Summary Safety Review - CODEINE PRESCRIPTION PRODUCTS Indicated for Cough - Further Assessing the Risk of Serious Breathing Problems in Children and Adolescents

December 9, 2015

Product

Codeine prescription products indicated for cough

Potential Safety Issue

Serious breathing problems in children and adolescents

Key Messages

• Codeine-containing products are opiate drugs used to treat pain and to reduce coughing.
• In 2013, Health Canada carried out a safety review to assess the risk of serious breathing problems and death, which concluded that codeine-containing products are not recommended in children less than 12 years of age regardless of the indication.
• Following a new safety review in 2015 to further assess the risk of serious breathing problems in children and adolescents, Health Canada maintains its recommendation that codeine prescription products not be recommended in children less than 12 years of age. No modifications were recommended to the Canadian prescribing information.

Overview

In 2013, Health Canada carried out a safety review to assess the risk of serious breathing problems, including death, which concluded that codeine is not recommended in children less than 12 years of age for any indication, including pain or cough. In 2015, the European Medicines Agency contraindicated the use of codeine for cough in children less than 12 years of age. Due to emerging new evidence, a new safety review was initiated in Canada to further assess the risk of serious breathing problems in children and adolescents treated with codeine prescription products for cough and to determine if additional restrictions were warranted to manage this risk.

Codeine is converted to morphine in the liver. Some people have genetic variations of liver enzymes which cause codeine to be converted to morphine faster and more completely than in other people. These people with genetic differences (ultra-rapid metabolizers) are more likely to have higher than normal amounts of morphine in their blood after taking codeine. High levels of morphine can result in breathing difficulty, which may cause death. This information is included in the Canadian prescribing information for codeine products.

Use in Canada

• Codeine-containing products are medicines approved for use in adults and children above 12 years of age to treat pain and reduce cough. Caution is advised regarding the use of codeine in patients with breathing conditions, including children.
• Codeine is available in Canada alone or in combination with acetaminophen or aspirin, and in some cough and cold medications. Some of these products are only available by prescription, while others are non-prescription.
• In recent years, the number of prescriptions in Canada for codeine products for pediatric use has decreased by more than 70% in children less than 12 years of age and by more than 30% in patients 13-18 years of age.

Safety Review Findings

• At the time of the current review, no Canadian cases of breathing problems with codeine for the treatment of cough in children and adolescents were reported to Health Canada.
• Since Health Canada's 2013 review, one new international case was identified in the literature, which involved serious breathing problems with the use of codeine to reduce coughing. The case resulted in the death of a six year old patient. However, a direct role for codeine could not be established due to medication error and pre-existing breathing problems.
• Taken together, Health Canada's reviews identified a total of 16 published case reports in relation to serious side effects involving breathing problems with the use of codeine to reduce coughing. The ages of the children ranged from 17 days to 6 years. Out of these 16 cases, death was reported in 5 cases. In 13 of these 16 cases, there was a pre-existing respiratory disease described in addition to cough, such as respiratory tract infections.

Conclusions and Actions

• Health Canada maintains its warnings and recommendations to manage the risk of serious breathing problems and death, that codeine prescription products not be recommended in children less than 12 years of age. No modifications were recommended to the Canadian prescribing information.
• Health Canada will continue to monitor side effect information involving codeine, including non-prescription codeine products, as it does for all health products on the Canadian market, and will take additional actions, if warranted.

Additional Information

The analysis that was carried out for this safety review included scientific and medical literature, Canadian and international reports of side effects, and what is known about the use of these products both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.