FDA Adds Boxed Warning to Tofacitinib for Risks of Blood Clots, Death with Higher Dose

Officials with the FDA have added a Boxed Warning to Pfizer’s tofacitinib (Xeljanz, Xeljanz, XR) due to an increased risk of blood clots and death associated with higher doses of the medication, according to a drug safety communication.

The agency has also limited the approved use of tofacitinib for ulcerative colitis (UC) to patients who have failed or do not tolerate tumor necrosis factor (TNF) blockers or other medications.

Based on a review of clinical data from a safety trial, the FDA previously issued a warning pointing to safety issues with the 10-mg twice daily dosing regimen of tofacitinib in patients with rheumatoid arthritis (RA). The study demonstrated an increased risk of blood clots in the lungs and death associated with this dosing regimen, according to a press release.

Although approved for the treatment of UC, the 10-mg dosing regimen for tofacitinib is not approved for use in RA. However, these risks may also apply to those taking tofacitinib for UC, according to the FDA.

Tofacitinib, which was first approved in 2012 for RA and subsequently approved for additional indications in RA and psoriatic arthritis (PsA), works by decreasing the activity of the immune system. Since its initial approval, tofacitinib has been undergoing an ongoing postmarketing safety trial in patients with RA on background methotrexate. The trial is studying both 5-mg twice daily doses of tofacitinib and 10-mg twice daily doses in comparison with a TNF blocker.

According to the FDA, the interim results showed:

• Nineteen cases of blood clots in the lung out of 3884 patient-years of follow-up in patients who received tofacitinib 10-mg twice daily, compared with 3 cases out of 3982 patient-years in patients who received TNF blockers.
• Forty-five cases of death from all causes out of 3884 patient-years of follow-up in patients who received tofacitinib 10-mg twice daily, compared with 25 cases out of 3982 patient-years in patients who received TNF blockers.

Due to the risks, the FDA said that health care professionals should discontinue tofacitnib and promptly evaluate patients with symptoms of thrombosis.

If used in the treatment of UC, patients should only take the lowest effective dose and the 10-mg twice daily dose should be limited to the shortest duration needed, according to the FDA.

Reference

FDA approves Boxed Warning about increased risk of blood clots and death with higher dose of arthritis and ulcerative colitis medicine tofacitinib (Xeljanz, Xeljanz XR) [FDA Drug Safety Communication]. FDA. https://www.fda.gov/drugs/drug-safety-and-availability/fda-approves-boxed-warning-about-increased-risk-blood-clots-and-death-higher-dose-arthritis-and. Accessed July 26, 2019.