Xeljanz

(Tofacitinib)

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Xeljanz Prescribing Information

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.
- o
  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 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.
  •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 who have had an inadequate response or intolerance to one or more TNF blockers.
- o
  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 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.
  )
•
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.
- o
  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 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.
  )
•
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.
- o
  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 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.
- o
  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 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.
  )

Administration Instructions

•XELJANZ XR (tofacitinib extended-release tablets) is not interchangeable or substitutable with XELJANZ Oral Solution. (
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/mm³or 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.
)
•Changes between XELJANZ and XELJANZ XR should be made by the healthcare provider. (
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/mm³or 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.
)
•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 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/mm³or 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.
)

Recommended Dosage

Rheumatoid Arthritis

•XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily. (

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.

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)]

moderate or severe renal impairment

[see Use in Specific Populations (8.7)]

moderate hepatic impairment

[see Use in Specific Populations (8.8)]

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

Table 1: Recommended Dosage of XELJANZ and XELJANZ XR in Patients with Rheumatoid Arthritis, Psoriatic ArthritisXELJANZ/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., and Ankylosing Spondylitis
	XELJANZ tablet	XELJANZ XR extended-release tablet
Adult patients	5 mg twice daily	11 mg once daily
Patients receiving:
5 mg once daily	Reduce to XELJANZ 5 mg once daily
Patients with:
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.
Patients with lymphocyte count less than 500 cells/mm³, confirmed by repeat testing	Discontinue dosing.
Patients with ANC 500 to 1000 cells/mm³	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.
Patients with ANC less than 500 cells/mm³	Discontinue dosing.
Patients with hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL	Interrupt dosing until hemoglobin values have normalized.

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.

)

•Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is XELJANZ 5 mg once daily. (

2 DOSAGE AND ADMINISTRATION

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.
•Do not initiate XELJANZ/XELJANZ XR/XELJANZ Oral Solution if absolute lymphocyte count <500 cells/mm³, an absolute neutrophil count (ANC) <1000 cells/mm³or hemoglobin <9 g/dL.

Recommended Dosage

Rheumatoid Arthritis

•XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily.
•Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is XELJANZ 5 mg once daily.

Psoriatic Arthritis (in combination with nonbiologic DMARDs)

•XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily.
•Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is XELJANZ 5 mg once daily.

Ankylosing Spondylitis

•XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily.
•Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is XELJANZ 5 mg once daily.

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.
•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.
•Dosage adjustment is needed in patients with moderate and severe renal impairment or moderate hepatic impairment: see full prescribing information.

Polyarticular Course Juvenile Idiopathic Arthritis

•XELJANZ/XELJANZ Oral Solution 5 mg twice daily or weight-based equivalent twice daily.
•Dosage adjustment is needed in patients with moderate and severe renal impairment or moderate hepatic impairment: see full prescribing information.

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

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/mm³or 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

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)]

moderate or severe renal impairment

[see Use in Specific Populations (8.7)]

moderate hepatic impairment

[see Use in Specific Populations (8.8)]

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

Table 1: Recommended Dosage of XELJANZ and XELJANZ XR in Patients with Rheumatoid Arthritis, Psoriatic ArthritisXELJANZ/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., and Ankylosing Spondylitis
	XELJANZ tablet	XELJANZ XR extended-release tablet
Adult patients	5 mg twice daily	11 mg once daily
Patients receiving:
5 mg once daily	Reduce to XELJANZ 5 mg once daily
Patients with:
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.
Patients with lymphocyte count less than 500 cells/mm³, confirmed by repeat testing	Discontinue dosing.
Patients with ANC 500 to 1000 cells/mm³	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.
Patients with ANC less than 500 cells/mm³	Discontinue dosing.
Patients with hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL	Interrupt dosing until hemoglobin values have normalized.

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.

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)]

moderate or severe renal impairment

[see Use in Specific Populations (8.7)]

moderate hepatic impairment

[see Use in Specific Populations (8.8)]

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

Table 2: Recommended Dosage of XELJANZ/XELJANZ XR in Patients with UC
	XELJANZ tablet	XELJANZ XR extended-release tablet
Adult patients	Induction: 10 mg twice daily for at least 8 weeks [see Clinical Studies (14.4)] ; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed continue 10 mg twice daily for a maximum of 16 weeks. Discontinue 10 mg twice daily after 16 weeks if adequate therapeutic response is not achieved. Maintenance: 5 mg twice daily. For patients with loss of response during maintenance treatment, a dosage of 10 mg twice 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 .	Induction: 22 mg once daily for at least 8 weeks; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed continue 22 mg once daily for a maximum of 16 weeks. Discontinue 22 mg once daily after 16 weeks if adequate therapeutic response is not achieved. Maintenance: 11 mg once daily. For patients with loss of response during maintenance treatment, a dosage of 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.
Patients receiving:
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
Patients with:
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.
Patients with lymphocyte count less than 500 cells/mm³, confirmed by repeat testing	Discontinue dosing.
Patients with ANC 500 to 1000 cells/mm³	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.
Patients with ANC less than 500 cells/mm³	Discontinue dosing.
Patients with hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL	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 (8.7)]

, with moderate hepatic impairment

[see Use in Specific Populations (8.8)]

, with lymphopenia, neutropenia, or anemia.

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 solutionPatients treated with 5 mL XELJANZ Oral Solution may be switched to a XELJANZ 5 mg tablet.) twice dailystrong CYP3A4 inhibitors (e.g., ketoconazole), or

a moderate CYP3A4 inhibitor(s) with a strong CYP2C19 inhibitor(s) (e.g., fluconazole)

[see Drug Interactions (7)]

moderate or severe renal impairment

[see Use in Specific Populations (8.7)]

moderate hepatic impairment

[see Use in Specific Populations (8.8)]

XELJANZ/XELJANZ Oral Solution is not recommended for patients with severe hepatic impairment.

Table 3: Recommended Dosage of XELJANZ/XELJANZ Oral Solution in Patients with pcJIA
	XELJANZ tablets/XELJANZ Oral Solution
pcJIA patients
Patients receiving:
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.
Patients with:
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.
Patients with lymphocyte count less than 500 cells/mm³, confirmed by repeat testing	Discontinue dosing.
Patients with ANC 500 to 1000 cells/mm³	Interrupt dosing until ANC is greater than 1000 cells/mm³.
Patients with ANC less than 500 cells/mm³	Discontinue dosing.
Patients with hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL	Interrupt dosing until hemoglobin values have normalized.

Administer XELJANZ Oral Solution using the included press-in bottle adapter and oral dosing syringe

[see Instructions for Use]

8.7 Renal Impairment

Moderate and Severe Impairment

XELJANZ-treated patients with moderate or severe renal impairment had greater tofacitinib blood concentrations than XELJANZ-treated patients with normal renal function. Therefore, dosage adjustment of XELJANZ/XELJANZ XR/XELJANZ Oral Solution is recommended in patients with moderate or severe renal impairment (including but not limited to those with severe insufficiency who are undergoing hemodialysis)

[see Dosage and Administration (2.2, 2.3, 2.4)]

Mild impairment

No dosage adjustment is required in patients with mild renal impairment.

8.8 Hepatic Impairment

Severe Impairment

XELJANZ/XELJANZ XR/XELJANZ Oral Solution has not been studied in patients with severe hepatic impairment; therefore, use of XELJANZ/XELJANZ XR/XELJANZ Oral Solution in patients with severe hepatic impairment is not recommended.

Moderate Impairment

XELJANZ-treated patients with moderate hepatic impairment had greater tofacitinib blood concentration than XELJANZ-treated patients with normal hepatic function

[see Clinical Pharmacology (12.3)]

. Higher blood concentrations may increase the risk of some adverse reactions. Therefore, dosage adjustment of XELJANZ/XELJANZ XR/XELJANZ Oral Solution is recommended in patients with moderate hepatic impairment

[see Dosage and Administration (2.2, 2.3, 2.4)]

Mild Impairment

No dosage adjustment of XELJANZ/XELJANZ XR/XELJANZ Oral Solution is required in patients with mild hepatic impairment.

Hepatitis B or C Serology

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

)

Psoriatic Arthritis (in combination with nonbiologic DMARDs)

•XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily. (

2.2 Recommended Dosage in Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis

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)]

moderate or severe renal impairment

[see Use in Specific Populations (8.7)]

moderate hepatic impairment

[see Use in Specific Populations (8.8)]

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

Table 1: Recommended Dosage of XELJANZ and XELJANZ XR in Patients with Rheumatoid Arthritis, Psoriatic ArthritisXELJANZ/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., and Ankylosing Spondylitis
	XELJANZ tablet	XELJANZ XR extended-release tablet
Adult patients	5 mg twice daily	11 mg once daily
Patients receiving:
5 mg once daily	Reduce to XELJANZ 5 mg once daily
Patients with:
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.
Patients with lymphocyte count less than 500 cells/mm³, confirmed by repeat testing	Discontinue dosing.
Patients with ANC 500 to 1000 cells/mm³	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.
Patients with ANC less than 500 cells/mm³	Discontinue dosing.
Patients with hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL	Interrupt dosing until hemoglobin values have normalized.

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.

)

•Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is XELJANZ 5 mg once daily. (

2 DOSAGE AND ADMINISTRATION

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.
•Do not initiate XELJANZ/XELJANZ XR/XELJANZ Oral Solution if absolute lymphocyte count <500 cells/mm³, an absolute neutrophil count (ANC) <1000 cells/mm³or hemoglobin <9 g/dL.

Recommended Dosage

Rheumatoid Arthritis

•XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily.
•Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is XELJANZ 5 mg once daily.

Psoriatic Arthritis (in combination with nonbiologic DMARDs)

•XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily.
•Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is XELJANZ 5 mg once daily.

Ankylosing Spondylitis

•XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily.
•Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is XELJANZ 5 mg once daily.

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.
•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.
•Dosage adjustment is needed in patients with moderate and severe renal impairment or moderate hepatic impairment: see full prescribing information.

Polyarticular Course Juvenile Idiopathic Arthritis

•XELJANZ/XELJANZ Oral Solution 5 mg twice daily or weight-based equivalent twice daily.
•Dosage adjustment is needed in patients with moderate and severe renal impairment or moderate hepatic impairment: see full prescribing information.

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

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/mm³or 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

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)]

moderate or severe renal impairment

[see Use in Specific Populations (8.7)]

moderate hepatic impairment

[see Use in Specific Populations (8.8)]

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

Table 1: Recommended Dosage of XELJANZ and XELJANZ XR in Patients with Rheumatoid Arthritis, Psoriatic ArthritisXELJANZ/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., and Ankylosing Spondylitis
	XELJANZ tablet	XELJANZ XR extended-release tablet
Adult patients	5 mg twice daily	11 mg once daily
Patients receiving:
5 mg once daily	Reduce to XELJANZ 5 mg once daily
Patients with:
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.
Patients with lymphocyte count less than 500 cells/mm³, confirmed by repeat testing	Discontinue dosing.
Patients with ANC 500 to 1000 cells/mm³	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.
Patients with ANC less than 500 cells/mm³	Discontinue dosing.
Patients with hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL	Interrupt dosing until hemoglobin values have normalized.

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

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)]

moderate or severe renal impairment

[see Use in Specific Populations (8.7)]

moderate hepatic impairment

[see Use in Specific Populations (8.8)]

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

Table 2: Recommended Dosage of XELJANZ/XELJANZ XR in Patients with UC
	XELJANZ tablet	XELJANZ XR extended-release tablet
Adult patients	Induction: 10 mg twice daily for at least 8 weeks [see Clinical Studies (14.4)] ; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed continue 10 mg twice daily for a maximum of 16 weeks. Discontinue 10 mg twice daily after 16 weeks if adequate therapeutic response is not achieved. Maintenance: 5 mg twice daily. For patients with loss of response during maintenance treatment, a dosage of 10 mg twice 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 .	Induction: 22 mg once daily for at least 8 weeks; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed continue 22 mg once daily for a maximum of 16 weeks. Discontinue 22 mg once daily after 16 weeks if adequate therapeutic response is not achieved. Maintenance: 11 mg once daily. For patients with loss of response during maintenance treatment, a dosage of 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.
Patients receiving:
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
Patients with:
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.
Patients with lymphocyte count less than 500 cells/mm³, confirmed by repeat testing	Discontinue dosing.
Patients with ANC 500 to 1000 cells/mm³	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.
Patients with ANC less than 500 cells/mm³	Discontinue dosing.
Patients with hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL	Interrupt dosing until hemoglobin values have normalized.

Switching from XELJANZ Tablets to XELJANZ XR Extended-Release Tablets

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.

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

a moderate CYP3A4 inhibitor(s) with a strong CYP2C19 inhibitor(s) (e.g., fluconazole)

[see Drug Interactions (7)]

moderate or severe renal impairment

[see Use in Specific Populations (8.7)]

moderate hepatic impairment

[see Use in Specific Populations (8.8)]

XELJANZ/XELJANZ Oral Solution is not recommended for patients with severe hepatic impairment.

Table 3: Recommended Dosage of XELJANZ/XELJANZ Oral Solution in Patients with pcJIA
	XELJANZ tablets/XELJANZ Oral Solution
pcJIA patients
Patients receiving:
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.
Patients with:
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.
Patients with lymphocyte count less than 500 cells/mm³, confirmed by repeat testing	Discontinue dosing.
Patients with ANC 500 to 1000 cells/mm³	Interrupt dosing until ANC is greater than 1000 cells/mm³.
Patients with ANC less than 500 cells/mm³	Discontinue dosing.
Patients with hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL	Interrupt dosing until hemoglobin values have normalized.

Administer XELJANZ Oral Solution using the included press-in bottle adapter and oral dosing syringe

[see Instructions for Use]

8.7 Renal Impairment

Moderate and Severe Impairment

[see Dosage and Administration (2.2, 2.3, 2.4)]

Mild impairment

No dosage adjustment is required in patients with mild renal impairment.

8.8 Hepatic Impairment

Severe Impairment

Moderate Impairment

XELJANZ-treated patients with moderate hepatic impairment had greater tofacitinib blood concentration than XELJANZ-treated patients with normal hepatic function

[see Clinical Pharmacology (12.3)]

[see Dosage and Administration (2.2, 2.3, 2.4)]

Mild Impairment

No dosage adjustment of XELJANZ/XELJANZ XR/XELJANZ Oral Solution is required in patients with mild hepatic impairment.

Hepatitis B or C Serology

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

)

Ankylosing Spondylitis

•XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily. (

2.2 Recommended Dosage in Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis

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)]

moderate or severe renal impairment

[see Use in Specific Populations (8.7)]

moderate hepatic impairment

[see Use in Specific Populations (8.8)]

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

Table 1: Recommended Dosage of XELJANZ and XELJANZ XR in Patients with Rheumatoid Arthritis, Psoriatic ArthritisXELJANZ/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., and Ankylosing Spondylitis
	XELJANZ tablet	XELJANZ XR extended-release tablet
Adult patients	5 mg twice daily	11 mg once daily
Patients receiving:
5 mg once daily	Reduce to XELJANZ 5 mg once daily
Patients with:
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.
Patients with lymphocyte count less than 500 cells/mm³, confirmed by repeat testing	Discontinue dosing.
Patients with ANC 500 to 1000 cells/mm³	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.
Patients with ANC less than 500 cells/mm³	Discontinue dosing.
Patients with hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL	Interrupt dosing until hemoglobin values have normalized.

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.

)

•Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is XELJANZ 5 mg once daily. (

2 DOSAGE AND ADMINISTRATION

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.
•Do not initiate XELJANZ/XELJANZ XR/XELJANZ Oral Solution if absolute lymphocyte count <500 cells/mm³, an absolute neutrophil count (ANC) <1000 cells/mm³or hemoglobin <9 g/dL.

Recommended Dosage

Rheumatoid Arthritis

•XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily.
•Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is XELJANZ 5 mg once daily.

Psoriatic Arthritis (in combination with nonbiologic DMARDs)

•XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily.
•Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is XELJANZ 5 mg once daily.

Ankylosing Spondylitis

•XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily.
•Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is XELJANZ 5 mg once daily.

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.
•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.
•Dosage adjustment is needed in patients with moderate and severe renal impairment or moderate hepatic impairment: see full prescribing information.

Polyarticular Course Juvenile Idiopathic Arthritis

•XELJANZ/XELJANZ Oral Solution 5 mg twice daily or weight-based equivalent twice daily.
•Dosage adjustment is needed in patients with moderate and severe renal impairment or moderate hepatic impairment: see full prescribing information.

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

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/mm³or 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

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)]

moderate or severe renal impairment

[see Use in Specific Populations (8.7)]

moderate hepatic impairment

[see Use in Specific Populations (8.8)]

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

Table 1: Recommended Dosage of XELJANZ and XELJANZ XR in Patients with Rheumatoid Arthritis, Psoriatic ArthritisXELJANZ/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., and Ankylosing Spondylitis
	XELJANZ tablet	XELJANZ XR extended-release tablet
Adult patients	5 mg twice daily	11 mg once daily
Patients receiving:
5 mg once daily	Reduce to XELJANZ 5 mg once daily
Patients with:
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.
Patients with lymphocyte count less than 500 cells/mm³, confirmed by repeat testing	Discontinue dosing.
Patients with ANC 500 to 1000 cells/mm³	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.
Patients with ANC less than 500 cells/mm³	Discontinue dosing.
Patients with hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL	Interrupt dosing until hemoglobin values have normalized.

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

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)]

moderate or severe renal impairment

[see Use in Specific Populations (8.7)]

moderate hepatic impairment

[see Use in Specific Populations (8.8)]

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

Table 2: Recommended Dosage of XELJANZ/XELJANZ XR in Patients with UC
	XELJANZ tablet	XELJANZ XR extended-release tablet
Adult patients	Induction: 10 mg twice daily for at least 8 weeks [see Clinical Studies (14.4)] ; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed continue 10 mg twice daily for a maximum of 16 weeks. Discontinue 10 mg twice daily after 16 weeks if adequate therapeutic response is not achieved. Maintenance: 5 mg twice daily. For patients with loss of response during maintenance treatment, a dosage of 10 mg twice 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 .	Induction: 22 mg once daily for at least 8 weeks; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed continue 22 mg once daily for a maximum of 16 weeks. Discontinue 22 mg once daily after 16 weeks if adequate therapeutic response is not achieved. Maintenance: 11 mg once daily. For patients with loss of response during maintenance treatment, a dosage of 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.
Patients receiving:
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
Patients with:
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.
Patients with lymphocyte count less than 500 cells/mm³, confirmed by repeat testing	Discontinue dosing.
Patients with ANC 500 to 1000 cells/mm³	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.
Patients with ANC less than 500 cells/mm³	Discontinue dosing.
Patients with hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL	Interrupt dosing until hemoglobin values have normalized.

Switching from XELJANZ Tablets to XELJANZ XR Extended-Release Tablets

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.

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

a moderate CYP3A4 inhibitor(s) with a strong CYP2C19 inhibitor(s) (e.g., fluconazole)

[see Drug Interactions (7)]

moderate or severe renal impairment

[see Use in Specific Populations (8.7)]

moderate hepatic impairment

[see Use in Specific Populations (8.8)]

XELJANZ/XELJANZ Oral Solution is not recommended for patients with severe hepatic impairment.

Table 3: Recommended Dosage of XELJANZ/XELJANZ Oral Solution in Patients with pcJIA
	XELJANZ tablets/XELJANZ Oral Solution
pcJIA patients
Patients receiving:
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.
Patients with:
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.
Patients with lymphocyte count less than 500 cells/mm³, confirmed by repeat testing	Discontinue dosing.
Patients with ANC 500 to 1000 cells/mm³	Interrupt dosing until ANC is greater than 1000 cells/mm³.
Patients with ANC less than 500 cells/mm³	Discontinue dosing.
Patients with hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL	Interrupt dosing until hemoglobin values have normalized.

Administer XELJANZ Oral Solution using the included press-in bottle adapter and oral dosing syringe

[see Instructions for Use]

8.7 Renal Impairment

Moderate and Severe Impairment

[see Dosage and Administration (2.2, 2.3, 2.4)]

Mild impairment

No dosage adjustment is required in patients with mild renal impairment.

8.8 Hepatic Impairment

Severe Impairment

Moderate Impairment

XELJANZ-treated patients with moderate hepatic impairment had greater tofacitinib blood concentration than XELJANZ-treated patients with normal hepatic function

[see Clinical Pharmacology (12.3)]

[see Dosage and Administration (2.2, 2.3, 2.4)]

Mild Impairment

No dosage adjustment of XELJANZ/XELJANZ XR/XELJANZ Oral Solution is required in patients with mild hepatic impairment.

Hepatitis B or C Serology

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

)

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 Recommended Dosage in Ulcerative Colitis

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)]

moderate or severe renal impairment

[see Use in Specific Populations (8.7)]

moderate hepatic impairment

[see Use in Specific Populations (8.8)]

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

Table 2: Recommended Dosage of XELJANZ/XELJANZ XR in Patients with UC
	XELJANZ tablet	XELJANZ XR extended-release tablet
Adult patients	Induction: 10 mg twice daily for at least 8 weeks [see Clinical Studies (14.4)] ; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed continue 10 mg twice daily for a maximum of 16 weeks. Discontinue 10 mg twice daily after 16 weeks if adequate therapeutic response is not achieved. Maintenance: 5 mg twice daily. For patients with loss of response during maintenance treatment, a dosage of 10 mg twice 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 .	Induction: 22 mg once daily for at least 8 weeks; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed continue 22 mg once daily for a maximum of 16 weeks. Discontinue 22 mg once daily after 16 weeks if adequate therapeutic response is not achieved. Maintenance: 11 mg once daily. For patients with loss of response during maintenance treatment, a dosage of 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.
Patients receiving:
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
Patients with:
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.
Patients with lymphocyte count less than 500 cells/mm³, confirmed by repeat testing	Discontinue dosing.
Patients with ANC 500 to 1000 cells/mm³	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.
Patients with ANC less than 500 cells/mm³	Discontinue dosing.
Patients with hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL	Interrupt dosing until hemoglobin values have normalized.

Switching from XELJANZ Tablets to XELJANZ XR Extended-Release Tablets

)

•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 Recommended Dosage in Ulcerative Colitis

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)]

moderate or severe renal impairment

[see Use in Specific Populations (8.7)]

moderate hepatic impairment

[see Use in Specific Populations (8.8)]

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

Table 2: Recommended Dosage of XELJANZ/XELJANZ XR in Patients with UC
	XELJANZ tablet	XELJANZ XR extended-release tablet
Adult patients	Induction: 10 mg twice daily for at least 8 weeks [see Clinical Studies (14.4)] ; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed continue 10 mg twice daily for a maximum of 16 weeks. Discontinue 10 mg twice daily after 16 weeks if adequate therapeutic response is not achieved. Maintenance: 5 mg twice daily. For patients with loss of response during maintenance treatment, a dosage of 10 mg twice 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 .	Induction: 22 mg once daily for at least 8 weeks; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed continue 22 mg once daily for a maximum of 16 weeks. Discontinue 22 mg once daily after 16 weeks if adequate therapeutic response is not achieved. Maintenance: 11 mg once daily. For patients with loss of response during maintenance treatment, a dosage of 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.
Patients receiving:
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
Patients with:
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.
Patients with lymphocyte count less than 500 cells/mm³, confirmed by repeat testing	Discontinue dosing.
Patients with ANC 500 to 1000 cells/mm³	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.
Patients with ANC less than 500 cells/mm³	Discontinue dosing.
Patients with hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL	Interrupt dosing until hemoglobin values have normalized.

Switching from XELJANZ Tablets to XELJANZ XR Extended-Release Tablets

)

•Dosage adjustment is needed in patients with moderate and severe renal impairment or moderate hepatic impairment: see full prescribing information. (

2.3 Recommended Dosage in Ulcerative Colitis

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)]

moderate or severe renal impairment

[see Use in Specific Populations (8.7)]

moderate hepatic impairment

[see Use in Specific Populations (8.8)]

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

Table 2: Recommended Dosage of XELJANZ/XELJANZ XR in Patients with UC
	XELJANZ tablet	XELJANZ XR extended-release tablet
Adult patients	Induction: 10 mg twice daily for at least 8 weeks [see Clinical Studies (14.4)] ; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed continue 10 mg twice daily for a maximum of 16 weeks. Discontinue 10 mg twice daily after 16 weeks if adequate therapeutic response is not achieved. Maintenance: 5 mg twice daily. For patients with loss of response during maintenance treatment, a dosage of 10 mg twice 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 .	Induction: 22 mg once daily for at least 8 weeks; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed continue 22 mg once daily for a maximum of 16 weeks. Discontinue 22 mg once daily after 16 weeks if adequate therapeutic response is not achieved. Maintenance: 11 mg once daily. For patients with loss of response during maintenance treatment, a dosage of 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.
Patients receiving:
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
Patients with:
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.
Patients with lymphocyte count less than 500 cells/mm³, confirmed by repeat testing	Discontinue dosing.
Patients with ANC 500 to 1000 cells/mm³	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.
Patients with ANC less than 500 cells/mm³	Discontinue dosing.
Patients with hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL	Interrupt dosing until hemoglobin values have normalized.

Switching from XELJANZ Tablets to XELJANZ XR Extended-Release Tablets

)

Polyarticular Course Juvenile Idiopathic Arthritis

•XELJANZ/XELJANZ Oral Solution 5 mg twice daily or weight-based equivalent twice daily. (

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.

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

a moderate CYP3A4 inhibitor(s) with a strong CYP2C19 inhibitor(s) (e.g., fluconazole)

[see Drug Interactions (7)]

moderate or severe renal impairment

[see Use in Specific Populations (8.7)]

moderate hepatic impairment

[see Use in Specific Populations (8.8)]

XELJANZ/XELJANZ Oral Solution is not recommended for patients with severe hepatic impairment.

Table 3: Recommended Dosage of XELJANZ/XELJANZ Oral Solution in Patients with pcJIA
	XELJANZ tablets/XELJANZ Oral Solution
pcJIA patients
Patients receiving:
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.
Patients with:
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.
Patients with lymphocyte count less than 500 cells/mm³, confirmed by repeat testing	Discontinue dosing.
Patients with ANC 500 to 1000 cells/mm³	Interrupt dosing until ANC is greater than 1000 cells/mm³.
Patients with ANC less than 500 cells/mm³	Discontinue dosing.
Patients with hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL	Interrupt dosing until hemoglobin values have normalized.

Administer XELJANZ Oral Solution using the included press-in bottle adapter and oral dosing syringe

[see Instructions for Use]

)

•Dosage adjustment is needed in patients with moderate and severe renal impairment or moderate hepatic impairment: see full prescribing information. (

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.

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

a moderate CYP3A4 inhibitor(s) with a strong CYP2C19 inhibitor(s) (e.g., fluconazole)

[see Drug Interactions (7)]

moderate or severe renal impairment

[see Use in Specific Populations (8.7)]

moderate hepatic impairment

[see Use in Specific Populations (8.8)]

XELJANZ/XELJANZ Oral Solution is not recommended for patients with severe hepatic impairment.

Table 3: Recommended Dosage of XELJANZ/XELJANZ Oral Solution in Patients with pcJIA
	XELJANZ tablets/XELJANZ Oral Solution
pcJIA patients
Patients receiving:
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.
Patients with:
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.
Patients with lymphocyte count less than 500 cells/mm³, confirmed by repeat testing	Discontinue dosing.
Patients with ANC 500 to 1000 cells/mm³	Interrupt dosing until ANC is greater than 1000 cells/mm³.
Patients with ANC less than 500 cells/mm³	Discontinue dosing.
Patients with hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL	Interrupt dosing until hemoglobin values have normalized.

Administer XELJANZ Oral Solution using the included press-in bottle adapter and oral dosing syringe

[see Instructions for Use]

)

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 Recommended Dosage in Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis

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)]

moderate or severe renal impairment

[see Use in Specific Populations (8.7)]

moderate hepatic impairment

[see Use in Specific Populations (8.8)]

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

Table 1: Recommended Dosage of XELJANZ and XELJANZ XR in Patients with Rheumatoid Arthritis, Psoriatic ArthritisXELJANZ/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., and Ankylosing Spondylitis
	XELJANZ tablet	XELJANZ XR extended-release tablet
Adult patients	5 mg twice daily	11 mg once daily
Patients receiving:
5 mg once daily	Reduce to XELJANZ 5 mg once daily
Patients with:
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.
Patients with lymphocyte count less than 500 cells/mm³, confirmed by repeat testing	Discontinue dosing.
Patients with ANC 500 to 1000 cells/mm³	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.
Patients with ANC less than 500 cells/mm³	Discontinue dosing.
Patients with hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL	Interrupt dosing until hemoglobin values have normalized.

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

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)]

moderate or severe renal impairment

[see Use in Specific Populations (8.7)]

moderate hepatic impairment

[see Use in Specific Populations (8.8)]

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

Table 2: Recommended Dosage of XELJANZ/XELJANZ XR in Patients with UC
	XELJANZ tablet	XELJANZ XR extended-release tablet
Adult patients	Induction: 10 mg twice daily for at least 8 weeks [see Clinical Studies (14.4)] ; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed continue 10 mg twice daily for a maximum of 16 weeks. Discontinue 10 mg twice daily after 16 weeks if adequate therapeutic response is not achieved. Maintenance: 5 mg twice daily. For patients with loss of response during maintenance treatment, a dosage of 10 mg twice 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 .	Induction: 22 mg once daily for at least 8 weeks; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed continue 22 mg once daily for a maximum of 16 weeks. Discontinue 22 mg once daily after 16 weeks if adequate therapeutic response is not achieved. Maintenance: 11 mg once daily. For patients with loss of response during maintenance treatment, a dosage of 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.
Patients receiving:
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
Patients with:
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.
Patients with lymphocyte count less than 500 cells/mm³, confirmed by repeat testing	Discontinue dosing.
Patients with ANC 500 to 1000 cells/mm³	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.
Patients with ANC less than 500 cells/mm³	Discontinue dosing.
Patients with hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL	Interrupt dosing until hemoglobin values have normalized.

Switching from XELJANZ Tablets to XELJANZ XR Extended-Release Tablets

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.

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

a moderate CYP3A4 inhibitor(s) with a strong CYP2C19 inhibitor(s) (e.g., fluconazole)

[see Drug Interactions (7)]

moderate or severe renal impairment

[see Use in Specific Populations (8.7)]

moderate hepatic impairment

[see Use in Specific Populations (8.8)]

XELJANZ/XELJANZ Oral Solution is not recommended for patients with severe hepatic impairment.

Table 3: Recommended Dosage of XELJANZ/XELJANZ Oral Solution in Patients with pcJIA
	XELJANZ tablets/XELJANZ Oral Solution
pcJIA patients
Patients receiving:
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.
Patients with:
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.
Patients with lymphocyte count less than 500 cells/mm³, confirmed by repeat testing	Discontinue dosing.
Patients with ANC 500 to 1000 cells/mm³	Interrupt dosing until ANC is greater than 1000 cells/mm³.
Patients with ANC less than 500 cells/mm³	Discontinue dosing.
Patients with hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL	Interrupt dosing until hemoglobin values have normalized.

Administer XELJANZ Oral Solution using the included press-in bottle adapter and oral dosing syringe

[see Instructions for Use]

8.7 Renal Impairment

Moderate and Severe Impairment

[see Dosage and Administration (2.2, 2.3, 2.4)]

Mild impairment

No dosage adjustment is required in patients with mild renal impairment.

8.8 Hepatic Impairment

Severe Impairment

Moderate Impairment

XELJANZ-treated patients with moderate hepatic impairment had greater tofacitinib blood concentration than XELJANZ-treated patients with normal hepatic function

[see Clinical Pharmacology (12.3)]

[see Dosage and Administration (2.2, 2.3, 2.4)]

Mild Impairment

No dosage adjustment of XELJANZ/XELJANZ XR/XELJANZ Oral Solution is required in patients with mild hepatic impairment.

Hepatitis B or C Serology

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

)

•Use of XELJANZ/XELJANZ XR/XELJANZ Oral Solution in patients with severe hepatic impairment is not recommended in any patient population. (

2.2 Recommended Dosage in Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis

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)]

moderate or severe renal impairment

[see Use in Specific Populations (8.7)]

moderate hepatic impairment

[see Use in Specific Populations (8.8)]

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

Table 1: Recommended Dosage of XELJANZ and XELJANZ XR in Patients with Rheumatoid Arthritis, Psoriatic ArthritisXELJANZ/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., and Ankylosing Spondylitis
	XELJANZ tablet	XELJANZ XR extended-release tablet
Adult patients	5 mg twice daily	11 mg once daily
Patients receiving:
5 mg once daily	Reduce to XELJANZ 5 mg once daily
Patients with:
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.
Patients with lymphocyte count less than 500 cells/mm³, confirmed by repeat testing	Discontinue dosing.
Patients with ANC 500 to 1000 cells/mm³	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.
Patients with ANC less than 500 cells/mm³	Discontinue dosing.
Patients with hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL	Interrupt dosing until hemoglobin values have normalized.

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

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)]

moderate or severe renal impairment

[see Use in Specific Populations (8.7)]

moderate hepatic impairment

[see Use in Specific Populations (8.8)]

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

Table 2: Recommended Dosage of XELJANZ/XELJANZ XR in Patients with UC
	XELJANZ tablet	XELJANZ XR extended-release tablet
Adult patients	Induction: 10 mg twice daily for at least 8 weeks [see Clinical Studies (14.4)] ; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed continue 10 mg twice daily for a maximum of 16 weeks. Discontinue 10 mg twice daily after 16 weeks if adequate therapeutic response is not achieved. Maintenance: 5 mg twice daily. For patients with loss of response during maintenance treatment, a dosage of 10 mg twice 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 .	Induction: 22 mg once daily for at least 8 weeks; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed continue 22 mg once daily for a maximum of 16 weeks. Discontinue 22 mg once daily after 16 weeks if adequate therapeutic response is not achieved. Maintenance: 11 mg once daily. For patients with loss of response during maintenance treatment, a dosage of 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.
Patients receiving:
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
Patients with:
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.
Patients with lymphocyte count less than 500 cells/mm³, confirmed by repeat testing	Discontinue dosing.
Patients with ANC 500 to 1000 cells/mm³	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.
Patients with ANC less than 500 cells/mm³	Discontinue dosing.
Patients with hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL	Interrupt dosing until hemoglobin values have normalized.

Switching from XELJANZ Tablets to XELJANZ XR Extended-Release Tablets

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.

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

a moderate CYP3A4 inhibitor(s) with a strong CYP2C19 inhibitor(s) (e.g., fluconazole)

[see Drug Interactions (7)]

moderate or severe renal impairment

[see Use in Specific Populations (8.7)]

moderate hepatic impairment

[see Use in Specific Populations (8.8)]

XELJANZ/XELJANZ Oral Solution is not recommended for patients with severe hepatic impairment.

Table 3: Recommended Dosage of XELJANZ/XELJANZ Oral Solution in Patients with pcJIA
	XELJANZ tablets/XELJANZ Oral Solution
pcJIA patients
Patients receiving:
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.
Patients with:
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.
Patients with lymphocyte count less than 500 cells/mm³, confirmed by repeat testing	Discontinue dosing.
Patients with ANC 500 to 1000 cells/mm³	Interrupt dosing until ANC is greater than 1000 cells/mm³.
Patients with ANC less than 500 cells/mm³	Discontinue dosing.
Patients with hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL	Interrupt dosing until hemoglobin values have normalized.

Administer XELJANZ Oral Solution using the included press-in bottle adapter and oral dosing syringe

[see Instructions for Use]

8.8 Hepatic Impairment

Severe Impairment

Moderate Impairment

XELJANZ-treated patients with moderate hepatic impairment had greater tofacitinib blood concentration than XELJANZ-treated patients with normal hepatic function

[see Clinical Pharmacology (12.3)]

[see Dosage and Administration (2.2, 2.3, 2.4)]

Mild Impairment

No dosage adjustment of XELJANZ/XELJANZ XR/XELJANZ Oral Solution is required in patients with mild hepatic impairment.

Hepatitis B or C Serology

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

)

•XELJANZ Tablets: 5 mg, 10 mg tofacitinib (
3 DOSAGE FORMS AND STRENGTHS
•XELJANZ Tablets: 5 mg, 10 mg tofacitinib
•XELJANZ XR Tablets: 11 mg, 22 mg tofacitinib
•XELJANZ Oral Solution: 1 mg/mL tofacitinib
XELJANZ Tablets:
o5 mg tofacitinib: White, round, immediate-release film-coated tablets, debossed with "Pfizer" on one side, and "JKI 5" on the other side.
o10 mg tofacitinib: Blue, round, immediate-release film-coated tablets, debossed with "Pfizer" on one side, and "JKI 10" on the other side.
XELJANZ XR Tablets:
o11 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.
o22 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.
)
•XELJANZ XR Tablets: 11 mg, 22 mg tofacitinib (
3 DOSAGE FORMS AND STRENGTHS
•XELJANZ Tablets: 5 mg, 10 mg tofacitinib
•XELJANZ XR Tablets: 11 mg, 22 mg tofacitinib
•XELJANZ Oral Solution: 1 mg/mL tofacitinib
XELJANZ Tablets:
o5 mg tofacitinib: White, round, immediate-release film-coated tablets, debossed with "Pfizer" on one side, and "JKI 5" on the other side.
o10 mg tofacitinib: Blue, round, immediate-release film-coated tablets, debossed with "Pfizer" on one side, and "JKI 10" on the other side.
XELJANZ XR Tablets:
o11 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.
o22 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.
)
•XELJANZ Oral Solution: 1 mg/mL tofacitinib (
3 DOSAGE FORMS AND STRENGTHS
•XELJANZ Tablets: 5 mg, 10 mg tofacitinib
•XELJANZ XR Tablets: 11 mg, 22 mg tofacitinib
•XELJANZ Oral Solution: 1 mg/mL tofacitinib
XELJANZ Tablets:
o5 mg tofacitinib: White, round, immediate-release film-coated tablets, debossed with "Pfizer" on one side, and "JKI 5" on the other side.
o10 mg tofacitinib: Blue, round, immediate-release film-coated tablets, debossed with "Pfizer" on one side, and "JKI 10" on the other side.
XELJANZ XR Tablets:
o11 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.
o22 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.
)

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Serious Infections
: Avoid use of XELJANZ/XELJANZ XR/XELJANZ Oral Solution during an active serious infection, including localized infections. (
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)].
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/XELJANZ XR/XELJANZ Oral Solution in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but who have risk factors for tuberculosis infection. Consultation with a physician with expertise in the treatment of tuberculosis is recommended to aid in the decision about whether initiating anti-tuberculosis therapy is appropriate for an individual patient.
Patients should be closely monitored for the development of signs and symptoms of tuberculosis, including patients who tested negative for latent tuberculosis infection prior to initiating therapy.
Patients with latent tuberculosis should be treated with standard antimycobacterial therapy before administering XELJANZ/XELJANZ XR/XELJANZ Oral Solution.
Viral Reactivation
Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster), were observed in clinical studies with XELJANZ/XELJANZ Oral Solution. Postmarketing cases of hepatitis B reactivation have been reported in patients treated with XELJANZ. The impact of XELJANZ/XELJANZ XR/XELJANZ Oral Solution on chronic viral hepatitis reactivation is unknown. Patients who screened positive for hepatitis B or C were excluded from clinical trials. Screening for viral hepatitis should be performed in accordance with clinical guidelines before starting therapy with XELJANZ/XELJANZ XR/XELJANZ Oral Solution. The risk of herpes zoster is increased in patients treated with XELJANZ/XELJANZ XR/XELJANZ Oral Solution and appears to be higher in patients treated with XELJANZ in Japan and Korea.
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Gastrointestinal Perforations
: Use with caution in patients that may be at increased risk. (
5.6 Gastrointestinal Perforations
Events of gastrointestinal perforation have been reported in clinical studies with XELJANZ, although the role of JAK inhibition in these events is not known. In these studies, many patients with rheumatoid arthritis were receiving background therapy with Nonsteroidal Anti-Inflammatory Drugs (NSAIDs).
There was no discernable difference in frequency of gastrointestinal perforation between the placebo and the XELJANZ arms in clinical trials of patients with UC, and many of them were receiving background corticosteroids.
XELJANZ/XELJANZ XR/XELJANZ Oral Solution should be used with caution in patients who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs). Patients presenting with new onset abdominal symptoms should be evaluated promptly for early identification of gastrointestinal perforation
[see Adverse Reactions (6.1)].
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Laboratory Monitoring
: Recommended due to potential changes in lymphocytes, neutrophils, hemoglobin, liver enzymes and lipids. (
5.8 Laboratory Abnormalities
Lymphocyte Abnormalities
Treatment with XELJANZ was associated with initial lymphocytosis at one month of exposure 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/mm³were associated with an increased incidence of treated and serious infections.
Avoid initiation of XELJANZ/XELJANZ XR/XELJANZ Oral Solution treatment in patients with a low lymphocyte count (i.e., less than 500 cells/mm³). In patients who develop a confirmed absolute lymphocyte count less than 500 cells/mm³, treatment with XELJANZ/XELJANZ XR/XELJANZ Oral Solution is not recommended.
Monitor lymphocyte counts at baseline and every 3 months thereafter. For recommended modifications based on lymphocyte counts
[see Dosage and Administration (2.2, 2.3, 2.4)]
.
Neutropenia
Treatment with XELJANZ was associated with an increased incidence of neutropenia (less than 2000 cells/mm³) compared to placebo.
Avoid initiation of XELJANZ/XELJANZ XR/XELJANZ Oral Solution 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 XELJANZ/XELJANZ XR/XELJANZ Oral Solution 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 XELJANZ/XELJANZ XR/XELJANZ Oral Solution is not recommended.
Monitor neutrophil counts at baseline and after 4–8 weeks of treatment and every 3 months thereafter. For recommended modifications based on ANC results
[see Dosage and Administration (2.2, 2.3)]
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Anemia
Avoid initiation of XELJANZ/XELJANZ XR/XELJANZ Oral Solution treatment in patients with a low hemoglobin level (i.e., less than 9 g/dL). Treatment with XELJANZ/XELJANZ XR/XELJANZ Oral Solution should be interrupted in patients who develop hemoglobin levels less than 8 g/dL or whose hemoglobin level drops greater than 2 g/dL on treatment.
Monitor hemoglobin at baseline and after 4–8 weeks of treatment and every 3 months thereafter. For recommended modifications based on hemoglobin results
[see Dosage and Administration (2)]
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Liver Enzyme Elevations
Treatment with XELJANZ was associated with an increased incidence of liver enzyme elevation compared to placebo. Most of these abnormalities occurred in studies with background DMARD (primarily methotrexate) therapy.
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, the administration of XELJANZ/XELJANZ XR/XELJANZ Oral Solution should be interrupted until this diagnosis has been excluded.
Lipid Elevations
Treatment with XELJANZ was associated with dose-dependent increases in lipid parameters including total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol. Maximum effects 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.
Assessment of lipid parameters should be performed approximately 4–8 weeks following initiation of XELJANZ/XELJANZ XR/XELJANZ Oral Solution therapy.
Manage patients according to clinical guidelines [e.g., National Cholesterol Educational Program (NCEP)] for the management of hyperlipidemia.
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Immunizations
: Live vaccines: Avoid use with XELJANZ/XELJANZ XR/XELJANZ Oral Solution. (
5.9 Vaccinations
Avoid use of live vaccines concurrently with XELJANZ/XELJANZ XR/XELJANZ Oral Solution. The interval between live vaccinations and initiation of tofacitinib therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents.
A patient experienced dissemination of the vaccine strain of varicella zoster virus, 16 days after vaccination with live attenuated (Zostavax) virus vaccine and 2 days after treatment start with tofacitinib 5 mg twice daily. The patient was varicella virus naïve, as evidenced by no previous history of varicella infection and no anti-varicella antibodies at baseline. Tofacitinib was discontinued and the patient recovered after treatment with standard doses of antiviral medication.
Update immunizations in agreement with current immunization guidelines prior to initiating XELJANZ/XELJANZ XR/XELJANZ Oral Solution therapy.
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