Summary Safety Review - Mercaptopurine - Assessing the Potential Risk of Hypoglycemia

• Mercaptopurine is authorized for sale in Canada as maintenance therapy for a specific type of cancer of the blood and bone marrow (acute lymphoblastic/lymphocytic leukemia) in combination with other drugs in adults and children.

• Health Canada reviewed the potential risk of hypoglycemia with the use of mercaptopurine. The safety review was triggered by a labelling update for mercaptopurine-containing products marketed in the United States (U.S.) and by reported cases of hypoglycemia in patients taking mercaptopurine.

• Health Canada’s review concluded that there may be a link between the use of mercaptopurine and the risk of hypoglycemia in children (less than 18 years of age). A large proportion of the reported cases were in children under 6 years of age.

• Health Canada is working with the manufacturers to update the product safety information in the Canadian product monograph (CPM) for mercaptopurine-containing products to include the risk of hypoglycemia in children.

Health Canada reviewed the potential risk of hypoglycemia with the use of mercaptopurine. This safety review was triggered by a U.S. Food and Drug Administration update to the product safety information for mercaptopurine-containing products to include the risk of hypoglycemia in children, as well as Canadian and international cases reported to the Canada Vigilance Program.

Hypoglycemia is a condition in which an individual’s blood sugar level is lower than normal. Signs and symptoms of hypoglycemia may include shakiness, sweating and irritability. As hypoglycemia gets worse, symptoms may include confusion and loss of consciousness.

• Mercaptopurine is a prescription drug authorized for sale in Canada as maintenance therapy for acute lymphoblastic/lymphocytic leukemia in combination with other drugs in adults and children.

• Mercaptopurine has been marketed in Canada since 1954. It is currently available as 50 mg tablets under the brand name Purinethol and as a generic.

• There were over 200,000 prescriptions for mercaptopurine dispensed by Canadian retail pharmacies between January 2017 and January 2022.

• Health Canada reviewed information provided by the manufacturer, and from searches of the Canada Vigilance database^a and published literature.

• Health Canada reviewed 23 cases (1 Canadian, 22 international) of hypoglycemia in patients taking mercaptopurine. Of the 23 cases assessed, 22 were reported in children under 18 years of age, with 12 of these cases in children under 6 years of age.

• Of the 23 cases, 6 were found to be probably linked to the use of mercaptopurine, 15 (1 Canadian) were found to be possibly linked and 2 were unlikely to be linked.

• Health Canada also reviewed 8 articles published in the scientific literature, which showed a possible link between the use of mercaptopurine and the risk of hypoglycemia in children. In some of the studies, there was an increased number of cases seen in children under 6 years of age.

• Health Canada’s review of the available information concluded that there may be a link between the use of mercaptopurine and the potential risk of hypoglycemia in children (less than 18 years of age). A large proportion of the cases were in children under 6 years of age.

• Health Canada is working with the manufacturers of mercaptopurine-containing products to update the CPM to include the risk of hypoglycemia in children.

• Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of mercaptopurine and other health products to the Canada Vigilance Program.

• Health Canada will continue to monitor safety information involving mercaptopurine, 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 should new health risks be identified.

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

For additional information, contact the Marketed Health Products Directorate.

1. Canadian reports can be accessed through the Canada Vigilance Database