What is tofacitinib?
Tofacitinib (brand name Xeljanz, also available as Xeljanz XR extended-release) is a medication used to treat rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and juvenile idiopathic arthritis. It was the first JAK inhibitor approved for rheumatoid arthritis (in 2012) and is taken as a pill by mouth — no injections needed.
How it works
Tofacitinib is a JAK1/JAK3 inhibitor. Like other JAK inhibitors, it is a small molecule that works inside the cell, blocking enzymes called Janus kinases that relay inflammatory signals. By inhibiting JAK1 and JAK3, tofacitinib reduces the activity of multiple inflammatory pathways that contribute to joint damage, skin disease, and gut inflammation.
How to take it
- Immediate-release (Xeljanz): 5 mg twice daily
- Extended-release (Xeljanz XR): 11 mg once daily
- Dosing may vary depending on your specific condition
Take the tablet with or without food. Swallow extended-release tablets whole — do not crush, split, or chew them.
What to expect when starting
Improvement typically begins within 2 to 4 weeks, with the full effect developing over 8 to 12 weeks. Some patients notice reduced stiffness and pain relatively quickly, while others require more time. Be patient and continue taking the medication as prescribed.
Side effects to watch for
Common side effects include:
- Upper respiratory infections and other infections
- Herpes zoster (shingles) reactivation — the Shingrix vaccine is strongly recommended before starting
- Elevated cholesterol
- Elevated liver enzymes
- Low blood counts (white blood cells, red blood cells, or platelets)
FDA Boxed Warning: Tofacitinib carries an FDA boxed warning based on the ORAL Surveillance study, which compared tofacitinib to TNF inhibitor biologics in RA patients over age 50 with at least one cardiovascular risk factor. This study found increased risks of:
- Major cardiovascular events (heart attack, stroke)
- Certain cancers (particularly lung cancer, especially in current or former smokers)
- Blood clots (deep vein thrombosis and pulmonary embolism)
This study is the reason all JAK inhibitors now carry a class-wide boxed warning.
Putting this in perspective: These increased risks were observed in a specific population — older patients with existing cardiovascular risk factors. For many patients, especially those who have not responded to other treatments, the benefits of tofacitinib outweigh the risks. Your rheumatologist has carefully considered your individual risk factors — including your age, cardiovascular health, smoking history, and cancer history — in deciding whether this medication is right for you. If you have questions or concerns, bring them up. An open conversation about your personal risk-benefit balance is important.
Required screening before starting
Your rheumatologist will order the following before treatment begins:
- Tuberculosis (TB) testing
- Hepatitis B and hepatitis C screening
- Complete blood count (CBC)
- Lipid panel (cholesterol levels)
- Liver function tests (LFTs)
- Shingrix vaccination — strongly recommended before starting if you have not already received it
Lab monitoring
Regular lab monitoring is required while on tofacitinib:
- 4 weeks after starting
- 8 weeks after starting
- Every 3 months thereafter
Labs typically include CBC, liver function, lipids, and kidney function. This schedule allows your rheumatologist to catch any changes early.
Things to avoid
- Live vaccines — should not be given while on tofacitinib
- Strong CYP3A4 inhibitors and strong CYP2C19 inhibitors — certain medications interact with tofacitinib. Always inform your rheumatologist and pharmacist about all medications you take, including over-the-counter drugs and supplements.
- Other biologics or JAK inhibitors — tofacitinib cannot be combined with biologic medications or other JAK inhibitors
- Pregnancy — tofacitinib is not safe during pregnancy and must be stopped before conception. Discuss family planning with your rheumatologist well in advance.
Frequently asked questions
Is this drug safe? The boxed warning sounds concerning. All medications have risks, and the boxed warning deserves a thoughtful discussion. Here is what is important to understand: the risks identified in the ORAL Surveillance study were concentrated in older patients (over 50) who already had cardiovascular risk factors such as smoking, high blood pressure, or diabetes. If you do not fit that profile, your personal risk may be quite different from the study population. Your rheumatologist prescribed this medication because, after weighing your individual risk factors, they believe the benefits outweigh the risks for you. If you remain concerned, ask your doctor to walk through your specific risk profile — that conversation is always worthwhile.
Why is the shingles vaccine so important? JAK inhibitors increase the risk of shingles (herpes zoster reactivation). The Shingrix vaccine is highly effective at preventing shingles and should ideally be completed before starting tofacitinib.
What is the difference between Xeljanz and Xeljanz XR? Xeljanz is taken twice daily, while Xeljanz XR (extended-release) is taken once daily. They contain the same active ingredient; the XR formulation simply releases the medication more slowly throughout the day.
Can I take this instead of a biologic injection? Yes. JAK inhibitors are an oral alternative to biologic injections. For many patients, the convenience of a daily pill is a significant advantage. Efficacy is comparable to many biologic medications.
What if I miss a dose? Take the missed dose as soon as you remember, unless it is almost time for your next dose. Do not double up. If you are on the twice-daily formulation and miss a dose, simply take the next one at the regular time.
How long will I need to take tofacitinib? Tofacitinib is typically a long-term medication. Your rheumatologist will periodically reassess whether it continues to be the best option for you.
This handout is for informational purposes only and does not replace the advice of your rheumatologist. Always discuss your specific medical situation, including all medications and health conditions, with your provider before starting or changing any treatment.