Notice: Limiting the Strength of Acetaminophen to 325 mg per Dosage Unit in Prescription Combination Products

This Notice serves to inform sponsors that effective immediately, Health Canada is limiting the strength of acetaminophen in prescription combination drug products to 325 mg per capsule, tablet, or other dosage unit. Acetaminophen is an ingredient found in a wide range of non-prescription (OTC) and prescription (Rx) products. Prescription acetaminophen products are predominately found in combination with an opioid, such as codeine, oxycodone, or tramadol and generally indicated for the relief of moderate to moderately severe pain which may be accompanied by fever. Acetaminophen is considered safe when used as directed; however, if too much is taken or if it is taken for longer than recommended, it can cause liver damage, Acute Liver Failure (ALF), and in severe cases can be fatal. The risk of liver injury mainly comes from exceeding the maximum daily dose. Due to its widespread use, acetaminophen is a leading cause of serious liver injuries in Canada and in other countries including the United States, the United Kingdom and Australia.

Health Canada is taking additional steps to minimize the risk of liver damage and to improve the safe use of acetaminophen by consumers. This action follows the completion of a Health Canada review that assessed acetaminophen and liver injury in the Canadian context, a summary of which is available on Health Canada's website. The review found that the risk of overdose and liver injuries with acetaminophen was higher among users of prescription products combined with an opioid as compared to other combination or single ingredient acetaminophen products. There is an increased risk of acetaminophen-related liver injury with prescription acetaminophen products because of their tendency to be used for prolonged periods of time for chronic pain, together with other acetaminophen-containing products, or be misused/abused.

Effective immediately, Health Canada is asking drug sponsors to continue to limit the strength of acetaminophen to 325 mg per dosage unit in prescription combination drug products. This action is intended to protect the health and safety of Canadians by preventing higher strength products from entering the market and ensuring current prescription acetaminophen products remain safe for use as directed. Over-the-counter combination products containing acetaminophen, such as many cough and cold medications, are not currently affected by this action.

Health Canada is continuing to evaluate ways to reduce the risk of acetaminophen-related liver injury. Limiting the strength of acetaminophen in prescription combination products is just one way. Health Canada is also revising the label requirements for acetaminophen containing products to make these medications safer to use by including stronger warnings related to liver injury, a drug facts table, and plain language. These changes will help ensure that consumers can more easily identify products that contain acetaminophen and understand the risks of liver injury and use the products as directed. For further information related to this initiative, please refer to the following documents on the Health Canada website:

Health Canada taking new action to improve acetaminophen safety, reminds Canadians about safe use

Summary Safety Review - Acetaminophen Liver Injury

Questions regarding this notice should be directed to:
Bureau of Cardiology, Allergy and Neurological Sciences (BCANS)
Therapeutic Products Directorate
Health Products and Food Branch
Health Canada
1600 Scott Street, Tower B
2nd Floor, Address Locator 0202A1
Ottawa, Ontario
K1A 0K9

Fax: 613-941-1668
E-mail: bcans_enquiries@hc-sc.gc.ca