FDA Warns of Risk for PE, Death With Higher Dose Tofacitinib (Xeljanz) for RA

Troy Brown, RN


February 25, 2019

The US Food and Drug Administration (FDA) is warning of an increased risk for pulmonary embolism and death in patients with rheumatoid arthritis who received tofacitinib (Xeljanz, Xeljanz XR, Pfizer) 10 mg twice daily in a postmarketing study.

"[T]his dose is only approved for patients with ulcerative colitis," according to an FDA safety alert.

The FDA approved tofacitinib for rheumatoid arthritis in 2012. As a condition of approval, the FDA required Pfizer to conduct a postmarketing safety trial to study the risk for heart-related events, cancer, and opportunistic infections with two doses of tofacitinib (10 mg twice daily and 5 mg twice daily) in combination with methotrexate compared with a tumor necrosis factor (TNF) inhibitor.

The study required patients to be aged 50 years or older and have one or more cardiovascular risk factor.

"During the most recent analysis of the trial, an external data safety monitoring committee found an increased occurrence of blood clots in the lungs and death in patients treated with tofacitinib 10 mg twice daily compared to patients treated with tofacitinib 5 mg twice daily or a TNF inhibitor," the FDA explains in the safety alert.

The FDA urges clinicians to prescribe tofacitinib according to the recommended doses for the condition being treated. Clinicians should watch patients for signs and symptoms of pulmonary embolism (PE) and instruct them to seek medical care immediately if they occur.

Warning Signs

Patients should not discontinue tofacitinib or change the dose before speaking with their healthcare provider, as these may make their condition worse. Patients taking tofacitinib should seek immediate medical attention if PE symptoms or other unusual symptoms occur, including:

  • Sudden difficulty breathing or shortness of breath,

  • Pain in chest or back,

  • Coughing up blood,

  • Severe sweating, or

  • Skin that is clammy or bluish-colored.

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. A report can be made by completing an online form  or by calling 1-800-332-1088.

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