FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots and death from Janus Kinase inhibitors

Sept. 3, 2021

The U.S. Food and Drug Administration is requiring revisions to the Boxed Warning, FDA’s most prominent warning, for Xeljanz/Xeljanz XR (tofacitinib), Olumiant (baricitinib) and Rinvoq (upadacitinib) to include information about the risks of serious heart-related events, cancer, blood clots and death.

Based on the review of a large randomized safety clinical trial, the FDA has concluded there is an increased risk of serious heart-related events such as heart attack or stroke, cancer, blood clots and death with the arthritis and ulcerative colitis medicines Xeljanz and Xeljanz XR. 

This trial compared Xeljanz with another type of medicine used to treat arthritis called tumor necrosis factor (TNF) blockers in patients with rheumatoid arthritis. The trial’s final results also showed an increased risk of blood clots and death with the lower dose of Xeljanz.

The FDA is requiring new and updated warnings for two other arthritis medicines in the same drug class as Xeljanz, called JAK inhibitors, Olumiant and Rinvoq. Olumiant and Rinvoq have not been studied in trials similar to the large safety clinical trial with Xeljanz, so the risks have not been adequately evaluated. However, since they share mechanisms of action with Xeljanz, FDA considers that these medicines may have similar risks as seen in the Xeljanz safety trial.

Two other JAK inhibitors, Jakafi (ruxolitinib) and Inrebic (fedratinib), are not indicated for the treatment of arthritis and other inflammatory conditions and so are not a part of the updates being required to the prescribing information for Xeljanz, Xeljanz XR, Olumiant, and Rinvoq.

FDA warning release