Tofacitinib is a prescription medication called a janus kinase (JAK) inhibitor. It is a disease modifying anti-rheumatic drug (DMARD), which works by suppressing the immune system. Tofacitinib is available in the form of a tablet (Xeljanz), an extended release tablet (Xeljanz XR) and as an oral solution.

It is used to treat certain inflammatory conditions in people who have already tried tumor necrosis factor (TNF) blockers.

When tofacitinib was approved by the FDA in 2012, it was the first approved JAK inhibitor for the treatment of rheumatoid arthritis and also the first new oral DMARD to be approved for the condition in more than a decade.

What is tofacitinib used for?

• Tofacitinib tablets and tofacitinib XR are used to treat adults with moderately to severely active rheumatoid arthritis when 1 or more medicines called TNF blockers have been used and did not work well or cannot be tolerated.
• Tofacitinib tablets and tofacitinib XR are used to treat adults with active psoriatic arthritis when 1 or more TNF blocker medicines have been used, and did not work well or cannot be tolerated.
• Tofacitinib tablets and tofacitinib XR are used to treat adults with active ankylosing spondylitis when 1 or more TNF blocker medicines have been used and did not work well or cannot be tolerated.
• Tofacitinib tablets and tofacitinib XR are used to treat adults with moderately to severely active ulcerative colitis when 1 or more TNF blocker medicines have been used, and did not work well or cannot be tolerated.
• Tofacitinib tablets and oral solution is used to treat people 2 years of age and older with active polyarticular course juvenile arthritis when 1 or more TNF blocker medicines have been used, and did not work well or cannot be tolerated.

It is not known if tofacitinib tablets and tofacitinib XR are safe and effective in people with Hepatitis B or C.

Tofacitinib is not recommended for people with severe liver problems.

It is not known if tofacitinib tablets and oral solution are safe and effective in children for treatment other than active polyarticular course juvenile arthritis.

It is not known if tofacitinib XR is safe and effective in children.

Tofacitinib may cause serious side effects including:

1. Serious infections.

Tofacitinib is a medicine that affects your immune system. Tofacitinib can lower the ability of your immune system to fight infections. Some people can have serious infections while taking tofacitinib, including tuberculosis (TB), and infections caused by bacteria, fungi, or viruses that can spread throughout the body. Some people have died from these infections.

• Your healthcare provider should test you for TB before starting tofacitinib and during treatment.
• Your healthcare provider should monitor you closely for signs and symptoms of TB infection during treatment with tofacitinib.

You should not start taking tofacitinib if you have any kind of infection unless your healthcare provider tells you it is okay. You may be at a higher risk of developing shingles (herpes zoster).

People with ulcerative colitis taking the higher dose of tofacitinib (10 mg twice daily) or tofacitinib XR (22 mg one time each day) have a higher risk of serious infections and shingles.

Before starting tofacitinib, tell your healthcare provider if you:

• think you have an infection or have symptoms of an infection such as:
  • fever, sweating, or chills
  • cough
  • blood in phlegm
  • warm, red, or painful skin or sores on your body
  • burning when you urinate or urinating more often than normal
  • muscle aches
  • shortness of breath
  • weight loss
  • diarrhea or stomach pain
  • feeling very tired
• are being treated for an infection.
• get a lot of infections or have infections that keep coming back.
• have diabetes, chronic lung disease, HIV, or a weak immune system. People with these conditions have a higher chance for infections.
• have TB, or have been in close contact with someone with TB.
• live or have lived, or have traveled to certain parts of the country (such as the Ohio and Mississippi River valleys and the Southwest) where there is an increased chance for getting certain kinds of fungal infections (histoplasmosis, coccidioidomycosis, or blastomycosis). These infections may happen or become more severe if you take tofacitinib. Ask your healthcare provider if you do not know if you have lived in an area where these infections are common.
• have or have had hepatitis B or C.
  
  After starting tofacitinib, call your healthcare provider right away if you have any symptoms of an infection. tofacitinib can make you more likely to get infections or make worse any infection that you have.

2. Increased risk of death in people 50 years of age and older who have at least 1 heart disease (cardiovascular) risk factor and are taking tofacitinib 5 mg twice daily or tofacitinib 10 mg twice daily.

3. Cancer and immune system problems.

Tofacitinib may increase your risk of certain cancers by changing the way your immune system works.

• Lymphoma and other cancers including skin cancers can happen in people taking tofacitinib. People taking tofacitinib 5 mg twice daily or tofacitinib 10 mg twice daily have a higher risk of certain cancers including lymphoma and lung cancer, especially if you are a current or past smoker. People with ulcerative colitis taking the higher dose of tofacitinib (10 mg twice daily) or tofacitinib XR (22 mg one time each day) have a higher risk of skin cancers. Tell your healthcare provider if you have ever had any type of cancer.
• Some people who have taken tofacitinib with certain other medicines to prevent kidney transplant rejection have had a problem with certain white blood cells growing out of control (Epstein Barr Virus-associated post-transplant lymphoproliferative disorder).

4. Increased risk of major cardiovascular events such as heart attack, stroke or death in people 50 years of age and older who have at least 1 heart disease (cardiovascular) risk factor and are taking tofacitinib 5 mg twice daily or tofacitinib 10 mg twice daily, especially if you are a current or past smoker.

Get emergency help right away if you have any symptoms of a heart attack or stroke while taking tofacitinib, including:

• discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back
• severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw
• pain or discomfort in your arms, back, neck, jaw, or stomach
• shortness of breath with or without chest discomfort
• breaking out in a cold sweat
• nausea or vomiting
• feeling lightheaded
• weakness in one part or on one side of your body
• slurred speech

5. Blood clots in the lungs, veins of the legs or arms, and arteries. Blood clots in the lungs (pulmonary embolism, PE), veins of the legs (deep vein thrombosis, DVT) and arteries (arterial thrombosis) have happened more often in people who are 50 years of age and older and with at least 1 heart disease (cardiovascular) risk factor taking tofacitinib 5 mg twice daily or tofacitinib 10 mg twice daily. Blood clots in the lungs have also happened in people with ulcerative colitis. Some people have died from these blood clots.

• Stop taking tofacitinib and tell your healthcare provider right away if you develop signs and symptoms of a blood clot, such as sudden shortness of breath or difficulty breathing, chest pain, swelling of the leg or arm, leg pain or tenderness, or redness or discoloration in the leg or arm.

6. Tears (perforation) in the stomach or intestines.

• Tell your healthcare provider if you have had diverticulitis (inflammation in parts of the large intestine) or ulcers in your stomach or intestines. Some people taking tofacitinib can get tears in their stomach or intestines. This happens most often in people who also take nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or methotrexate.
  Tell your healthcare provider right away if you have fever and stomach-area pain that does not go away, and a change in your bowel habits.

7. Allergic reactions.

• Symptoms such as swelling of your lips, tongue, or throat, or hives (raised, red patches of skin that are often very itchy) that may mean you are having an allergic reaction have been seen in people taking tofacitinib and tofacitinib XR. Some of these reactions were serious. If any of these symptoms occur while you are taking tofacitinib, stop tofacitinib and call your healthcare provider right away.

8. Changes in certain laboratory test results. Your healthcare provider should do blood tests before you start taking tofacitinib and while you take tofacitinib to check for the following side effects:

• changes in lymphocyte counts. Lymphocytes are white blood cells that help the body fight off infections.
• low neutrophil counts. Neutrophils are white blood cells that help the body fight off infections.
• low red blood cell count. This may mean that you have anemia, which may make you feel weak and tired.

Your healthcare provider should routinely check certain liver tests.

You should not take tofacitinib if your lymphocyte count, neutrophil count, or red blood cell count is too low or your liver tests are too high.

Your healthcare provider may stop your tofacitinib treatment for a period of time if needed because of changes in these blood test results.

You may also have changes in other laboratory tests, such as your blood cholesterol levels. Your healthcare provider should do blood tests to check your cholesterol levels 4 to 8 weeks after you start taking tofacitinib, and as needed after that. Normal cholesterol levels are important to good heart health.

See "What are the side effect of tofacitinib?" below for more information about side effects.

Take tofacitinib exactly as your healthcare provider tells you to take it.

• Take tofacitinib tablets and oral solution 2 times a day with or without food.
• Take tofacitinib XR 1 time a day with or without food.
• Swallow tofacitinib XR whole and intact. Do not crush, split, or chew.
• When you take tofacitinib XR, you may see something in your stool that looks like a tablet. This is the empty shell from the tablet after the medicine has been absorbed by your body.
• For the treatment of psoriatic arthritis, take tofacitinib tablets and tofacitinib XR in combination with methotrexate, sulfasalazine or leflunomide as instructed by your healthcare provider.
• Tofacitinib XR should not be used instead of tofacitinib oral solution.

Administration Instructions

• Tofacitinib XR not interchangeable or substitutable with tofacitinib oral solution.
• Changes between tofacitinib tablets and tofacitinib XR should be made by the healthcare provider.
• Do not initiate tofacitinib if absolute lymphocyte count <500 cells/mm3, an absolute neutrophil count (ANC) <1000 cells/mm3 or hemoglobin <9 g/dL. (2.1)

Recommended Dosage

• Rheumatoid Arthritis
  • Tofacitinib 5 mg twice daily or tofacitinib XR11 mg once daily.
  • Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is tofacitinib 5 mg once daily.
• Psoriatic Arthritis (in combination with nonbiologic DMARDs)
  • Tofacitinib 5 mg twice daily or tofacitinib XR 11 mg once daily.
  • Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is tofacitinib 5 mg once daily.
• Ankylosing Spondylitis
  • tofacitinib 5 mg twice daily or tofacitinib XR 11 mg once daily.
  • Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is tofacitinib 5 mg once daily.
• Ulcerative Colitis
  • Induction: Tofacitinib 10 mg twice daily or tofacitinib XR 22 mg once daily for 8 weeks; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed, continue tofacitinib 10 mg twice daily or tofacitinib XR 22 mg once daily for a maximum of 16 weeks. Discontinue tofacitinib 10 mg twice daily or tofacitinib XR 22 mg once daily after 16 weeks if adequate therapeutic response is not achieved.
  • Maintenance: tofacitinib 5 mg twice daily or tofacitinib XR 11 mg once daily. For patients with loss of response during maintenance treatment, tofacitinib 10 mg twice daily or tofacitinib. XR 22 mg once daily may be considered and limited to the shortest duration, with careful consideration of the benefits and risks for the individual patient. Use the lowest effective dose needed to maintain response.
  • Dosage adjustment is needed in patients with moderate and severe renal impairment or moderate hepatic impairment: see full prescribing information.
• Polyarticular Course Juvenile Idiopathic Arthritis
  • Tofacitinib tablets or tofacitinib oral solution 5 mg twice daily or weight-based equivalent twice daily.
  • Dosage adjustment is needed in patients with moderate and severe renal impairment or moderate hepatic impairment: see full prescribing information.

Before taking tofacitinib, tell your healthcare provider about all of your medical conditions, including if you:

• have an infection. See "Important information" above.
• are a current or past smoker.
• have had any type of cancer.
• have had a heart attack, other heart problems or stroke.
• have had blood clots in the veins of your legs, arms, or lungs, or clots in the arteries in the past.
• have liver problems.
• have kidney problems.
• have any stomach area (abdominal) pain or been diagnosed with diverticulitis or ulcers in your stomach or intestines.
• have had a reaction to tofacitinib or any of the ingredients in tofacitinib.
• have recently received or are scheduled to receive a vaccine. People who take tofacitinib should not receive live vaccines. People taking tofacitinib can receive non-live vaccines.

If you take too much tofacitinib, call your healthcare provider or go to the nearest hospital emergency room right away.

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Discard any unused solution 60 days after opening the bottle.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

Unless your doctor tells you otherwise, continue your normal diet.

Tofacitinib may cause serious side effects, including:

• See "Important information" above.
• Hepatitis B or C activation infection in people who carry the virus in their blood. If you are a carrier of the hepatitis B or C virus (viruses that affect the liver), the virus may become active while you use tofacitinib. Your healthcare provider may do blood tests before you start treatment with tofacitinib and while you are taking tofacitinib. Tell your healthcare provider if you have any of the following symptoms of a possible hepatitis B or C infection:
  • feel very tired
  • little or no appetite
  • clay-colored bowel movements
  • chills
  • muscle aches
  • skin rash
  • skin or eyes look yellow
  • vomiting
  • fevers
  • stomach discomfort
  • dark urine

Common side effects of tofacitinib tablets and tofacitinib XR in people with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis include:

• upper respiratory tract infections (common cold, sinus infections)
• headache
• diarrhea
• nasal congestion, sore throat, and runny nose (nasopharyngitis)
• high blood pressure (hypertension)

Common side effects of tofacitinib tablets and tofacitinib XR in people with ulcerative colitis include:

• nasal congestion, sore throat, and runny nose (nasopharyngitis)
• increased cholesterol levels
• headache
• upper respiratory tract infections (common cold, sinus infections)
• increased muscle enzyme levels
• rash
• diarrhea
• shingles (herpes zoster)

Common side effects of tofacitinib tablets and tofacitinib oral solution in people with polyarticular course juvenile arthritis include:

• upper respiratory tract infections (common cold, sinus infections)
• nasal congestion, sore throat, and runny nose (nasopharyngitis)
• headache
• fever
• nausea
• vomiting

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of tofacitinib. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

You may also report side effects to Pfizer at 1-800-438-1985.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Tofacitinib and other medicines may affect each other causing side effects.

Especially tell your healthcare provider if you take:

• any other medicines to treat your rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis or polyarticular course juvenile arthritis. You should not take tocilizumab (Actemra), etanercept (Enbrel), adalimumab (Humira), infliximab (Remicade), rituximab (Rituxan), abatacept (Orencia), anakinra (Kineret), certolizumab (Cimzia), golimumab (Simponi), ustekinumab (Stelara), secukinumab (Cosentyx), vedolizumab (Entyvio), ixekizumab (Taltz), azathioprine, cyclosporine, or other immunosuppressive drugs while you are taking tofacitinib. Taking tofacitinib with these medicines may increase your risk of infection.
• medicines that affect the way certain liver enzymes work. Ask your healthcare provider if you are not sure if your medicine is one of these.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests before and during your treatment to check your body's response to tofacitinib.

If you are taking the extended-release tablets you may notice something that looks like a tablet in your bowel movement. This is just the empty tablet shell, and this does not mean that you did not get your full dose of medication.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.