Serious Warnings and Precautions
SERIOUS INFECTIONS
Patients treated with XELJANZ/XELJANZ XR (tofacitinib) are at increased risk for developing serious infections that may lead to hospitalization or death (see 7 WARNINGS AND PRECAUTIONS and 8.2 Clinical Trial Adverse Reactions). Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.
If a serious infection develops, interrupt XELJANZ/XELJANZ XR until the infection is controlled.
Reported infections include:
- Active tuberculosis, which may present with pulmonary or extrapulmonary disease. Patients should be tested for latent tuberculosis before XELJANZ/XELJANZ XR use and during therapy. Treatment for latent infection should be initiated prior to XELJANZ/XELJANZ XR use.
- Invasive fungal infections, including cryptococcosis and pneumocystosis. Patients with invasive fungal infections may present with disseminated, rather than localized disease.
- Bacterial, viral, and other infections due to opportunistic pathogens.
Treatment with XELJANZ/XELJANZ XR should not be initiated in patients with active infections including chronic or localized infection.
Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with XELJANZ/XELJANZ XR, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy (see 8 ADVERSE REACTIONS).
MALIGNANCIES
Lymphoma and other malignancies have been observed in patients treated with XELJANZ. Epstein Barr Virus-associated post-transplant lymphoproliferative disorder has been observed at an increased rate in renal transplant patients treated with XELJANZ and concomitant immunosuppressive medications. An increase in malignancies, including lung cancer, were observed in rheumatoid arthritis patients 50 years or older with at least one additional cardiovascular (CV) risk factor who were taking tofacitinib compared with TNF inhibitors (see 8.2 Clinical Trial Adverse Reactions). Caution should be applied when using XELJANZ/XELJANZ XR in geriatric patients, patients who are current or past smokers, and patients with other malignancy risk factors (see 7 WARNINGS AND PRECAUTIONS).
THROMBOSIS
Rheumatoid arthritis patients with at least one CV risk factor had a higher rate of all-cause mortality and thrombosis, including pulmonary embolism, deep venous thrombosis, and arterial thrombosis, with XELJANZ 10 mg twice daily (BID) compared to those treated with 5 mg BID or TNF blockers. Many of these adverse events were serious and some resulted in death. Avoid XELJANZ/XELJANZ XR in patients at risk of thrombosis. Discontinue XELJANZ/XELJANZ XR and promptly evaluate patients with symptoms of thrombosis (see 7 WARNINGS AND PRECAUTIONS).
For patients with ulcerative colitis (UC), use XELJANZ at the lowest effective dose and for the shortest duration needed to achieve/maintain therapeutic response (see 4 DOSAGE AND ADMINISTRATION).
MAJOR ADVERSE CARDIOVASCULAR EVENTS
Major adverse cardiovascular events, including non-fatal myocardial infarction, were observed more frequently with tofacitinib compared to TNF inhibitors in rheumatoid arthritis patients who were 50 years or older with at least one additional CV risk factor (see 8.2 Clinical Trial Adverse Reactions). Caution should be applied when using XELJANZ/XELJANZ XR in geriatric patients, patients who are current or past smokers, and patients with other CV risk factors (see 7 WARNINGS AND PRECAUTIONS).