Xeljanz Side Effects at 10mg Dose Lead EMA To Place Restrictions on Use

Amid continuing concerns worldwide about the potential side effects of Xeljanz, European drug regulators have decided to place new restrictions on the rheumatoid arthritis drug while an investigation continues into the risk of potentially deadly blood clots, which may migrate to a patient’s lungs and cause a pulmonary embolism.

The European Medicines Agency (EMA) announced the new Xeljanz restrictions (PDF) across Europe on May 17, indicating that it’s safety committee, the PRAC, recommended doctors not prescribe Xeljanz’s in its 10 mg, twice-daily dose, to patients at high risk of pulmonary embolism.

“The new advice means that, since 10 mg is the only recommended starting dose for ulcerative colitis, patients with this condition who are at high risk of blood clots must not be started on Xeljanz,” the EMA warning states. “Patients at high risk currently taking this dose for any condition must be switched to alternative treatments.”

In the United States, Xeljanz (tofacitinib) was first by the FDA in 2012, to treat adults with rheumatoid arthritis, an autoimmune disorder that causes inflammation of the joints in approximately one percent of the population. The drug was designed to block the activity of certain enzymes in the body that affect immune system function and is commonly used as an alternative for patients who have tried methotrexate and other medications without success.

Use of the medication was expanded in December 2017, after the FDA authorized use of Xeljanz and Xeljanz XR for the treatment of active psoriatic arthritis (PsA), and then approval was expanded again in May 2018 to include treatment of moderate to severe active ulcerative colitis. Generally, it is given at the 5 mg per day dose to treat arthritis, and at 10 mg per day to treat ulcerative colitis.

After evaluating data from the Xeljanz clinical trial results, the drug manufacturer Pfizer announced in February that patients receiving 10mg doses of Xeljanz twice per day were found to have a significantly higher risk of experiencing pulmonary embolisms and had an overall higher rate of mortality when compared to patients taking 5mg doses of Xeljanz for ulcerative colitis.

Additional concerns raised in the clinical trial found patients taking Xeljanz were at an increased risk for developing serious infections including tuberculosis, invasive fungal infections and bacterial and viral infections that resulted in hospitalizations and deaths. Pfizer announced if a patients develops an infection while using Xeljanz, treatment should be interrupted until the infection is controlled.

The FDA issued a warning about Xeljanz pulmonary embolism that month. That was followed by a similar warning by the EMA in March.

The EMA indicates these latest restrictions are temporary and that these may change after it finishes reviewing all available evidence and updates guidance on Xeljanz use.