On Friday July 26, 2019, the US FDA updated the XELJANZ full prescribing information and posted a statement. Pfizer also issued a media statement announcing that the U.S. full prescribing information for XELJANZ^® (tofacitinib)/XELJANZ XR has been updated based on the U.S. Food and Drug Administration’s (FDA) review of data from an ongoing post-marketing safety study.

As a result of this review, two additional warnings for Mortality and Thrombosis were included in the Boxed Warning and related Warnings and Precautions section of the prescribing information and in the Most Important Information I Should Know section of the patient Medication Guide for XELJANZ/​XELJANZ XR. Additionally, changes to the ulcerative colitis (UC) approved use and recommended dosing were made.

The new Boxed Warning information regarding Mortality discusses the increased risk of death in people 50 years of age and older with rheumatoid arthritis who have at least 1 heart disease (cardiovascular) risk factor and who are taking a higher than recommended dose of XELJANZ/​XELJANZ XR. The FDA recommended dose in adult patients with rheumatoid arthritis or psoriatic arthritis is XELJANZ 5 mg twice daily or XELJANZ XR 11 mg one time each day.

The new Boxed Warning information regarding Thrombosis includes information on the risk of blood clots. 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 patients with rheumatoid arthritis who are 50 years of age and older and with at least 1 heart disease (cardiovascular) risk factor taking a higher than recommended dose of XELJANZ/​XELJANZ XR. Blood clots in the lungs have also happened in patients with ulcerative colitis. Some people have died from these blood clots.

Patients should stop taking XELJANZ/​XELJANZ XR and seek medical attention immediately if they experience any signs or symptoms of a blood clot such as:

• Sudden shortness of breath or difficulty breathing
• Chest pain
• Swelling, pain, or tenderness in leg or arm
• Redness or discoloration in leg or arm

Patients should tell their healthcare provider if they have had blood clots in the veins of their legs, arms, or lungs, or clots in arteries in the past.

Patients should always ask their doctors for medical advice about adverse events. You are encouraged to report adverse events related to Pfizer products by calling 1-800-438-1985 (U.S. only). If you prefer, you may contact the U.S. Food and Drug Administration (FDA) directly. Visit http://www.fda.gov/MedWatch or call 1-800-FDA-1088.

The FDA approved use of XELJANZ for adults with moderately to severely active ulcerative colitis (UC) now recommends use after medicines called tumor necrosis factor (TNF) blockers did not work well or cannot be tolerated. Healthcare providers are advised to use the lowest effective dose to maintain response in patients with UC.

If you have any questions about these updates talk to your healthcare provider.

The updated Important Safety Information and Indications for XELJANZ/​XELJANZ XR are included on the following pages for your review.

It is also important to read the patient Medication Guide you receive with your XELJANZ/​XELJANZ XR prescriptions, which explains the important things you need to know about the medicine. These include side effects, what the medicine is used for, how to take and store it properly, and other things to watch for when you’re taking the medicine.

Information about Ongoing Post-Marketing Safety Study

This safety study is being conducted in patients 50 years of age and older with rheumatoid arthritis (RA) with at least one heart disease (cardiovascular) risk factor to evaluate the risk of heart-related events and cancer using XELJANZ at two doses (10 mg twice daily and 5 mg twice daily) in combination with methotrexate in comparison to another drug called a tumor necrosis factor (TNF) inhibitor in combination with methotrexate. The FDA recommended dose in adult patients with rheumatoid arthritis or psoriatic arthritis is XELJANZ 5 mg twice daily or XELJANZ XR 11 mg one time each day. XELJANZ/​XELJANZ XR 10 mg twice daily is not approved for adult patients with rheumatoid arthritis or psoriatic arthritis.

IMPORTANT SAFETY INFORMATION

XELJANZ/​XELJANZ XR may cause serious side effects, including:

Serious infections. XELJANZ/​XELJANZ XR can lower the ability of your immune system to fight infections. Some people can have serious infections while taking XELJANZ/​XELJANZ XR, 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 and during XELJANZ/​XELJANZ XR treatment, and monitor you closely for signs and symptoms of TB infection during treatment.

You should not start taking XELJANZ/​XELJANZ XR 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 taking the higher dose (10 mg twice daily) of XELJANZ have a higher risk of serious infections and shingles.

Before starting XELJANZ/​XELJANZ XR, 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; or 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 use XELJANZ/​XELJANZ XR. 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 XELJANZ/​XELJANZ XR, call your healthcare provider right away if you have any symptoms of an infection. XELJANZ/​XELJANZ XR can make you more likely to get infections or make worse any infection that you have.

Increased risk of death in people 50 years of age and older with rheumatoid arthritis who have at least 1 heart disease (cardiovascular) risk factor and who are taking a higher than recommended dose of XELJANZ/​XELJANZ XR. The recommended dose in patients with rheumatoid arthritis and psoriatic arthritis is XELJANZ 5 mg twice daily or XELJANZ XR 11 mg one time each day.

Cancer and immune system problems. XELJANZ/​XELJANZ XR 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 patients taking XELJANZ/​XELJANZ XR. People taking the higher dose (10 mg twice daily) of XELJANZ 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 XELJANZ 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).

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 patients with rheumatoid arthritis who are 50 years of age and older and with at least 1 heart disease (cardiovascular) risk factor taking a higher than recommended dose of XELJANZ/​XELJANZ XR.  The recommended dose in patients with rheumatoid arthritis and psoriatic arthritis is XELJANZ 5 mg twice daily or XELJANZ XR 11 mg one time each day. Blood clots in the lungs have also happened in patients with ulcerative colitis.  Some people have died from these blood clots.

• Stop taking XELJANZ/​ XELJANZ XR and tell your healthcare provider right away if you have any signs and symptoms of a blood clot such as sudden shortness of breath, difficulty breathing, chest pain, swelling of a leg or arm, leg pain or tenderness, or red or discolored skin in the leg or arm

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 XELJANZ/​XELJANZ XR can get tears in their stomach or intestine. 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.

Serious allergic reactions have happened in patients taking XELJANZ/​XELJANZ XR.  If you have swelling of your lips, tongue, throat, or get hives, stop XELJANZ/​XELJANZ XR and call your healthcare provider right away.

Changes in certain lab test results. Your healthcare provider should do blood tests before you start receiving XELJANZ/​XELJANZ XR, and while you take XELJANZ/​XELJANZ XR, 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 receive XELJANZ/​XELJANZ XR 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 XELJANZ/​XELJANZ XR 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 XELJANZ/​XELJANZ XR, and as needed after that.

What should I tell my healthcare provider before taking XELJANZ/​XELJANZ XR?

Before taking XELJANZ/​XELJANZ XR, tell your healthcare provider about all of your medical conditions, including if you:

• have an infection
• 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 XELJANZ/​XELJANZ XR
• have recently received or are scheduled to receive a vaccine. People taking XELJANZ/​XELJANZ XR should not receive live vaccines but can receive non-live vaccines
• plan to become pregnant or are pregnant. XELJANZ/​XELJANZ XR may affect the ability of females to get pregnant. It is not known if this will change after stopping XELJANZ/​XELJANZ XR. It is not known if XELJANZ/​XELJANZ XR will harm an unborn baby.
• Pregnancy Registry: Pfizer has a registry for pregnant women who take XELJANZ/​XELJANZ XR. The purpose of this registry is to check the health of the pregnant mother and her baby. If you are pregnant or become pregnant while taking XELJANZ/​XELJANZ XR, talk to your healthcare provider about how you can join this pregnancy registry or you may contact the registry at 1-877-311-8972 to enroll
• plan to breastfeed or are breastfeeding. You and your healthcare provider should decide if you will take XELJANZ/​XELJANZ XR or breastfeed. You should not do both. After you stop your treatment with XELJANZ/​XELJANZ XR do not start breastfeeding again until 18 hours after your last dose of XELJANZ or 36 hours after your last dose of XELJANZ XR.
• Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your healthcare provider about any other medicines to treat your rheumatoid arthritis, psoriatic arthritis, or ulcerative colitis. 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^®), azathioprine, cyclosporine, or other immunosuppressive drugs while you are taking XELJANZ or XELJANZ XR. Taking XELJANZ or XELJANZ XR with these medicines may increase your risk of infection.
• Tell your healthcare provider if you are taking 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.

Taking XELJANZ/​XELJANZ XR

• Take XELJANZ 2 times a day with or without food.
• Take XELJANZ XR 1 time a day with or without food for rheumatoid or psoriatic arthritis. Do not take XELJANZ XR for ulcerative colitis.
• When you take XELJANZ 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 XELJANZ/​XELJANZ XR in combination with methotrexate, sulfasalazine or leflunomide as instructed by your healthcare provider.

What are other possible side effects of XELJANZ/​XELJANZ XR?

XELJANZ/​XELJANZ XR may cause serious side effects, including 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 XELJANZ/​XELJANZ XR. Your healthcare provider may do blood tests before you start treatment with XELJANZ/​XELJANZ XR and while you are using XELJANZ/​XELJANZ XR. 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, or dark urine.

Common side effects of XELJANZ/​XELJANZ XR in rheumatoid arthritis and psoriatic arthritis patients include upper respiratory tract infections (common cold, sinus infections), headache, diarrhea, nasal congestion, sore throat, and runny nose (nasopharyngitis), and high blood pressure (hypertension).

Common side effects of XELJANZ in ulcerative colitis patients 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, and shingles (herpes zoster).

Please see full Prescribing Information, including BOXED WARNING and Medication Guide.