FDA Requires Boxed Warning for Tofacitinib

The U.S. Food and Drug Administration (FDA) has issued a Safety Announcement for the Janus kinase (JAK) inhibitor tofacitinib, after finding that patients taking a 10 mg twice-daily dose for the treatment of rheumatoid arthritis (RA) could be at a higher risk for pulmonary embolism (PE) and death. The label for tofacitinib, which is manufactured and marketed by Pfizer as Xeljanz and Xeljanz XR, now includes a boxed warning about these risks.

In February of this year, the FDA issued a safety announcement after a postmarketing trial of tofacitinib revealed an increased risk of PE and death at this dose level.

Tofacitinib is currently approved at a dose of 5 mg twice daily for the treatment of RA; the higher 10-mg twice-daily dose is approved for the treatment of patients with ulcerative colitis. While the increased risks of PE and death were seen in patients taking the higher dose for RA, the FDA is concerned that these risks may also apply to those taking tofacitinib for ulcerative colitis.

The boxed warning indicates that tofacitinib should be discontinued in patients with symptoms of thrombosis. Health care professionals are advised to monitor patients being treated with tofacitinib for the signs and symptoms of PE and report adverse effects involving tofacitinib to the FDA MedWatch program.

Sources: FDA Safety Announcement, July 26, 2019; The Wall Street Journal, July 26, 2019.