Health Canada safety review finds link between the use of Xeljanz and Xeljanz XR (tofacitinib) and increased risk of serious heart-related issues and cancer

UPDATE - January 12, 2022: Safety Review found a link between the use of Xeljanz/Xeljanz XR (tofacitinib) and the risks of serious heart-related problems and cancer

Health Canada completed a safety review that confirmed a link between the use of Xeljanz/Xeljanz XR and the increased risks of serious heart-related problems and cancer, especially in older patients, patients who are current or past smokers, and patients with cardiovascular or cancer risk factors. Health Canada’s review also found that all patients treated with Xeljanz 10 mg twice daily had a higher risk of death, blood clots and serious infections, compared to patients treated with Xeljanz 5 mg twice daily or tumour necrosis factor inhibitors (TNFi).

As a result, Health Canada has worked with the manufacturer to update the product labels to further strengthen the warnings on the risks of serious heart-related problems and cancer. Healthcare professionals have been informed of these updates in order to advise their patients.

To ensure the benefits outweigh the risks in patients receiving Xeljanz/Xeljanz XR, the approved use for rheumatoid arthritis, an immune system disease that causes damage and inflammation of joints, is now limited to certain patients who are unable to use other drugs for this condition or when at least two different other drugs do not work. The higher dose of Xeljanz 10 mg twice daily is only authorized for patients with ulcerative colitis, a large intestine inflammation causing sores and bleeding, who have not responded well to other medications. For patients with ulcerative colitis, the prescribing information recommends that they use the lowest effective dose and for the shortest duration needed to help them improve their condition.

Health Canada has also initiated a new safety review of the potential risks of serious heart-related problems, cancer and blood clots with two other drugs of the same class as Xeljanz/Xeljanz XR (i.e. Olumiant and Rinvoq) that work similarly for the treatment of similar diseases.

Health Canada will continue to monitor safety information involving Xeljanz/Xeljanz XR, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should new health risks be identified.

What you should do:

• Talk to your healthcare professional about possible heart disease risk factors before you start taking Xeljanz/Xeljanz XR.
• Contact your healthcare professional right away and stop taking Xeljanz/Xeljanz XR if you develop signs and symptoms of a heart problem. Symptoms may include:
  • new or worsening chest pain;
  • shortness of breath;
  • irregular heartbeats; or
  • swelling of the legs.
• Talk to your healthcare professional before you take Xeljanz/Xeljanz XR if you have or had any type of cancer.
• Be aware that blood clots in the veins of your legs or arms (deep vein thrombosis, DVT), arteries (arterial thrombosis) or lungs (pulmonary embolism, PE) can happen in some people taking Xeljanz/Xeljanz XR. This may be life-threatening and cause death.
• Stop Xeljanz/Xeljanz XR and seek immediate medical help if you develop any signs or symptoms of a blood clot in your leg or arm (such as swelling, pain or tenderness in the leg or arm) or in your lung (such as sudden unexplained chest pain or shortness of breath). 
• Contact your healthcare professional if you have any signs or symptoms of an infection (such as fever, sweating, chills, cough, etc.). If a serious infection develops, stop taking XELJANZ/XELJANZ XR and contact your healthcare professional right away.

Patients should contact their healthcare professional for more details on this new safety information.

If you are a healthcare professional:

• Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with Xeljanz/Xeljanz XR, particularly in geriatric patients, in patients who are current or past smokers, those with other cardiovascular or malignancy risk factors, those who develop a malignancy, and those with a known malignancy other than a successfully treated non-melanoma skin cancer.
• Inform patients that Xeljanz/Xeljanz XR may increase their risk of major adverse cardiovascular events including non-fatal myocardial infarction. Instruct all patients, especially geriatric patients, current or past smokers, or patients with other cardiovascular risk factors, to be alert for signs and symptoms of cardiovascular events
• Inform patients that Xeljanz/Xeljanz XR may increase their risk of certain cancers, and that lung cancer, lymphoma and other cancers have been observed in patients taking Xeljanz. Instruct patients to inform their healthcare provider if they have ever had any type of cancer.
• Advise patients to stop taking Xeljanz/Xeljanz XR and to call their healthcare professional right away if they experience any symptoms of thrombosis (sudden shortness of breath, chest pain worsened with breathing, swelling of leg or arm, leg pain or tenderness, red or discoloured skin in the affected leg or arm).
• Avoid Xeljanz/Xeljanz XR in patients who may be at increased risk of thrombosis.
• Closely monitor patients for signs and symptoms of infection during and after treatment with Xeljanz/Xeljanz XR.
• Xeljanz/Xeljanz XR should be interrupted if a patient develops a serious infection, an opportunistic infection, or sepsis. If a patient develops a new infection during treatment with Xeljanz/Xeljanz XR, they should undergo prompt and complete diagnostic testing appropriate for an immunocompromised patient, and appropriate antimicrobial therapy should be initiated.
• Use Xeljanz 5 mg twice daily or Xeljanz XR 11 mg once daily for the treatment of rheumatoid arthritis, and Xeljanz 5 mg twice daily for the treatment of psoriatic arthritis. Health Canada has not authorized the sale of the higher dose of 10 mg twice daily for rheumatoid arthritis or psoriatic arthritis.
• In patients with ulcerative colitis, use Xeljanz at the lowest effective dose and for the shortest duration needed to achieve/maintain therapeutic response.
• Be aware that the indication for Xeljanz/Xeljanz XR in rheumatoid arthritis patients is now limited to certain patients who have not responded well to other medications.

To report a side effect to a health product to Health Canada:

• Call toll-free at 1-866-234-2345.
• Visit Health Canada's Web page on Adverse Reaction Reporting for information on how to report online, by mail or by fax.

April 6, 2021: Health Canada has initiated a safety review on Xeljanz and Xeljanz XR (tofacitinib), used to treat arthritis and ulcerative colitis

Health Canada is informing Canadians and health care professionals that it is conducting a safety review of Xeljanz and Xeljanz XR (tofacitinib) after a clinical trial identified an increased risk of serious heart-related issues and cancer in trial participants.

Xeljanz and Xeljanz XR (tofacitinib) is a prescription drug used to treat adults with moderate to severely active rheumatoid arthritis, active psoriatic arthritis, or moderate to severely active ulcerative colitis who have not responded well to other medications.

The clinical trial investigated the long-term safety of Xeljanz and Xeljanz XR (tofacitinib) at two doses (5 mg twice a day and 10 mg twice a day) in patients with rheumatoid arthritis, who are at least 50 years of age and have at least one cardiovascular risk factor. Pfizer, the manufacturer of the drug, conducted the trial in multiple countries, including Canada.

The current Canadian label includes serious warnings and precautions for cancer and information on heart attacks, which were the most frequently reported serious heart-related problems in this trial.

Health Canada has not authorized the sale of the higher dose of 10 mg twice a day for rheumatoid arthritis or psoriatic arthritis; this dose is only authorized for patients with ulcerative colitis who have not responded well to other medications. For patients with ulcerative colitis, the Canadian prescribing information recommends that they use the lowest effective dose possible to lower the risk of adverse reactions.

Previously, Health Canada had conducted a safety review of this drug after increased risks of blood clots in the lungs and death were discovered during a clinical trial. Following this safety review in 2019, Health Canada worked with Pfizer to update the Canadian labelling for Xeljanz and Xeljanz XR (tofacitinib) to include thrombosis as a warning, and informed Canadians and health care professionals of the findings.

Health Canada is working with Pfizer to evaluate the available safety information for Xeljanz and Xeljanz XR (tofacitinib) and will inform the public of any new safety findings, as needed, once the review is completed.

What you should do:

If you are a patient taking Xeljanz/Xeljanz XR (tofacitinib):

• Do not stop or change your dose of Xeljanz or Xeljanz XR (tofacitinib) without first talking to your health care professional.

If you are a health care professional:

• Consider the benefits and risks of Xeljanz and Xeljanz XR (tofacitinib) when deciding whether to prescribe or keep patients on the drug.
• Follow the recommendations in the Xeljanz and Xeljanz XR (tofacitinib) product monograph for the specific condition you are treating.
• Report health or safety concerns.

To report a side effect to a health product to Health Canada:

• Call toll-free at 1-866-234-2345.
• Visit Health Canada's Web page on Adverse Reaction Reporting for information on how to report online, by mail or by fax.