Summary Safety Review - Codeine-containing products - Further Assessing the Risk of Serious Breathing Problems in Children and Adolescents

July 28, 2016

Product

Codeine-containing products

Potential Safety Issue

Serious breathing problems (respiratory depression) in children and adolescents.

Key Messages

• Codeine-containing products are opiate medications used to treat pain and reduce coughing.
• Health Canada continues to recommend that prescription and non-prescription codeine should not be used in children under 12 years of age.
• Health Canada is working with manufacturers to update the safety information for prescription products so that they are no longer recommended for use after surgery to remove tonsils or adenoids in patients under 18 years of age.

Overview

In 2013 and 2015, Health Canada carried out safety reviews on codeine-containing products as they relate to the risk of potentially life-threatening breathing problems. At the time, it was recommended that codeine-containing products no longer be used in children under 12 years of age. New safety reviews were carried out to further assess the risk of serious breathing problems in children and adolescents treated with codeine to decide if more should be done to manage this risk in this age group.

Codeine is changed into morphine by the liver; both drugs belong to the family of opioids. It is known that opioids can slow the pace of breathing. Having too much of an opioid can slow down breathing enough to be life-threatening. Some people are ultra-rapid metabolizers, which means that they convert codeine into morphine more quickly and completely. They are more likely to have greater than expected amounts of morphine in their blood after taking codeine-containing products, which can be more dangerous.

Use in Canada

• Codeine-containing medicines are used to treat pain and reduce cough.
• Codeine is available either alone or in combination with other medications. Some codeine-containing products are only available by prescription while others are non-prescription. For non-prescription codeine-containing products, consumers must have a discussion with a pharmacist before they can purchase it.
• The safety information for codeine-containing products warns against using them if you have conditions that would make breathing difficult, such as asthma, chronic lung disease or other breathing problems.

Safety Review Findings

Prescription codeine

• At the time of the review activities, Health Canada had received a total of 8 Canadian cases ^{Footnote 1} of breathing problems in patients under 18 years of age, possibly linked to prescription codeine for the treatment of pain. Six of these cases occurred in children under 12 years of age, including 3 who died. Four of the 8 cases occurred in children after surgery to remove tonsils or adenoids. It was also noted that other medications that were taken at the same time as the codeine-containing product could have contributed to the breathing problems.
• Prescription codeine was also found to have been probably linked to serious breathing problems in 7 published international cases, in patients under 18 years of age, in which it was used for the treatment of pain. Six of the 7 cases occurred in children under 12 years of age, including 4 deaths. Five of the 7 cases occurred in children after surgery to remove tonsils or adenoids. It was also noted that these children had other medical conditions that could have contributed to the breathing problems.

Non-prescription codeine

• Since the 2013 review, Health Canada has not received any Canadian cases of serious breathing problems with the use of non-prescription codeine products for pain or cough in children or adolescents. Among the international case reports for patients 12 to 18 years of age (including ones prior to the 2013 review), there was not enough information to conclude that codeine caused the reported side effects. The reports also did not contain enough information regarding the dose of codeine used and if it was similar in strength to the non-prescription products used in Canada.
• No new cases involving the use of non-prescription strengths of codeine have been reported in the scientific literature since the 2013 review.
• Overall, no new evidence was found that would suggest a change in the risk of serious breathing problems with non-prescription codeine use compared to what was learned from the 2013 review.

Conclusions and Actions

• There are well-described reports of life-threatening breathing problems in patients under 18 years of age, when prescription codeine is used as part of treating pain after surgery to remove tonsils or adenoids. Therefore, Health Canada is working with manufacturers to update the product safety information so that prescription codeine is no longer used in children and adolescents for this purpose.
• Health Canada continues to recommend that, codeine-containing products should not be used in children under 12 years of age. Caution is also advised when using codeine in patients with breathing conditions, regardless of age.
• Health Canada will continue to monitor side effect information involving codeine, as it does for all health products on the Canadian market, to identify and assess potential harms. This review will be used to help inform further proposals to improve the overall safety of all codeine-containing products.

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.