FDA Requires Boxed Warning for Tofacitinib

The U.S. Food and Drug Administration (FDA) has issued a Safety Announcement requiring a boxed warning for the Janus kinase (JAK) inhibitor tofacitinib, indicating 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 warning comes just months after a safety trial found risks for PE and death in patients taking this dose as treatment for RA, prompting an FDA investigation.

The 10 mg twice daily dose of the immediate-release formulation of the drug, which is manufactured and marketed by Pfizer as Xeljanz (immediate-release) and Xeljanz XR (extended-release), is currently approved only for the treatment of patients with ulcerative colitis, but the FDA is concerned that the risks seen in patients with RA could also affect those being treated for ulcerative colitis.  The approved dose in RA is 5 mg twice daily for the immediate-release form and 11 mg once daily for the extended-release formulation.  This JAK inhibitor is not approved for hematological disease.

Tofacitinib should be discontinued in patients with evidence 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.