Summary Safety Review - Levetiracetam and Methotrexate - Assessing the Potential Risk of Drug-Drug Interaction
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: 2016-10-24
Product
Levetiracetam and methotrexate
Potential Safety Issue
Drug-drug interaction
Overview
Use in Canada
- Levetiracetam is a drug used to help epilepsy treatment be more effective. Levetiracetam is available in Canada as oral tablets. It has been marketed under the brand name Keppra since 2003. Generic versions are also available.
- Methotrexate is a drug used to treat cancer and also arthritis at a lower dose. Methotrexate is available in Canada as oral tablets and as an injectable liquid. It has been marketed since 1955 under various brand names and generic versions are also available.
- Given its potential serious side effects, methotrexate is used to treat life-threatening stages of cancers, and in patients with disease in the joints (arthritis) severe enough to cause disability, and when standard treatments have failed.
Safety Review Findings
- At the time of the review, there were no reported cases, in the Canada Vigilance Database, of patients who had received levetiracetam and methotrexate at the same time.
- The manufacturer of levetiracetam provided 13 international reports of a potential interaction between levetiracetam and methotrexate. The review of these reports was limited by many factors such as pre-existing diseases, other medications taken, and lack of laboratory data (e.g. blood levels of methotrexate).
- Of these 13 reports, 5 reports noted that patients who were taking both levetiracetam and methotrexate at the same time had greater amounts of methotrexate in their blood.
- Some of these 13 reports noted side effects to the kidneys when levetiracetam and methotrexate were taken together. Kidney damage and a sudden failure of the kidneys is a known potential side effect when taking methotrexate; this risk is mentioned in the product safety information.
Conclusions and actions
- Health Canada's safety review found that there is a potentially greater risk of side effects when levetiracetam and methotrexate are taken together.
- The assessment recommended that the product information for levetiracetam and methotrexate products be updated to inform about this drug interaction. Product labelling now recommends that blood methotrexate and levetiracetam levels should be carefully monitored in patients treated with the two drugs at the same time.
- Health Canada will continue to monitor side effect information involving levetiracetam and methotrexate, 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 if and when any new health risks are identified.
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.
References
- Bain E, Birhiray RE, Reeves DJ. Drug-drug interaction between methotrexate and levetiracetam resulting in delayed methotrexate elimination. Ann Pharmacother. 2014;48(2):292-6.