Upadacitinib may lower your ability to fight infections. This may make you more likely to get a serious (rarely fatal) infection or make any infection you have worse. The most common serious infections include pneumonia and skin infections. The risk for infections may be higher if you also take other drugs that suppress the immune system (such as methotrexate, corticosteroids). Tell your doctor right away if you have any signs of infection (such as a sore throat that doesn't go away, fever, chills, cough, non-healing skin sores, painful/frequent urination, white patches in your mouth or on your tongue).

You should have a tuberculosis (TB) skin test before and during treatment with this medication. Tell your doctor if you have been near someone with tuberculosis or have lived or traveled in areas where certain fungal infections (such as coccidioidomycosis, histoplasmosis) are common. These areas include the Ohio and Mississippi River valleys and the southwestern United States.

Though it is very unlikely to occur, there may be a risk of developing cancer (such as lymphoma, skin cancer, lung cancer) with this medication. Your risk may be higher if you are a current or past smoker. Protect your skin from the sun. Avoid prolonged sun exposure, tanning booths, and sunlamps. Use a sunscreen and wear protective clothing when outdoors. Tell your doctor right away if you develop symptoms such as fever or cough that doesn't go away, wheezing, unusual lumps/growths, unexplained weight loss, night sweats, change in appearance or size of moles, or unusual skin changes.

Upadacitinib may rarely cause serious (sometimes fatal) problems from blood clots (such as heart attack, stroke, blood clots in the lungs or legs). You may be at an increased risk for blood clots if you are a current or past smoker, or are 50 years of age or older and have at least one risk factor for heart disease. Discuss the risks and benefits of treatment with your doctor. Get medical help right away if you develop symptoms of blood clots, such as shortness of breath/rapid breathing, chest/jaw/left arm pain, unusual sweating, confusion, sudden dizziness/fainting, pain/swelling/warmth in the groin/calf, sudden/severe headaches, trouble speaking, weakness on one side of the body, or sudden vision changes.