Xeljanz should be used with caution in all patients at high risk of thrombus formation
The PRAC review concluded that Xeljanz (tofacitinib) may increase the risk of blood clots in the lungs and deep veins in patients who already have a high risk of thrombosis.
As a result of the review, PRAC recommends using Xeljanz with caution in patients at high risk of blood clots. In addition, maintenance doses of 10 mg 2 times daily should not be used in patients at high risk of ulcerative colitis without appropriate alternative treatment. Also, PRAC recommends that patients older than 65 years use Xeljanz only when there is no alternative treatment.
Patients at high risk of blood clot formation are those who have had a heart attack or have heart failure, cancer, inherited blood clotting disorders or a history of blood clots, as well as patients taking combined hormonal contraceptives, receiving hormone replacement therapy, who have undergone major surgery, or who are bedridden. Physicians should also consider other factors that may increase the risk of blood clot formation – age, obesity, diabetes, hypertension or smoking.
These recommendations are consistent with the PRAC review that was conducted during a study (study A3921133) in patients with rheumatoid arthritis and an increased risk of cardiovascular disease. This study showed an increased risk of blood clots in the deep veins and lungs with Xeljanz at doses of 5 mg and 10 mg 2 times daily compared with patients taking tumor necrosis factor inhibitors. PRAC also reviewed additional data from earlier studies. All pooled data showed that the risk of blood clots was higher in patients taking Xeljanz, especially at a dose of 10 mg 2 times daily and in those treated with the medicine for a long time. The results also showed a further increase in the risk of serious infections and fatal infections in patients older than 65 years.
The instructions for medical use of Xeljanz will be updated with new warnings and recommendations based on study data, namely the addition of information on thrombosis as an adverse reaction with a frequency of 1 from 1000 to 1 per 100 patients.
PRAC also recommends updating the physician guide and the patient alert card with advice to minimize the risk of blood clots. Patients who have questions about their treatment or the risk of blood clots should consult their doctor.
The new recommendations replace the measures taken at the start of the review in May 2019, when PRAC recommended that doctors stop prescribing the Xeljanz 10 mg 2 times daily dose to patients at high risk of pulmonary blood clots, while reviewing data from the A3921133 study. The PRAC recommendations will now be sent to the CHMP committee, which will make a decision.
More about the medicinal product
On 22 March 2017, Xeljanz (tofacitinib) was first authorized in the EU for the treatment of adults with moderate to severe rheumatoid arthritis. In 2018, the indications for Xeljanz were expanded, and the drug is indicated for the treatment of adults with psoriatic arthritis and severe ulcerative colitis.
The active substance in Xeljanz is tofacitinib, which blocks the action of enzymes known as Janus kinases. These enzymes play an important role in the inflammation process that occurs in rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. By blocking the action of the enzymes, tofacitinib helps reduce inflammation and other symptoms of these diseases.
More about the procedure
The review of Xeljanz was started on 15 May 2019 at the request of the European Commission (Article 20 of Regulation (EC) No. 726/2004). The review was carried out by the PRAC committee, which made a number of recommendations. The PRAC recommendations will now be sent to the CHMP committee, which will make a decision. The final stage of the review procedure is the adoption by the European Commission of a legally binding decision applicable in all EU Member States.
Link to the EMA press releasehttps://www.ema.europa.eu/en/documents/referral/xeljanz-article-20-procedure-xeljanz-be-used-caution-all-patients-high-risk-blood-clots_en.pdf
List of medicinal products Xeljanz (tofacitinib) approved for medical use in Ukraine (according to the State Register of Medicinal Products as of 05.11.2019)
