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Xeljanz Black Box Warning

People taking Xeljanz or Xeljanz XR for rheumatoid arthritis should discuss the Food and Drug Administration's JAK inhibitor black box warning with their doctors. The warning is for a possible increased risk of blood clots, cancer or severe infections that may lead to hospitalization or even death.

Last Modified: October 10, 2023
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What Is the Black Box Warning for Xeljanz?

Xeljanz, the brand name of the generic drug tofacitinib, has a boxed warning advising patients of the link between Xeljanz and blood clots, cancer and serious infections. Boxed warnings – formerly called black box warnings – are the highest safety-related warning that the U.S. Food and Drug Administration assigns. The intent is to bring the public’s attention to the major risks of the drug.

Xeljanz Warning Key Facts
  • Final Xeljanz trial results in September 2021 revealed higher incidences of serious heart-related events, cancer, blood clots and death with lower doses 5mg or 10 mg doses vs. another medication.
  • The FDA added a boxed warning in July 2019 about increased risk of blood clots and death with 10 mg twice-daily tofacitinib for ulcerative colitis.
  • Approval of continued use of Xeljanz for UC was limited in 2019 to patients with severe side effects from or lack of positive results with certain other medications.

The FDA’s revised boxed warning for Xeljanz and Xeljanz XR stated health care professionals should carefully weigh the risks and benefits of the drug before initiating or renewing prescriptions for their patients. This is especially the case for patients who are current or past smokers, have cardiovascular risk factors or have a history of cancer. The FDA limited approval to patients who have not responded well to, or cannot tolerate, TNF blockers.

Why Is There a Boxed Warning for Xeljanz?

The boxed warning for Xeljanz was issued because of an increased risk of serious and potentially life-threatening side effects associated with the medication. The warnings include cardiac complications, cancer and potentially fatal blood clots.

FDA Warnings Highlight Risks
  • Blood Clots and Death: The boxed warning notes an increased risk of blood clots and death, especially at the 10 mg twice- daily dosage used in patients with ulcerative colitis.
  • Cancer Risk: Patients taking Xeljanz may have a higher risk of developing certain cancers, including lymphomas. In particular, doctors observed a higher rate of lymphomas in patients treated with Xeljanz compared to those treated with other medications for rheumatoid arthritis.
  • Cardiac Events: Xeljanz has been associated with an increased risk of serious heart-related events, including heart attack and stroke.

The boxed warning serves to alert healthcare professionals and patients about these potential risks so that they can make informed decisions about the use of Xeljanz and closely monitor patients for any signs of adverse Xeljanz side effects. It emphasizes the importance of weighing the benefits of Xeljanz treatment against the risks, particularly in patients with certain risk factors or medical conditions.

Xeljanz Heart Attack Warning

Studies have shown an increased risk of serious heart-related events, including heart attack, with the use of Xeljanz. An FDA_mandated post-marketing safety clinical trial identified this risk after the initial approval of Xeljanz.

A 2023 study compared the risk of major adverse cardiovascular events between two medications, tofacitinib and tumor necrosis factor inhibitors. Events like heart attacks and sudden cardiac death were higher in patients taking tofacitinib, specifically in those with a history of heart disease. For patients without a history of heart disease but with other cardiovascular risk factors, the risk from tofacitinib and TNFi appeared similar.

The trial evaluated the safety of Xeljanz in patients with rheumatoid arthritis who were taking methotrexate along with Xeljanz. The trial studied two doses of Xeljanz, 5 mg twice daily (the approved dosage for RA) and a higher 10 mg twice daily dosage, compared to a TNF blocker also used to treat RA.

The results of the trial indicated a higher rate of serious heart-related events, such as heart attacks and strokes, in patients treated with both doses of Xeljanz compared to those treated with TNF blockers. An increased risk of heart attacks was observed in both doses of Xeljanz, not just the higher dosage, as previously identified in interim results.

Cancer Warning

The FDA issued warnings regarding the cancer risk associated with tofacitinib. It found an increased risk of cancer, including lymphomas, in patients taking Xeljanz compared to those treated with TNFi for rheumatoid arthritis. Cancers named in Xeljanz lawsuits include breast, colon, lung, non-Hodgkin’s lymphoma and prostate cancer.

Findings presented at the British Society for Rheumatology showed that Janus kinase inhibitors like Xeljanz increase the risk of cancer as compared to TNFi drugs. This was not the case, however, when compared to placebo or methotrexate.

Cancer incidence was highest in patients with a history of atherosclerotic cardiovascular disease or increasing cardiovascular risk. This may be because of shared risk factors for cardiovascular risk and cancer.

Xeljanz Blood Clot Warning

The FDA issued a boxed warning in 2019 for Xeljanz because of an increased risk of blood clots and death found in a safety clinical trial. The trial revealed that patients 50 or older with rheumatoid arthritis and at least one cardiovascular risk factor who took the higher dose of Xeljanz, 10 mg twice daily, had a higher incidence of blood clots in the lungs and death.

The warning also applied to Xeljanz use in ulcerative colitis patients, although the 10 mg twice daily dose was only approved for limited situations in this condition. The FDA communicated these findings to the public in February 2019. Later in July 2019 the agency added the boxed warning to the drug’s label. Pfizer, the manufacturer, had previously not included a warning about the blood clot risk in its Xeljanz label.

Studies have searched for a biomarker that explains the increased risk of venous thromboembolism in patients with rheumatoid arthritis who receive tofacitinib or TNFi medications. Results have been inconclusive so far.

Xeljanz Serious Infections Warning

Xeljanz carries a significant risk of serious infections. Some infections have been severe enough to require hospitalization and have even been fatal. The conclusions of one study suggests these findings should inform the treatment decisions of health care providers.

Clinical trials showed a higher incidence of serious infections in patients who took Xeljanz compared to those on a placebo. Pneumonia, cellulitis and urinary tract infections were the most common.

The boxed warning for Xeljanz highlights the reported infections, which include tuberculosis, bacterial, viral (e.g., herpes zoster) and fungal (e.g., cryptococcosis, pneumocystis) infections. A study conducted in August 2022 revealed a higher risk of infection with Xeljanz compared to TNFis.

The most predictive risk factors for serious infection events include age, baseline opioid use, a history of chronic lung disease and use of corticosteroids. Research found the risk of infection increases with higher doses of the drug. Infection risk is especially high when Xeljanz is used in combination with other immunosuppressant medications like methotrexate or corticosteroids.

What Do I Do If I Experience Xeljanz Complications?

If you experience any Xeljanz side effects, speak to your doctor or seek immediate medical attention. Keep all medical records in relation to your condition.

You may be eligible to file a Xeljanz lawsuit if you or a loved one took the drug for rheumatoid arthritis, ulcerative colitis or psoriatic arthritis and suffered blood clots, cardiovascular problems such as a heart attack or cancer. You may be entitled to damages for your injuries.

Contact an expert attorney in the field of Xeljanz lawsuits. Suing a large pharmaceutical company is a complex matter requiring an experienced attorney.

Are There Xeljanz Alternatives?

Patients concerned about medication complications can discuss Xeljanz alternatives with their doctors. Alternatives can include other medications, lifestyle changes and physical therapy.

Treatments for rheumatoid arthritis aim to reduce joint inflammation, relieve pain, slow down joint damage and improve overall function. Although there is no cure, early treatment can limit its impact and reduce the risk of joint damage.

Xeljanz Alternatives
  • Assistive Devices: Adaptations or assistive devices can reduce joint stress during daily activities.
  • Biologics: Biological treatments target specific immune responses and inflammatory molecules.
  • Corticosteroids: Drugs like prednisone, provide short-term relief of inflammation and pain.
  • Diet: A balanced and nutritious diet can help support joint health.
  • DMARDs: Disease-modifying anti-rheumatic drugs such as methotrexate, leflunomide, hydroxychloroquine and sulfasalazine slow down disease progression and reduce inflammation.
  • Exercise: Regular exercise can improve joint flexibility, muscle strength and overall function.
  • NSAIDs: Nonsteroidal anti-inflammatory drugs alleviate pain and reduce inflammation.
  • Occupational Therapy: Strategies for daily living and workplace adaptations can be developed in occupational therapy..
  • Physical Therapy: Joint function and mobility can be improved with physical therapy.
  • Rest: Rest and pacing activities to manage fatigue and avoid overuse of affected joints.

In severe cases, surgery for joint replacement may be necessary. If you have a diagnosis of rheumatoid arthritis, it’s a good idea to work closely with your healthcare team to develop a comprehensive treatment plan that addresses your unique needs and maximizes symptom relief and disease management.

Please seek the advice of a medical professional before making health care decisions.