Summary Safety Review - Ketamine - Assessing the Potential Risk of Liver and Bile Duct Damage
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: 2020-06-10
Product
Ketamine-containing products
Potential Safety Issue
Liver and bile duct damage
Overview
Use in Canada
- In Canada, ketamine-containing products are authorized for use by healthcare professionals to make patients unconscious (anesthesia) during surgery or medical procedures.
- Ketamine has been marketed in Canada since 1972 under the brand name Ketalar and is available as 10 mg/mL and 50 mg/mL injection for intramuscular or intravenous use only by healthcare professionals. Generic versions of ketamine are also available for sale in Canada.
- In 2019, 1,907,962 units of 10 mg/mL ketamine injection and 964,460 units of 50 mg/mL ketamine injection were sold to Canadian drugstores and hospitals.
Safety Review Findings
- The review was triggered by a risk communication published by the French regulatory agency related to the potential risk of liver and bile duct damage with the use of ketamine-containing products.
- Health Canada reviewed information from searches of the Canada Vigilance databasea and international databases of published literature and clinical studies.
- Health Canada's assessment focused on 19 international epidemiologic studies conducted in many patients and 22 individual patient case reports (21 international and one Canadian) of liver and bile duct damages related to ketamine use.
- The review of the 19 epidemiologic studies could not confirm or refute a link between the liver and/or bile duct damages and the use of ketamine due to various study method limitations, such as the presence of confounding factors, possibility of pre-existing liver damage prior to the use of ketamine, or a small number of participants in the study.
- Of the 22 individual case reports, one report was found to be probably linked to the use of ketamine, 17 reports were found to be possibly linked; one report was not likely to be linked, and 3 reports did not have enough information to be assessed. Only one of the 22 case reports was from Canada where liver and bile duct damage was found to be possibly linked to the use of ketamine.
- Findings from the epidemiologic studies and case reports showed that:
- The use of ketamine products for a few hours to many days may result in some chemical changes in the blood suggesting problems with liver function or the bile flow.
- The use of ketamine products for an extended period of time such as months to years may be linked to liver damage and enlargement of ducts that drain the bile.
- If a patient stops taking ketamine, the damage may be reversed.
Conclusions and actions
- Health Canada's review concluded that there is a potential link between the use of ketamine-containing products and damage to the liver and bile duct. If a patient stops taking ketamine, these damages may be reversed.
- Health Canada will work with manufacturers to update the product safety information of all ketamine-containing products to inform about this potential risk and advise treatment discontinuation with the first signs of liver or bile duct damage.
- A Health Product InfoWatch article will be published to further inform Canadians and healthcare professionals about this potential risk.
- Health Canada will continue to monitor safety information involving ketamine to identify and assess potential risks, as it does for all health products on the Canadian market. Health Canada will take appropriate and timely action if and when new health risks are identified.
Additional information
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 these drugs both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
Footnotes
- Canadian reports can be accessed through the Canada Vigilance Online Database.