EMA Updates Advice on Risk of Blood Clots With Tofacitinib (Xeljanz)

Megan Brooks

October 31, 2019

Following a safety review, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) has concluded that tofacitinib (Xeljanz, Pfizer) could increase the risk of pulmonary embolism (PE) and deep vein thrombosis (DVT) in patients who are already at high risk.

Therefore, at its meeting held this week, the committee recommended that tofacitinib be used with caution in "all patients" at high risk risk for blood clots.

In addition, the maintenance doses of 10 mg twice daily should not be used in patients with ulcerative colitis who are at high risk unless there is no suitable alternative treatment, the committee said.

This new recommendation updates temporary restrictions placed on tofacitinib at the start of the PRAC review this past May. 

At that time, PRAC recommended that clinicians stop prescribing the 10 mg twice daily dose of tofacitinib for patients at high risk of PE, as reported by Medscape Medical News

The PRAC has also recommended that patients over age 65 years be treated with tofacitinib only when there is no alternative treatment.

The committee reviewed data from a study (A3921133) of patients with rheumatoid arthritis at increased risk of cardiovascular disease, which showed an increased risk of DVT and PE with both the 5 mg and 10 mg twice daily doses of tofacitinib as compared with patients taking tumor necrosis factor (TNF)-inhibitors.

The PRAC also reassessed additional data from earlier studies.

"All data combined showed that the risk of blood clots was higher in patients taking Xeljanz, especially with the 10 mg twice daily dose and in those being treated for an extended period. Results also showed a further increased risk of serious and fatal infections in patients older than 65 years of age," the EMA said in a statement.  The product information for tofacitinib will be updated with new warnings and recommendations based on data from the study and will list blood clots as an uncommon side effect occurring in between 1 in 1000 and 1 in 100 patients, the EMA said.

The PRAC has also recommended updating the physician's guide and the patient alert card with advice to minimize the risk of blood clots.

The US Food and Drug Administration (FDA) has also flagged the blood clot risk with tofacitinib. In July, as reported by Medscape Medical News, the agency added a boxed warning to the drug noting an increased risk of PE and death with the 10 mg twice-daily dose of the drug, which is used in patients with ulcerative colitis

The PRAC's updated recommendations will now be sent to the EMA's human medicines committee (CHMP), which will adopt the agency's final opinion.

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