On Mar 20, 2019 the European Medical Agency (EMA) has issued advice to healthcare professionals and patients on the increased risk of blood clots in the lungs and death when exceeding dose of Xeljanz (tofacitinib) for treating rheumatoid arthritis then the recommended dose14. In the European Union (EU), 5 mg twice daily is the recommended dose for rheumatoid arthritis and psoriatic arthritis. The higher dose of 10 mg twice daily is approved for the initial treatment of patients with ulcerative colitis.

The advice follows early results from an ongoing, open-label clinical study (A3921133) evaluating the safety of tofacitinib 5 mg twice daily and tofacitinib 10 mg twice daily compared with a tumour necrosis factor (TNF) inhibitor in patients with rheumatoid arthritis. Patients in the study are 50 years of age or older with at least one additional cardiovascular risk factor. The preliminary results of the study showed the overall incidence of pulmonary embolism to be 5-fold higher in the tofacitinib 10 mg twice daily arm of the study compared with the TNF inhibitor arm, and approximately 3-fold higher than tofacitinib in other studies across the tofacitinib program.

While full results are awaited, EMA has published advice:

For patients:

  • If you are being treated with Xeljanz, you should not change the dose or stop taking the medicine without discussing it with your doctor.
  • You should seek medical attention immediately if you experience the sign and symptoms which of a blood clot in your lungs such as: difficulty breathing, chest pain or pain in your upper back, coughing up blood, excessive sweating and bluish skin.
  • If you have any concerns about your medicine, you should discuss them with a healthcare professional.

For healthcare professionals:

  • While further assessment of the study results continues, prescribers should continue to adhere to the authorised dose of 5 mg twice daily for the treatment of rheumatoid arthritis.
  • Patients receiving tofacitinib, irrespective of indication, should be monitored for the signs and symptoms of pulmonary embolism, and be advised to seek medical attention immediately if they experience them.

Moreover, a letter is also being sent to all healthcare professionals expected to prescribe the medicine to inform them of the preliminary results of the study and the current treatment recommendations.

About Xeljanz (tofacitinib)

Xeljanz is a prescription medicine called a Janus kinase (JAK) inhibitor indicated to treat adults with moderate to severe rheumatoid arthritis and psoriatic arthritis. In these indications, Xeljanz is used together with methotrexate after treatment with one or more medicines known as disease-modifying anti-rheumatic drugs (DMARDs) has not worked well enough or has led to troublesome side effects. In patients with rheumatoid arthritis, Xeljanz can also be used alone in patients who cannot take or are intolerant to methotrexate. Xeljanz is also authorised to treat adults with moderate to severe ulcerative colitis (a disease causing inflammation and ulcers in the lining of the gut), after treatment with other medicines has not worked well, has stopped working or has led to troublesome side effects.


 14 https://www.ema.europa.eu/en/news/increased-risk-blood-clots-lungs-death-higher-dose-xeljanz-tofacitinib-rheumatoid-arthritis

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