Summary Safety Review - Bcr-Abl Tyrosine Kinase Inhibitors - Assessing the Potential Harm to the Fetus

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: 2016-03-02

Product

Bcr-Abl tyrosine kinase inhibitors (Gleevec [and its generics], Sprycel, Tasigna, and Bosulif)

Potential Safety Issue

Assessing the Potential Harm to the Fetus

Key Messages

  • Bcr-Abl tyrosine kinase inhibitors are used to treat blood cancers. The potential for these drugs to cause harm to the fetus is known and is included in the Canadian label. The label further tells women to use effective birth control during treatment.
  • Based on additional safety information received from the manufacturers, Health Canada carried out a safety review to further assess the risk of fetal harm with Bcr-Abl tyrosine kinase inhibitors.
  • Following the completion of the safety review, the manufacturer has updated the prescribing information for Gleevec to tell doctors to confirm by pregnancy test that female patients are not pregnant before starting treatment.

Overview

Based on additional safety information received from the manufacturers, Health Canada carried out this safety review to further assess the risk of fetal harm when Bcr-Abl tyrosine kinase inhibitors are used by either parent (father or mother) in order to determine if there is a need for additional warnings in the prescribing information. The potential for these drugs to cause harm to the fetus (i.e., birth defects and miscarriage) is known and is mentioned in the Canadian label. The label further tells women to use effective birth control during treatment.

Use in Canada

  • There are currently four brand name Bcr-Abl tyrosine kinase inhibitors sold in Canada: Gleevec (imatinib), Sprycel (dasatinib), Tasigna (nilotinib), and Bosulif (bosutinib). Generic versions of imatinib are also available in Canada.
  • These drugs are taken orally to treat blood cancers. Gleevec is also used to treat some solid tumours.
  • Gleevec has been sold in Canada since September 2001, Sprycel since April 2007, Tasigna since September 2008, and Bosulif since April 2014.

Safety Review Findings

  • No Canadian cases of harm to the fetus have been received through the Canada Vigilance program with any Bcr-Abl tyrosine kinase inhibitors.
  • At the time of the review, a total of 27 published international studies and case reports of pregnant women treated with Gleevec were found in the scientific literature. After review of these studies and according to the outcomes reported by the authors, overall healthy babies were the most reported outcomes (50.2%), followed by elective abortions (30.7%), miscarriages (10.6%) and birth defects (8.4%).
  • Based on the information reviewed, including the scientific literature, there were no new findings on the effects of Sprycel (dasatinib), Tasigna (nilotinib) and Bosulif (bosutinib) on pregnancy outcome.

Conclusions and actions

  • At the time of the review, the prescribing information for Bcr-Abl tyrosine kinase inhibitors included wording regarding the potential harm to a fetus, including birth defects and miscarriage. Women are also told to use effective birth control during treatment.
  • Further to this safety review, the manufacturer has updated the prescribing information for Gleevec to tell doctors to confirm by pregnancy test that female patients are not pregnant before starting treatment. No modifications were recommended for the prescribing information of the other tyrosine kinase inhibitors, at this point in time based on the lack of evidence of increased fetal harm and because of differences in the mechanism of action of these medications.
  • The review did not find additional safety concerns for the unborn child when Bcr-Abl tyrosine kinase inhibitors are used by the father. Health Canada has determined that there is no need to modify the warnings already included in the Canadian prescribing information regarding this particular risk when these drugs are used by the father.
  • Health Canada will continue to monitor side effect information involving Bcr-Abl tyrosine kinase inhibitors, 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 was carried out for this safety review took into consideration information from scientific and medical literature, Canadian and international adverse reaction reports as well as what is known about the use of this drug in Canada and internationally. For additional information, contact the Marketed Health Products Directorate.
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