Summary Safety Review - Dimethyl Fumarate - Assessing the Potential Risk of Gastrointestinal Events of Perforation, Ulceration, Hemorrhage and Obstruction

Dimethyl fumarate-containing products

Gastrointestinal events of perforation (hole in the wall of the gastrointestinal tract), ulceration (open sore on the lining of the gastrointestinal tract), hemorrhage (bleeding in the gastrointestinal tract) and obstruction (blockage of the gastrointestinal tract)

• Health Canada’s review found a possible link between the use of dimethyl fumarate and the risk of gastrointestinal events of perforation, ulceration, hemorrhage and obstruction.

• Health Canada will work with the manufacturers to update the product safety information in the Canadian product monograph (CPM) for all dimethyl fumarate-containing products to include the risk of gastrointestinal events of perforation, ulceration, hemorrhage and obstruction. Health Canada will also inform healthcare professionals about this update through a Health Product InfoWatch communication.

Health Canada reviewed the potential risk of gastrointestinal events of perforation, ulceration, hemorrhage and obstruction with the use of dimethyl fumarate. The safety review was triggered by a labelling update in the United States for all dimethyl fumarate-containing products.

• Dimethyl fumarate is a prescription drug authorized for sale in Canada for the treatment of adult patients with relapsing remitting multiple sclerosis. Dimethyl fumarate helps to reduce the number of relapses (flare-ups) and delay physical problems due to multiple sclerosis.

• Dimethyl fumarate has been marketed in Canada since 2013. It is currently available as 120 mg and 240 mg delayed-release capsules, under the brand name Tecfidera, and as generics.

• There were 279,470 prescriptions for dimethyl fumarate dispensed by Canadian retail pharmacies between 2019 and January 2025.

• Health Canada reviewed the available information provided by the manufacturer of Tecfidera, as well as from searches of the Canada Vigilance database^a, international databases and the scientific literature.

• At the time of the review, Health Canada had received 51 Canadian reports of gastrointestinal events of perforation, ulceration, hemorrhage or obstruction, in patients taking dimethyl fumarate. However, these cases did not meet the criteria for further assessment to determine if there was a link. This was due to incomplete information, the reported events not meeting the definition of perforation, ulceration, hemorrhage or obstruction, or the presence of confounders (other factors that may have contributed to the occurrence of gastrointestinal events), such as underlying medical conditions that are known to affect the gastrointestinal tract.

• Health Canada reviewed 22 international cases of gastrointestinal events of perforation, ulceration, hemorrhage or obstruction, in patients taking dimethyl fumarate, including 2 cases from the published literature.^1,2 Of the 22 cases, 18 cases (11 of hemorrhage unrelated to an ulcer, 4 of hemorrhage and ulcer, 2 of ulceration and 1 of ulcer perforation) were found to be possibly linked, 1 case of obstruction was unlikely to be linked, and 3 cases (2 of hemorrhage and 1 of ulcer perforation) were unassessable due to limited or conflicting clinical information. No deaths were reported.

• Health Canada also reviewed 3 articles published in the scientific literature, which included the 2 cases from the published literature mentioned above.^1-3 They supported a link between the use of dimethyl fumarate and the risk of gastrointestinal events of perforation, ulceration, hemorrhage and obstruction.

• Health Canada’s review found a possible link between the use of dimethyl fumarate and the risk of gastrointestinal events of perforation, ulceration, hemorrhage and obstruction.

• Health Canada will work with the manufacturers to update the CPM for all dimethyl fumarate-containing products to include the risk of gastrointestinal events of perforation, ulceration, hemorrhage and obstruction.

• Health Canada will also inform healthcare professionals about this update through a Health Product InfoWatch communication.

• Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of dimethyl fumarate, and other health products, to the Canada Vigilance Program.

• Health Canada will continue to monitor safety information involving dimethyl fumarate, 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 should new health risks be identified.

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 dimethyl fumarate both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.

1. Bajwa N.A., Bajwa A.A., Ghazala S., Masood U. Dimethyl Fumarate - Associated Enterocolitis. Am J Ther. 2024;31(4):e448 EP. Doi:10.1097/MJT.0000000000001660

2. Rinker J.R., Bashir K., Meador W., Dasher C.A. Atypical colitis as a possible delayed consequence of dimethyl fumarate for multiple sclerosis. Mult Scler. 2017;23:34 EP. doi:10.1177/1352458517693959

3. Kim T., Brinker A., Croteau D., et al. Severe gastrointestinal adverse reactions including perforation, ulceration, hemorrhage, and obstruction: A fumaric acid ester class new safety risk. Mult Scler J. 2025. doi:10.1177/13524585251316518

1. Canadian reports can be accessed through the Canada Vigilance Online Database.