` ----------------------- DOSAGE AND ADMINISTRATION -----------------------
`Administration Instructions
`• XELJANZ XR (tofacitinib extended-release tablets) is not
`interchangeable or substitutable with XELJANZ Oral Solution. (2.1)
`• Changes between XELJANZ and XELJANZ XR should be made by the
`healthcare provider. (2.1)
`• Do not initiate XELJANZ/XELJANZ XR/XELJANZ Oral Solution if
`absolute lymphocyte count <500 cells/mm3, an absolute neutrophil count
`(ANC) <1000 cells/mm3 or hemoglobin <9 g/dL. (2.1)
`Recommended Dosage
`Rheumatoid Arthritis
`• XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily. (2.2)
`• Recommended dosage in patients with moderate and severe renal
`impairment or moderate hepatic impairment is XELJANZ 5 mg once
`daily. (2, 8.7, 8.8)
`Psoriatic Arthritis (in combination with nonbiologic DMARDs)
`• XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily. (2.2)
`• Recommended dosage in patients with moderate and severe renal
`impairment or moderate hepatic impairment is XELJANZ 5 mg once
`daily. (2, 8.7, 8.8)
`Ulcerative Colitis
`• Induction: XELJANZ 10 mg twice daily or XELJANZ XR 22 mg once
`daily for 8 weeks; evaluate patients and transition to maintenance therapy
`depending on therapeutic response. If needed, continue XELJANZ 10 mg
`twice daily or XELJANZ XR 22 mg once daily for a maximum of
`16 weeks. Discontinue XELJANZ 10 mg twice daily or XELJANZ XR
`22 mg once daily after 16 weeks if adequate therapeutic response is not
`achieved. (2.3)
`• Maintenance: XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once
`daily. For patients with loss of response during maintenance treatment,
`XELJANZ 10 mg twice daily or XELJANZ XR 22 mg once daily may be
`considered and limited to the shortest duration, with careful consideration
`of the benefits and risks for the individual patient. Use the lowest
`effective dose needed to maintain response. (2.3)
`• Dosage adjustment is needed in patients with moderate and severe renal
`impairment or moderate hepatic impairment: see full prescribing
`information. (2.3)
`Polyarticular Course Juvenile Idiopathic Arthritis
`• XELJANZ/XELJANZ Oral Solution 5 mg twice daily or weight-based
`equivalent twice daily. (2.4)
`• Dosage adjustment is needed in patients with moderate and severe renal
`impairment or moderate hepatic impairment: see full prescribing
`information. (2.4)
`Dosage Adjustment
`• See the full prescribing information for dosage adjustments by indication
`for patients receiving CYP2C19 and/or CYP3A4 inhibitors; in patients
`with moderate or severe renal impairment or moderate hepatic impairment;
`and patients with lymphopenia, neutropenia, or anemia. (2.2, 2.3, 2.4, 8.7,
`8.8)
`• Use of XELJANZ/XELJANZ XR/XELJANZ Oral Solution in patients
`with severe hepatic impairment is not recommended in any patient
`population. (2.2, 2.3, 2.4, 8.8)
`
`
` --------------------- DOSAGE FORMS AND STRENGTHS----------------------
`XELJANZ Tablets: 5 mg, 10 mg tofacitinib (3)
`•
`•
`XELJANZ XR Tablets: 11 mg, 22 mg tofacitinib (3)
`•
`XELJANZ Oral Solution: 1 mg/mL tofacitinib (3)
`
`
` ------------------------------ CONTRAINDICATIONS ------------------------------
`None (4)
`
` ----------------------- WARNINGS AND PRECAUTIONS -----------------------
`• Serious Infections: Avoid use of XELJANZ/XELJANZ XR/XELJANZ
`Oral Solution during an active serious infection, including localized
`infections. (5.1)
`• Gastrointestinal Perforations: Use with caution in patients that may be at
`increased risk. (5.6)
`• Laboratory Monitoring: Recommended due to potential changes in
`lymphocytes, neutrophils, hemoglobin, liver enzymes and lipids. (5.8)
`• Immunizations: Live vaccines: Avoid use with XELJANZ/XELJANZ
`XR/XELJANZ Oral Solution. (5.9)
`
`
`HIGHLIGHTS OF PRESCRIBING INFORMATION
`These highlights do not include all the information needed to use
`XELJANZ/XELJANZ XR/XELJANZ Oral Solution safely and
`effectively. See full prescribing information for XELJANZ/XELJANZ
`XR/XELJANZ Oral Solution.
`
`XELJANZ® (tofacitinib) tablets, for oral use
`XELJANZ® XR (tofacitinib) extended-release tablets, for oral use
`XELJANZ® (tofacitinib) Oral Solution
`Initial U.S. Approval: 2012
`
`WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY,
`MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE), AND
`THROMBOSIS
`See full prescribing information for complete boxed warning.
`
` •
`
`
`
`Increased risk of serious bacterial, fungal, viral, and opportunistic
`infections leading to hospitalization or death, including tuberculosis
`(TB). Interrupt treatment with XELJANZ/XELJANZ XR/XELJANZ
`Oral Solution 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
`death with XELJANZ vs. TNF blockers in rheumatoid arthritis (RA)
`patients. (5.2)
`• Malignancies have occurred in patients treated with XELJANZ.
`Higher rate of lymphomas and lung cancers with XELJANZ vs. TNF
`blockers in RA patients. (5.3)
`• Higher rate of MACE (defined as cardiovascular death, myocardial
`infarction, and stroke) with XELJANZ vs. TNF blockers in RA
`patients. (5.4)
`• Thrombosis has occurred in patients treated with XELJANZ.
`Increased incidence of pulmonary embolism, venous and arterial
`thrombosis with XELJANZ vs. TNF blockers in RA patients. (5.5)
`
`
` --------------------------- RECENT MAJOR CHANGES ---------------------------
`Boxed Warning
`12/2021
`Indications and Usage (1)
`12/2021
`12/2021
`Warnings and Precautions (5.2)
`Warnings and Precautions (5.3)
`12/2021
`Warnings and Precautions (5.4)
`12/2021
`Warnings and Precautions (5.5)
`12/2021
`
` --------------------------- INDICATIONS AND USAGE ----------------------------
`XELJANZ/XELJANZ XR/XELJANZ Oral Solution is a Janus kinase (JAK)
`inhibitor indicated for:
`• Rheumatoid Arthritis: XELJANZ/XELJANZ XR is indicated for the
`treatment of adult patients with moderately to severely active rheumatoid
`arthritis who have had an inadequate response or intolerance to one or
`more TNF blockers.
`○ Limitations of Use: Use of XELJANZ/XELJANZ XR in combination
`with biologic DMARDs or potent immunosuppressants such as
`azathioprine and cyclosporine is not recommended. (1)
`• Psoriatic Arthritis: XELJANZ/XELJANZ XR is indicated for the
`treatment of adult patients with active psoriatic arthritis who have had an
`inadequate response or intolerance to one or more TNF blockers.
`○ Limitations of Use: Use of XELJANZ/XELJANZ XR in combination
`with biologic DMARDs or potent immunosuppressants such as
`azathioprine and cyclosporine is not recommended. (1)
`• Ulcerative Colitis: XELJANZ/XELJANZ XR is indicated for the
`treatment of adult patients with moderately to severely active ulcerative
`colitis (UC), who have had an inadequate response or intolerance to one
`or more TNF blockers.
`○ Limitations of Use: Use of XELJANZ/XELJANZ XR in combination
`with biological therapies for UC or with potent immunosuppressants
`such as azathioprine and cyclosporine is not recommended. (1)
`• Polyarticular Course Juvenile Idiopathic Arthritis: XELJANZ/XELJANZ
`Oral Solution is indicated for the treatment of active polyarticular course
`juvenile idiopathic arthritis (pcJIA) in patients 2 years of age and older
`who have had an inadequate response or intolerance to one or more
`TNF blockers.
`○ Limitations of Use: Use of XELJANZ/XELJANZ Oral Solution in
`combination with biologic DMARDs or potent immunosuppressants
`such as azathioprine and cyclosporine is not recommended. (1)
`
`Reference ID: 4898129
`
`

`

`• Polyarticular Course Juvenile Idiopathic Arthritis: Consistent with
`common adverse reactions reported in adult rheumatoid arthritis patients.
`(6.1)
`To report SUSPECTED ADVERSE REACTIONS, contact Pfizer, Inc. at
`1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
`
` ------------------------------ DRUG INTERACTIONS-------------------------------
`See full prescribing information for clinically relevant drug interactions. (2, 7)
`
` ----------------------- USE IN SPECIFIC POPULATIONS -----------------------
`Lactation: Advise not to breastfeed. (8.2)
`
`See 17 for PATIENT COUNSELING INFORMATION and Medication
`Guide.
`
`Revised: 12/2021
`
`
`
` ------------------------------ ADVERSE REACTIONS-------------------------------
`Most common adverse reactions are:
`• Rheumatoid and Psoriatic Arthritis: Reported during the first 3 months in
`rheumatoid arthritis controlled clinical trials and occurring in ≥2% of
`patients treated with XELJANZ monotherapy or in combination with
`DMARDs: upper respiratory tract infection, nasopharyngitis, diarrhea,
`and headache. (6.1)
`• Ulcerative Colitis: Reported in ≥5% of patients treated with either 5 mg or
`10 mg twice daily of XELJANZ and ≥1% greater than reported in patients
`receiving placebo in either the induction or maintenance clinical trials:
`nasopharyngitis, elevated cholesterol levels, headache, upper respiratory
`tract infection, increased blood creatine phosphokinase, rash, diarrhea,
`and herpes zoster. (6.1)
`
`Reference ID: 4898129
`
`

`

`
`FULL PRESCRIBING INFORMATION: CONTENTS*
`
`WARNING: SERIOUS INFECTIONS, MORTALITY,
`MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR
`EVENTS, AND THROMBOSIS
`INDICATIONS AND USAGE
`1
`2 DOSAGE AND ADMINISTRATION
`2.1
`Important Administration Instructions
`2.2 Recommended Dosage in Rheumatoid Arthritis and Psoriatic
`Arthritis
`2.3 Recommended Dosage in Ulcerative Colitis
`2.4 Recommended Dosage in Polyarticular Course Juvenile
`Idiopathic Arthritis
`3 DOSAGE FORMS AND STRENGTHS
`4 CONTRAINDICATIONS
`5 WARNINGS AND PRECAUTIONS
`5.1
`Serious Infections
`5.2 Mortality
`5.3 Malignancy and Lymphoproliferative Disorders
`5.4 Major Adverse Cardiovascular Events
`5.5
`Thrombosis
`5.6 Gastrointestinal Perforations
`5.7 Hypersensitivity
`5.8
`Laboratory Abnormalities
`5.9 Vaccinations
`5.10 Risk of Gastrointestinal Obstruction with a Non-Deformable
`Extended-Release Formulation such as XELJANZ XR
`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 Use in Diabetics
`8.7 Renal Impairment
`8.8 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 Rheumatoid Arthritis
`14.2 Psoriatic Arthritis
`14.3 Ulcerative Colitis
`14.4 Polyarticular Course Juvenile Idiopathic Arthritis
`14.5 Safety Study
`16 HOW SUPPLIED/STORAGE AND HANDLING
`17 PATIENT COUNSELING INFORMATION
`
`*Sections or subsections omitted from the Full Prescribing Information
`are not listed.
`
`
`Reference ID: 4898129
`
`2
`
`

`

`
`
`FULL PRESCRIBING INFORMATION
`
`
`WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR
`ADVERSE CARDIOVASCULAR EVENTS, AND THROMBOSIS
`
`
`SERIOUS INFECTIONS
`Patients treated with XELJANZ/XELJANZ XR/XELJANZ Oral Solution are at increased
`risk for developing serious infections that may lead to hospitalization or death [see
`Warnings and Precautions (5.1), Adverse Reactions (6.1)]. Most patients who developed
`these infections were taking concomitant immunosuppressants such as methotrexate or
`corticosteroids.
`
`If a serious infection develops, interrupt XELJANZ/XELJANZ XR/XELJANZ Oral
`Solution until the infection is controlled.
`
`Reported infections include:
`
` •
`
` Active tuberculosis, which may present with pulmonary or extrapulmonary disease.
`Patients should be tested for latent tuberculosis before XELJANZ/XELJANZ
`XR/XELJANZ Oral Solution use and during therapy. Treatment for latent infection
`should be initiated prior to XELJANZ/XELJANZ XR/XELJANZ Oral Solution use.
`• Invasive fungal infections, including cryptococcosis and pneumocystosis. Patients with
`invasive fungal infections may present with disseminated, rather than localized, disease.
`• Bacterial, viral, including herpes zoster, and other infections due to opportunistic
`pathogens.
`
`The risks and benefits of treatment with XELJANZ/XELJANZ XR/XELJANZ Oral
`Solution should be carefully considered prior to initiating therapy in patients with chronic
`or recurrent infection.
`
`Patients should be closely monitored for the development of signs and symptoms of
`infection during and after treatment with XELJANZ/XELJANZ XR/XELJANZ Oral
`Solution, including the possible development of tuberculosis in patients who tested negative
`for latent tuberculosis infection prior to initiating therapy [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 one cardiovascular risk factor comparing XELJANZ
`5 mg twice a day or XELJANZ 10 mg twice a day to tumor necrosis factor (TNF) blockers,
`a higher rate of all-cause mortality, including sudden cardiovascular death, was observed
`with XELJANZ 5 mg twice a day or XELJANZ 10 mg twice a day [see Warnings and
`Precautions (5.2)]. A XELJANZ/XELJANZ Oral Solution 10 mg twice daily (or a
`XELJANZ XR 22 mg once daily) dosage is not recommended for the treatment of RA or
`PsA [see Dosage and Administration (2.2)].
`
`
`Reference ID: 4898129
`
`3
`
`

`

`
`
`MALIGNANCIES
`Malignancies, including lymphomas and solid tumors, have occurred in patients treated
`with XELJANZ and other Janus kinase inhibitors used to treat inflammatory conditions.
`In RA patients, a higher rate of malignancies (excluding NMSC) was observed in patients
`treated with XELJANZ 5 mg twice a day or XELJANZ 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
`XELJANZ 5 mg twice a day or XELJANZ 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.
`
`Epstein Barr Virus-associated post-transplant lymphoproliferative disorder has been
`observed at an increased rate in renal transplant patients treated with XELJANZ and
`concomitant immunosuppressive medications [see Warnings and Precautions (5.3)].
`
`MAJOR ADVERSE CARDIOVASCULAR EVENTS
`RA patients 50 years of age and older with at least one cardiovascular risk factor, treated
`with XELJANZ 5 mg twice daily or XELJANZ 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
`XELJANZ/XELJANZ XR/XELJANZ Oral Solution 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 XELJANZ 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 XELJANZ 5 mg twice daily or XELJANZ 10 mg
`twice daily compared to TNF blockers had an observed increase in incidence of these
`events. Avoid XELJANZ/XELJANZ XR/XELJANZ Oral Solution in patients at risk.
`Discontinue XELJANZ/XELJANZ XR/XELJANZ Oral Solution and promptly evaluate
`patients with symptoms of thrombosis [see Warnings and Precautions (5.5)].
`
`
` 1
`
` INDICATIONS AND USAGE
`
`
`Rheumatoid Arthritis
`XELJANZ/XELJANZ XR is indicated for the treatment of adult patients with moderately to
`severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to
`one or more TNF blockers.
`
`
`Reference ID: 4898129
`
`4
`
`

`

`
`
`• Limitations of Use: Use of XELJANZ/XELJANZ XR in combination with biologic
`disease-modifying antirheumatic drugs (DMARDs) or with potent immunosuppressants such
`as azathioprine and cyclosporine is not recommended.
`
`
`Psoriatic Arthritis
`XELJANZ/XELJANZ XR is indicated for the treatment of adult patients with active psoriatic
`arthritis (PsA) who have had an inadequate response or intolerance to one or more TNF blockers.
`
`Limitations of Use: Use of XELJANZ/XELJANZ XR in combination with biologic DMARDs or
`with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.
`
`Ulcerative Colitis
`XELJANZ/XELJANZ XR is indicated for the treatment of adult patients with moderately to
`severely active ulcerative colitis (UC), who have an inadequate response or intolerance to one or
`more TNF blockers.
`• Limitations of Use: Use of XELJANZ/XELJANZ XR in combination with biological
`therapies for UC or with potent immunosuppressants such as azathioprine and cyclosporine is
`not recommended.
`
`
`Polyarticular Course Juvenile Idiopathic Arthritis
`XELJANZ/XELJANZ Oral Solution is indicated for the treatment of active polyarticular course
`juvenile idiopathic arthritis (pcJIA) in patients 2 years of age and older who have had an
`inadequate response or intolerance to one or more TNF blockers.
`• Limitations of Use: Use of XELJANZ/XELJANZ Oral Solution in combination with biologic
`DMARDs or with potent immunosuppressants such as azathioprine and cyclosporine is not
`recommended.
`
`
`
`•
`
`
`
`Reference ID: 4898129
`
`5
`
` 2
`
` DOSAGE AND ADMINISTRATION
`
`
`2.1 Important Administration Instructions
`• XELJANZ XR (tofacitinib extended-release tablets) is not interchangeable or
`substitutable with XELJANZ Oral Solution.
`• Changes between XELJANZ and XELJANZ XR should be made by the healthcare
`provider [see Dosage and Administration (2.2)].
`• Do not initiate XELJANZ/XELJANZ XR/XELJANZ Oral Solution in patients with an
`absolute lymphocyte count less than 500 cells/mm3, an absolute neutrophil count (ANC)
`less than 1000 cells/mm3 or who have hemoglobin levels less than 9 g/dL.
`• Dose interruption is recommended for management of lymphopenia, neutropenia, and
`anemia [see Warnings and Precautions (5.8), Adverse Reactions (6.1)].
`Interrupt use of XELJANZ/XELJANZ XR/XELJANZ Oral Solution if a patient develops
`a serious infection until the infection is controlled [see Warnings and Precautions (5.1)].
`• Take XELJANZ/XELJANZ XR/XELJANZ Oral Solution with or without food [see
`Clinical Pharmacology (12.3)].
`• Swallow XELJANZ XR tablets whole and intact. Do not crush, split, or chew.
`
`

`

`2.2 Recommended Dosage in Rheumatoid Arthritis and Psoriatic Arthritis
`Table 1 displays the recommended adult daily dosage of XELJANZ and XELJANZ XR and
`dosage adjustments for patients receiving CYP2C19 and/or CYP3A4 inhibitors, in patients with
`moderate or severe renal impairment (including but not limited to those with severe insufficiency
`who are undergoing hemodialysis) or moderate hepatic impairment, with lymphopenia,
`neutropenia, or anemia.
`
`Table 1: Recommended Dosage of XELJANZ and XELJANZ XR in Patients with
`Rheumatoid Arthritis and Psoriatic Arthritis1
`XELJANZ
`tablet
`5 mg twice daily
`
`
`
`
`
`Adult patients
`Patients receiving:
`• Strong CYP3A4 inhibitors (e.g.,
`ketoconazole), or
`• a moderate CYP3A4 inhibitor(s)
`with a strong CYP2C19
`inhibitor(s) (e.g., fluconazole)
`[see Drug Interactions (7)]
`Patients with:
`• moderate or severe renal
`impairment [see Use in Specific
`Populations (8.7)]
`• moderate hepatic impairment
`[see Use in Specific Populations
`(8.8)]*
`
`
`
`XELJANZ XR
`extended-release tablet
`11 mg once daily
`
`5 mg once daily
`
`Reduce to
`XELJANZ 5 mg once daily
`
`5 mg once daily
`
`Reduce to
`XELJANZ 5 mg once daily
`
`For patients undergoing hemodialysis, dose should be administered after
`the dialysis session on dialysis days. If a dose was taken before the
`dialysis procedure, supplemental doses are not recommended in patients
`after dialysis.
`
`Discontinue dosing.
`
`Patients with lymphocyte count less
`than 500 cells/mm3, confirmed by
`repeat testing
`Patients with ANC 500 to
`1000 cells/mm3
`
`Interrupt dosing.
`Interrupt dosing.
`When ANC is greater than 1000,
`When ANC is greater than 1000,
`resume 11 mg once daily.
`resume 5 mg twice daily.
`Discontinue dosing.
`
`Interrupt dosing until hemoglobin values have normalized.
`
`Patients with ANC less than
`500 cells/mm3
`Patients with hemoglobin less than
`8 g/dL or a decrease of more than
`2 g/dL
`1 XELJANZ/XELJANZ XR is used in combination with nonbiologic disease-modifying antirheumatic drugs
`(DMARDs) in psoriatic arthritis. The efficacy of XELJANZ/XELJANZ XR as a monotherapy has not been
`studied in psoriatic arthritis.
`* Use of XELJANZ/XELJANZ XR in patients with severe hepatic impairment is not recommended.
`
`Switching from XELJANZ Tablets to XELJANZ XR Extended-Release Tablets
`Patients treated with XELJANZ tablets 5 mg twice daily may be switched to XELJANZ XR
`extended-release tablets 11 mg once daily the day following the last dose of XELJANZ 5 mg.
`
`
`Reference ID: 4898129
`
`6
`
`

`

`
`
`Adult patients
`
`Patients receiving:
`• Strong CYP3A4 inhibitors (e.g.,
`ketoconazole), or
`• a moderate CYP3A4 inhibitor(s)
`with a strong CYP2C19 inhibitor(s)
`(e.g., fluconazole)
`[see Drug Interactions (7)]
`Patients with:
`• moderate or severe renal
`impairment [see Use in Specific
`Populations (8.7)]
`• moderate hepatic impairment [see
`Use in Specific Populations (8.8)]*
`
`
`
`Patients with lymphocyte count less
`than 500 cells/mm3, confirmed by
`repeat testing
`
`2.3 Recommended Dosage in Ulcerative Colitis
`Table 2 displays the recommended adult daily dosage of XELJANZ/XELJANZ XR and dosage
`adjustments for patients receiving CYP2C19 and/or CYP3A4 inhibitors, with moderate or severe
`renal impairment (including but not limited to those with severe insufficiency who are
`undergoing hemodialysis) or moderate hepatic impairment, with lymphopenia, neutropenia or
`anemia.
`
`Table 2: Recommended Dosage of XELJANZ/XELJANZ XR in Patients with UC
`
`XELJANZ
`XELJANZ XR
`tablet
`extended-release tablet
`Induction: 10 mg twice daily for
`Induction: 22 mg once daily for at
`at least 8 weeks [see Clinical
`least 8 weeks; evaluate patients and
`Studies (14.3)]; evaluate patients
`transition to maintenance therapy
`and transition to maintenance
`depending on therapeutic response.
`therapy depending on therapeutic
`If needed continue 22 mg once
`response. If needed continue 10 mg
`daily for a maximum of 16 weeks.
`twice daily for a maximum of
`Discontinue 22 mg once daily after
`16 weeks. Discontinue 10 mg
`16 weeks if adequate therapeutic
`twice daily after 16 weeks if
`response is not achieved.
`
`adequate therapeutic response is
`Maintenance: 11 mg once daily.
`not achieved.
`
`
`Maintenance: 5 mg twice daily.
`For patients with loss of response
`
`during maintenance treatment, a
`For patients with loss of response
`dosage of 22 mg once daily may be
`during maintenance treatment, a
`considered and limited to the
`dosage of 10 mg twice daily may
`shortest duration, with careful
`be considered and limited to the
`consideration of the benefits and
`shortest duration, with careful
`risks for the individual patient. Use
`consideration of the benefits and
`the lowest effective dose needed to
`maintain response.
`risks for the individual patient. Use
`the lowest effective dose needed to
`maintain response.
`If taking 10 mg twice daily, reduce
`to 5 mg twice daily.
`
`If taking 5 mg twice daily, reduce
`to 5 mg once daily.
`
`If taking 22 mg once daily, reduce
`to 11 mg once daily.
`
`If taking 11 mg once daily, reduce
`to XELJANZ 5 mg once daily
`
`If taking 10 mg twice daily, reduce
`to 5 mg twice daily.
`
`If taking 5 mg twice daily, reduce
`to 5 mg once daily.
`
`If taking 22 mg once daily, reduce
`to 11 mg once daily.
`
`If taking 11 mg once daily, reduce
`to XELJANZ 5 mg once daily.
`
`For patients undergoing hemodialysis, dose should be administered after
`the dialysis session on dialysis days. If a dose was taken before the
`dialysis procedure, supplemental doses are not recommended in patients
`after dialysis.
`
`Discontinue dosing.
`
`Reference ID: 4898129
`
`7
`
`

`

`
`
`
`
`Patients with ANC 500 to
`1000 cells/mm3
`
`XELJANZ
`tablet
`If taking 10 mg twice daily, reduce
`to 5 mg twice daily. When ANC is
`greater than 1000, increase to 10
`mg twice daily based on clinical
`response.
`
`If taking 5 mg twice daily,
`interrupt dosing. When ANC is
`greater than 1000, resume 5 mg
`twice daily.
`
`XELJANZ XR
`extended-release tablet
`If taking 22 mg once daily, reduce
`to 11 mg once daily. When ANC is
`greater than 1000, increase to
`22 mg once daily based on clinical
`response.
`
`If taking 11 mg once daily,
`interrupt dosing. When ANC is
`greater than 1000, resume 11 mg
`once daily.
`
`Discontinue dosing.
`
`Interrupt dosing until hemoglobin values have normalized.
`
`Patients with ANC less than
`500 cells/mm3
`Patients with hemoglobin less than
`8 g/dL or a decrease of more than 2
`g/dL
`*Use of XELJANZ/XELJANZ XR in patients with severe hepatic impairment is not recommended.
`
`Switching from XELJANZ Tablets to XELJANZ XR Extended-Release Tablets
`Patients treated with XELJANZ 5 mg tablets twice daily may be switched to XELJANZ XR
`extended-release tablets 11 mg once daily the day following the last dose of XELJANZ tablets
`5 mg. Patients treated with XELJANZ 10 mg tablets twice daily may be switched to XELJANZ
`XR extended-release tablets 22 mg once daily the day following the last dose of XELJANZ
`10 mg.
`
`2.4 Recommended Dosage in Polyarticular Course Juvenile Idiopathic Arthritis
`Table 3 displays the recommended body weight-based dosages for XELJANZ tablets/XELJANZ
`Oral Solution and dosage adjustments for patients receiving CYP2C19 and/or CYP3A4
`inhibitors [see Drug Interactions (7)], in patients with moderate or severe renal impairment,
`including but not limited to those undergoing hemodialysis [see Use in Specific Populations
`(8.7)], with moderate hepatic impairment [see Use in Specific Populations (8.8)], with
`lymphopenia, neutropenia, or anemia.
`
`Table 3: Recommended Dosage of XELJANZ/XELJANZ Oral Solution in Patients with
`pcJIA
`
`XELJANZ tablets/XELJANZ Oral Solution
`• 10 kg ≤ body weight <20 kg:
`3.2 mg (3.2 mL oral solution) twice daily
`
` •
`
` 20 kg ≤ body weight <40 kg:
`4 mg (4 mL oral solution) twice daily
`
` •
`
` Body weight ≥40 kg:
`5 mg (one 5 mg tablet or 5 mL oral solutionb) twice
`daily
`If taking 3.2 mg twice daily, reduce to 3.2 mg once daily.
`
`If taking 4 mg twice daily, reduce to 4 mg once daily.
`
`If taking 5 mg twice daily, reduce to 5 mg once daily.
`
`
`
`pcJIA patients
`
`Patients receiving:
`• strong CYP3A4 inhibitors (e.g., ketoconazole), or
`• a moderate CYP3A4 inhibitor(s) with a strong
`CYP2C19 inhibitor(s) (e.g., fluconazole)
`[see Drug Interactions (7)]
`
`Reference ID: 4898129
`
`8
`
`

`

`
`
`
`Patients with:
`• moderate or severe renal impairment [see Use in
`Specific Populations (8.7)]
`• moderate hepatic impairment [see Use in Specific
`Populations (8.8)]a
`
`Patients with lymphocyte count less than
`500 cells/mm3, confirmed by repeat testing
`Patients with ANC 500 to 1000 cells/mm3
`
`XELJANZ tablets/XELJANZ Oral Solution
`If taking 3.2 mg twice daily, reduce to 3.2 mg once daily.
`
`If taking 4 mg twice daily, reduce to 4 mg once daily.
`
`If taking 5 mg twice daily, reduce to 5 mg once daily.
`
`For patients undergoing hemodialysis, dose should be
`administered after the dialysis session on dialysis days. If
`a dose was taken before the dialysis procedure,
`supplemental doses are not recommended in patients after
`dialysis.
`Discontinue dosing.
`Interrupt dosing until ANC is greater than
`1000 cells/mm3.
`Discontinue dosing.
`Patients with ANC less than 500 cells/mm3
`Interrupt dosing until hemoglobin values have
`Patients with hemoglobin less than 8 g/dL or a
`normalized.
`decrease of more than 2 g/dL
`a XELJANZ/XELJANZ Oral Solution is not recommended for patients with severe hepatic impairment.
`b Patients treated with 5 mL XELJANZ Oral Solution may be switched to a XELJANZ 5 mg tablet.
`
`Administer XELJANZ Oral Solution using the included press-in bottle adapter and oral dosing
`syringe [see Instructions for Use].
`
`
`
`XELJANZ XR Tablets:
`○ 11 mg tofacitinib: Pink, oval, extended-release film-coated tablets with a drilled hole at
`one end of the tablet band and “JKI 11” printed on one side of the tablet.
`○ 22 mg tofacitinib: Beige, oval, extended-release film-coated tablets with a drilled hole at
`one end of the tablet band and “JKI 22” printed on one side of the tablet.
`
`
`XELJANZ Oral Solution:
`1 mg/mL tofacitinib: Clear, colorless oral solution.
`
`
` 4
`
` CONTRAINDICATIONS
`
`
`None.
`
`
`
`Reference ID: 4898129
`
`9
`
` 3
`
` DOSAGE FORMS AND STRENGTHS
`
`
`XELJANZ Tablets:
`○ 5 mg tofacitinib: White, round, immediate-release film-coated tablets, debossed with
`“Pfizer” on one side, and “JKI 5” on the other side.
`○ 10 mg tofacitinib: Blue, round, immediate-release film-coated tablets, debossed with
`“Pfizer” on one side, and “JKI 10” on the other side.
`
`

`

`
`
`5 WARNINGS AND PRECAUTIONS
`
`5.1 Serious Infections
`Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or
`other opportunistic pathogens have been reported in patients receiving XELJANZ. The most
`common serious infections reported with XELJANZ included pneumonia, cellulitis, herpes
`zoster, urinary tract infection, diverticulitis, and appendicitis. Among opportunistic infections,
`tuberculosis and other mycobacterial infections, cryptococcosis, histoplasmosis, esophageal
`candidiasis, pneumocystosis, multidermatomal herpes zoster, cytomegalovirus infections, BK
`virus infection, and listeriosis were reported with XELJANZ. 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, XELJANZ treatment with 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 XELJANZ 10 mg twice daily.
`
`Other serious infections that were not reported in clinical studies may also occur (e.g.,
`coccidioidomycosis).
`
`Avoid use of XELJANZ/XELJANZ XR/XELJANZ Oral Solution in patients with an active,
`serious infection, including localized infections. The risks and benefits of treatment should be
`considered prior to initiating XELJANZ/XELJANZ XR/XELJANZ Oral Solution in patients:
`• with chronic or recurrent infection
`• who have been exposed to tuberculosis
`• with a history of a serious or an opportunistic infection
`• who have resided or traveled in areas of endemic tuberculosis or endemic mycoses; or
`• with underlying conditions that may predispose them to infection.
`
`Patients should be closely monitored for the development of signs and symptoms of infection
`during and after treatment with XELJANZ/XELJANZ XR/XELJANZ Oral Solution.
`XELJANZ/XELJANZ XR/XELJANZ Oral Solution should be interrupted if a patient develops a
`serious infection, an opportunistic infection, or sepsis. A patient who develops a new infection
`during treatment with XELJANZ/XELJANZ XR/XELJANZ Oral Solution should undergo
`prompt and complete diagnostic testing appropriate for an immunocompromised patient;
`appropriate antimicrobial therapy should be initiated, and the patient should be closely
`monitored.
`
`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 (2.2, 2.3, 2.4)].
`
`Reference ID: 4898129
`
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`

`
`
`
`Tuberculosis
`Patients should be evaluated and tested for latent or active infection prior to and per applicable
`guidelines during administration of XELJANZ/XELJANZ XR/XELJANZ Oral Solution.
`
`Anti-tuberculosis therapy should also be considered prior to administration of
`XELJANZ/X