The Food and Drug Administration (FDA) has recently modified the labeling of tofacitinib (Xeljanz, Xeljanz XR) to include a new boxed warning of an increased risk of thrombosis and death with the 10-mg twice-daily dose. The drug also carries boxed warnings for risk of serious infections, including tuberculosis, as well as for lymphoma and other malignancies.

Tofacitinib, a Janus kinase inhibitor that works by suppressing an overactive immune system, is approved for use in treating rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. The dose approved for these indications is 5 mg twice daily; 10 mg twice daily is only approved as an induction dose for ulcerative colitis. The FDA has revised the product's warnings based on interim safety data from an ongoing, required postmarketing trial evaluating the risk of heart-related events, cancer, and infections in patients with rheumatoid arthritis and at least one cardiovascular risk factor who were treated with either the 5-mg or the 10-mg twice-daily dose of tofacitinib compared with a tumor necrosis factor (TNF) blocker, also prescribed for rheumatoid arthritis.

In the clinical trial, patients who received tofacitinib 10 mg twice daily (but not 5 mg twice daily) were more likely than those receiving a TNF blocker to develop thrombosis, including pulmonary embolism, deep vein thrombosis, and arterial thrombosis (19 cases per 3,884 patient-years of follow-up versus three cases per 3,982 patient-years of follow-up), and to die from all causes (45 deaths per 3,884 patient-years of follow-up versus 25 cases per 3,982 patient-years of follow-up). Based on these interim findings, patients in the tofacitinib 10-mg twice-daily group were treated with 5 mg twice daily for the remainder of the trial. Although the increased risk of blood clots and death with tofacitinib 10 mg twice daily was seen in rheumatoid arthritis patients, it's likely that patients with ulcerative colitis will have a similarly increased risk.

NPs should make sure to prescribe the recommended dose of tofacitinib for the condition they are treating. For rheumatoid arthritis and psoriatic arthritis (that haven't been controlled by methotrexate), the dose is 5 mg twice daily. For ulcerative colitis, tofacitinib should be limited to patients who haven't responded to TNF blockers. The 10-mg twice-daily dose should be used only for induction and for the shortest duration needed to achieve a therapeutic effect, after which the patient should be switched to 5 mg twice daily. If an adequate therapeutic response is not achieved within 16 weeks of starting tofacitinib at the 10-mg twice-daily dose, the drug should be discontinued. The ongoing use of 10 mg twice daily may be considered in rare cases, but only after carefully weighing the benefits and risks for the individual patient. Clinicians should avoid prescribing tofacitinib if patients have risk factors predisposing them to thrombosis.

Nurses and NPs should assess patients taking tofacitinib for signs and symptoms of thrombosis and tell them to seek emergency medical help if they experience symptoms such as sudden shortness of breath, chest pain that worsens with breathing, swelling of an arm or leg, leg pain or tenderness, or red or discolored skin in the painful or swollen extremity. Patients should continue to be counseled on the risk of serious infections, lymphomas and malignancies, and hypersensitivity reactions with tofacitinib treatment.

The FDA encourages health care providers and patients to report any adverse effects of tofacitinib to the MedWatch program at http://www.fda.gov/safety/medwatch-fda-safety-information-and-adverse-event-repo.

To read the FDA Drug Safety Communication concerning tofacitinib, go to http://www.fda.gov/drugs/drug-safety-and-availability/fda-approves-boxed-warning.