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
  [seeDosage 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
  [seeWarnings 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
  [seeWarnings and Precautions (5.1)]
  .
- •Take XELJANZ/XELJANZ XR/XELJANZ Oral Solution with or without food
  [seeClinical 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
  [seeDosage 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
  [seeWarnings 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
  [seeWarnings and Precautions (5.1)]
  .
- •Take XELJANZ/XELJANZ XR/XELJANZ Oral Solution with or without food
  [seeClinical 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
  [seeDosage 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
  [seeWarnings 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
  [seeWarnings and Precautions (5.1)]
  .
- •Take XELJANZ/XELJANZ XR/XELJANZ Oral Solution with or without food
  [seeClinical 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)

[seeDrug Interactions (7)]

moderate or severe renal impairment

[seeUse in Specific Populations (8.7)]

moderate hepatic impairment

[seeUse 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. (2.1)
•Changes between XELJANZ and XELJANZ XR should be made by the healthcare provider. (2.1)
•Do not initiate XELJANZ/XELJANZ XR/XELJANZ Oral Solution if absolute lymphocyte count <500 cells/mm³, an absolute neutrophil count (ANC) <1000 cells/mm³or hemoglobin <9 g/dL. (2.1)

Recommended Dosage

Rheumatoid Arthritis

•XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily. (2.2)
•Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is XELJANZ 5 mg once daily. (2,8.7,8.8)

Psoriatic Arthritis (in combination with nonbiologic DMARDs)

•XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily. (2.2)
•Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is XELJANZ 5 mg once daily. (2,8.7,8.8)

Ankylosing Spondylitis

•XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily. (2.2)
•Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is XELJANZ 5 mg once daily. (2,8.7,8.8)

Ulcerative Colitis

•Induction: XELJANZ 10 mg twice daily or XELJANZ XR 22 mg once daily for 8 weeks; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed, continue XELJANZ 10 mg twice daily or XELJANZ XR 22 mg once daily for a maximum of 16 weeks. Discontinue XELJANZ 10 mg twice daily or XELJANZ XR 22 mg once daily after 16 weeks if adequate therapeutic response is not achieved. (2.3)
•Maintenance: XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily. For patients with loss of response during maintenance treatment, XELJANZ 10 mg twice daily or XELJANZ XR 22 mg once daily may be considered and limited to the shortest duration, with careful consideration of the benefits and risks for the individual patient. Use the lowest effective dose needed to maintain response. (2.3)
•Dosage adjustment is needed in patients with moderate and severe renal impairment or moderate hepatic impairment: see full prescribing information. (2.3)

Polyarticular Course Juvenile Idiopathic Arthritis

•XELJANZ/XELJANZ Oral Solution 5 mg twice daily or weight-based equivalent twice daily. (2.4)
•Dosage adjustment is needed in patients with moderate and severe renal impairment or moderate hepatic impairment: see full prescribing information. (2.4)

Dosage Adjustment

•See the full prescribing information for dosage adjustments by indication for patients receiving CYP2C19 and/or CYP3A4 inhibitors; in patients with moderate or severe renal impairment or moderate hepatic impairment; and patients with lymphopenia, neutropenia, or anemia. (2.2,2.3,2.4,8.7,8.8)
•Use of XELJANZ/XELJANZ XR/XELJANZ Oral Solution in patients with severe hepatic impairment is not recommended in any patient population. (2.2,2.3,2.4,8.8)

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
[seeDosage 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
[seeWarnings 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
[seeWarnings and Precautions (5.1)]
.
•Take XELJANZ/XELJANZ XR/XELJANZ Oral Solution with or without food
[seeClinical 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)

[seeDrug Interactions (7)]

moderate or severe renal impairment

[seeUse in Specific Populations (8.7)]

moderate hepatic impairment

[seeUse 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)

[seeDrug Interactions (7)]

moderate or severe renal impairment

[seeUse in Specific Populations (8.7)]

moderate hepatic impairment

[seeUse 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 [seeClinical 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

[seeDrug Interactions (7)]

, in patients with moderate or severe renal impairment, including but not limited to those undergoing hemodialysis

[seeUse in Specific Populations (8.7)]

, with moderate hepatic impairment

[seeUse 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)

[seeDrug Interactions (7)]

moderate or severe renal impairment

[seeUse in Specific Populations (8.7)]

moderate hepatic impairment

[seeUse 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

[seeInstructions 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)

[seeDosage 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

[seeClinical 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

[seeDosage 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)

[seeDrug Interactions (7)]

moderate or severe renal impairment

[seeUse in Specific Populations (8.7)]

moderate hepatic impairment

[seeUse 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. (2.1)
•Changes between XELJANZ and XELJANZ XR should be made by the healthcare provider. (2.1)
•Do not initiate XELJANZ/XELJANZ XR/XELJANZ Oral Solution if absolute lymphocyte count <500 cells/mm³, an absolute neutrophil count (ANC) <1000 cells/mm³or hemoglobin <9 g/dL. (2.1)

Recommended Dosage

Rheumatoid Arthritis

•XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily. (2.2)
•Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is XELJANZ 5 mg once daily. (2,8.7,8.8)

Psoriatic Arthritis (in combination with nonbiologic DMARDs)

•XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily. (2.2)
•Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is XELJANZ 5 mg once daily. (2,8.7,8.8)

Ankylosing Spondylitis

•XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily. (2.2)
•Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is XELJANZ 5 mg once daily. (2,8.7,8.8)

Ulcerative Colitis

•Induction: XELJANZ 10 mg twice daily or XELJANZ XR 22 mg once daily for 8 weeks; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed, continue XELJANZ 10 mg twice daily or XELJANZ XR 22 mg once daily for a maximum of 16 weeks. Discontinue XELJANZ 10 mg twice daily or XELJANZ XR 22 mg once daily after 16 weeks if adequate therapeutic response is not achieved. (2.3)
•Maintenance: XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily. For patients with loss of response during maintenance treatment, XELJANZ 10 mg twice daily or XELJANZ XR 22 mg once daily may be considered and limited to the shortest duration, with careful consideration of the benefits and risks for the individual patient. Use the lowest effective dose needed to maintain response. (2.3)
•Dosage adjustment is needed in patients with moderate and severe renal impairment or moderate hepatic impairment: see full prescribing information. (2.3)

Polyarticular Course Juvenile Idiopathic Arthritis

•XELJANZ/XELJANZ Oral Solution 5 mg twice daily or weight-based equivalent twice daily. (2.4)
•Dosage adjustment is needed in patients with moderate and severe renal impairment or moderate hepatic impairment: see full prescribing information. (2.4)

Dosage Adjustment

•See the full prescribing information for dosage adjustments by indication for patients receiving CYP2C19 and/or CYP3A4 inhibitors; in patients with moderate or severe renal impairment or moderate hepatic impairment; and patients with lymphopenia, neutropenia, or anemia. (2.2,2.3,2.4,8.7,8.8)
•Use of XELJANZ/XELJANZ XR/XELJANZ Oral Solution in patients with severe hepatic impairment is not recommended in any patient population. (2.2,2.3,2.4,8.8)

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
[seeDosage 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
[seeWarnings 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
[seeWarnings and Precautions (5.1)]
.
•Take XELJANZ/XELJANZ XR/XELJANZ Oral Solution with or without food
[seeClinical 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)

[seeDrug Interactions (7)]

moderate or severe renal impairment

[seeUse in Specific Populations (8.7)]

moderate hepatic impairment

[seeUse 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)

[seeDrug Interactions (7)]

moderate or severe renal impairment

[seeUse in Specific Populations (8.7)]

moderate hepatic impairment

[seeUse 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 [seeClinical 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

[seeDrug Interactions (7)]

, in patients with moderate or severe renal impairment, including but not limited to those undergoing hemodialysis

[seeUse in Specific Populations (8.7)]

, with moderate hepatic impairment

[seeUse 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)

[seeDrug Interactions (7)]

moderate or severe renal impairment

[seeUse in Specific Populations (8.7)]

moderate hepatic impairment

[seeUse 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

[seeInstructions for Use]

8.7 Renal Impairment

Moderate and Severe Impairment

[seeDosage 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

[seeClinical Pharmacology (12.3)]

[seeDosage 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)

[seeDrug Interactions (7)]

moderate or severe renal impairment

[seeUse in Specific Populations (8.7)]

moderate hepatic impairment

[seeUse 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. (2.1)
•Changes between XELJANZ and XELJANZ XR should be made by the healthcare provider. (2.1)
•Do not initiate XELJANZ/XELJANZ XR/XELJANZ Oral Solution if absolute lymphocyte count <500 cells/mm³, an absolute neutrophil count (ANC) <1000 cells/mm³or hemoglobin <9 g/dL. (2.1)

Recommended Dosage

Rheumatoid Arthritis

•XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily. (2.2)
•Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is XELJANZ 5 mg once daily. (2,8.7,8.8)

Psoriatic Arthritis (in combination with nonbiologic DMARDs)

•XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily. (2.2)
•Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is XELJANZ 5 mg once daily. (2,8.7,8.8)

Ankylosing Spondylitis

•XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily. (2.2)
•Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is XELJANZ 5 mg once daily. (2,8.7,8.8)

Ulcerative Colitis

•Induction: XELJANZ 10 mg twice daily or XELJANZ XR 22 mg once daily for 8 weeks; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed, continue XELJANZ 10 mg twice daily or XELJANZ XR 22 mg once daily for a maximum of 16 weeks. Discontinue XELJANZ 10 mg twice daily or XELJANZ XR 22 mg once daily after 16 weeks if adequate therapeutic response is not achieved. (2.3)
•Maintenance: XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily. For patients with loss of response during maintenance treatment, XELJANZ 10 mg twice daily or XELJANZ XR 22 mg once daily may be considered and limited to the shortest duration, with careful consideration of the benefits and risks for the individual patient. Use the lowest effective dose needed to maintain response. (2.3)
•Dosage adjustment is needed in patients with moderate and severe renal impairment or moderate hepatic impairment: see full prescribing information. (2.3)

Polyarticular Course Juvenile Idiopathic Arthritis

•XELJANZ/XELJANZ Oral Solution 5 mg twice daily or weight-based equivalent twice daily. (2.4)
•Dosage adjustment is needed in patients with moderate and severe renal impairment or moderate hepatic impairment: see full prescribing information. (2.4)

Dosage Adjustment

•See the full prescribing information for dosage adjustments by indication for patients receiving CYP2C19 and/or CYP3A4 inhibitors; in patients with moderate or severe renal impairment or moderate hepatic impairment; and patients with lymphopenia, neutropenia, or anemia. (2.2,2.3,2.4,8.7,8.8)
•Use of XELJANZ/XELJANZ XR/XELJANZ Oral Solution in patients with severe hepatic impairment is not recommended in any patient population. (2.2,2.3,2.4,8.8)

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
[seeDosage 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
[seeWarnings 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
[seeWarnings and Precautions (5.1)]
.
•Take XELJANZ/XELJANZ XR/XELJANZ Oral Solution with or without food
[seeClinical 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)

[seeDrug Interactions (7)]

moderate or severe renal impairment

[seeUse in Specific Populations (8.7)]

moderate hepatic impairment

[seeUse 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)

[seeDrug Interactions (7)]

moderate or severe renal impairment

[seeUse in Specific Populations (8.7)]

moderate hepatic impairment

[seeUse 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 [seeClinical 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

[seeDrug Interactions (7)]

, in patients with moderate or severe renal impairment, including but not limited to those undergoing hemodialysis

[seeUse in Specific Populations (8.7)]

, with moderate hepatic impairment

[seeUse 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)

[seeDrug Interactions (7)]

moderate or severe renal impairment

[seeUse in Specific Populations (8.7)]

moderate hepatic impairment

[seeUse 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

[seeInstructions for Use]

8.7 Renal Impairment

Moderate and Severe Impairment

[seeDosage 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

[seeClinical Pharmacology (12.3)]

[seeDosage 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)

[seeDrug Interactions (7)]

moderate or severe renal impairment

[seeUse in Specific Populations (8.7)]

moderate hepatic impairment

[seeUse 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 [seeClinical 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)

[seeDrug Interactions (7)]

moderate or severe renal impairment

[seeUse in Specific Populations (8.7)]

moderate hepatic impairment

[seeUse 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 [seeClinical 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)

[seeDrug Interactions (7)]

moderate or severe renal impairment

[seeUse in Specific Populations (8.7)]

moderate hepatic impairment

[seeUse 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 [seeClinical 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

[seeDrug Interactions (7)]

, in patients with moderate or severe renal impairment, including but not limited to those undergoing hemodialysis

[seeUse in Specific Populations (8.7)]

, with moderate hepatic impairment

[seeUse 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)

[seeDrug Interactions (7)]

moderate or severe renal impairment

[seeUse in Specific Populations (8.7)]

moderate hepatic impairment

[seeUse 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

[seeInstructions 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

[seeDrug Interactions (7)]

, in patients with moderate or severe renal impairment, including but not limited to those undergoing hemodialysis

[seeUse in Specific Populations (8.7)]

, with moderate hepatic impairment

[seeUse 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)

[seeDrug Interactions (7)]

moderate or severe renal impairment

[seeUse in Specific Populations (8.7)]

moderate hepatic impairment

[seeUse 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

[seeInstructions 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)

[seeDrug Interactions (7)]

moderate or severe renal impairment

[seeUse in Specific Populations (8.7)]

moderate hepatic impairment

[seeUse 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)

[seeDrug Interactions (7)]

moderate or severe renal impairment

[seeUse in Specific Populations (8.7)]

moderate hepatic impairment

[seeUse 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 [seeClinical 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

[seeDrug Interactions (7)]

, in patients with moderate or severe renal impairment, including but not limited to those undergoing hemodialysis

[seeUse in Specific Populations (8.7)]

, with moderate hepatic impairment

[seeUse 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)

[seeDrug Interactions (7)]

moderate or severe renal impairment

[seeUse in Specific Populations (8.7)]

moderate hepatic impairment

[seeUse 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

[seeInstructions for Use]

8.7 Renal Impairment

Moderate and Severe Impairment

[seeDosage 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

[seeClinical Pharmacology (12.3)]

[seeDosage 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)

[seeDrug Interactions (7)]

moderate or severe renal impairment

[seeUse in Specific Populations (8.7)]

moderate hepatic impairment

[seeUse 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)

[seeDrug Interactions (7)]

moderate or severe renal impairment

[seeUse in Specific Populations (8.7)]

moderate hepatic impairment

[seeUse 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 [seeClinical 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

[seeDrug Interactions (7)]

, in patients with moderate or severe renal impairment, including but not limited to those undergoing hemodialysis

[seeUse in Specific Populations (8.7)]

, with moderate hepatic impairment

[seeUse 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)

[seeDrug Interactions (7)]

moderate or severe renal impairment

[seeUse in Specific Populations (8.7)]

moderate hepatic impairment

[seeUse 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

[seeInstructions 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

[seeClinical Pharmacology (12.3)]

[seeDosage 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.

)

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