Xeljanz XR Side Effects: What to Expect and When to Call Your Doctor

Xeljanz XR (tofacitinib extended-release) is a JAK inhibitor that works by suppressing parts of the immune system to reduce inflammation. Like all immunosuppressive medications, it carries both common, manageable side effects and serious risks that require monitoring. Knowing what to watch for — and when to call your doctor — is essential for using Xeljanz XR safely.

Xeljanz XR Boxed Warnings: The Most Serious Risks

The FDA requires a Boxed Warning — the strongest warning the FDA issues — on Xeljanz XR's label. These warnings were updated in September 2021 based on post-marketing safety data. The four areas covered are:

Serious Infections: Tofacitinib can lower your immune system's ability to fight infections, including tuberculosis (TB), bacterial, fungal, and viral infections. Serious infections leading to hospitalization or death have been reported.

All-Cause Mortality: In a large post-marketing study (ORAL Surveillance), RA patients aged 50+ with at least one cardiovascular risk factor who took tofacitinib had a higher rate of death compared to those who took a TNF blocker.

Malignancy: Higher rates of lymphoma and lung cancer were observed with tofacitinib compared to TNF blockers in RA patients. Other cancers including breast cancer, melanoma, and prostate cancer have also been reported.

Thrombosis: Blood clots including pulmonary embolism (PE), deep vein thrombosis (DVT), and arterial thrombosis have been reported. Some cases were fatal.

Common Side Effects of Xeljanz XR

Most patients on Xeljanz XR experience some common side effects, particularly in the first months of treatment. These are generally manageable:

Upper respiratory tract infections (common cold symptoms, sinus congestion, cough)

Nasopharyngitis (runny nose, sore throat)

Headache

Diarrhea

Elevated cholesterol (both LDL and HDL typically rise; your doctor will monitor this)

High blood pressure (hypertension)

Nausea

Rash

Herpes zoster (shingles) — more common in patients on Xeljanz XR than in the general population

Serious Side Effects: Call Your Doctor Right Away

Contact your doctor or seek emergency care immediately if you experience:

Signs of serious infection: high fever, chills, unusual fatigue, shortness of breath, night sweats, persistent cough, painful skin sores, or burning with urination

Signs of blood clot: sudden leg pain, redness or swelling in a limb (DVT); or chest pain, difficulty breathing, racing heart (PE)

Signs of stroke or heart attack: sudden weakness on one side, slurred speech, chest pain radiating to the arm or jaw

Signs of cancer: unexplained weight loss, swollen lymph nodes, persistent fatigue, non-healing sores on skin

Severe allergic reaction: facial swelling, difficulty swallowing, hives — stop the medication and seek care immediately

Blood Test Monitoring Schedule

Because of these risks, your doctor will order blood tests on a regular schedule while you're on Xeljanz XR. Don't skip these — they are how problems are caught early:

CBC (complete blood count) — at baseline, 4–8 weeks after starting, then every 3 months

Lipid panel — at baseline and 4–8 weeks after starting

Liver function tests — at baseline and periodically

TB screening — before starting and during therapy

Special Precautions: Who Should Use Xeljanz XR with Extra Caution

Talk to your doctor about whether Xeljanz XR is right for you if you:

Are 50+ with cardiovascular risk factors (diabetes, smoking, high blood pressure, high cholesterol)

Are a current or former smoker (increased lung cancer risk)

Have a history of blood clots or are at high risk for thrombosis

Have had or currently have cancer (other than treated non-melanoma skin cancer)

Are pregnant or planning to become pregnant (tofacitinib may cause fetal harm)

For information about which other medications interact with Xeljanz XR, read our guide on Xeljanz XR drug interactions.

If you're having trouble finding Xeljanz XR at a pharmacy near you, medfinder can help.