TOFACITINIB tablet, film coated [AvKARE]

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NDC Code(s): 73190-100-60,73190-101-60 Category: HUMAN PRESCRIPTION DRUG LABEL Marketing Status: Abbreviated New Drug Application If you are a consumer or patient please visit this version. Download DRUG LABEL INFO: PDF XML Official Label (Printer Friendly) HIGHLIGHTS OF PRESCRIBING INFORMATION TOFACITINIB tablets, for oral use These highlights do not include all the information needed to use TOFACITINIB TABLETS safely and effectively. See full prescribing information for TOFACITINIB TABLETS. Initial U. S. Approval: 2012 WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS, and THROMBOSIS See full prescribing information for complete boxed warning. Increased risk of serious bacterial, fungal, viral, and opportunistic infections, including tuberculosis (TB), leading to hospitalization or death. Interrupt tofacitinib tablets treatment if serious infection occurs until the infection is controlled. Test for latent TB before and during therapy;

treat latent TB prior to use. Monitor all patients for active TB during treatment, even patients with initial negative latent TB test. ( 5.1) Higher rate of all-cause mortality, including sudden cardiovascular (CV) death with tofacitinibtablets vs. TNF blockers in rheumatoid arthritis (RA) patients. ( 5.2) Malignancies have occurred in patients treated with tofacitinib tablets. Higher rate of lymphomas and lung cancers with tofacitinib tablets vs. TNF blockers in RA patients. ( 5.3) Higher rate of major adverse CV events (defined as CV death, myocardial infarction, and stroke) with tofacitinib tablets vs. TNF blockers in RA patients. ( 5.4) Thrombosis has occurred in patients treated with tofacitinib tablets. Increased incidence of pulmonary embolism, venous and arterial thrombosis with tofacitinib tablets vs. TNF blockers in RA patients. ( 5.5) RECENT MAJOR CHANGES Boxed Warning 10/2025 Indications and Usage, Psoriatic Arthritis ( 1.2) 10/2025 Dosage and Administration, Recommended Dosage in Pediatric Patients 2 Years of Age and Older with Psoriatic Arthritis or Polyarticular Course Juvenile Idiopathic Arthritis ( 2.4) 10/2025 Warnings and Precautions, Serious Infections ( 5.1) 03/2026 INDICATIONS AND USAGE Tofacitinib tablets are Janus kinase (JAK) inhibitors. Tofacitinib tablets are 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. Active psoriatic arthritis (PsA), who have had an inadequate response or intolerance to one or more TNF blockers. Active ankylosing spondylitis (AS), who have had an inadequate response or intolerance to one or more TNF blockers. Moderately to severely active ulcerative colitis (UC), who have had an inadequate response or intolerance to one or more TNF blockers. Tofacitinib tablets are indicated for the treatment of pediatric patients 2 years of age and older with: Active PsA, who have had an inadequate response or intolerance to one or more TNF blockers. Active polyarticular course juvenile idiopathic arthritis (pcJIA), who have had an inadequate response or intolerance to one or more TNF blockers. Limitations of Use: Use of tofacitinib tablets for RA, AS, PsA, or pcJIA in combination with biologic DMARDs or potent immunosuppressants such as azathioprine and cyclosporine is not recommended. ( 1.1,1.2,1.3,1.4) Use of tofacitinib tablets for UC in combination with biological therapies for UC or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended. ( 1.5) DOSAGE AND ADMINISTRATION Recommended Evaluations and Immunization Prior to Treatment Initiation Prior to initiating tofacitinib tablets, consider performing an active and latent TB evaluation, viral hepatitis screening, a complete blood count, and updating immunizations. Avoid tofacitinib tablets initiation if absolute lymphocyte count Table of Contents FULL PRESCRIBING INFORMATION: CONTENTS* WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS, and THROMBOSIS 1 INDICATIONS AND USAGE 1.1 Rheumatoid Arthritis 1.2 Psoriatic Arthritis 1.3 Ankylosing Spondylitis 1.4 Polyarticular Course Juvenile Idiopathic Arthritis 1.5 Ulcerative Colitis 2 DOSAGE AND ADMINISTRATION 2.1 Recommended Evaluations and Immunization Prior to TreatmentInitiation 2.2 Important Administration Instructions 2.3 Recommended Dosage in Adults with RheumatoidArthritis, Psoriatic Arthritis, and Ankylosing Spondylitis 2.4 Recommended Dosage in Pediatric Patients 2 Years ofAge and Older with Psoriatic Arthritis or Polyarticular Course JuvenileIdiopathic Arthritis 2.5 Recommended Dosage in Adults with Ulcerative Colitis 3 DOSAGE FORMS AND STRENGTHS 4 CONTRAINDICATIONS 5 WARNINGS AND PRECAUTIONS 5.1 Serious Infections 5.2 Increased Risk of Mortality 5.3 Malignancy and Lymphoproliferative Disorders 5.4 Major Adverse Cardiovascular Events 5.5 Thrombosis 5.6 Gastrointestinal Perforations 5.7 Hypersensitivity Reactions 5.8 Laboratory Abnormalities 5.9 Vaccinations 6 ADVERSE REACTIONS 6.1 Clinical Trials Experience 6.2 Postmarketing Experience 7 DRUG INTERACTIONS 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy 8.2 Lactation 8.3 Females and Males of Reproductive Potential 8.4 Pediatric Use 8.5 Geriatric Use 8.6 Renal Impairment 8.7 Hepatic Impairment 10 OVERDOSAGE 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 12.2 Pharmacodynamics 12.3 Pharmacokinetics 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 14 CLINICAL STUDIES 14.1 Clinical Studies in Rheumatoid Arthritis 14.2 Clinical Studies in Psoriatic Arthritis 14.3 Clinical Studies in Ankylosing Spondylitis 14.4 Clinical Studies in Polyarticular Course Juvenile Idiopathic Arthritis 14.5 Clinical Studies in Ulcerative Colitis 14.6 Safety Study in Adults with Rheumatoid Arthritis (Tofacitinib Tablets Versus TNF-blocker) 16 HOW SUPPLIED/STORAGE AND HANDLING 17 PATIENT COUNSELING INFORMATION * Sections or subsections omitted from the full prescribing information are not listed. BOXED WARNING (What is this?

) WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS, and THROMBOSIS SERIOUS INFECTIONS Patients treated with tofacitinib tabletsareat increased risk for developing serious bacterial, fungal, viral, and opportunistic infections, including tuberculosis (TB), that may lead to hospitalization or death [see Warnings and Precautions (5.1)and Adverse Reactions (6.1)]. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Reported infections included: Active TB, which may present with pulmonary or extrapulmonary disease. Patients should be tested for latent TB before tofacitinib tablets use and during therapy. Treatment for latent infection should be initiated prior to tofacitinib tablets 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 tofacitinib tablets treatment 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 tofacitinib tablets treatment, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy. If a serious infection develops, interrupt tofacitinib tablets until the infection is controlled [see Warnings and Precautions (5.1)]. MORTALITY In a large, randomized, postmarketing safety study in rheumatoid arthritis (RA) patients 50 years of age and older with at least onecardiovascular(CV) risk factor comparing tofacitinib tablets 5 mg or 10 mg twice a day to tumor necrosis factor (TNF) blockers, a higher rate of all-causemortality, including sudden CV death, was observed with tofacitinib tablets 5 mg or 10 mg twice a day [see Warnings and Precautions (5.2)]. Tofacitinibtablets 10 mg twice daily dosage is not recommended for the treatment of RA, psoriatic arthritis (PsA), ankylosingspondylitis(AS), or polyarticular course juvenile idiopathic arthritis (pcJIA) [see Dosage and Administration (2.3,2.4)]. MALIGNANCIES Malignancies, including lymphomas and solid tumors, have occurred in patients treated with tofacitinib tablets and other Janus kinase inhibitors used to treat inflammatory conditions. In RA patients, a higher rate of malignancies (excluding non-melanoma skin cancer (NMSC)) was observed in patients treated with tofacitinib tablets 5 mg or 10 mg twice a day compared with TNF blockers [see Warnings and Precautions (5.3)]. Lymphomas and lung cancers were observed at a higher rate in patients treated with tofacitinib tablets 5 mg or 10 mg twice a day in RA patients compared to those treated with TNF blockers. Patients who are current or past smokers are at additional increased risk. MAJOR ADVERSE CARDIOVASCULAR EVENTS RA patients 50 years of age and older with at least one cardiovascular risk factor, treated with tofacitinib tablets 5 mg or 10 mg twice daily, had a higher rate of major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke), compared to those treated with TNF blockers. Patients who are current or past smokers are at additional increased risk. Discontinue tofacitinibtablets in patients that have experienced a myocardial infarction or stroke [see Warnings and Precautions (5.4)]. THROMBOSIS Thrombosis, including pulmonary embolism, deep venous thrombosis, and arterial thrombosis have occurred in patients treated with tofacitinib tablets and other Janus kinase inhibitors used to treat inflammatory conditions. Many of these events were serious and some resulted in death. RA patients 50 years of age and older with at least one cardiovascular risk factor treated with tofacitinib tablets 5 mg or 10 mg twice daily compared to TNF blockers had an observed increase in incidence of these events. Avoid tofacitinib tablets in patients at risk. Discontinue tofacitinib tablets and promptly evaluate patients with symptoms of thrombosis [see Warnings and Precautions (5.5)]. 1 INDICATIONS AND USAGE 1.1 Rheumatoid Arthritis Tofacitinib tablets are 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. Limitations of Use Use of tofacitinib tablets in combination with biologic disease-modifying antirheumatic drugs (DMARDs) or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended. 1.2 Psoriatic Arthritis Tofacitinibtablets are indicated for the treatment of adult and pediatric patients 2 yearsofage and older with active psoriatic arthritis (PsA), who have had aninadequateresponse or intolerance to one or more TNF blockers. Limitations ofUse Use of tofacitinibtabletsin combination with biologic DMARDs or with potent immunosuppressants such as azathioprine and cyclosporine is notrecommended. 1.3 Ankylosing Spondylitis Tofacitinib tablets are indicated for the treatment of adult patients with active ankylosing spondylitis (AS), who have had an inadequate response or intolerance to one or more TNF blockers. Limitations of Use Use of tofacitinib tablets in combination with biologic DMARDs or potent immunosuppressants such as azathioprine and cyclosporine is not recommended. 1.4 Polyarticular Course Juvenile Idiopathic Arthritis Tofacitinib tablets are indicated for the treatment of pediatric patients 2 years of age and older with of active polyarticular course juvenile idiopathic arthritis (pcJIA), who have had an inadequate response or intolerance to one or more TNF blockers. Limitations of Use Use of tofacitinib tablets in combination with biologic DMARDs or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended. 1.5 Ulcerative Colitis Tofacitinib tablets are 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. Limitations of Use Use of tofacitinib tablets in combination with biological therapies for UC or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended. 2 DOSAGE AND ADMINISTRATION 2.1 Recommended Evaluations and Immunization Prior to TreatmentInitiation Prior to initiating tofacitinib tablets, consider performing the following: Active and latent tuberculosis (TB) infection evaluation: If the patient has latent TB, treat for TB prior to tofacitinib tablets treatment [see Warnings and Precautions (5.1)]. Viral hepatitis screening in accordance with clinical guidelines [see Warnings and Precautions (5.1)]. A complete blood count: Avoid initiation of tofacitinib tablets treatment in patients with a lymphocyte count less than 500 cells/mm 3, absolute neutrophil count less than 1000 cells/mm3, or hemoglobin level less than 9 g/dL [see Warnings and Precautions (5.8)]. Baseline hepatic function evaluation: Tofacitinib tablets are not recommended for patients with severe hepatic impairment [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)]. Update immunizations according to current immunization guidelines. The interval between live vaccinations and initiation of tofacitinib tablets should be in accordance with current vaccination guidelines regarding immunosuppressive agents [see Warnings and Precautions (5.9)]. 2.2 Important Administration Instructions XELJANZ XR (extended-release tablets) is not substitutable with tofacitinib tablets. Switching between tofacitinib tablets and XELJANZ XR should be made by the healthcare provider. Dose interruption is recommended for management of lymphopenia, neutropenia, and anemia [see Warnings and Precautions (5.8)and Adverse Reactions (6.1)]. Interrupt use of tofacitinib tablets if a patient develops a serious infection until the infection is controlled [see Warnings and Precautions (5.1)]. Take tofacitinib tablets with or without food [see Clinical Pharmacology (12.3)]. 2.3 Recommended Dosage in Adults with RheumatoidArthritis, Psoriatic Arthritis, and Ankylosing Spondylitis Table 1 displays the recommended dosage of tofacitinib tablets for adults with RA, PsA, and AS [see Indication and Usage (1.1,1.2,1.3)] with and without renal impairment (including thosewho are undergoing hemodialysis) or hepatic impairment [see Use in Specific Populations (8.6,8.7)]. The table also displays the recommended dosage modifications for patients concomitantly using CYP2C19 and/or CYP3A4 inhibitors [see Drug Interactions (7)and Clinical Pharmacology (12.3)], and patients with lymphopenia, neutropenia, or anemia. Table 1: Recommended Dosage of Tofacitinib Tablets in Adults with Rheumatoid Arthritis, Psoriatic Arthritis, or Ankylosing Spondylitis Adults Tofacitinib Tablets Patients with Normal Renal and Hepatic Function a 5 mg twice daily Recommended Dosage in Patients with Renal Impairment (RI) b Mild RI (CLcr >50 and ≤80 mL/min) 5 mg twice daily Moderate RI (CLcr ≥30 and ≤50 mL/min) 5 mg once daily Severe RI (CLcr 50 and ≤80 mL/min (mild renal impairment);

≥30 and ≤50 mL/min (moderate renal impairment);

3 DOSAGE FORMS AND STRENGTHS Tofacitinib tablets: 5 mg tofacitinib: White to off white colored, round shaped, biconvex, film-coated tablets, debossed with “T1” on one side and “M” on other side. 10 mg tofacitinib: Blue colored, round shaped, biconvex, film-coated tablets, debossed with “T2” on one side and “M” on other side. 5 WARNINGS AND PRECAUTIONS 5.1 Serious Infections Seriousand sometimes fatal infections may occur with tofacitinib tablets. Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported in patients receiving tofacitinib tablets. The most common serious infections reported with tofacitinib tablets included pneumonia, urinary tract infection, cellulitis, herpes zoster, bronchitis, septic shock, diverticulitis, gastroenteritis, appendicitis, and sepsis. Among opportunistic infections, tuberculosis and other mycobacterial infections, cryptococcosis, histoplasmosis, esophageal candidiasis, pneumocystosis, multi-dermatomal herpes zoster, cytomegalovirus infections, BK virus infection, and listeriosis were reported with tofacitinib tablets. Some patients have presented with disseminated rather than localized disease, and were often taking concomitant immunomodulating agents such as methotrexate or corticosteroids. In the UC population, treatment with tofacitinib tablets 10 mg twice daily was associated with greater risk of serious infections compared to 5 mg twice daily. Additionally, opportunistic herpes zoster infections (including meningoencephalitis, ophthalmologic, and disseminated cutaneous) were seen in patients who were treated with tofacitinib tablets 10 mg twice daily. Other serious infections that were not reported in clinical studies may also occur (e. g. , coccidioidomycosis). Avoid use of tofacitinib tablets in patients with an active, serious infection, including localized infections. The risks and benefits of treatment should be considered prior to initiating tofacitinib tablets 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. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with tofacitinib tablets. Interrupt tofacitinib tablets if a patient develops a serious infection, an opportunistic infection, or sepsis. In patients who develop a new infection during treatment with tofacitinib tablets, promptly complete diagnostic testing appropriate for an immunocompromised patient;

initiate appropriate antimicrobial therapy, and monitor the patients closely. 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. Risk of infection may be higher with increasing degrees of lymphopenia and consideration should be given to lymphocyte counts when assessing individual patient risk of infection. Discontinuation and monitoring criteria for lymphopenia are recommended [see Dosage and Administration (2.3,2.4,2.5)]. Tuberculosis Evaluate and test patients for latent or active tuberculosis (TB) infection prior to and per applicable guidelines during administration of tofacitinib tablets. Consider anti-TB therapy prior to administration of tofacitinib tablets in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent TB but who have risk factors for TB infection. Consultation with a physician with expertise in the treatment of TB is recommended to aid in the decision about whether initiating anti- TB therapy is appropriate for an individual patient. Monitor patients closely for the development of signs and symptoms of TB, including patients who tested negative for latent TB infection prior to initiating therapy. Treat patients with latent TB with standard antimycobacterial therapy before administering tofacitinib tablets. Viral Reactivation Viral reactivation, including cases of herpes virus reactivation (e. g. , herpes zoster), were observed in clinical studies with tofacitinib tablets. Postmarketing cases of hepatitis B reactivation have been reported in patients treated with tofacitinib tablets. The impact of tofacitinibtablets on chronic viral hepatitis reactivation is unknown. Patients who screened positive for hepatitis B or C were excluded from clinical trials. Perform screening for viral hepatitis in accordance with clinical guidelines before starting therapy with tofacitinib tablets. The risk of herpes zoster is increased in patients treated with tofacitinibtablets and appears to be higher in patients treated with tofacitinibtablets in Japan and Korea. 5.2 Increased Risk of Mortality Increased risk of mortality may occur with tofacitinib tablets. Adult patients with rheumatoid arthritis (RA), 50 years of age and older, with at least one cardiovascular risk factor treated with tofacitinib tablets 5 mg or 10 mg twice a day had a higher observed rate of all-cause mortality, including sudden cardiovascular death, compared to those treated with TNF blockers in a large, randomized, postmarketing safety study (RA Safety Study 1). The incidence rate of all-cause mortality per 100 patient-years was 1.23 for tofacitinib tablets 10 mg twice a day, 0.88 for tofacitinib tablets 5 mg twice a day, and 0.69 for TNF blockers [see Clinical Studies (14.6)]. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with tofacitinib tablets. Tofacitinib tablets 10 mg twice daily dosages are not recommended for the treatment of RA, PsA, AS, or pcJIA [see Dosage and Administration (2.3,2.4)]. For the treatment of UC, use tofacitinib tablets at the lowest effective dose and for the shortest duration needed to achieve/maintain therapeutic response [see Dosage and Administration (2.5)]. 5.3 Malignancy and Lymphoproliferative Disorders Malignancies and lymphoproliferative disorders may occur with tofacitinib tablets. Malignancies, including lymphomas and solid cancers, were observed in clinical studies of tofacitinib tablets [see Adverse Reactions (6.1)]. Other malignancies were observed in tofacitinib tablets clinical studies and the postmarketing setting, including, but not limited to, lung cancer, breast cancer, melanoma, prostate cancer, and pancreatic cancer. In RA Safety Study 1, a higher rate of malignancies (excluding non-melanoma skin cancer (NMSC)) was observed in patients treated with tofacitinib tablets 5 mg or 10 mg twice a day compared with TNF blockers. The incidence rate of malignancies (excluding NMSC) per 100 patient-years was 1.13 for tofacitinib tablets 10 mg twice a day, 1.13 for tofacitinib tablets 5 mg twice a day, and 0.77 for TNF blockers. Patients who are current or past smokers are at additional increased risk [see Clinical Studies (14.6)]. Lymphomas and lung cancers, which are a subset of all malignancies in RA Safety Study 1, were observed at a higher rate in patients treated with tofacitinib tablets 5 mg twice a day and tofacitinib tablets 10 mg twice a day compared to those treated with TNF blockers. The incidence rate of lymphomas per 100 patient-years was 0.11 for tofacitinib tablets 10 mg twice a day, 0.07 for tofacitinib tablets 5 mg twice a day, and 0.02 for TNF blockers. The incidence rate of lung cancers per 100 patient-years among current and past smokers was 0.59 for tofacitinib tablets 10 mg twice a day, 0.48 for tofacitinib tablets 5 mg twice a day, and 0.27 for TNF blockers [see Clinical Studies (14.6)]. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with tofacitinib tablets, particularly in patients with a known malignancy (other than a successfully treated NMSC), patients who develop a malignancy while on treatment, and patients who are current or past smokers. Tofacitinib tablets 10 mg twice daily dosages are not recommended for the treatment of RA, PsA, AS, or pcJIA [see Dosage and Administration (2.3,2.4)]. Non-Melanoma Skin Cancer Non-melanoma skin cancers (NMSCs) have been reported in patients treated with tofacitinib tablets. Periodic skin examination is recommended for patients who are at increased risk for skin cancer. In the UC population, treatment with tofacitinib tablets 10 mg twice daily was associated with greater risk of NMSC than treatment with placebo. 5.4 Major Adverse Cardiovascular Events Major adverse cardiovascular events may occur with tofacitinib tablets. In RA Safety Study 1, patients with RA who were 50 years of age and older with at least one cardiovascular risk factor and treated with tofacitinib tablets 5 mg or 10 mg twice daily had a higher rate of major adverse cardiovascular events (MACE) defined as cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke, compared to those treated with TNF blockers. The incidence rate of MACE per 100 patient-years was 1.11 for tofacitinib tablets 10 mg twice a day, 0.91 for tofacitinib tablets 5 mg twice a day, and 0.79 for TNF blockers. The incidence rate of fatal or non-fatal myocardial infarction per 100 patient-years was 0.39 for tofacitinib tablets 10 mg twice a day, 0.36 for tofacitinib tablets 5 mg twice a day, and 0.2 for TNF blockers [see Clinical Studies (14.6)]. Patients who are current or past smokers are at additional increased risk. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with tofacitinib tablets, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Inform patients about the symptoms of serious cardiovascular events and the steps to take if they occur. Discontinue tofacitinib tablets in patients that have experienced a MI or stroke. Tofacitinib tablets 10 mg twice daily dosages are not recommended for the treatment of RA, PsA, AS, or pcJIA [see Dosage and Administration (2.3,2.4)]. 5.5 Thrombosis Thrombosis may occur with tofacitinib tablets. Thrombosis, including pulmonary embolism (PE), deep venous thrombosis (DVT), and arterial thrombosis, have occurred in patients treated with tofacitinib tablets and other Janus kinase (JAK) inhibitors used to treat inflammatory conditions. Many of these events were serious and some resulted in death [see Warnings and Precautions (5.2)]. Patients with RA 50 years of age and older with at least one cardiovascular risk factor treated with tofacitinib tablets 5 mg or 10 mg twice daily compared to TNF blockers in RA Safety Study 1 had an observed increase in incidence of these thrombotic events. The incidence rate of DVT per 100 patient-years was 0.28 for tofacitinib tablets 10 mg twice a day, 0.22 for tofacitinib tablets 5 mg twice a day, and 0.16 for TNF blockers. The incidence rate of PE per 100 patient-years was 0.49 for tofacitinib tablets 10 mg twice a day, 0.18 for tofacitinib tablets 5 mg twice a day, and 0.05 for TNF blockers [see Clinical Studies (14.6)]. Tofacitinib tablets 10 mg twice daily dosages are not recommended for the treatment of RA, PsA, AS, or pcJIA [see Dosage and Administration (2.3,2.4)]. In a long-term extension study in patients with UC, five cases of pulmonary embolism were reported in patients taking tofacitinib tablets 10 mg twice daily, including one death in a patient with advanced cancer. Promptly evaluate patients with symptoms of thrombosis and discontinue tofacitinibtablets in patients with symptoms of thrombosis. Avoid tofacitinibtablets in patients that may be at increased risk of thrombosis. For the treatment of UC, use tofacitinib tablets at the lowest effective dose and for the shortest duration needed to achieve/maintain therapeutic response [see Dosage and Administration (2.5)]. 5.6 Gastrointestinal Perforations Gastrointestinal perforations may occur with tofacitinib tablets. Events of gastrointestinal perforation have been reported in clinical studies with tofacitinib tablets, although the role of JAK inhibition in these events is not known. In these studies, many patients with RA received background therapy with nonsteroidal anti-inflammatory drugs (NSAIDs). There was no discernable difference in frequency of gastrointestinal perforation between the placebo and the tofacitinib tablets treatment groups in clinical trials of patients with UC, and many of them were receiving background corticosteroids. Promptly evaluate patients treated with tofacitinib tablets who may be at increased risk for gastrointestinal perforation (e. g. , patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1)]. 5.7 Hypersensitivity Reactions Hypersensitivity reactions may occur with tofacitinib tablets. Reactions such as angioedema and urticaria that may reflect drug hypersensitivity have been observed in patients receiving tofacitinib tablets. Some events were serious. If a serious hypersensitivity reaction occurs, promptly discontinue tofacitinib tablets while evaluating the potential cause or causes of the reaction [see Adverse Reactions (6.2)]. 5.8 Laboratory Abnormalities Laboratory abnormalities may occur with tofacitinib tablets. Lymphocyte Abnormalities Treatment with tofacitinib tablets was associated with initial lymphocytosis at one month of tofacitinib tablets treatment followed by a gradual decrease in mean absolute lymphocyte counts below the baseline of approximately 10% during 12 months of therapy. Lymphocyte counts less than 500 cells/mm 3in these patients were associated with an increased incidence of treated and serious infections. Monitor lymphocyte counts at baseline and every 3 months thereafter. Avoid initiation of tofacitinib tablets treatment in patients with a low lymphocyte count (i. e. , less than 500 cells/mm 3). In patients who develop a confirmed absolute lymphocyte count less than 500 cells/mm 3, treatment with tofacitinib tablets is not recommended. Neutropenia Treatment with tofacitinib tablets was associated with an increased incidence of neutropenia (less than 2000 cells/mm 3) compared to treatment with placebo. Monitor neutrophil counts at baseline and after 4-8 weeks of treatment and every 3 months thereafter. Avoid initiation of tofacitinibtablets treatment in patients with a low neutrophil count (i. e. , ANC less than 1000 cells/mm3). For patients who develop a persistent ANC of 500 to 1000 cells/mm3, interrupt dosing until ANC is greater than or equal to 1000 cells/mm3. In patients who develop an ANC less than 500 cells/mm3, treatment with tofacitinib tablets is not recommended. Anemia Monitor hemoglobin at baseline and after 4-8 weeks of treatment and every 3 months thereafter. Avoid initiation of tofacitinib tablets treatment in patients with a low hemoglobin level (i. e. , less than 9 g/dL). Interrupt treatment with tofacitinibtablets in patients who develop hemoglobin levels less than 8 g/dL or whose hemoglobin level drops greater than 2 g/dL on treatment until hemoglobin values have normalized. Liver Enzyme Elevations Treatment with tofacitinib tablets was associated with an increased incidence of liver enzyme elevation compared to treatment with placebo. Most of these abnormalities occurred in studies with background DMARD therapy (primarily methotrexate). Routine monitoring of liver tests and prompt investigation of the causes of liver enzyme elevations is recommended to identify potential cases of drug-induced liver injury. If drug-induced liver injury is suspected, interrupt the administration of tofacitinib tablets until this diagnosis has been excluded. Lipid Elevations Treatment with tofacitinib tablets was associated with dose-dependent increases in lipid parameters including total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol. Maximum changes in these lipid parameters were generally observed within 6 weeks. There were no clinically relevant changes in LDL/HDL cholesterol ratios. The effect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined. Perform assessment of lipid parameters approximately 4-8 weeks following initiation of tofacitinib tablets therapy. Manage patients according to clinical guidelines [e. g. , National Cholesterol Educational Program (NCEP)] for the management of hyperlipidemia. 5.9 Vaccinations Avoid use of live vaccines concurrently with tofacitinib tablets. Prior to initiating tofacitinib tablets therapy, update immunizations in agreement with current immunization guidelines. The interval between live vaccinations and initiation of tofacitinib tablets therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents. 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Serious Infections [see Warnings and Precautions (5.1)] Increased Risk of Mortality [see Warnings and Precautions (5.2)] Malignancy and Lymphoproliferative Disorders [see Warnings and Precautions (5.3)] Major Adverse Cardiovascular Events [see Warnings and Precautions (5.4)] Thrombosis [see Warnings and Precautions (5.5)] Gastrointestinal Perforations [see Warnings and Precautions (5.6)] Hypersensitivity Reactions [see Warnings and Precautions (5.7)] Laboratory Abnormalities [see Warnings and Precautions (5.8)] 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not predict the rates observed in a broader patient population in clinical practice. The clinical studies described in this subsection were conducted using tofacitinib tablets and/or XELJANZ oral solution. Adverse Reactions in Adults with Rheumatoid Arthritis In RA Safety Study 1,1,455 adults were treated with tofacitinib tablets 5 mg twice daily, 1,456 adults were treated with 10 mg twice daily, and 1,451 adults were treated with a TNF blocker for a median of 4 years [see Clinical Studies (14.6)]. A dosage of tofacitinib tablets 10 mg twice daily is not recommended for the treatment of RA because of increased risks [see Dosage and Administration (2.3)and Warnings and Precautions (5)]. For the treatment of adults with moderately to severely active RA [see Indications and Usage (1.1)], the recommended dosage of tofacitinib tablets is 5 mg twice daily. The safety of tofacitinib tablets was also evaluated in two Phase 2 and five Phase 3 double-blind, placebo-controlled, multicenter trials in patients with RA. In these trials, adults were randomized to receive: Tofacitinib tablets (monotherapy) 5 mg twice daily (292 patients) or 10 mg twice daily (306 patients), In combination with DMARDs (including methotrexate), tofacitinib tablets 5 mg twice daily (1044 patients) or 10 mg twice daily (1043 patients) and Placebo (809 patients). All seven trials included provisions for patients taking placebo to receive treatment with tofacitinib tablets at Month 3 or Month 6 either by patient response (based on uncontrolled disease activity) or by design, so that adverse events cannot always be unambiguously attributed to a given treatment. Therefore, some analyses that follow include patients who changed treatment by design or by patient response from placebo to tofacitinib tablets in both the placebo and tofacitinib tablets group of a given interval. Comparisons between placebo and tofacitinib tablets groups were based on the first 3 months of exposure, and comparisons between tofacitinib tablets 5 mg twice daily and tofacitinib tablets 10 mg twice daily were based on the first 12 months of exposure. The long-term safety population includes all adults with RA who participated in a double-blind, placebo-controlled trial (including earlier development phase studies) and then participated in one of two long-term safety studies. The design of the long-term safety studies allowed for modification of tofacitinib tablets doses according to clinical judgment. This limits the interpretation of the long-term safety data with respect to dose. The most common serious adverse reactions were serious infections [see Warnings and Precautions (5.1)]. The proportion of patients who discontinued treatment due to any adverse reaction during the 0 to 3 months exposure in the double-blind, placebo-controlled trials was 4% for tofacitinib tablets-treated patients and 3% for placebo-treated patients. Overall Infections In the seven placebo-controlled trials in patients with RA, during the 0 to 3 months exposure, the overall frequency of infections was 20% and 22% in the tofacitinib tablets 5 mg twice daily and tofacitinib tablets 10 mg twice daily groups, respectively, and 18% in the placebo group. The most commonly reported infections with tofacitinib tabletswere upper respiratory tract infections, nasopharyngitis, and urinary tract infections (4%, 3%, and 2% of patients, respectively). Serious Infections: In the seven placebo-controlled trials in patients with RA, during the 0 to 3 months exposure, serious infections were reported in 1 patient (0.5 events per 100 patient-years) who received placebo and 11 patients (1.7 events per 100 patient-years) who received tofacitinib tablets 5 mg or 10 mg twice daily. The rate difference between treatment groups (and the corresponding 95% confidence interval) was 1.1 (- 0.4,2.5) events per 100 patient-years for the combined tofacitinib tablets 5 mg twice daily and 10 mg twice daily group minus placebo. In the seven placebo-controlled trials, during the 0 to 12 months exposure, serious infections were reported in 34 patients (2.7 events per 100 patient-years) who received tofacitinib tablets 5 mg twice daily and 33 patients (2.7 events per 100 patient-years) who received tofacitinib tablets 10 mg twice daily. The rate difference between tofacitinib tablets doses (and the corresponding 95% confidence interval) was -0.1 (-1.3,1.2) events per 100 patient-years for tofacitinib tablets 10 mg twice daily minus tofacitinib tablets 5 mg twice daily. The most common serious infections included pneumonia, cellulitis, herpes zoster, and urinary tract infection [see Warnings and Precautions (5.1)]. Tuberculosis: In the seven placebo-controlled trials in patients with RA, during the 0 to 3 months exposure, tuberculosis (TB) was not reported in patients who received placebo, tofacitinib tablets 5 mg twice daily, or tofacitinib tablets 10 mg twice daily. In the seven placebo-controlled trials, during the 0 to 12 months exposure, TB was reported in 0 patients who received tofacitinib tablets 5 mg twice daily and 6 patients (0.5 events per 100 patient-years) who received tofacitinib tablets 10 mg twice daily. The rate difference between tofacitinib tablets doses (and the corresponding 95% confidence interval) was 0.5 (0.1,0.9) events per 100 patient-years for tofacitinib tablets 10 mg twice daily minus tofacitinib tablets 5 mg twice daily. Cases of disseminated TB were also reported. The median tofacitinib tabletsexposure prior to diagnosis of TB was 10 months (range from 152 to 960 days) [see Warnings and Precautions (5.1)]. Opportunistic Infections (excluding tuberculosis): In the seven placebo-controlled trials in patients with RA, during the 0 to 3 months exposure, opportunistic infections were not reported in patients who received placebo, tofacitinib tablets 5 mg twice daily, or tofacitinib tablets 10 mg twice daily. In the seven placebo-controlled trials, during the 0 to 12 months exposure, opportunistic infections were reported in 4 patients (0.3 events per 100 patient-years) who received tofacitinib tablets 5 mg twice daily and 4 patients (0.3 events per 100 patient-years) who received tofacitinib tablets 10 mg twice daily. The rate difference between tofacitinib tabletsdoses (and the corresponding 95% confidence interval) was 0 (-0.5,0.5) events per 100 patient-years for tofacitinib tablets 10 mg twice daily minus tofacitinib tablets 5 mg twice daily. The median tofacitinib tablets exposure prior to diagnosis of an opportunistic infection was 8 months (range from 41 to 698 days) [see Warnings and Precautions (5.1)]. Malignancies In the seven placebo-controlled trials in patients with RA, during the 0 to 3 months exposure, malignancies excluding NMSC were reported in 0 patients who received placebo and 2 patients (0.3 events per 100 patient-years) who received either tofacitinib tablets 5 mg or 10 mg twice daily. The rate difference between treatment groups (and the corresponding 95% confidence interval) was 0.3 (-0.1,0.7) events per 100 patient-years for the combined tofacitinib tablets 5 mg and 10 mg twice daily group minus placebo. In the seven placebo-controlled trials, during the 0 to 12 months exposure, malignancies excluding NMSC were reported in 5 patients (0.4 events per 100 patient-years) who received tofacitinib tablets 5 mg twice daily and 7 patients (0.6 events per 100 patient-years) who received tofacitinib tablets 10 mg twice daily. The rate difference between tofacitinib tablets doses (and the corresponding 95% confidence interval) was 0.2 (-0.4,0.7) events per 100 patient-years for tofacitinib tablets 10 mg twice daily minus tofacitinib tablets 5 mg twice daily. One of these malignancies was a case of lymphoma that occurred during the 0-to-12 month period in a patient treated with tofacitinib tablets 10 mg twice daily. The most common types of malignancy, including malignancies observed during the long-term extension in tofacitinib tablets-treated patients, were lung and breast cancer, followed by gastric, colorectal, renal cell, prostate cancer, lymphoma, and malignant melanoma [see Warnings and Precautions ( 5.3)]. Laboratory Abnormalities Lymphopenia: In the placebo-controlled clinical trials in patients with RA, confirmed decreases in absolute lymphocyte counts below 500 cells/mm 3occurred in 0.04% of patients for the tofacitinib tablets 5 mg twice daily and 10 mg twice daily groups combined during the first 3 months of exposure. Confirmed lymphocyte counts less than 500 cells/mm 3were associated with an increased incidence of treated and serious infections [see Warnings and Precautions (5.8)]. Neutropenia: In the placebo-controlled clinical trials in patients with RA, confirmed decreases in ANC below 1,000 cells/mm 3occurred in 0.07% of patients for the tofacitinib tablets 5 mg twice daily and 10 mg twice daily groups combined during the first 3 months of exposure. There were no confirmed decreases in ANC below 500 cells/mm 3observed in any treatment group. There was no clear relationship between neutropenia and the occurrence of serious infections. In the long-term safety population, the pattern and incidence of confirmed decreases in ANC remained consistent with what was seen in the placebo-controlled clinical trials [seeWarnings and Precautions (5.8)]. Liver Enzyme Elevations: Confirmed increases in liver enzymes greater than 3 times the upper limit of normal (3x ULN) were observed in patients with RA treated with tofacitinib tablets. In patients experiencing liver enzyme elevation, modification of treatment regimen, such as reduction in the dose of concomitant DMARD, interruption of tofacitinib tablets, or reduction in tofacitinib tablets dosage, resulted in decrease or normalization of liver enzymes. In the placebo-controlled monotherapy trials (0-3 months), no differences in the incidence of ALT or AST elevations were observed between the placebo, and tofacitinib tablets 5 mg, and 10 mg twice daily groups. In the placebo-controlled background DMARD trials (0-3 months), ALT elevations greater than 3x ULN were observed in 1.0%, 1.3% and 1.2% of patients who received placebo, tofacitinib tablets 5 mg, and 10 mg twice daily, respectively. In these trials, AST elevations greater than 3x ULN were observed in 0.6%, 0.5% and 0.4% of patients who received placebo, tofacitinib tablets 5 mg, and 10 mg twice daily, respectively. One case of drug-induced liver injury was reported in a patient treated with tofacitinib tablets 10 mg twice daily for approximately 2.5 months. The patient developed symptomatic elevations of AST and ALT greater than 3x ULN and bilirubin elevations greater than 2x ULN, which required hospitalizations and a liver biopsy. Lipid Elevations: In the placebo-controlled clinical trials in patients with RA, dose-related elevations in lipid parameters (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides) were observed at one month of exposure and remained stable thereafter. Changes in lipid parameters during the first 3 months of exposure in the placebo-controlled clinical trials are summarized below: Mean LDL cholesterol increased by 15% in the tofacitinib tablets 5 mg twice daily arm and 19% in the tofacitinib tablets 10 mg twice daily arm. Mean HDL cholesterol increased by 10% in the tofacitinib tablets 5 mg twice daily arm and 12% in the tofacitinib tablets 10 mg twice daily arm. Mean LDL/HDL ratios were essentially unchanged in tofacitinib tablets-treated patients. In a placebo-controlled clinical trial, elevations in LDL cholesterol and ApoB decreased to pretreatment levels in response to statin therapy. In the long-term safety population, elevations in lipid parameters remained consistent with what was seen in the placebo-controlled clinical trials. Serum Creatinine Elevations: In the placebo-controlled clinical trials in patients with RA, dose-related elevations in serum creatinine were observed with tofacitinib tablets treatment. The mean increase in serum creatinine was 7 DRUG INTERACTIONS Table 7 includes drugs with clinically significant drug interactions when concomitantly used with tofacitinib tablets and instructions for preventing or managing them. Table 7: Clinically Significant Interactions Affecting Tofacitinib Tablets When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e. g. , ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of tofacitinibtablets is recommended [see Dosage and Administration (2), Clinical Pharmacology, Figure 3 (12.3)] Moderate CYP3A4 Inhibitors Concomitantly Used with Strong CYP2C19 Inhibitors (e. g. , fluconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of tofacitinibtablets is recommended [see Dosage and Administration (2), Clinical Pharmacology, Figure 3 (12.3)] Strong CYP3A4 Inducers (e. g. , rifampin) Clinical Impact Decreased exposure to tofacitinib and may result in loss of or reduced clinical response Intervention Concomitant use with tofacitinib tabletsis not recommended [see Clinical Pharmacology, Figure 3 (12.3)] Immunosuppressive Drugs (e. g. , azathioprine, tacrolimus, cyclosporine) Clinical Impact Risk of added immunosuppression;

concomitant use of tofacitinib tabletswith biologic DMARDs or potent immunosuppressants has not been studied in patients with RA, PsA, AS, UC, or pcJIA. Intervention Concomitant use with tofacitinib tablets is not recommended [see Indications and Usage (1), Clinical Pharmacology, Figure 3 (12.3)] 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary The available data with tofacitinib 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 tofacitinib 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 tofacitinib tablets(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 tofacitinib 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 tofacitinib tablets in pediatric patients for indications, other than in patients with active pcJIA and PsA, have not been established. The safety and effectiveness of tofacitinibtablets have not been established in pediatric patients less than 2 years of age. Polyarticular Course Juvenile Idiopathic Arthritis (pcJIA) The safety and effectiveness of tofacitinib tablets 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 tofacitinibtablets for this indication is supported by evidence from adequate and well-controlled studies of tofacitinib 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 tofacitinibtablets 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 tofacitinib tabletswere consistent with those reported in adults with RA [see Adverse Reactions (6.1)]. Psoriatic Arthritis The safety and effectiveness of tofacitinib tablets 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 tofacitinibtablets for this indication is supported by evidence from well-controlled studies of tofacitinib tablets in adults with PsA, PK data from adults with PsA, and PK data from a clinical trial of tofacitinib tabletsin 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 tofacitinib tabletsdosage 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 tofacitinibtablets 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 tofacitinib tablets(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 tofacitinib tabletsand 31 patients to placebo. The study data were insufficient to demonstrate efficacy and, therefore, tofacitinibtablets arenot recommended for the treatment of sJIA. Adverse reactions observed in pediatric patients with sJIA receiving tofacitinibtablets 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 tofacitinib tablets-treated patients 65 years of age and older was higher than among those adults under the age of 65. Of the 1156 tofacitinib 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 tofacitinib tablets 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 tofacitinib 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 tofacitinib 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 Tofacitinib tablets-treated patients with moderate renal impairment (RI) (CLcr ≥30 and ≤50 mL/minute) or severe RI (80 mL/minute). The recommended dosage of tofacitinib 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 Tofacitinib tablets have not been studied in patients with severe hepatic impairment (HI) (Child-Pugh C);

therefore, use of tofacitinib tablets in patients with severe HI is not recommended. Moderate Hepatic Impairment Tofacitinib tablets-treated patients with moderate hepatic impairment (Child-Pugh B) had greater tofacitinib blood concentration than tofacitinib tablets-treated patients with normal hepatic function [see Clinical Pharmacology (12.3)]. Higher blood concentrations may increase the risk of some adverse reactions. The recommended tofacitinib 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 tofacitinib tablets 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 tofacitinib tablets have not been studied in patients with positive hepatitis B virus or hepatitis C virus serology. 10 OVERDOSAGE There is no specific antidote for overdose with tofacitinib tablets. In case of an overdose, it is recommended that the patient be monitored for signs and symptoms of adverse reactions. In a study in patients with end-stage renal disease (ESRD) undergoing hemodialysis, plasma tofacitinib concentrations declined more rapidly during the period of hemodialysis and dialyzer efficiency, calculated as dialyzer clearance/blood flow entering the dialyzer, was high. However, due to the significant non-renal clearance of tofacitinib, the fraction of total elimination occurring by hemodialysis was small, and thus, limits the value of hemodialysis for treatment of overdose with tofacitinib tablets. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations. 11 DESCRIPTION Tofacitinib tablets are formulated with the citrate salt of tofacitinib, a JAK inhibitor. Tofacitinib citrate is a white to off-white powder with the following chemical name: (3R, 4R)-4-methyl-3-(methyl-7H-pyrrolo pyrimidin-4-ylamino)-ß-oxo-1-piperidinepropanenitrile, 2-hydroxy-1,2,3-propanetricarboxylate (1: 1). Tofacitinib citrate is sparingly soluble in 20% aqueous acetic acid, slightly soluble in methanol, water and insoluble in dichloromethane Tofacitinib citrate has a molecular weight of 504.5 Daltons (or 312.4 Daltons as the tofacitinib free base) and a molecular formula of C 16H 20N 6O•C 6H 😯 7. The chemical structure of tofacitinib citrate is: Tofacitinib tablets are supplied for oral administration as a: 5 mg white to off white colored, round shaped, biconvex, immediate-release film-coated tablet. Each tablet of tofacitinib contains 5 mg tofacitinib (equivalent to 8.08 mg tofacitinib citrate) and the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, hypromellose, titanium dioxide, polyethylene glycol and triacetin. 10 mg blue colored, round shaped, biconvex, immediate-release film-coated tablet. Each tablet of tofacitinib contains 10 mg tofacitinib (equivalent to 16.16 mg tofacitinib citrate) and the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, hypromellose, titanium dioxide, polyethylene glycol, triacetin, FD&C Blue No. 2 and FD&C Blue No. 1.12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Tofacitinib is a Janus kinase (JAK) inhibitor. JAKs are intracellular enzymes which transmit signals arising from cytokine or growth factor-receptor interactions on the cellular membrane to influence cellular processes of hematopoiesis and immune cell function. Within the signaling pathway, JAKs phosphorylate and activate Signal Transducers and Activators of Transcription (STATs) which modulate intracellular activity including gene expression. Tofacitinib modulates the signaling pathway at the point of JAKs, preventing the phosphorylation and activation of STATs. JAK enzymes transmit cytokine signaling through pairing of JAKs (e. g. , JAK1/JAK3, JAK1/JAK2, JAK1/TyK2, JAK2/JAK2). Tofacitinib inhibited the in vitroactivities of JAK1/JAK2, JAK1/JAK3, and JAK2/JAK2 combinations with IC 50of 406,56, and 1377 nM, respectively. However, the relevance of specific JAK combinations to therapeutic effectiveness is not known. 12.2 Pharmacodynamics Treatment with tofacitinib tabletswas associated with dose-dependent reductions of circulating CD16/56+ natural killer cells, with estimated maximum reductions occurring at approximately 8-10 weeks after initiation of therapy. These changes generally resolved within 2-6 weeks after discontinuation of treatment. Treatment with tofacitinib tabletswas associated with dose-dependent increases in B cell counts. Changes in circulating T-lymphocyte counts and T-lymphocyte subsets (CD3+, CD4+ and CD8+) were small and inconsistent. The clinical significance of these changes is unknown. Total serum IgG, IgM, and IgA levels after 6-month dosing in patients with rheumatoid arthritis (RA) were lower than in patients who received placebo;

however, changes were small and not dose-dependent. After treatment with tofacitinibtablets in patients with RA, rapid decreases in serum C-reactive protein (CRP) were observed and maintained throughout dosing. Changes in CRP observed with tofacitinib tabletstreatment do not reverse fully within 2 weeks after discontinuation, indicating a longer duration of pharmacodynamic activity compared to the pharmacokinetic half-life. Similar changes in T cells, B cells, and serum CRP have been observed in patients with active psoriatic arthritis (PsA) although reversibility was not assessed. Total serum immunoglobulins were not assessed in patients with active PsA. 12.3 Pharmacokinetics Following oral administration of tofacitinib tablets, peak plasma concentrations were reached within 0.5 hour -1 hour, elimination half-life was about 3 hours and a dose-proportional increase in systemic exposure was observed in the therapeutic dosage range. Steady state concentrations were achieved in 24-48 hours with negligible accumulation after twice daily administration. Table 8 describes the pharmacokinetic parameters of tofacitinib tablets. Table 8: Pharmacokinetic Parameters of Tofacitinib Tablets Following Multiple Oral Dosing PK Parameters a (CV%) Tofacitinib Tablets Dosing Regimen 5 mg Twice Daily 10 mg Twice Daily AUC 24 (ng. hr/mL) 263.4 (15) 539.6 (22) C max (ng/mL) 42.7 (26) 84.7 (18) C min (ng/mL) 1.41 (40) 3.10 (54) T max (hours) 1.0 (0.5 to14.0 b) 0.8 (0.5 to 14.0 b) Abbreviations: AUC24 = area under the concentration time profile from time 0 to 24 hours;

C max= maximum plasma concentration; C min= minimum plasma concentration; T max= time to C max;

CV = Coefficient of variation. a Values represent the geometric mean, except T max, for which is the median (range) is shown. b Values beyond 12 hours were after the evening dose which was administered 12 hours after the morning dose of twice-daily tofacitinibtablets. Absorption Tofacitinibtablets The absolute oral bioavailability of tofacitinib tablets is 74%. Coadministration of tofacitinib tablets with a high-fat meal resulted in no changes in AUC while C maxwas reduced by 32%. In clinical trials, tofacitinib tablets were administered without regard to meals [see Dosage and Administration (2.2)]. Distribution After intravenous administration, the volume of distribution was 87 L. The protein binding of tofacitinib is approximately 40%. Tofacitinib binds predominantly to albumin and does not appear to bind to α1-acid glycoprotein. Tofacitinib distributes equally between red blood cells and plasma. Metabolism and Excretion Clearance mechanisms for tofacitinib are approximately 70% hepatic metabolism and 30% renal excretion of the parent drug. The metabolism of tofacitinib is primarily mediated by CYP3A4 with minor contribution from CYP2C19. In a human radiolabeled study, more than 65% of the total circulating radioactivity was accounted for by unchanged tofacitinib, with the remaining 35% attributed to 8 metabolites, each accounting for less than 8% of total radioactivity. The pharmacologic activity of tofacitinib is attributed to the parent molecule. Pharmacokinetics in Patients with RA, PsA, AS, and UC Population pharmacokinetic (PK) analyses indicated that PK characteristics were similar between patients with RA, PsA, ankylosing spondylitis, and UC. The coefficient of variation (%) in AUC of tofacitinib were generally similar across different disease patients, ranging from 22% to 34% (Table 9). Table 9: Tofacitinib Exposure in Patients with RA, PsA, AS, and UC After Administration of Tofacitinib Tablets 5 mg Twice Daily or 10 mg Twice Daily Pharmacokinetic Parameters a Geometric Mean (CV%) Tofacitinib Tablets5 mg Twice Daily Tofacitinib Tablets10 mg Twice Daily Rheumatoid Arthritis Psoriatic Arthritis Ankylosing Spondylitis Ulcerative Colitis Ulcerative Colitis AUC 0-24, ss 504 419 381 423 807 (ng·h/mL) (22.0%) (34.1%) (25.4%) (22.6%) (24.6%) Abbreviations: AUC0-24, ss=area under the plasma concentration-time curve over 24 hours at steady state;

CV=coefficient of variation. a Pharmacokinetic parameters estimated based on population pharmacokinetic analysis. Specific Populations Covariate evaluation as part of population PK analyses in adult patient populations indicated no clinically relevant change in tofacitinib exposure, after accounting for differences in renal function (i. e. , creatinine clearance) between patients, based on age, weight, biological sex and race (Figure 1). An approximately linear relationship between body weight and volume of distribution was observed, resulting in higher peak (C max) and lower trough (C min) concentrations in lighter patients. However, this difference is not considered to be clinically relevant. Covariate evaluation as part of population PK analyses in pediatric patients with pcJIA, including PsA, identified body weight significantly impacting tofacitinib exposure, which supports weight-based dosing in this population. There were no identified clinically significant differences in tofacitinib exposure with different age, biological sex, racial, or pcJIA or PsA disease severity groups. The effect of renal and hepatic impairment and other intrinsic factors on the PK of tofacitinib is shown in Figure 1. Figure 1: Impact of Intrinsic Factors on Tofacitinib Pharmacokinetics Note: Reference values for weight, age, biological sex, and race comparisons are 70 kg, 55 years, male, and white, respectively;

reference groups for renal and hepatic impairment data are patients with normal renal and hepatic function. Renal function was estimated using creatinine clearance by Cockcroft-Gault method and hepatic function was estimated using Child-Pugh scoring method. In patients with end-stage renal disease maintained on hemodialysis, mean AUC was approximately 40% higher compared with historical healthy subject data, consistent with approximately 30% contribution of renal clearance to the total clearance of tofacitinib. [see Dosage and Administration (2.3,2.4,2.5)and Use in Specific Populations (8.6)]. Drug Interaction Studies Potential for tofacitinib tablets to Influence the PK of Other Drugs In vitro studies indicate that tofacitinib does not significantly inhibit or induce the activity of the major human drug-metabolizing CYPs (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) at concentrations corresponding to the steady state C maxof a 10 mg twice daily dose. These in vitro results were confirmed by a human drug interaction study showing no changes in the pharmacokinetics of midazolam, a highly sensitive CYP3A4 substrate, when concomitantly administered with tofacitinib tablets. In vitrostudies indicate that tofacitinib does not significantly inhibit the activity of the major human drug-metabolizing uridine 5'-diphospho-glucuronosyltransferases (UGTs) [UGT1A1, UGT1A4, UGT1A6, UGT1A9, and UGT2B7] at concentrations exceeding 250 times the steady state C maxof a 10 mg twice daily dose. In patients with RA, the oral clearance of tofacitinib does not vary with time, indicating that tofacitinib does not normalize CYP enzyme activity in patients with RA. Therefore, concomitant use with tofacitinib tofacitinib tabletsis not expected to result in clinically relevant increases in the metabolism of CYP substrates in patients with RA. In vitro data indicate that the potential for tofacitinib to inhibit transporters such as P-glycoprotein, organic anionic or cationic transporters at therapeutic concentrations is low. The impact of tofacitinib on the PK of other drugs for the concomitant drugs are shown in Figure 2. Figure 2: Impact of Tofacitinib on the Pharmacokinetics of Other Drugs Note: Reference group is administration of concomitant medication alone;

OCT = Organic Cationic Transporter;

MATE = Multidrug and Toxic Compound Extrusion. Potential for Other Drugs to Influence the Pharmacokinetics of Tofacitinib Since tofacitinib is metabolized by CYP3A4, interaction with drugs that inhibit or induce CYP3A4 is likely. Inhibitors of CYP2C19 alone or P-glycoprotein are unlikely to substantially alter the pharmacokinetics of tofacitinib (see Figure 3). Figure 3: Impact of Other Drugs on the Pharmacokinetics of Tofacitinib Note: Reference group is administration of tofacitinib tabletsalone. 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility In a 39-week toxicology study in monkeys, tofacitinib at exposure levels approximately 6 times the recommended dose of 5 mg twice daily, and approximately 3 times the 10 mg twice daily dose (on an AUC basis at oral doses of 5 mg/kg twice daily) produced lymphomas. No lymphomas were observed in this study at exposure levels 1 times the recommended dose of 5 mg twice daily, and approximately 0.5 times the 10 mg twice daily dose (on an AUC basis at oral doses of 1 mg/kg twice daily). The carcinogenic potential of tofacitinib was assessed in 6-month rasH2 transgenic mouse carcinogenicity and 2-year rat carcinogenicity studies. Tofacitinib, at exposure levels approximately 34 times the recommended dose of 5 mg twice daily, and approximately 17 times the 10 mg twice daily dose (on an AUC basis at oral doses of 200 mg/kg/day) was not carcinogenic in mice. In the 24-month oral carcinogenicity study in Sprague-Dawley rats, tofacitinib caused benign Leydig cell tumors, hibernomas (malignancy of brown adipose tissue), and benign thymomas at doses greater than or equal to 30 mg/kg/day (approximately 42 times the exposure levels at the recommended dose of 5 mg twice daily, and approximately 21 times the 10 mg twice daily dose on an AUC basis). The relevance of benign Leydig cell tumors to human risk is not known. Tofacitinib was not mutagenic in the bacterial reverse mutation assay. It was positive for clastogenicity in the in vitro chromosome aberration assay with human lymphocytes in the presence of metabolic enzymes, but negative in the absence of metabolic enzymes. Tofacitinib was negative in the in vivo rat micronucleus assay and in the in vitroCHO-HGPRT assay and the in vivorat hepatocyte unscheduled DNA synthesis assay. In rats, tofacitinib at exposure levels approximately 17 times the recommended dose of 5 mg twice daily, and approximately 8.3 times the 10 mg twice daily dose (on an AUC basis at oral doses of 10 mg/kg/day) reduced female fertility due to increased post-implantation loss. There was no impairment of female rat fertility at exposure levels of tofacitinib equal to the recommended dose of 5 mg twice daily, and approximately 0.5 times the 10 mg twice daily dose (on an AUC basis at oral doses of 1 mg/kg/day). Tofacitinib exposure levels at approximately 133 times the recommended dose of 5 mg twice daily, and approximately 67 times the 10 mg twice daily dose (on an AUC basis at oral doses of 100 mg/kg/day) had no effect on male fertility, sperm motility, or sperm concentration. 14 CLINICAL STUDIES 14.1 Clinical Studies in Rheumatoid Arthritis The rheumatoid arthritis (RA) clinical development program with tofacitinib tablets included six randomized controlled trials in adults with moderate to severe active RA. Trial Design Study RA-I (NCT00814307) was a 6-month monotherapy trial in which 610 patients with moderate to severe active RA who had an inadequate response to a DMARD (nonbiologic or biologic) received tofacitinib tablets 5 mg or 10 mg twice daily or placebo added to their background DMARD. At the Month 3 visit, all patients randomized to placebo treatment were switched in a blinded fashion to a second predetermined treatment of tofacitinib tablets 5 mg or 10 mg twice daily. The primary endpoints at Month 3 were the proportion of patients who achieved an ACR20 response, changes in Health Assessment Questionnaire – Disability Index (HAQ-DI), and rates of Disease Activity Score DAS28-4(ESR) less than 2.6. Study RA-II (NCT00856544) was a 12-month trial in which 792 patients with moderate to severe active RA who had an inadequate response to a nonbiologic DMARD received tofacitinib tablets 5 mg or 10 mg twice daily or placebo added to background DMARD treatment (excluding potent immunosuppressive treatments such as azathioprine or cyclosporine). At the Month 3 visit, nonresponding patients were switched in a blinded fashion to a second predetermined treatment of tofacitinib tablets 5 mg or 10 mg twice daily. At the end of Month 6, all patients treated with placebo were switched to their second predetermined tofacitinib tabletstreatment in a blinded fashion. The primary endpoints were the proportion of patients who achieved an ACR20 response at Month 6, changes in HAQ-DI at Month 3, and rates of DAS28-4(ESR) less than 2.6 at Month 6. Study RA-III (NCT00853385) was a 12-month trial in 717 patients with moderate to severe active RA who had an inadequate response to methotrexate (MTX). Patients received tofacitinib tablets 5 mg or 10 mg orally twice daily, adalimumab 40 mg subcutaneously every other week, or placebo added to background MTX. Patients treated with placebo were switched as in Study RA- II. The primary endpoints were the proportion of patients who achieved an ACR20 response at Month 6, HAQ-DI at Month 3, and DAS28-4(ESR) less than 2.6 at Month 6. Study RA-IV (NCT00847613) was a 2-year trial with a planned analysis at 1 year in which 797 patients with moderate to severe active RA who had an inadequate response to MTX received tofacitinib tablets 5 mg or 10 mg twice daily or placebo added to background MTX. Patients treated with placebo were switched as in Study RA- II. The primary endpoints were the proportion of patients who achieved an ACR20 response at Month 6, mean change from baseline in van der Heijde-modified total Sharp Score (mTSS) at Month 6, HAQ-DI at Month 3, and DAS28-4(ESR) less than 2.6 at Month 6. Study RA-V (NCT00960440) was a 6-month trial in which 399 patients with moderate to severe active RA who had an inadequate response to at least one approved TNF blocking biological product received tofacitinib tablets 5 mg or 10 mg twice daily or placebo added to background MTX. At the Month 3 visit, all patients randomized to placebo treatment were switched in a blinded fashion to a second predetermined treatment of tofacitinib tablets 5 or 10 mg twice daily. The primary endpoints at Month 3 were the proportion of patients who achieved an ACR20 response, HAQ-DI, and DAS28-4(ESR) less than 2.6. Study RA-VI (NCT01039688) was a 2-year monotherapy trial with a planned analysis at 1 year in which 952 MTX-naïve patients with moderate to severe active RA received tofacitinib tablets 5 or 10 mg twice daily or MTX dose-titrated over 8 weeks to 20 mg weekly. The primary endpoints were mean change from baseline in van der Heijde-modified Total Sharp Score (mTSS) at Month 6 and the proportion of patients who achieved an ACR70 response at Month 6. Although other dosages have been studied, the recommended dosage of tofacitinib tablets is 5 mg twice daily. Tofacitinib tablets 10 mg twice daily is not recommended for the treatment of RA [see Dosage and Administration (2.3)]. Clinical Response The percentages of tofacitinib tablets-treated patients who achieved ACR20, ACR50, and ACR70 responses in Studies RA-I, IV, and V are shown in Table 10. Similar results were observed with Studies RA-II and III. In trials RA-I through V, patients treated with 5 mg twice daily tofacitinib tabletshad higher ACR20, ACR50, and ACR70 response rates versus patients treated with placebo, with or without background DMARD treatment, at Month 3 and Month 6. Higher ACR20 response rates were observed within 2 weeks compared to placebo. In the 12-month trials, ACR response rates in tofacitinib tablets-treated patients were consistent at 6 and 12 months. Table 10: Proportion of Adults with Moderate to Severe Active RA with an ACR Response at Months 3 and 6 in Studies RA-I, IV, and V Monotherapy in Nonbiologic or Biologic DMARD Inadequate Responders c MTX Inadequate Responders d TNF Blocker Inadequate Responders e Study RA-I Study RA-IV Study RA-V N aPlacebo + background DMARD122 Tofacitinib Tablets 5 mg Twice Daily + background DMARD243 Placebo + background MTX160 Tofacitinib Tablets 5 mg Twice Daily + background MTX321 Placebo + background MTX132 Tofacitinib Tablets 5 mg Twice Daily + background MTX133 ACR20 Month 3 Month 6 26% NA b 59% 69% 27% 25% 55% 50% 24% NA 41% 51% ACR50 Month 3 Month 6 12% NA 31% 42% 8% 9% 29% 32% 8% NA 26% 37% ACR70 Month 3 Month 6 6% NA 15% 22% 3% 1% 11% 14% 2% NA 14% 16% a N is number of randomized and treated patients. b NA (not applicable), as data for placebo treatment is not available beyond 3 months in Studies RA- I and RA- V due to placebo advancement. c Inadequate response to at least one DMARD (biologic or nonbiologic) due to lack of efficacy or toxicity. d Inadequate response to MTX defined as the presence of sufficient residual disease activity to meet the entry criteria. e Inadequate response to a least one TNF blocker due to lack of efficacy and/or intolerance. In Study RA-IV, a greater proportion of patients treated with tofacitinib tablets 5 mg twice daily plus MTX achieved a low level of disease activity as measured by a DAS28-4(ESR) less than 2.6 at 6 months compared to those treated with MTX alone (Table 11). Table 11: Proportion and Numbers of Adults with Moderate to Severe Active RA with DAS28-4(ESR) Less Than 2.6 with Number of Residual Active Joints at Month 6 in Study RA-IV Study RA- IV DAS28-4(ESR) Less Than 2.6 Placebo + MTX 160 Tofacitinib Tablets5 mg Twice Daily + MTX 321 Proportion of responders at Month 6 (n) 1% (2) 6% (19) Of responders, proportion with 0 active joints (n) 50% (1) 42% (8) Of responders, proportion with 1 active joint (n) 0 5% (1) Of responders, proportion with 2 active joints (n) 0 32% (6) Of responders, proportion with 3 or more active joints (n) 50% (1) 21% (4) The results of the components of the ACR response criteria for Study RA-IV are shown in Table 12. Similar results were observed for tofacitinibtablets in Studies RA-I, II, III, V, and VI. Table 12: Components of ACR Response in Adults with Moderate to Severe Active RA at Baseline and Month 3 in Study RA-IV Study RA-IV Placebo + MTX N=160 Tofacitinib Tablets5 mg Twice Daily + MTX N=321 Component (mean) a Baseline Month 3 a Baseline Month 3 a Number of tender joints (0-68) 23 (13) 18 (14) 24 (14) 13 (14) Number of swollen joints (0-66) 14 (9) 10 (9) 14 (8) 6 (8) Pain b 55 (24) 47 (24) 58 (23) 34 (23) Patient global assessment b 54 (23) 47 (24) 58 (24) 35 (23) Disability index (HAQ-DI) c 1.32 (0.67) 1.19 (0.68) 1.41 (0.68) 0.99 (0.65) Physician global assessment b 56 (18) 43 (22) 59 (16) 30 (19) CRP (mg/L) 13.7 (14.9) 14.6 (18.7) 15.3 (19.0) 7.1 (19.1) a Data shown is mean (Standard Deviation) at Month 3. b Visual analog scale: 0 = best, 100 = worst. c Health Assessment Questionnaire Disability Index: 0 = best, 3 = worst;

20 questions;

categories: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities. The percent of ACR20 responders by visit for Study RA-IV is shown in Figure 4. Similar responses were observed for tofacitinibtablets in Studies RA-I, II, III, V, and VI. Figure 4: Percentage of ACR20 Responders by Visit Through Month 6 in Study RA-IV Radiographic Response Two studies were conducted to evaluate the effect of tofacitinib tabletson structural joint damage. In Study RA-IV and Study RA-VI, progression of structural joint damage was assessed radiographically and expressed as change from baseline in mTSS and its components, the erosion score and joint space narrowing score, at Months 6 and 12. The proportion of patients with no radiographic progression (mTSS change less than or equal to 0) was also assessed. In Study RA-IV, tofacitinib tablets 5 mg twice daily reduced the mean progression of structural damage (not statistically significant) as shown in Table 13. Analyses of erosion and joint space narrowing scores were consistent with the overall results. In the placebo plus MTX group, 74% of patients experienced no radiographic progression at Month 6 compared to 84% of patients treated with tofacitinib tabletsplus MTX 5 mg twice daily. In Study RA-VI, tofacitinib tablets monotherapy inhibited the progression of structural damage compared to MTX at Months 6 and 12 as shown in Table 13. Analyses of erosion and joint space narrowing scores were consistent with the overall results. In the MTX group, 55% of patients experienced no radiographic progression at Month 6 compared to 73% of patients treated with tofacitinib tablets 5 mg twice daily. Table 13: Radiographic Changes in Adults with Moderate to Severe Active RA at Months 6 and 12 in Studies RA-IV and VI Study RA-IV Placebo N=139 Mean (SD) aTofacitinib Tablets 5 mg Twice Daily N=277 Mean (SD) a Tofacitinib Tablets 5 mg Twice Daily Mean Difference from Placebo b(CI) mTSSc Baseline Month 6 33 (42) 0.5 (2.0) 31 (48) 0.1 (1.7) – -0.3 (-0.7,0.0) Study RA-VI MTX N=166 Mean (SD) a Tofacitinib Tablets 5 mg Twice Daily N=346 Mean (SD) a Tofacitinib Tablets 5 mg Twice Daily Mean Difference from MTX b(CI) mTSSc Baseline Month 6 Month 12 17 (29) 0.8 (2.7) 1.3 (3.7) 20 (40) 0.2 (2.3) 0.4 (3.0) – -0.7 (-1.0, -0.3) -0.9 (-1.4, -0.4) aSD = Standard Deviation bDifference between least squares means tofacitinib tablets minus placebo or MTX (95% CI = 95% confidence interval) cMonth 6 and Month 12 data are mean change from baseline. Physical Function Response Improvement in physical functioning was measured by the HAQ-DI. Patients who received tofacitinib tablets 5 mg twice daily demonstrated greater improvement from baseline in physical functioning compared to patients who received placebo at Month 3. The mean (95% CI) difference from placebo in HAQ-DI improvement from baseline at Month 3 in Study RA-III was -0.22 (-0.35, -0.10) in patients who received 5 mg tofacitinib tabletstwice daily. Similar results were obtained in Studies RA-I, II, IV and V. In the 12-month trials, HAQ-DI results in tofacitinib tablets-treated patients were consistent at 6 and 12 months. Other Health-Related Outcomes General health status was assessed by the Short Form health survey (SF-36). In Studies RA-I, IV, and V, patients who received tofacitinib tablets 5 mg twice daily demonstrated greater improvement from baseline compared to placebo in physical component summary (PCS), mental component summary (MCS) scores and in all 8 domains of the SF-36 at Month 3.14.2 Clinical Studies in Psoriatic Arthritis The psoriatic arthritis (PsA) clinical development program with tofacitinib tablets included 2 multicenter, randomized, double-blind, placebo-controlled trials in 816 adults with active PsA (Studies PsA-I and PsA-II). Trial Designs and Population All patients had active PsA for at least 6 months based upon the Classification Criteria for Psoriatic Arthritis (CASPAR), at least 3 tender/painful joints and at least 3 swollen joints, and active plaque psoriasis. Patients randomized and treated across the 2 clinical trials represented different PsA subtypes at screening, including 0.05) (Tables 14 and 15). Table 14: Proportion of Adults with Active PsA with an ACR Response at Month 3 in Study PsA-I* [Nonbiologic DMARD Inadequate Responders (TNF Blocker-Naïve)]** Treatment Group Placebo Tofacitinib Tablets 5 mg Twice Daily + Background Nonbiologic DMARD Na 105 107 Response Rate Response Rate Difference (%) 95% CI from Placebo Month 3 ACR20 ACR50 ACR70 33% 10% 5% 50% 28% 17% 17.1 (4.1,30.2) 18.5 (8.3,28.7) 12.1 (3.9,20.2) Patients with missing data were treated as non-responders. * Patients received one concomitant nonbiologic DMARD. ** Tofacitinib tablets are not approved for use in TNF blocker-naïve patients [see Indications and Usage (1.2)]. a N is number of randomized and treated patients. Table 15: Proportion of Adults with Active PsA with an ACR Response at Month 3 in Study PsA-II* (TNF Blocker Inadequate Responders) Treatment Group Placebo Tofacitinib Tablets5 mg Twice Daily Na 131 131 Response Rate Response Rate Difference (%) 95% CI from Placebo Month 3 ACR20 ACR50 ACR70 24% 15% 10% 50% 30% 17% 26.0 (14.7,37.2) 15.3 (5.4,25.2) 6.9 (-1.3,15.1) Patients with missing data were treated as non-responders. * Patients received one concomitant nonbiologic DMARD. a N is number of randomized and treated patients. Improvements from baseline in the ACR response criteria components for both studies are shown in Table 16. Table 16: Components of ACR Response in Adults with Active PsA at Baseline and Month 3 in Studies PsA-I and PsA-II Nonbiologic DMARD Inadequate Responders (TNF Blocker-Naïve) TNF Blocker Inadequate Responders Study PsA-I*, ** Study PsA-II* Treatment Group Placebo Tofacitinib Tablets 5 mg Twice Daily Placebo Tofacitinib Tablets 5 mg Twice Daily N at Baseline 105 107 131 131 ACR Componenta Number of tender/painful joints (0-68) Baseline Month 3 20.6 14.6 20.5 12.2 19.8 15.1 20.5 11.5 Number of swollen joints (0-66) Baseline Month 3 11.5 7.1 12.9 6.3 10.5 7.7 12.1 4.8 Patient assessment of arthritis painb Baseline Month 3 53.2 44.7 55.7 34.7 54.9 48.0 56.4 36.1 Patient global assessment of arthritisb Baseline Month 3 53.9 44.4 54.7 35.5 55.8 49.2 57.4 36.9 HAQ-DIc Baseline Month 3 1.11 0.95 1.16 0.81 1.25 1.09 1.26 0.88 Physician’s Global Assessment of Arthritisb Baseline Month 3 53.8 35.4 54.6 29.5 53.7 36.4 53.5 27.0 CRP (mg/L) Baseline Month 3 10.4 8.6 10.5 4.0 12.1 11.4 13.8 7.7 * Patients received one concomitant nonbiologic DMARD. ** Tofacitinib tablets are not approved for use in TNF blocker-naïve patients [seeIndications and Usage (1.2)]. a Data shown are mean value at baseline and at Month 3. b Visual analog scale (VAS): 0 = best, 100 = worst. c HAQ-DI = Health Assessment Questionnaire – Disability Index: 0 = best, 3 = worst;

20 questions; categories: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities. The percentage of ACR20 responders by visit for Study PsA-I is shown in Figure 5. Similar responses were observed in Study PsA-II. In both studies, improvement in ACR20 response on tofacitinib tablets was observed at the first visit after baseline (Week 2). Figure 5: Percentage of ACR20 Responders by Visit Through Month 3 in Study PsA-I*, ** BID=twice daily;

SE=standard error. Patients with missing data were treated as non-responders. * Subjects received one concomitant nonbiologic DMARD. ** Tofacitinib tablets are not approved for use in TNF blocker-naïve patients [see Indications and Usage (1.2)]. In patients with active PsA evidence of benefit in enthesitis and dactylitis was observed with tofacitinib tablets treatment. Physical Function Improvement in physical functioning was measured by the HAQ-DI. Patients receiving tofacitinib tablets 5 mg twice daily demonstrated significantly greater improvement (p ≤0.05) from baseline in physical functioning compared to placebo at Month 3 (Table 17). Table 17: Change from Baseline in HAQ-DI in Adults with Active PsA at Month 3 Studies PsA-I and PsA-II Least Squares Mean Change from Baseline In HAQ-DI at Month 3 Nonbiologic DMARD Inadequate Respondersb (TNF Blocker-Naïve) TNF Blocker Inadequate Respondersc Study PsA-I*, ** Study PsA-II* Treatment Group Placebo Tofacitinib Tablets 5 mg Twice Daily Placebo Tofacitinib Tablets 5 mg Twice Daily N a 104 107 131 129 LSM Change from Baseline -0.18 -0.35 -0.14 -0.39 Difference from Placebo (95% CI) – -0.17 (-0.29, -0.05) – -0.25 (-0.38, -0.13) * Patients received one concomitant nonbiologic DMARD. ** Tofacitinib tablets are not approved for use in TNF blocker-naïve patients [see Indications and Usage (1.2)]. a N is the total number of patients in the statistical analysis. b Inadequate response to at least one nonbiologic DMARD due to lack of efficacy and/or intolerability. c Inadequate response to at least one TNF blocker due to lack of efficacy and/or intolerability. In Study PsA-I, the HAQ-DI responder rate (response defined as having improvement from baseline of ≥0.35) at Month 3 was 53% in patients receiving tofacitinib tablets 5 mg twice daily and 31% in patients receiving placebo. Similar responses were observed in Study PsA-II. Other Health-Related Outcomes General health status was assessed by the Short Form health survey (SF-36). In Studies PsA-I and PsA-II, patients receiving tofacitinib tablets 5 mg twice daily had greater improvement from baseline compared to placebo in Physical Component Summary (PCS) score, but not in Mental Component Summary (MCS) score at Month 3. Patients receiving tofacitinib tablets 5 mg twice daily reported consistently greater improvement relative to placebo in the domains of Physical Functioning, Bodily Pain, Vitality, and Social Functioning, but not in Role-Physical, General Health, Role-Emotional, or Mental Health. Radiographic Response Treatment effect on inhibition of radiographic progression in PsA could not be established from the results of Study PsA-I. 14.3 Clinical Studies in Ankylosing Spondylitis The ankylosing spondylitis (AS) clinical development program with tofacitinib tablets included one placebo-controlled trial (Study AS-I) in adults with active AS. Patients had active disease as defined by both Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and back pain score (BASDAI question 2) of greater or equal to 4 despite non-steroidal anti-inflammatory drug (NSAID), corticosteroid or disease modifying anti-rheumatic drug (DMARD) therapy. Trial Design Study AS-I was a randomized, double-blind, placebo-controlled, 48-week clinical trial in 269 adult patients who had an inadequate response (inadequate clinical response or intolerance) to at least 2 NSAIDs. Although Study AS-I included some patients who are TNF blocker-naïve, tofacitinib tablets are not approved for use in TNF blocker-naïve patients [see Indications and Usage (1.3)]. Patients were randomized and treated with tofacitinib tablets 5 mg twice daily or placebo for 16 weeks of blinded treatment and then all received treatment of tofacitinib tablets 5 mg twice daily for additional 32 weeks. The primary endpoint was to evaluate the proportion of patients who achieved an ASAS20 response at Week 16. Approximately 7% and 21% of patients used concomitant methotrexate or sulfasalazine, respectively from baseline to Week 16. Twenty-two percent of patients had an inadequate response to 1 or 2 TNF blockers. Clinical Response Patients treated with tofacitinib tablets 5 mg twice daily achieved greater improvements in ASAS20 and ASAS40 responses compared to patients treated with placebo at Week 16 (Table 18). Consistent results were observed in the subgroup of patients who had an inadequate response to TNF blockers for both the ASAS20 (primary endpoint) and ASAS40 (secondary endpoint) at Week 16 (Table 18). Table 18: ASAS20 and ASAS40 Responses in Adults with Active AS at Week 16 in Study AS-I Placebo Tofacitinib Tablets 5 mg Twice Daily Difference from Placebo (95% CI) All patients (N) N=136 N=133 ASAS20 response*, % 29 56 27 (16,38)** ASAS40 response*, % 13 41 28 (18,38)** TNFi-IR patients (N) N=30 N=29 ASAS20 response, % 17 41 25 (2,47) ASAS40 response, % 7 28 21 (2,39) * type I error-controlled. ** p-value 16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Information for Tofacitinib Tablets How supplied information for tofacitinib tablets is shown in Table 23. Storage and Handling for Tofacitinib Tablets Store tofacitinib tablets at 20°C to 25°C (68°F to 77°F). [See USP Controlled Room Temperature]. Do not repackage. 17 PATIENT COUNSELING INFORMATION Advise patients to read the FDA-approved patient labeling (Medication Guide). Serious Infections Inform patients that tofacitinib tablets may lower the ability of their immune system to fight infections. Advise patients not to start taking tofacitinib tablets if they have an active infection. Instruct patients to contact their healthcare provider immediately during treatment if symptoms suggesting infection appear to ensure rapid evaluation and appropriate treatment [see Warnings and Precautions (5.1)]. Advise patients that the risk of herpes zoster, some cases of which can be serious, is increased in patients treated with tofacitinib tablets [see Warnings and Precautions (5.1)]. Malignancies and Lymphoproliferative Disorders Inform patients that tofacitinib tablets may increase their risk of certain cancers, and that lymphoma and other cancers have been observed in patients taking tofacitinib tablets. Instruct patients to inform their healthcare provider if they have ever had any type of cancer [see Warnings and Precautions (5.3)]. Major Adverse Cardiovascular Events Inform patients that tofacitinib tablets may increase their risk of major adverse cardiovascular events (MACE) defined as myocardial infarction, stroke, and cardiovascular death. Instruct all patients, especially current or past smokers or patients with other cardiovascular risk factors, to be alert for the development of signs and symptoms of cardiovascular events [see Warnings and Precautions (5.4)]. Thrombosis Advise patients to stop taking tofacitinib tablets and to call their healthcare provider right away if they experience any symptoms of thrombosis (sudden shortness of breath, chest pain worsened with breathing, swelling of leg or arm, leg pain or tenderness, red or discolored skin in the affected leg or arm) [see Warnings and Precautions (5.5)]. Hypersensitivity Advise patients to stop taking tofacitinib tablets and to call their healthcare provider right away if they experience any symptoms of allergic reactions while taking tofacitinib tablets [see Warnings and Precautions (5.7)]. Important Information on Laboratory Abnormalities Inform patients that tofacitinib tablets may affect certain lab test results, and that blood tests are required before and during tofacitinib tablets treatment [see Warnings and Precautions (5.8)]. Pregnancy Advise pregnant females and females of reproductive potential of the potential risk to a fetus. Advise females to inform their prescriber of a known or suspected pregnancy [see Use in Specific Populations (8.1)]. Lactation Advise women not to breastfeed during treatment with tofacitinib tablets and for at least 18 hours after the last dose of tofacitinib tablets [see Use in Specific Populations (8.2)]. Infertility Advise females of reproductive potential that tofacitinib tablets may impair fertility [see Use in Specific Populations (8.3), Nonclinical Toxicology (13.1)]. It is not known if this effect is reversible. This product’s label may have been updated. For current full prescribing information, please visit www. novadozpharma. com. Xeljanz XR is a registered trademark of Pfizer, Inc. Xeljanz Oral Solution is a registered trademark of Pfizer, Inc. All trademarks are the property of their respective owners. Manufactured by: MSN Pharmaceuticals Inc. Piscataway, NJ 08854-3714 Manufactured for: AvKARE Pulaski, TN 38478 Issued: 06/2026 MEDICATION GUIDE Tofacitinib (toe″ fa sye' ti nib) tablets, for oral use What is the most important information I should know about tofacitinib tablets?

Tofacitinib tablets may cause serious side effects including: 1. Serious infections. Tofacitinib tablets are a medicine that affects your immune system. Tofacitinib tablets can lower the ability of your immune system to fight infections. Some people can have serious infections while taking tofacitinib tablets, 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 tablets and during treatment. Your healthcare provider should monitor you closely for signs and symptoms of TB infection during treatment with tofacitinib tablets. You should not start taking tofacitinib tablets 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 tablets (10 mg twice daily) have a higher risk of serious infections and shingles. Before starting tofacitinib tablets, tell your healthcare provider if you: think you have an infection or have symptoms of an infection such as: fever, sweating, or chills muscle aches cough shortness of breath blood in phlegm weight loss warm, red, or painful skin or sores on your body diarrhea or stomach pain burning when you urinate or urinating more often than normal 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 tablets. 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 tablets, call your healthcare provider right away if you have any symptoms of an infection. Tofacitinib tablets 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 heartdisease (cardiovascular) risk factor and are takingtofacitinib tablets 5 mg or 10 mg twice daily. 3. Cancer and immune system problems. Tofacitinib tablets 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 tablets. People taking tofacitinib tablets 5 mg twice daily or tofacitinib tablets 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 tablets (10 mg twice daily) 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 tofacitinib tablets 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 tofacitinib tablets, 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 tablets 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 tofacitinib tablets 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 tablets 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 tablets. Some of these reactions were serious. If any of these symptoms occur while you are taking tofacitinib tablets, stop tofacitinib tablets 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 tablets and while you take tofacitinib tablets 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 tablets 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 tablets 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 tocheck your cholesterol levels 4 to 8 weeks after you start taking tofacitinib tablets, and as needed after that. Normal cholesterol levels are important to good heart health. See “What are the possible side effects of tofacitinib tablets?

”for more information about side effects. What are tofacitinib tablets?

Tofacitinib tablets are a prescription medicine called a Janus kinase (JAK) inhibitor. Tofacitinib tablets are 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. Tofacitinib tablets are used to treat adults and 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. Tofacitinib tablets 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 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 are 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 tofacitinib tablets are safe and effective in people with Hepatitis B or C. Tofacitinib tablets are not recommended for people with severe liver problems. It is not known if tofacitinib tablets are safe and effective in children for treatment other than active polyarticular course juvenile arthritis and psoriatic arthritis. What should I tell my healthcare provider before taking tofacitinib tablets?

Before taking tofacitinib tablets, 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 tofacitinib tablets?

” 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 tablets. have recently received or are scheduled to receive a vaccine. People who take tofacitinib tablets should not receive live vaccines. People taking tofacitinib tablets can receive non-live vaccines. plan to become pregnant or are pregnant. Tofacitinib tablets may affect the ability of females to get pregnant. It is not known if this will change after stopping tofacitinib tablets. It is not known if tofacitinib tablets will harm an unborn baby. plan to breastfeed or are breastfeeding. You and your healthcare provider should decide if you will take tofacitinib tablets or breastfeed. You should not do both. After you stop your treatment with tofacitinib tablets do not start breastfeeding again until: 18 hours after your last dose of tofacitinib tablets Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Tofacitinib tablets 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 tablets. Taking tofacitinib tablets 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 tofacitinib tablets?

Take tofacitinib tablets exactly as your healthcare provider tells you to take it. Take tofacitinib tablets 2 times a day with or without food. If you take too many tofacitinib tablets, call your healthcare provider or go to the nearest hospital emergency room right away. For the treatment of psoriatic arthritis, take tofacitinib tablets in combination with methotrexate, sulfasalazine or leflunomide as instructed by your healthcare provider. What are the possible side effects of tofacitinib tablets?

Tofacitinib tablets may cause serious side effects, including: See “What is the most important information I should know about tofacitinib tablets?

” Hepatitis B or C activation infectionin 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 tablets. Your healthcare provider may do blood tests before you start treatment with tofacitinib tablets and while you are taking tofacitinib tablets. Tell your healthcare provider if you have any of the following symptoms of a possible hepatitis B or C infection: feel very tired skin or eyes look yellow little or no appetite vomiting clay-colored bowel movements fevers chills stomach discomfort muscle aches dark urine skin rash Common side effects of tofacitinib tablets 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 tofacitinib tablets 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 tofacitinib tablets in children with polyarticular course juvenile arthritis and psoriatic arthritisinclude: 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 tofacitinib tablets. 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 www. avkare. com at 1-855-361-3993. How should I store tofacitinib tablets?

Store tofacitinib tablets at room temperature between 68°F to 77°F (20°C to 25°C). Keep tofacitinib tablets and all medicines out of the reach of children. General information about the safe and effective use of tofacitinib tablets. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use tofacitinib tablets for a condition for which it was not prescribed. Do not give tofacitinib tablets 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 tofacitinib tablets. If you would like more information, talk to your healthcare provider. You can ask your pharmacist or healthcare provider for information about tofacitinib tablets that is written for health professionals. What are the ingredients in tofacitinib tablets 5 mg?

Active ingredient: tofacitinib citrate Inactive ingredients: Colloidal silicon dioxide, croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, hypromellose, titanium dioxide, polyethylene glycol and triacetin. What are the ingredients in tofacitinib tablets 10 mg?

Active ingredient: tofacitinib citrate Inactive ingredients: Colloidal silicon dioxide, croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, hypromellose, titanium dioxide, polyethylene glycol, triacetin and FD&C Blue No. 2 and FD&C Blue No. 1. For more information, go to www. avkare. com or call AvKARE at 1-855-361-3993. Manufactured by: MSN Pharmaceuticals Inc. Piscataway, NJ 08854-3714 Manufactured for: AvKARE Pulaski, TN 38478 This Medication Guide has been approved by the U. S. Food and Drug Administration. Issued: 06/2026 PACKAGE LABEL. PRINCIPAL DISPLAY PANEL 73190-100-60 73190-101-60 INGREDIENTS AND APPEARANCE TOFACITINIB tofacitinib tablet, film coated Product Information Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 73190-100 Route of AdministrationORAL Active Ingredient/Active Moiety Ingredient NameBasis of StrengthStrength TOFACITINIB CITRATE (UNII: O1FF4DIV0D) (TOFACITINIB – UNII: 87LA6FU830) TOFACITINIB5 mg Inactive Ingredients Ingredient NameStrength SILICON DIOXIDE (UNII: ETJ7Z6XBU4) CROSCARMELLOSE SODIUM (UNII: M28OL1HH48) LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X) MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U) MAGNESIUM STEARATE (UNII: 70097M6I30) HYPROMELLOSE, UNSPECIFIED (UNII: 3NXW29V3WO) TITANIUM DIOXIDE (UNII: 15FIX9V2JP) POLYETHYLENE GLYCOL 3350 (UNII: G2M7P15E5P) TRIACETIN (UNII: XHX3C3X673) Product Characteristics Colorwhite (white to off white) Scoreno score ShapeROUNDSize7mm FlavorImprint Code T1;

M Contains Packaging #Item CodePackage DescriptionMarketing Start DateMarketing End Date 1NDC: 73190-100-6060 in 1 BOTTLE;

Type 0: Not a Combination Product07/23/2026 Marketing Information Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date ANDAANDA21729907/23/2026 TOFACITINIB tofacitinib tablet, film coated Product Information Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 73190-101 Route of AdministrationORAL Active Ingredient/Active Moiety Ingredient NameBasis of StrengthStrength TOFACITINIB CITRATE (UNII: O1FF4DIV0D) (TOFACITINIB – UNII: 87LA6FU830) TOFACITINIB10 mg Inactive Ingredients Ingredient NameStrength SILICON DIOXIDE (UNII: ETJ7Z6XBU4) CROSCARMELLOSE SODIUM (UNII: M28OL1HH48) LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X) MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U) MAGNESIUM STEARATE (UNII: 70097M6I30) HYPROMELLOSE, UNSPECIFIED (UNII: 3NXW29V3WO) TITANIUM DIOXIDE (UNII: 15FIX9V2JP) POLYETHYLENE GLYCOL 3350 (UNII: G2M7P15E5P) TRIACETIN (UNII: XHX3C3X673) FD&C BLUE NO. 1 (UNII: H3R47K3TBD) FD&C BLUE NO. 2 (UNII: L06K8R7DQK) Product Characteristics ColorblueScoreno score ShapeROUNDSize9mm FlavorImprint Code T2;

M Contains Packaging #Item CodePackage DescriptionMarketing Start DateMarketing End Date 1NDC: 73190-101-6060 in 1 BOTTLE;

Type 0: Not a Combination Product07/23/2026 Marketing Information Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date ANDAANDA21729907/23/2026 Labeler – AvKARE (796560394) See 17 for PATIENT COUNSELING INFORMATION. 1.4 Polyarticular Course Juvenile Idiopathic Arthritis 2.1 Recommended Evaluations and Immunization Prior to TreatmentInitiation 2.2 Important Administration Instructions 2.3 Recommended Dosage in Adults with RheumatoidArthritis, Psoriatic Arthritis, and Ankylosing Spondylitis 2.4 Recommended Dosage in Pediatric Patients 2 Years ofAge and Older with Psoriatic Arthritis or Polyarticular Course JuvenileIdiopathic Arthritis