The US Food and Drug Administration (FDA) has added a boxed warning to tofacitinib (Xeljanz; Pfizer) noting an increased risk for pulmonary embolism (PE) and death with a dose of 10-mg twice-daily, which is used in patients with ulcerative colitis.
In addition, the agency has limited the use of tofacitinib for ulcerative colitis to patients who are not treated adequately or who experience severe adverse effects with other drugs.
The results from a postmarketing safety study of tofacitinib in patients with rheumatoid arthritis (RA) examined a lower dose as well as higher dose of the drug.
The study found an increased occurrence of blood clots and death in patients treated with tofacitinib 10 mg twice daily compared with patients treated with tofacitinib 5 mg twice daily or a tumour necrosis factor (TNF) blocker, reported the FDA in a safety communication posted on its website.
The 10-mg twice-daily dose of tofacitinib is only approved for ulcerative colitis for initial treatment and for long-term use in limited situations.
“While the increased risks of blood clots and of death were seen in patients taking this dose for rheumatoid arthritis (RA), these risks may also apply to those taking tofacitinib for ulcerative colitis,” the FDA warns.
The FDA recommends that clinicians take the following actions:
For ulcerative colitis, reserve tofacitinib as second-line therapy in patients who fail or do not tolerate TNF blockers; use the lowest effective dose and limit the use of the 10-mg twice-daily dose to the shortest duration needed.
The induction dose for ulcerative colitis is 10 mg twice daily for 8 weeks. Evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed, continue 10 mg twice daily for an additional 8 weeks or a maximum of 16 weeks. Discontinue 10 mg twice daily after 16 weeks if adequate therapeutic response is not achieved.
The maintenance dose is 5 mg twice daily. Use of 10 mg twice daily beyond induction should be limited to those with loss of response and used for the shortest duration, with careful consideration of the benefits and risks for the individual patient. Use the lowest effective dose needed to maintain response.
Discontinue tofacitinib and promptly evaluate patients with symptoms of thrombosis.
Counsel patients about the risks and advise them to seek medical attention immediately if they experience any unusual symptoms, including those of thrombosis. These include sudden shortness of breath, chest pain that worsens with breathing, swelling of a leg or arm, leg pain or tenderness, or red or discolored skin in the painful or swollen leg or arm.
Avoid the drug in patients who may have a higher risk for thrombosis.
The FDA encourages healthcare professionals and patients to report adverse events or side effects that occur while using tofacitinib to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.