XELJANZ / XELJANZ XR® (tofacitinib) 8 USE IN SPECIFIC POPULATIONS

(tofacitinib)

Prescribing Information

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

The available data with XELJANZ (tablets and oral solution) and XELJANZ XR (extended-release tablets) from a pregnancy exposure registry that enrolled 11 exposed pregnant females, pharmacovigilance, and published literature are insufficient to draw conclusions about a drug‑associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. There are risks to the mother and the fetus associated with RA and UC in pregnancy (see Clinical Considerations). In animal reproduction studies, fetocidal and teratogenic effects were noted when pregnant rats and rabbits received tofacitinib during the period of organogenesis at exposures multiples of 73-times and 6.3-times the maximum recommended dose of 10 mg twice daily, respectively. Further, in a peri- and post-natal study in rats, tofacitinib resulted in reductions in live litter size, postnatal survival, and pup body weights at exposure multiples of approximately 73-times the recommended dosage of 5 mg twice daily and approximately 36 times the maximum recommended dosage of 10 mg twice daily, respectively (see Data).

The background risks of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The background risks in the U.S. general population of major birth defects and miscarriages are 2 to 4% and 15 to 20% of clinically recognized pregnancies, respectively.

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk: Published data suggest that increased disease activity is associated with the risk of developing adverse pregnancy outcomes in women with RA or UC. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 grams) infants, and small for gestational age at birth.

Data

Animal Data: In a rat embryofetal developmental study, in which pregnant rats received tofacitinib during organogenesis, tofacitinib was teratogenic at exposure levels approximately 146 times the recommended dose of 5 mg twice daily, and approximately 73 times the maximum recommended dose of 10 mg twice daily (on an AUC basis at oral doses of 100 mg/kg/day in rats). Teratogenic effects consisted of external and soft tissue malformations of anasarca and membranous ventricular septal defects, respectively; and skeletal malformations or variations (absent cervical arch; bent femur, fibula, humerus, radius, scapula, tibia, and ulna; sternoschisis; absent rib; misshapen femur; branched rib; fused rib; fused sternebra; and hemicentric thoracic centrum). In addition, there was an increase in post-implantation loss, consisting of early and late resorptions, resulting in a reduced number of viable fetuses. Mean fetal body weight was reduced. No developmental toxicity was observed in rats at exposure levels approximately 58 times the recommended dose of 5 mg twice daily, and approximately 29 times the maximum recommended dose of 10 mg twice daily (on an AUC basis at oral doses of 30 mg/kg/day in pregnant rats).

In a rabbit embryofetal developmental study in which pregnant rabbits received tofacitinib during the period of organogenesis, tofacitinib was teratogenic at exposure levels approximately 13 times the recommended dose of 5 mg twice daily, and approximately 6.3 times the maximum recommended dose of 10 mg twice daily (on an AUC basis at oral doses of 30 mg/kg/day in rabbits) in the absence of signs of maternal toxicity. Teratogenic effects included thoracogastroschisis, omphalocele, membranous ventricular septal defects, and cranial/skeletal malformations (microstomia, microphthalmia), mid-line and tail defects. In addition, there was an increase in post-implantation loss associated with late resorptions. No developmental toxicity was observed in rabbits at exposure levels approximately 3 times the recommended dose of 5 mg twice daily, and approximately 1.5 times the maximum recommended dose of 10 mg twice daily (on an AUC basis at oral doses of 10 mg/kg/day in pregnant rabbits).

In a peri- and postnatal development study in pregnant rats that received tofacitinib from gestation day 6 through day 20 of lactation, there were reductions in live litter size, postnatal survival, and pup body weights at exposure levels approximately 73 times the recommended dose of 5 mg twice daily, and approximately 36 times the maximum recommended dose of 10 mg twice daily (on an AUC basis at oral doses of 50 mg/kg/day in rats). There was no effect on behavioral and learning assessments, sexual maturation or the ability of the F1 generation rats to mate and produce viable F2 generation fetuses in rats at exposure levels approximately 17 times the recommended dose of 5 mg twice daily, and approximately 8.3 times the maximum recommended dose of 10 mg twice daily (on an AUC basis at oral doses of 10 mg/kg/day in rats).

8.2 Lactation

Risk Summary

Based on published data, tofacitinib is present in human milk. Data on the effects of tofacitinib on the breastfed infant is limited to a small number of cases with no reported adverse effects. There are no data on the effects on milk production. Given the serious adverse reactions seen in patients treated with XELJANZ (tablets and oral solution) and XELJANZ XR (extended-release tablets), such as increased risk of serious infections, advise patients that breastfeeding is not recommended during treatment and for at least 18 hours after the last dose of XELJANZ or 36 hours after the last dose of XELJANZ XR (approximately 6 elimination half-lives).

Data

Following administration of tofacitinib to lactating rats, concentrations of tofacitinib in milk over time paralleled those in serum and were approximately 2 times higher in milk relative to maternal serum at all time points measured.

8.3 Females and Males of Reproductive Potential

Contraception

Females

In an animal reproduction study, tofacitinib at AUC multiples of 13 times the recommended dosage of 5 mg twice daily and 6.3 times the maximum recommended dosage of 10 mg twice daily demonstrated adverse embryo-fetal findings [see Use in Specific Populations (8.1)]. However, there is uncertainty as to how these animal findings relate to females of reproductive potential treated with the recommended clinical dosage. Consider pregnancy planning and prevention for females of reproductive potential.

Infertility

Females

Based on findings in rats, treatment with XELJANZ (tablets and oral solution) and XELJANZ XR (extended-release tablets) may result in reduced fertility in females of reproductive potential. It is not known if this effect is reversible [see Nonclinical Toxicology (13.1)].

8.4 Pediatric Use

The safety and effectiveness of XELJANZ (tablets and oral solution) in pediatric patients for indications, other than in patients with active pcJIA and PsA, have not been established.

The safety and effectiveness of XELJANZ have not been established in pediatric patients less than 2 years of age.

The safety and effectiveness of XELJANZ XR (extended-release tablets) in pediatric patients have not been established.

Polyarticular Course Juvenile Idiopathic Arthritis (pcJIA)

The safety and effectiveness of XELJANZ (tablets and oral solution) for the treatment of active pcJIA have been established in pediatric patients 2 years of age and older who have had an inadequate response or intolerance to one or more TNF blockers.

Use of XELJANZ for this indication is supported by evidence from adequate and well-controlled studies of XELJANZ tablets in adults with RA, pharmacokinetic (PK) data from adult patients with RA, and with additional safety, efficacy, and PK data from a clinical trial of XELJANZ in pediatric patients 2 years and older with active pcJIA (Study pcJIA-I) [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.1, 14.4)].

Adverse reactions observed in pediatric patients with pcJIA who received XELJANZ were consistent with those reported in adults with RA [see Adverse Reactions (6.1)].

Psoriatic Arthritis

The safety and effectiveness of XELJANZ (tablets and oral solution) for the treatment of active PsA have been established in pediatric patients 2 years of age and older who have had an inadequate response or intolerance to one or more TNF blockers.

Use of XELJANZ for this indication is supported by evidence from well-controlled studies of XELJANZ tablets in adults with PsA, PK data from adults with PsA, and PK data from a clinical trial of XELJANZ in 225 pediatric patients with JIA, and safety data from 280 pediatric patients 2 years of age and older with JIA [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.2)]. Following administration of the recommended XELJANZ dosage in pediatric patients 2 years of age and older with PsA, tofacitinib plasma exposures are predicted to be comparable to those observed in adults with PsA based on population PK modeling and simulation [see Clinical Pharmacology (12.3)].

Systemic Juvenile Idiopathic Arthritis

The safety and effectiveness of XELJANZ for the treatment of pediatric patients with systemic juvenile idiopathic arthritis (sJIA) have not been established.

The results from a two-part study (an open-label, run-in phase, followed by a double-blind, placebo-controlled, randomized event-driven withdrawal phase) in 100 patients 2 years to 17 years of age with sJIA with active systemic features did not demonstrate that XELJANZ (dosed at 5 mg twice daily or body weight-based equivalent twice daily) was efficacious in the treatment of sJIA with active systemic features.

Of the 100 patients enrolled in the open-label run-in phase, 59 (59%) patients achieved a clinical response and were eligible for the double-blind withdrawal phase. There were 28 patients randomized to XELJANZ and 31 patients to placebo. The study data were insufficient to demonstrate efficacy and, therefore, XELJANZ is not recommended for the treatment of sJIA.

Adverse reactions observed in pediatric patients with sJIA receiving XELJANZ/XELJANZ oral solution were consistent with those reported in pcJIA and RA patients [see Adverse Reactions (6.1)].

8.5 Geriatric Use

Of the 3315 adults who were enrolled in clinical trials with RA (Studies RA-I to V), a total of 505 patients were 65 years of age and older, including 71 patients 75 years and older. The frequency of serious infection among XELJANZ tablets-treated patients 65 years of age and older was higher than among those adults under the age of 65.

Of the 1156 XELJANZ tablet-treated patients in clinical trials of patients with UC, a total of 77 patients (7%) were 65 years of age or older. Clinical studies of XELJANZ in patients with UC did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger adult patients.

Of the 783 XELJANZ tablet-treated patients in clinical trials of patients with PsA, a total of 72 (9.2%) patients were 65 years of age and older, including 2 (0.3%) patients 75 years and older. These clinical studies did not include sufficient numbers of patients aged 65 years and older with PsA to determine if they respond differently from younger adult patients.

Of the 420 XELJANZ tablet-treated patients in clinical trials of patients with AS, a total of 12 (2.9%) patients were 65 years of age and older, including 1 (0.2%) patient 75 years and older. These clinical studies did not include sufficient numbers of patients aged 65 years and older with AS to determine if they respond differently from younger adult patients.

8.6 Renal Impairment

Moderate and Severe Renal Impairment

XELJANZ-treated patients with moderate renal impairment (RI) (CLcr ≥30 and ≤50 mL/minute) or severe RI (<30 mL/minute) had greater tofacitinib blood concentrations than XELJANZ-treated patients with normal renal function (CLcr >80 mL/minute). The recommended dosage of XELJANZ (tablets and oral solution) and XELJANZ XR (extended-release tablets) in patients with moderate or severe RI (including those with severe RI who are undergoing hemodialysis) is lower than the recommended dosage in patients with normal renal function [see Dosage and Administration (2.3, 2.4, 2.5)].

Mild Renal Impairment

The recommended dosage in patients with mild RI (CLcr >50 and ≤80 mL/minute) is the same as patients with normal renal function.

8.7 Hepatic Impairment

Severe Hepatic Impairment

XELJANZ (tablets and oral solution) and XELJANZ XR (extended-release tablets) has not been studied in patients with severe hepatic impairment (HI) (Child-Pugh C); therefore, use of XELJANZ/XELJANZ XR in patients with severe HI is not recommended.

Moderate Hepatic Impairment

XELJANZ-treated patients with moderate hepatic impairment (Child-Pugh B) had greater tofacitinib blood concentration than XELJANZ-treated patients with normal hepatic function [see Clinical Pharmacology (12.3)]. Higher blood concentrations may increase the risk of some adverse reactions. The recommended XELJANZ (tablets and oral solution) and XELJANZ XR (extended-release tablets) dosage in patients with moderate HI is lower than the recommended dosage in patients with normal hepatic function [see Dosage and Administration (2.3, 2.4, 2.5)].

Mild Hepatic Impairment

The recommended dosage of XELJANZ/XELJANZ XR in patients with mild hepatic impairment (Child-Pugh A) is the same as patients with normal hepatic function.

Hepatitis B or C Serology

The safety and efficacy of XELJANZ/XELJANZ XR have not been studied in patients with positive hepatitis B virus or hepatitis C virus serology.

Medication Guide

MEDICATION GUIDE

MEDICATION GUIDE
XELJANZ (ZEL' JANS') (tofacitinib) tablets, for oral use			XELJANZ XR (ZEL' JANS' EKS-AHR) (tofacitinib) extended-release tablets for oral use		XELJANZ (ZEL' JANS') (tofacitinib) oral solution
What is the most important information I should know about XELJANZ/XELJANZ XR/XELJANZ oral solution? XELJANZ/XELJANZ XR/XELJANZ oral solution may cause serious side effects including:
1.		Serious infections. XELJANZ/XELJANZ XR/XELJANZ oral solution are medicines that affect your immune system. XELJANZ/XELJANZ XR/XELJANZ oral solution can lower the ability of your immune system to fight infections. Some people can have serious infections while taking XELJANZ/XELJANZ XR/XELJANZ oral solution, 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 XELJANZ/XELJANZ XR/XELJANZ oral solution and during treatment. • Your healthcare provider should monitor you closely for signs and symptoms of TB infection during treatment with XELJANZ/XELJANZ XR/XELJANZ oral solution. You should not start taking XELJANZ/XELJANZ XR/XELJANZ oral solution 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 XELJANZ (10 mg twice daily) or XELJANZ XR (22 mg one time each day) have a higher risk of serious infections and shingles. Before starting XELJANZ/XELJANZ XR/XELJANZ oral solution, tell your healthcare provider if you: • think you have an infection or have symptoms of an infection such as:
		o fever, sweating, or chills o cough o blood in phlegm o warm, red, or painful skin or sores on your body o burning when you urinate or urinating more often than normal		o muscle aches o shortness of breath o weight loss o diarrhea or stomach pain o 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 XELJANZ/XELJANZ XR/XELJANZ oral solution. 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/XELJANZ oral solution, call your healthcare provider right away if you have any symptoms of an infection. XELJANZ/XELJANZ XR/XELJANZ oral solution 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 XELJANZ 5 mg or 10 mg twice daily.
3.		Cancer and immune system problems. XELJANZ/XELJANZ XR/XELJANZ oral solution 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 XELJANZ/XELJANZ XR/XELJANZ oral solution. People taking XELJANZ 5 mg twice daily or XELJANZ 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 XELJANZ (10 mg twice daily) or XELJANZ 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.
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 XELJANZ 5 mg or 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 XELJANZ/XELJANZ XR/XELJANZ oral solution, 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 XELJANZ 5 mg or 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 XELJANZ/XELJANZ XR/XELJANZ oral solution 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 XELJANZ/XELJANZ XR/XELJANZ oral solution 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 XELJANZ/XELJANZ XR. Some of these reactions were serious. If any of these symptoms occur while you are taking XELJANZ/XELJANZ XR/XELJANZ oral solution, stop XELJANZ/XELJANZ XR/XELJANZ oral solution 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 XELJANZ/XELJANZ XR/XELJANZ oral solution and while you take XELJANZ/XELJANZ XR/XELJANZ oral solution 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 XELJANZ/XELJANZ XR/XELJANZ oral solution 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/XELJANZ oral solution 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 XELJANZ/XELJANZ XR/XELJANZ oral solution, and as needed after that. Normal cholesterol levels are important to good heart health.
See "What are the possible side effects of XELJANZ/XELJANZ XR/XELJANZ oral solution?" for more information about side effects.
What is XELJANZ/XELJANZ XR/XELJANZ oral solution? • XELJANZ/XELJANZ XR/XELJANZ oral solution is a prescription medicine called a Janus kinase (JAK) inhibitor. XELJANZ/XELJANZ XR is used to treat adults with moderately to severely active rheumatoid arthritis when 1 or more medicines called tumor necrosis factor (TNF) blockers have been used and did not work well or cannot be tolerated. • XELJANZ/XELJANZ XR is used to treat adults and XELJANZ/XELJANZ oral solution is used to treat children 2 years of age and older with active psoriatic arthritis when 1 or more TNF blocker medicines have been used, and did not work well or cannot be tolerated. • XELJANZ/XELJANZ XR is 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. • XELJANZ/XELJANZ XR is 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. • XELJANZ/XELJANZ oral solution is used to treat children 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 XELJANZ/XELJANZ XR/XELJANZ oral solution is safe and effective in people with Hepatitis B or C. XELJANZ/XELJANZ XR/XELJANZ oral solution is not recommended for people with severe liver problems. It is not known if XELJANZ/XELJANZ oral solution is safe and effective in children for treatment other than active polyarticular course juvenile arthritis and psoriatic arthritis. It is not known if XELJANZ XR is safe and effective in children.
What should I tell my healthcare provider before taking XELJANZ/XELJANZ XR/XELJANZ oral solution? Before taking XELJANZ/XELJANZ XR/XELJANZ oral solution, tell your healthcare provider about all of your medical conditions, including if you: • have an infection. See "What is the most important information I should know about XELJANZ/XELJANZ XR/XELJANZ oral solution?" • 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 XELJANZ/XELJANZ XR/XELJANZ oral solution. • have recently received or are scheduled to receive a vaccine. People who take XELJANZ/XELJANZ XR/XELJANZ oral solution should not receive live vaccines. People taking XELJANZ/XELJANZ XR/XELJANZ oral solution can receive non-live vaccines. • plan to become pregnant or are pregnant. XELJANZ/XELJANZ XR/XELJANZ oral solution may affect the ability of females to get pregnant. It is not known if this will change after stopping XELJANZ/XELJANZ XR/XELJANZ oral solution. It is not known if XELJANZ/XELJANZ XR/XELJANZ oral solution will harm an unborn baby. • plan to breastfeed or are breastfeeding. You and your healthcare provider should decide if you will take XELJANZ/XELJANZ XR/XELJANZ oral solution or breastfeed. You should not do both. After you stop your treatment with XELJANZ/XELJANZ XR/XELJANZ oral solution do not start breastfeeding again until: o 18 hours after your last dose of XELJANZ/XELJANZ oral solution or o 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. XELJANZ/XELJANZ XR/XELJANZ oral solution 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 XELJANZ/XELJANZ XR/XELJANZ oral solution. Taking XELJANZ/XELJANZ XR/XELJANZ oral solution 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.
How should I take XELJANZ/XELJANZ XR/XELJANZ oral solution? Take XELJANZ/XELJANZ XR/XELJANZ oral solution exactly as your healthcare provider tells you to take it. • Take XELJANZ/XELJANZ oral solution 2 times a day with or without food. • Take XELJANZ XR 1 time a day with or without food. • Swallow XELJANZ XR tablets whole and intact. Do not crush, split, or chew. • 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. • If you take too much XELJANZ/XELJANZ XR/XELJANZ oral solution, call your healthcare provider or go to the nearest hospital emergency room right away. • For the treatment of psoriatic arthritis, take XELJANZ/XELJANZ XR/XELJANZ oral solution in combination with methotrexate, sulfasalazine or leflunomide as instructed by your healthcare provider. • XELJANZ XR should not be used instead of XELJANZ oral solution.
What are the possible side effects of XELJANZ/XELJANZ XR/XELJANZ oral solution? XELJANZ/XELJANZ XR/XELJANZ oral solution may cause serious side effects, including: • See "What is the most important information I should know about XELJANZ/XELJANZ XR/XELJANZ oral solution?" • 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/XELJANZ oral solution. Your healthcare provider may do blood tests before you start treatment with XELJANZ/XELJANZ XR/XELJANZ oral solution and while you are taking XELJANZ/XELJANZ XR/XELJANZ oral solution. Tell your healthcare provider if you have any of the following symptoms of a possible hepatitis B or C infection:
	o feel very tired o little or no appetite o clay-colored bowel movements o chills o muscle aches o skin rash			o skin or eyes look yellow o vomiting o fevers o stomach discomfort o dark urine
Common side effects of XELJANZ/XELJANZ XR/XELJANZ oral solution 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) • acne Common side effects of XELJANZ/XELJANZ 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 • acne • diarrhea • shingles (herpes zoster) Common side effects of XELJANZ/XELJANZ oral solution in children with polyarticular course juvenile arthritis and psoriatic arthritis include: • upper respiratory tract infections (common cold, sinus infections) • nasal congestion, sore throat, and runny nose (nasopharyngitis) • headache • fever • nausea • vomiting • acne 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 XELJANZ/XELJANZ XR/XELJANZ oral solution. 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.
How should I store XELJANZ/XELJANZ XR/XELJANZ oral solution? • Store XELJANZ/XELJANZ XR at room temperature between 68°F to 77°F (20°C to 25°C). • Store XELJANZ oral solution at room temperature between 68°F to 77°F (20°C to 25°C) in the original bottle and carton to protect from light. • Safely throw away XELJANZ oral solution that is out of date or no longer needed. Use XELJANZ oral solution within 60 days of opening the bottle. Throw away (discard) remaining oral solution after 60 days. Keep XELJANZ/XELJANZ XR/XELJANZ oral solution and all medicines out of the reach of children.
General information about the safe and effective use of XELJANZ/XELJANZ XR/XELJANZ oral solution. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use XELJANZ/XELJANZ XR/XELJANZ oral solution for a condition for which it was not prescribed. Do not give XELJANZ/XELJANZ XR/XELJANZ oral solution to other people, even if they have the same symptoms you have. It may harm them. This Medication Guide summarizes the most important information about XELJANZ/XELJANZ XR/XELJANZ oral solution. If you would like more information, talk to your healthcare provider. You can ask your pharmacist or healthcare provider for information about XELJANZ/XELJANZ XR/XELJANZ oral solution that is written for health professionals.
What are the ingredients in XELJANZ 5 mg? Active ingredient: tofacitinib citrate Inactive ingredients: croscarmellose sodium, HPMC 2910/Hypromellose 6cP, lactose monohydrate, macrogol/PEG3350, magnesium stearate, microcrystalline cellulose, titanium dioxide, and triacetin. What are the ingredients in XELJANZ 10 mg? Active ingredient: tofacitinib citrate Inactive ingredients: croscarmellose sodium, FD&C Blue #1/Brilliant Blue FCF Aluminum Lake, FD&C Blue #2/Indigo Carmine Aluminum Lake, HPMC 2910/Hypromellose 6cP, lactose monohydrate, macrogol/PEG3350, magnesium stearate, microcrystalline cellulose, titanium dioxide, and triacetin. What are the ingredients in XELJANZ XR 11 mg? Active ingredient: tofacitinib citrate Inactive ingredients: cellulose acetate, copovidone, hydroxyethyl cellulose, hydroxypropyl cellulose, HPMC 2910/Hypromellose, magnesium stearate, red iron oxide, sorbitol, titanium dioxide, and triacetin. Printing ink contains ammonium hydroxide, ferrosoferric oxide/black iron, propylene glycol, and shellac glaze. What are the ingredients in XELJANZ XR 22 mg? Active ingredient: tofacitinib citrate Inactive ingredients: cellulose acetate, copovidone, FD&C Blue #2 Aluminum Lake, hydroxyethyl cellulose, hydroxypropyl cellulose, HPMC 2910/Hypromellose, magnesium stearate, red iron oxide, sorbitol, titanium dioxide, triacetin, and yellow iron oxide. Printing ink contains ammonium hydroxide, ferrosoferric oxide/black iron oxide, propylene glycol, and shellac glaze. What are the ingredients in XELJANZ oral solution? Active ingredient: tofacitinib citrate Inactive ingredients: grape flavor (natural), hydrochloric acid, lactic acid, purified water, sodium benzoate, sucralose, and xylitol. This Medication Guide may have been updated. For the most recent Medication Guide, please visit www.pfizer.com. LAB-0535-16.0

This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: October 2025

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