Summary Safety Review - Xeljanz and Xeljanz XR (tofacitinib) and Jakavi (ruxolitinib) - Janus Kinase (JAK) inhibitors - Assessing the Potential Risk of Blood Clots in the Deep Veins (Venous Thromboembolic Events)
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: 2020-06-18
Product
Xeljanz and Xeljanz XR (tofacitinib), and Jakavi (ruxolitinib) - Janus Kinase (JAK) inhibitors
Potential Safety Issue
Blood clots in the deep veins (venous thromboembolic events)
Overview
Use in Canada
- When other medicines do not work, Xeljanz (tofacitinib), is used to treat:
- an immune system disease causing damage and inflammation of the joints (rheumatoid arthritis);
- inflammation of the joints with red scaly patches on the skin (psoriatic arthritis); or
- large intestine inflammation causing sores and bleeding (ulcerative colitis).
- When other medicines do not work, Xeljanz XR (tofacitinib), is used to treat rheumatoid arthritis.
- Xeljanz (tofacitinib) has been marketed in Canada since 2014 and is currently available as 5 mg and 10 mg tablets. Xeljanz XR (tofacitinib) has been marketed in Canada since 2018 and is currently available as 11 mg extended-release tablets.
- Jakavi (ruxolitinib) is used to treat certain rare blood cancers such as primary myelofibrosis and polycythemia vera.
- Jakavi (ruxolitinib) has been marketed in Canada since 2012 and is currently available as 5 mg, 10 mg, 15 mg and 20 mg tablets.
- There were about 100,000 prescriptions for Xeljanz and 40,000 prescriptions for Jakavi dispensed in Canada from 2014 to 2019.
Safety Review Findings
- The safety review found that an ongoing safety study for Xeljanz (tofacitinib) showed an increased risk of blood clots in the lungs and death when the drug was taken at a high dose of 10 mg twice a day. This study is being conducted in patients 50 years of age or older with rheumatoid arthritis and at least one cardiovascular risk factor.
- Health Canada's assessment focused on 51 cases (8 Canadian and 43 international) of VTE in people taking Xeljanz/Xeljanz XR. Of the 51 cases, 38 were found to be possibly linked to Xeljanz/Xeljanz XR, 3 were not likely to be linked and 10 cases did not have enough information to be assessed. Among the 51 cases, there were 2 deaths possibly linked to the use of Xeljanz/Xeljanz XR (tofacitinib). The patients described in the case reports also had inflammatory diseases that may increase the risk of VTE.
- Health Canada also assessed 8 Canadian cases of VTE in patients taking Jakavi (ruxolitinib). Of the 8 cases, 3 cases showed a possible link to Jakavi. Among the 8 cases, there was one death, but the report did not contain enough information to link the death to the use of Jakavi. The patients described in the case reports also had blood disorders that may increase the risk of VTE.
- The information available from the published literature did not provide case reports or information that linked VTE with the use of Xeljanz/Xeljanz XR and/or Jakavi.
- The United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have included the risk of VTE in the product safety information for Xeljanz.
Conclusions and actions
- Health Canada's review has concluded that there is a link between the risk of VTE and the use of Xeljanz (tofacitinib). The review has concluded that Xeljanz/Xeljanz XR should be avoided in patients at increased risk of thrombosis and it should be discontinued in patients with signs of thrombosis. Xeljanz should be used at the lowest dose that works well and for the shortest duration in patients with ulcerative colitis.
- The product safety information for Xeljanz/ Xeljanz XR has been updated to include this new safety information.
- Health Canada published a Health Product Risk Communication1 to inform Canadians and healthcare professionals about the risk of thrombosis related to the use of Xeljanz/Xeljanz XR.
- Health Canada's review also found a possible link between Jakavi (ruxolitinib) and VTE. Health Canada will be working with the manufacturer to update the product safety information for Jakavi (ruxolitinib) to include the risk of VTE.
- Health Canada encourages consumers and health care professionals to report any side effects related to the use of these and other health products.
- Health Canada will continue to monitor safety information involving JAK inhibitors, 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 these drugs both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.