Drug Safety Alerts

Xeljanz® and Xeljanz XR Black Box Warning

07/26/2019

On July 26, 2019, the United States Food and Drug Administration (FDA) issued a Drug Safety Communication advising they have approved new warnings about an increased risk of blood clots and of death with the 10 mg twice daily dose of tofacitinib (Xeljanz®, Xeljanz XR), which is used in patients with ulcerative colitis. In addition, the approved use of tofacitinib (Xeljanz®, Xeljanz XR) for ulcerative colitis will be limited to certain patients who are not treated effectively or who experience severe side effects with certain other medicines. The FDA approved these changes, including adding the most prominent Boxed Warning, after reviewing interim data from an ongoing safety clinical trial of tofacitinib in patients with rheumatoid arthritis (RA) that examined a lower and this higher dose of the medicine.

Tofacitinib (Xeljanz®, Xeljanz XR) works by decreasing the activity of the immune system; an overactive immune system contributes to RA, psoriatic arthritis (PsA), and ulcerative colitis. Tofacitinib (Xeljanz®, Xeljanz XR) was first approved in 2012 to treat adult patients with RA who did not respond well to the medicine methotrexate. When the FDA first approved tofacitinib in 2012, FDA required a post-marketing clinical trial in patients with RA on background methotrexate, to evaluate the risk of heart-related events, cancer, and infections. The trial is studying two different doses of tofacitinib (Xeljanz®, Xeljanz XR) (5 mg twice daily, which is the currently approved dose for RA, and a higher, 10 mg twice daily dosage) in comparison to a TNF blocker. In RA, the body attacks its own joints, causing pain, swelling, and loss of function. An interim analysis of the trial’s results found an increased occurrence of blood clots and of death in patients treated with tofacitinib 10 mg twice daily compared to patients treated with tofacitinib (Xeljanz®, Xeljanz XR) 5 mg twice daily or a TNF blocker. In 2017, the FDA approved the medicine to treat patients with a second condition that causes joint pain and swelling, PsA, who did not respond well to methotrexate or other similar medicines. In 2018, the FDA approved tofacitinib (Xeljanz®, Xeljanz XR) to treat ulcerative colitis, which is a chronic, inflammatory disease affecting the colon.

The FDA recommends that patients should tell their health care professionals if they have a history of blood clots or heart problems, and talk to them about any questions or concerns. Patients should stop taking tofacitinib (Xeljanz®, Xeljanz XR) and seek emergency medical attention right away if they experience any unusual symptoms, including those that may signal a blood clot such as:

• 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

Patients should not stop taking tofacitinib (Xeljanz®, Xeljanz XR) without first talking their health care professional, as doing so can worsen their condition. The FDA also recommends that health care providers reserve tofacitinib (Xeljanz®, Xeljanz XR) to treat ulcerative colitis for patients who have failed or do not tolerate tumor necrosis factor (TNF) blockers.

The FDA has provided the following information for healthcare professionals:

• The FDA has approved new warnings about an increased risk of thrombosis and death in patients treated with the 10 mg twice daily dose of tofacitinib (Xeljanz®, Xeljanz XR).

• Tofacitinib (Xeljanz®, Xeljanz XR) 10 mg twice daily is not approved or recommended for the treatment of rheumatoid arthritis or psoriatic arthritis.

• For the treatment of ulcerative colitis, reserve tofacitinib (Xeljanz®, Xeljanz XR) as second-line therapy for use in patients who have failed or cannot tolerate TNF blockers.

• For ulcerative colitis, use tofacitinib (Xeljanz®, Xeljanz XR) at the lowest effective dose and for the shortest duration needed to achieve/maintain therapeutic response.

• The induction dose 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 (Xeljanz®, Xeljanz XR) and promptly evaluate patients with symptoms of thrombosis.

• Avoid tofacitinib (Xeljanz®, Xeljanz XR) in patients who may be at increased risk of thrombosis.

• Counsel patients to seek medical attention immediately if they experience unusual symptoms, including those of thrombosis.

• Encourage patients to read the Medication Guide they receive with each tofacitinib (Xeljanz®, Xeljanz XR) prescription, which explains the safety risks and provides other important information.

• To help the FDA track safety issues with medicines, report adverse events involving tofacitinib (Xeljanz®, Xeljanz XR) or other medicines to the FDA MedWatch program.

• Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA.

CVS Caremark^® Response:

Please note: These products are not carried by CVS Caremark^® Mail Service Pharmacies.

If you are currently prescribing tofacitinib (Xeljanz®, Xeljanz XR) and have questions regarding this notice, please call the FDA at 1‑888‑INFO‑FDA (1‑888‑463‑6332) or visit https://www.fda.gov.