Tofacitinib has significant safety considerations. The current U.S. XELJANZ label contains a boxed warning covering serious infections, mortality, malignancy, major adverse cardiovascular events and thrombosis.
Serious infections
Tofacitinib can increase the risk of bacterial, fungal, viral and opportunistic infections, including tuberculosis. Treatment should not be initiated in certain circumstances involving active serious infection, and patients require appropriate TB evaluation.
Cardiovascular risk
The current U.S. boxed warning reports a higher rate of all-cause mortality and major adverse cardiovascular events compared with TNF blockers in the studied rheumatoid arthritis population.
Thrombosis
Pulmonary embolism, venous thrombosis and arterial thrombosis have occurred. The risk is particularly important when evaluating patients with underlying cardiovascular or thrombotic risk factors.
EMA has also required risk-minimization measures for JAK inhibitors, including caution in patients at increased risk of cardiovascular disease, cancer and thrombosis and additional restrictions in some higher-risk populations.
Malignancy
Malignancies have occurred during tofacitinib treatment. The U.S. label reports higher rates of lymphoma and lung cancer compared with TNF blockers in rheumatoid arthritis patients in the relevant safety study.
Gastrointestinal perforation
New abdominal symptoms in patients at increased risk should be evaluated promptly because gastrointestinal perforation has been reported.
Laboratory monitoring
Tofacitinib can affect lymphocytes, neutrophils, hemoglobin, liver enzymes and lipid levels. Laboratory monitoring is therefore part of safe treatment.
Vaccination
Live vaccines should be avoided during treatment according to the current U.S. label. Vaccination status should be reviewed before treatment begins.
Diabetes and hypoglycemia
The June 2026 U.S. label includes a warning concerning hypoglycemia in patients with diabetes and recommends considering increased glucose monitoring.
Pregnancy and lactation
Pregnancy and reproductive considerations should be discussed with a healthcare professional. Current U.S. labeling advises against breastfeeding during treatment.