to warn about the increased risk of infections.
  • Health Canada has requested the manufacturer to provide any new information on this safety issue.
  • Health Canada will continue to monitor safety information involving Zydelig, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified.

Additional information

The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.

The most recent update of the Canadian product information includes recommendations to use antibiotics against PJP and watch for CMV infection during treatment with Zydelig. It is also recommended that patients being treated with Zydelig should stop treatment if they develop either PJP or CMV infections. Zydelig is not authorized for use in first-line chronic lymphocytic leukemia and early-line indolent non-Hodgkin lymphoma outside of a clinical trial.

For additional information, contact the Marketed Health Products Directorate.

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