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
`
`
`Dosage and Administration (2.2)
`12/2021
`
`
`
`
`Warnings and Precautions (5.2)
`12/2021
`
`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. (1.1)
`
`• 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. (1.2)
`
`
`• Ankylosing Spondylitis: XELJANZ/XELJANZ XR is indicated for the
`
`
`
`treatment of adult patients with active ankylosing spondylitis 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. (1.3)
`
`
`• 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. (1.4)
`
`• 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
`
`
`
`
`Reference ID: 4904169
`
`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. (1.5)
`
`
`
`
`
`-----------------------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)
`
`
`Ankylosing Spondylitis
`
`• 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)
`
`
`
`------------------------------ ADVERSE REACTIONS------------------------------­
`
`
`Most common adverse reactions are:
`
`• Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis:
`
`
`
`
`Reported during the first 3 months in rheumatoid arthritis
`
`
`
`placebo-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)
`
`
`• 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
`
`
`
`
`
`Reference ID: 4904169
`
`

`

`Postmarketing Experience
`
`6.2
`
`
`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 Ankylosing Spondylitis
`
`
`
`14.4 Ulcerative Colitis
`
`
`
`14.5 Polyarticular Course Juvenile Idiopathic Arthritis
`
`
`
`
`14.6 Safety Study
`
`
`
`16 HOW SUPPLIED/STORAGE AND HANDLING
`
`
`17 PATIENT COUNSELING INFORMATION
`
`
`*Sections or subsections omitted from the Full Prescribing Information
`are not listed.
`
`
`
`
`FULL PRESCRIBING INFORMATION: CONTENTS*
`
`WARNING: SERIOUS INFECTIONS, MORTALITY,
`
`
`MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR
`
`EVENTS, AND THROMBOSIS
`
`
`INDICATIONS AND USAGE
`1
`
`
`1.1 Rheumatoid Arthritis
`
`
`
`1.2
`Psoriatic Arthritis
`
`
`
`1.3 Ankylosing Spondylitis
`
`
`
`1.4 Ulcerative Colitis
`
`
`
`1.5
`Polyarticular Course Juvenile Idiopathic Arthritis
`
`
`
`2 DOSAGE AND ADMINISTRATION
`
`
`
`Important Administration Instructions
`
`2.1
`
`
`2.2 Recommended Dosage in Rheumatoid Arthritis, Psoriatic
`
`
`
`Arthritis, and Ankylosing Spondylitis
`
`
`
`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
`
`
`
`
`
`
`
`
`
`
`
`Reference ID: 4904169
`
`
`
` 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: 4904169
`
`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
`
`
`1.1 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: 4904169
`
`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.
`
`
`
`1.2 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.
`
`
`
` 1.3 Ankylosing Spondylitis
`
`XELJANZ/XELJANZ XR is 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 XELJANZ/XELJANZ XR in combination with biologic
`
`
`
`
`DMARDs or potent immunosuppressants such as azathioprine and cyclosporine is not
`
`
`recommended.
`
`
`
`1.4 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.
`
`
`
`1.5 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.
`
`
`
`
`2 DOSAGE AND ADMINISTRATION
`
`
`2.1 Important Administration Instructions
`
`• XELJANZ XR (tofacitinib extended-release tablets) is not interchangeable or
`
`
`
`
`substitutable with XELJANZ Oral Solution.
`
`
`
`Reference ID: 4904169
`
`5
`
`
`
`

`

`
`
`
`
`
`
`
`•
`
`
`
` • 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, Psoriatic Arthritis, and Ankylosing
`
`Spondylitis
`
`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, Psoriatic Arthritis1, and Ankylosing Spondylitis
`
`
` XELJANZ XR
`
` XELJANZ
`
`
` tablet
` extended-release tablet
`
` 5 mg twice daily
`
`
`
`
` 11 mg once daily
`
`
`
`
`
`
`
`
`
` 5 mg once daily
`
`
`
`
`
` 5 mg once daily
`
`
`
` Reduce to
`
`
`
` XELJANZ 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.
`
`
`
` Interrupt dosing.
`
`
`
`
`
` When ANC is greater than 1000,
` resume 5 mg twice daily.
`
`
`
`
`
`
`
`
` Interrupt dosing.
` When ANC is greater than 1000,
`
`
`
` resume 11 mg once 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)]*
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Patients with lymphocyte count less
`
`
`
`
`
`
`
`
` than 500 cells/mm3, confirmed by
` repeat testing
`
`
` Patients with ANC 500 to
`
`
` 1000 cells/mm3
`
`
`
`
`
`
`
`
`
`Reference ID: 4904169
`
`6
`
`
`

`

`
`
`
`
`
`
`
`
`
`
`
`
` XELJANZ
`
` tablet
`
` XELJANZ XR
`
` extended-release tablet
`
` 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.
`
`
`
`
` 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 XR
`
`
`
` XELJANZ
` extended-release tablet
`
` tablet
`
`Induction: 22 mg once daily for
` Induction: 10 mg twice daily for
`
`
`
`
`
`
`
`
`
` at least 8 weeks; evaluate patients
`
`
`
`
` at least 8 weeks [see Clinical
`
`
`
`
`
`
` and transition to maintenance
`
`
`
`
` Studies (14.4)]; evaluate patients
`
`
` therapy depending on therapeutic
`
` and transition to maintenance
`
`
`
` response. If needed continue 22
`
`
`
`
`
` therapy depending on therapeutic
`
` mg once daily for a maximum of
`
`
`
` response. If needed continue
`
`
`
` 16 weeks. Discontinue 22 mg
`
`
` 10 mg twice daily for a maximum
`
`
`
`
`
` once daily after 16 weeks if
`
`
`
`
`
`
` of 16 weeks. Discontinue 10 mg
`
`
`
`
`
` adequate therapeutic response is
` twice daily after 16 weeks if
`
`
`
`
`
`
` adequate therapeutic response is
` not achieved.
`
`
`
` not achieved.
`Maintenance: 11 mg once daily.
`
`
`
`
`
`Maintenance: 5 mg twice daily.
`
`
`
`
`
`
` For patients with loss of response
`
`
`
`
`
`
`
`
`
`For patients with loss of response
`
`
`during maintenance treatment, a
` during maintenance treatment, a
`
`
`
` dosage of 22 mg once daily may
`
`
`
`
`
`
`
`
`
`
`dosage of 10 mg twice daily may
`
`
`
`
`
`
`be considered and limited to the
`
`
`
`
`
`
`be considered and limited to the
`
`
`
`
`shortest duration, with careful
`
`
`
`
`shortest duration, with careful
`
`
`
`
`
`consideration of the benefits and
`
`
`
`
`
`consideration of the benefits and
`
`
`
`
`
`risks for the individual patient.
`
`
`
`
`
`risks for the individual patient.
`
`
`Use the lowest effective dose
`
`
`
`Use the lowest effective dose
`needed to maintain response.
`
`needed to maintain response.
`
`
`
` Adult patients
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Reference ID: 4904169
`
`7
`
`
`

`

`
`
` 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
`
`
` Patients with ANC 500 to
`
`
` 1000 cells/mm3
`
`
`
`
`
`
`
`
`
`
`
` XELJANZ
`
` tablet
` 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 10 mg twice daily,
`
`
`
`
`
`
`reduce to 5 mg twice daily.
`
`
`
`
`If taking 5 mg twice daily, reduce
`
`
`
`
`to 5 mg once daily.
`
`
`
`
`
`
` XELJANZ XR
`
`
` extended-release tablet
` 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 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.
`
`
`
`
`
`
`
`
`
` 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.
`
`
`
`
`
`
`
` 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.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` 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.
`
`
`
` Interrupt dosing until hemoglobin values have normalized.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`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
`
`
`
`
`Reference ID: 4904169
`
`8
`
`
`
`

`

`
`
`
`
`
`
` pcJIA patients
`
`
`
` (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.
`
` 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
`
`
`