Summary Safety Review - Tramadol-containing Products - Assessing the Potential Risk of Serious Breathing Problems (Respiratory Depression) in Children and Adolescents

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: 2017-02-22

Product

Tramadol-containing products

Potential Safety Issue

Serious breathing problems (respiratory depression) in children and adolescents

Key Messages

  • Tramadol is an opioid prescription drug authorized for sale in Canada to treat moderate to moderately severe pain in adults.
  • After a safety review by Health Canada to further study codeine and the risk of serious breathing problems in children, it was decided that a similar review would be carried out for tramadol.
  • There was also evidence to show that the way in which certain people metabolize this drug may increase the risk of serious breathing problems. Health Canada's safety review found limited information regarding serious breathing problems with the use of tramadol in children.
  • The product information for tramadol-containing products has been updated to further manage the risk of serious breathing problems based on this evidence. A Health Product InfoWatch notice will give Canadians more details on this risk.
  • Health Canada reminds Canadians that tramadol is not recommended for use in patients under 18 years of age.

Overview

The product information for tramadol warns of the risk of serious breathing problems when too much is taken. Health Canada's safety review on codeine (another opioid drug) to study the risk of serious breathing problems in children and adolescents triggered this review for tramadol. Tramadol is an opioid drug authorized in Canada for the treatment of moderate to moderately severe pain but is not recommended for use in patients under 18 years of age. However, Health Canada is aware that this drug is being used in children and adolescents (known as off-label use).

Some people convert tramadol into its active drug form more quickly and completely than others. The use of tramadol in these patients, called "ultra-rapid metabolizers", may lead to unexpectedly high levels of active drug, and increase the risk of serious breathing problems.

Use in Canada

  • Tramadol is an opioid prescription drug authorized for sale in Canada to treat moderate to moderately severe pain in adults. It is not recommended for use in patients under 18 years of age because it has not been studied in this age group.
  • Tramadol has been marketed in Canada since 2005 and is available alone or together with acetaminophen. It is available by prescription only.

Safety Review Findings

  • At the time of the review, Health Canada had not received any Canadian reports of serious breathing problems related to the use of tramadol in children and adolescents.
  • This safety review found 1 international report of respiratory depression in the published literature, linked to the use of tramadol in a 5-year old child. The child was an ultra-rapid metabolizer and this may have played a role.
  • Many studies suggest that differences in how the liver works could affect the risk of side effects experienced by patients using tramadol. These studies help confirm that ultra-rapid metabolizer patients may be more at risk of developing respiratory depression with the use of tramadol.

Conclusions and actions

  • The product information for tramadol-containing products has been updated to further highlight the risk of serious breathing problems based on the evidence found in the safety review. This has included the addition of warnings that some patients treated with tramadol may be "ultra-rapid metabolizers" which can lead them to convert tramadol more quickly and completely than normal. This may result in an increased risk of serious breathing problems.
  • In addition, Health Canada will publish a Health Product InfoWatch notice to inform Canadians and healthcare professionals of label changes related to this risk.
  • Health Canada reminds Canadians that tramadol is not recommended for use in patients under 18 years of age.
  • Health Canada continues to monitor side effect information involving tramadol, 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.

For additional information, contact the Marketed Health Products Directorate.

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