Indicated for:

Rheumatoid Arthritis:

• XELJANZ/XELJANZ XR is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to one or more TNF blockers.

Use of XELJANZ/XELJANZ XR in combination with biologic disease-modifying antirheumatic drugs (DMARDs) or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.

Psoriatic Arthritis:

• XELJANZ/XELJANZ XR is indicated for the treatment of adult patients with active psoriatic arthritis (PsA) who have had an inadequate response or intolerance to one or more TNF blockers.

Use of XELJANZ/XELJANZ XR in combination with biologic DMARDs or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.

Ulcerative Colitis:

• XELJANZ/XELJANZ XR is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis (UC), who have an inadequate response or intolerance to one or more TNF blockers.

Use of XELJANZ/XELJANZ XR in combination with biological therapies for UC or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.

Polyarticular Course Juvenile Idiopathic Arthritis:

• XELJANZ/XELJANZ Oral Solution is indicated for the treatment of active polyarticular course juvenile idiopathic arthritis (pcJIA) in patients 2 years of age and older who have had an inadequate response or intolerance to one or more TNF blockers.

Use of XELJANZ/XELJANZ Oral Solution in combination with biologic DMARDs or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.

A dosage of XELJANZ/XELJANZ Oral Solution 10 mg twice daily or weight-based equivalent twice daily, or XELJANZ XR 22 mg once daily, is not recommended for the treatment of RA, PsA, or pcJIA.

XELJANZ XR (tofacitinib extended-release tablets) is not interchangeable or substitutable with XELJANZ Oral Solution.

Safety and efficacy of XELJANZ/XELJANZ Oral Solution in pediatric patients for indications other than pcJIA have not been established.

The safety and effectiveness of XELJANZ XR in pediatric patients have not been established.

Do not initiate XELJANZ/XELJANZ XR/XELJANZ Oral Solution in patients with an absolute lymphocyte count less than 500 cells/mm³, an absolute neutrophil count (ANC) less than 1000 cells/mm³ or who have hemoglobin levels less than 9 g/dL.

Dose interruption is recommended for management of lymphopenia, neutropenia, and anemia.

Clinical trials showed increased risk of blood clots in the lungs and death when a 10 mg twice daily dose of tofacitinib (Xeljanz, Xeljanz XR) was used in patients with rheumatoid arthritis (RA). The FDA has not approved this 10 mg twice daily dose for RA; this dose is only approved in the dosing regimen for patients with ulcerative colitis.

For patients with ulcerative colitis, use XELJANZ at the lowest effective dose and for the shortest duration needed to achieve/maintain therapeutic response.

Rheumatoid arthritis patients 50 years of age and older with at least one cardiovascular (CV) risk factor treated with XELJANZ 10 mg twice a day had a higher rate of all-cause mortality, including sudden CV death, compared to those treated with XELJANZ 5 mg given twice daily or TNF blockers in a large, ongoing, postmarketing safety study.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with XELJANZ/XELJANZ XR/XELJANZ Oral Solution, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur.

As there is a higher incidence of infections in the elderly population in general, caution should be used when treating the elderly.

Thrombosis, including pulmonary embolism, deep venous thrombosis, and arterial thrombosis, has been observed at an increased incidence in rheumatoid arthritis patients who were 50 years of age and older with at least one CV risk factor treated with XELJANZ 10 mg twice daily compared to XELJANZ 5 mg twice daily or TNF blockers in a large, ongoing postmarketing safety study. Many of these events were serious and some resulted in death.

Avoid XELJANZ/XELJANZ XR/XELJANZ Oral Solution in patients at risk. Discontinue XELJANZ/XELJANZ XR/XELJANZ Oral Solution and promptly evaluate patients with symptoms of thrombosis.

Treatment with XELJANZ was associated with dose-dependent increases in lipid parameters including total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol.

Patients treated with XELJANZ/XELJANZ XR/ XELJANZ Oral Solution are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.

If a serious infection develops, interrupt XELJANZ/XELJANZ XR/XELJANZ Oral Solution until the infection is controlled.

Reported infections include:

• Active tuberculosis, which may present with pulmonary or extrapulmonary disease. Patients should be tested for latent tuberculosis before XELJANZ/XELJANZ XR/XELJANZ Oral Solution use and during therapy. Treatment for latent infection should be initiated prior to XELJANZ/XELJANZ XR/XELJANZ Oral Solution use.
• Invasive fungal infections, including cryptococcosis and pneumocystosis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease.
• Bacterial, viral, including herpes zoster, and other infections due to opportunistic pathogens. 

The risks and benefits of treatment with XELJANZ/XELJANZ XR/XELJANZ Oral Solution should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection.

Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with XELJANZ/XELJANZ XR/XELJANZ Oral Solution, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy.

Lymphoma and other malignancies have been observed in patients treated with XELJANZ. Epstein Barr Virus-associated post-transplant lymphoproliferative disorder has been observed at an increased rate in renal transplant patients treated with XELJANZ and concomitant immunosuppressive medications

Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster), were observed in clinical studies with XELJANZ/XELJANZ XR/XELJANZ Oral Solution.

Avoid use of XELJANZ/XELJANZ XR/XELJANZ Oral Solution in patients with an active, serious infection, including localized infections. The risks and benefits of treatment should be considered prior to initiating XELJANZ/XELJANZ XR/XELJANZ Oral Solution in patients:

• with chronic or recurrent infection
• who have been exposed to tuberculosis
• with a history of a serious or an opportunistic infection
• who have resided or traveled in areas of endemic tuberculosis or endemic mycoses or
• with underlying conditions that may predispose them to infection

As there is a higher incidence of infection in diabetic population in general, caution should be used when treating patients with diabetes.

Consider the risks and benefits of XELJANZ/XELJANZ XR/XELJANZ Oral Solution treatment prior to initiating therapy in patients with a known malignancy other than a successfully treated non-melanoma skin cancer (NMSC) or when considering continuing XELJANZ/XELJANZ XR/XELJANZ Oral Solution in patients who develop a malignancy. Malignancies were observed in clinical studies of XELJANZ.

Non-melanoma skin cancers (NMSCs) have been reported in patients treated with XELJANZ. Periodic skin examination is recommended for patients who are at increased risk for skin cancer. In the UC population, treatment with XELJANZ 10 mg twice daily was associated with greater risk of NMSC. Other malignancies include lung cancer, breast cancer, melanoma, prostate cancer, and pancreatic cancer.

Malignancies, including lymphomas and solid cancers, were observed in clinical studies of XELJANZ.

Use of XELJANZ/XELJANZ XR/XELJANZ Oral Solution in patients with severe hepatic impairment is not recommended.

Caution is also recommended in patients with a history of chronic lung disease, or in those who develop interstitial lung disease, as they may be more prone to infections.

In a long-term extension study in patients with UC, four cases of pulmonary embolism were reported in patients taking XELJANZ 10 mg twice daily, including one death in a patient with advanced cancer.

Events of gastrointestinal perforation have been reported in clinical studies with XELJANZ/XELJANZ XR/XELJANZ Oral Solution in rheumatoid arthritis patients, although the role of JAK inhibition in these events is not known.

XELJANZ/XELJANZ XR/XELJANZ Oral Solution should be used with caution in patients who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs). Patients presenting with new onset abdominal symptoms should be evaluated promptly for early identification of gastrointestinal perforation.

Reactions such as angioedema and urticaria that may reflect drug hypersensitivity have been observed in patients receiving XELJANZ/XELJANZ XR/XELJANZ Oral Solution.

Avoid use of live vaccines concurrently with XELJANZ/XELJANZ XR/XELJANZ Oral Solution.

Co-administration with potent inducers of CYP3A4 (e.g., rifampin) with XELJANZ/ XELJANZ XR/XELJANZ Oral Solution may result in loss of or reduced clinical response to XELJANZ/XELJANZ XR/XELJANZ Oral Solution. Co-administration of potent inducers of CYP3A4 with XELJANZ/XELJANZ XR/XELJANZ Oral Solution is not recommended.

Use of XELJANZ/XELJANZ XR/XELJANZ Oral Solution in combination with biologic DMARDs or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended

Co-administration with strong CP3A4 Inhibitors (e.g., ketoconazole increased exposure to tofacitinib.

Co-administration with immunosuppressive drugs (e.g., azathioprine, tacrolimus, cyclosporine) is not recommended.

In the tofacitinib clinical development programs, birth defects and miscarriages were reported.

Females of reproductive potential should be advised to use effective contraception during treatment with XELJANZ/XELJANZ XR/XELJANZ Oral Solution and for at least 4 weeks after the last dose.

Given the serious adverse reactions seen in patients treated with XELJANZ/XELJANZ XR/XELJANZ Oral Solution, 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/XELJANZ Oral Solution or 36 hours after the last dose of XELJANZ XR.

GoToSource

• Use in patients under 2 years of age for active polyarticular course juvenile idiopathic arthritis. GoToSource

• Use of XELJANZ XR in patients under 18 years of age. GoToSource

• Use as monotherapy for psoriatic arthritis. GoToSource

• Use as first-line therapy for rheumatoid arthritis. GoToSource

• Inflammatory bowel disease. GoToSource

• Crohn’s disease. GoToSource

• Prevention of acute rejection in renal transplantation. GoToSource

• Ankylosing spondylitis. GoToSource

• Dry eye syndrome. GoToSource

• Hair loss. GoToSource

Non-melanoma skin cancers. GoToSource

Herpes zoster. GoToSource

Tuberculosis, opportunistic infections, death, decreased peripheral lymphocyte counts, decreased neutrophil counts, decreased hemoglobin and increased levels of high-density lipoprotein cholesterol and serum creatinine. GoToSource

Bronchitis, influenza, nasopharyngitis, pharyngitis, rash, upper respiratory tract infection and urinary tract infection. GoToSource

Gastrointestinal perforation and liver injury. GoToSource 

Non-hodgkin’s lymphoma, chronic lymphocytic leukemia, prostate cancer, burkitt’s B-cell lymphoma, colon cancer and gastric cancer. GoToSource

Pancreatitis (inflammation of the pancreas), cholecystitis (inflammation of the gallbladder) and diverticulitis (inflammation of small pouches in the wall of the digestive tract). GoToSource

Increased risk of serious heart-related problems. GoToSource

Lawsuits filed for herpes zoster, serious infections, lymphoma, liver damage, non-melanoma skin cancers and gastrointestinal perforation.