Tofacitinibdosage

Recommended Evaluations and Immunization Prior to Treatment Initiation Prior to initiating tofacitinib tablets, consider performing an active and latent TB evaluation, viral hepatitis screening, a complete blood count, and updating immunizations. Avoid tofacitinib tablets initiation if absolute lymphocyte count < 500 cells/mm 3, an absolute neutrophil count (ANC) < 1,000 cells/mm 3 or hemoglobin < 9 g/dL. Important Administration Instructions XELJANZ XR (extended-release tablets) is not substitutable with tofacitinib tablets. Switching between tofacitinib tablets and XELJANZ XR should be made by the healthcare provider. Recommended Dosage Adult Patients with RA, PsA or AS Tofacitinib tablets 5 mg twice daily. Pediatric Patients 2 Years of Age and Older with PsA or pcJIA Who Weigh At Least 10 kg Tofacitinib tablets 5 mg twice daily for those ≥ 40 kg or weight-based equivalent twice daily for those < 40 kg. Adult Patients with UC Induction: Tofacitinib tablets 10 mg twice daily for 8 weeks; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed, continue tofacitinib tablets 10 mg twice daily for a maximum of 16 weeks. Discontinue tofacitinib tablets 10 mg twice daily after 16 weeks if adequate therapeutic response is not achieved.

Maintenance: Tofacitinib tablets 5 mg twice daily. For patients with loss of response during maintenance treatment, tofacitinib tablets 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. Dosage in Patients with Renal Impairment or Hepatic Impairment Use of tofacitinib tablets in patients with severe HI is not recommended. See full prescribing information (FPI) for recommended dosage in patients with moderate or severe RI or moderate HI. Dosage Modification See the full prescribing information for dosage modification by indication for patients who concomitantly use CYP2C19 and/or CYP3A4 inhibitors and patients with lymphopenia, neutropenia, or anemia.

2.1 Recommended

Evaluations and Immunization Prior to Treatment Initiation Prior to initiating tofacitinib tablets, consider performing the following: Active and latent tuberculosis (TB) infection evaluation: If the patient has latent TB, treat for TB prior to tofacitinib tablets treatment. Viral hepatitis screening in accordance with clinical guidelines.

A complete blood count: Avoid initiation of tofacitinib tablets treatment in patients with a lymphocyte count less than 500 cells/mm 3, absolute neutrophil count less than 1,000 cells/mm 3, or hemoglobin level less than 9 g/dL.

Baseline hepatic function evaluation: tofacitinib tablets is not recommended for patients with severe hepatic impairment. Update immunizations according to current immunization guidelines. The interval between live vaccinations and initiation of tofacitinib tablets should be in accordance with current vaccination guidelines regarding immunosuppressive agents.

2.2 Important

Administration Instructions XELJANZ XR (extended-release tablets) is not substitutable with tofacitinib tablets. Switching between tofacitinib tablets and XELJANZ XR should be made by the healthcare provider. Dose interruption is recommended for management of lymphopenia, neutropenia, and anemia. Interrupt use of tofacitinib tablets if a patient develops a serious infection until the infection is controlled. Take tofacitinib tablets with or without food.

2.3 Recommended

Dosage in Adults with Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis Table 1 displays the recommended dosage of tofacitinib tablets for adults with RA, PsA, and AS with and without renal impairment (including those who are undergoing hemodialysis) or hepatic impairment. The table also displays the recommended dosage modifications for patients concomitantly using CYP2C19 and/or CYP3A4 inhibitors, and patients with lymphopenia, neutropenia, or anemia. Table 1 Recommended Dosage of Tofacitinib Tablets in Adults with Rheumatoid Arthritis, Psoriatic Arthritis, or Ankylosing Spondylitis Adults Tofacitinib Tablets Patients with Normal Renal and Hepatic Function a 5 mg twice daily Recommended Dosage in Patients with Renal Impairment (RI) b Mild RI (CLcr > 50 and ≤ 80 mL/min) 5 mg twice daily Moderate RI (CLcr ≥ 30 and ≤ 50 mL/min) 5 mg once daily Severe RI (CLcr < 30 mL/min) 5 mg once daily For patients undergoing hemodialysis, administer the dose after the dialysis session on dialysis days. If a dose was taken before the dialysis procedure, supplemental doses are not recommended after dialysis. Recommended Dosage in Patients with Hepatic Impairment (HI) Mild HI (Child-Pugh A) 5 mg twice daily Moderate HI (Child-Pugh B) 5 mg once daily Severe HI (Child-Pugh C) Use of tofacitinib tablets is not recommended. Dosage Modifications with Concomitant Use of CYP3A4 and/or CYP2C19 Inhibitor(s) Strong CYP2C19 inhibitor(s) 5 mg twice daily Moderate CYP2C19 inhibitor(s) Moderate CYP3A4 inhibitor(s) Moderate CYP3A4 inhibitor(s) with strong CYP2C19 inhibitor(s) (e.g., fluconazole) 5 mg once daily Strong CYP3A4 inhibitor(s) Dosage Modifications for Lymphopenia, Neutropenia, or Anemia Patients with lymphocyte count less than 500 cells/mm 3, confirmed by repeat testing Discontinue dosing. Patients with ANC less than 500 cells/mm 3 Discontinue dosing. Patients with ANC 500 cells/mm 3 to 1,000 cells/mm 3 Interrupt dosing. When ANC is greater than 1,000, resume 5 mg twice daily. Patients with hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL Interrupt dosing until hemoglobin values have normalized. a Excludes patients who concomitantly use tofacitinib tablets with strong CYP3A4 inhibitor(s) or moderate CYP3A4 inhibitor(s) and strong CYP2C19 inhibitor(s), as well as patients with lymphocyte count less than 500 cells/mm 3, ANC < 1,000 cells/mm 3, or hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL. b Tofacitinib PK was evaluated in subjects with varying degrees of renal impairment, where the severity of renal impairment was defined based on creatinine clearance (CLcr) estimated using the Cockcroft-Gault equation: CLcr > 80 mL/min (normal renal function); > 50 and ≤ 80 mL/min (mild renal impairment); ≥ 30 and ≤ 50 mL/min (moderate renal impairment); < 30 mL/min (severe renal impairment). Switching from Tofacitinib Tablets to XELJANZ XR Extended-Release Tablets Patients treated with tofacitinib 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 tofacitinib tablets 5 mg.

2.4 Recommended

Dosage in Pediatric Patients 2 Years of Age and Older with Psoriatic Arthritis or Polyarticular Course Juvenile Idiopathic Arthritis Table 2 displays the recommended body weight-based dosages for tofacitinib tablets in pediatric patients 2 years of age and older with PsA or pcJIA with and without renal impairment (including those who are undergoing hemodialysis) or hepatic impairment. The table also includes recommended dosage modification for pediatric patients concomitantly using CYP2C19 and/or CYP3A4 inhibitors, and pediatric patients with lymphopenia, neutropenia, or anemia. Table 2 Recommended Dosage of Tofacitinib Tablets in Pediatric Patients 2 Years of Age and Older with PsA or pcJIA Pediatric Patients 2 Years of Age and Older Tofacitinib tablets Patients with Normal Renal and Hepatic Function a Body weight ≥ 40 kg: 5 mg (one 5 mg tablet or 5 mL oral solution) twice daily b Recommended Dosage in Patients with Renal Impairment (RI) Mild RI Same as patients with normal renal function. Moderate RI Body weight ≥ 40 kg: 5 mg once daily b Severe RI Body weight ≥ 40 kg: 5 mg once daily b For patients undergoing hemodialysis, administer the dose after the dialysis session on dialysis days. If a dose was taken before the dialysis procedure, supplemental doses are not recommended after dialysis. Recommended Dosage in Patients with Hepatic Impairment (HI) Mild HI Same as patients with normal hepatic function. Moderate HI Body weight ≥ 40 kg: 5 mg once daily b Severe HI Use of tofacitinib tablets is not recommended. Dosage Modifications with Concomitant Use of CYP3A4 and/or CYP2C19 Inhibitor(s) Strong CYP2C19 inhibitor(s) No dosage modification is recommended. Moderate CYP2C19 inhibitor(s) Moderate CYP3A4 inhibitor(s) Moderate CYP3A4 inhibitor(s) with strong CYP2C19 inhibitor(s) (e.g., fluconazole) Body weight ≥ 40 kg: 5 mg once daily b Strong CYP3A4 inhibitor(s) Dosage Modifications for Lymphopenia, Neutropenia, or Anemia Patients with lymphocyte count less than 500 cells/mm 3, confirmed by repeat testing Discontinue dosing. Patients with ANC less than 500 cells/mm 3 Discontinue dosing. Patients with ANC 500 to 1,000 cells/mm 3 Interrupt dosing until ANC is greater than 1,000 cells/mm 3. Patients with hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL Interrupt dosing until hemoglobin values have normalized. a Excludes patients who concomitantly use tofacitinib tablets with strong CYP3A4 inhibitor(s) or moderate CYP3A4 inhibitor(s) and strong CYP2C19 inhibitor(s), as well as patients with lymphocyte count less than 500 cells/mm 3, ANC < 1,000 cells/mm 3, or hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL. b Patients treated with XELJANZ oral solution 5 mL may be switched to tofacitinib tablets 5 mg.

2.5 Recommended

Dosage in Adults with Ulcerative Colitis Table 3 displays the recommended dosage of tofacitinib tablets in adult patients with ulcerative colitis (UC) with and without renal impairment (including those who are undergoing hemodialysis) or hepatic impairment. Table 4 displays the recommended dosage modification for patients concomitantly using CYP2C19 and/or CYP3A4 inhibitors, and patients with lymphopenia, neutropenia, or anemia. Table 3 Recommended Dosage of tofacitinib tablets in Adults with Ulcerative Colitis With and Without Renal Impairment or Hepatic Impairment Adults Tofacitinib tablets Patients with Normal Renal and Hepatic Function a Induction: 10 mg twice daily for at least 8 weeks; 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, may consider a dosage of 10 mg twice daily (limited to the shortest duration), with careful consideration of the benefits and risks for the individual patient. Use the lowest effective dosage needed to maintain response. Recommended Dosage in Patients with Renal Impairment (RI) b Mild RI (CLcr > 50 and ≤ 80 mL/min) Same as patients with normal renal function. Moderate RI (CLcr ≥ 30 and ≤ 50 mL/min) Induction: 5 mg twice daily for at least 8 weeks; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed continue 5 mg twice daily for a maximum of 16 weeks. Discontinue 5 mg twice daily after 16 weeks if adequate therapeutic response is not achieved.

Maintenance: 5 mg once daily. For patients with loss of response during maintenance treatment, may consider a dosage of 5 mg twice daily (limited to the shortest duration), with careful consideration of the benefits and risks for the individual patient. Use the lowest effective dosage needed to maintain response. Severe RI (CLcr < 30 mL/min) For patients undergoing hemodialysis, administer the dose after the dialysis session on dialysis days. If a dose was taken before the dialysis procedure, supplemental doses are not recommended after dialysis. Recommended Dosage in Patients with Hepatic Impairment (HI) Mild HI (Child-Pugh A) Same as patients with normal hepatic function. Moderate HI (Child-Pugh B) Induction: 5 mg twice daily for at least 8 weeks; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed continue 5 mg twice daily for a maximum of 16 weeks. Discontinue 5 mg twice daily after 16 weeks if adequate therapeutic response is not achieved.

Maintenance: 5 mg once daily. For patients with loss of response during maintenance treatment, may consider a dosage of 5 mg twice daily (limited to the shortest duration), with careful consideration of the benefits and risks for the individual patient. Use the lowest effective dosage needed to maintain response. Severe HI (Child-Pugh C) Use of tofacitinib tablets is not recommended. a Excludes patients who concomitantly use tofacitinib tablets with strong CYP3A4 inhibitor(s) or moderate CYP3A4 inhibitor(s) and strong CYP2C19 inhibitor(s), as well as patients with lymphocyte count less than 500 cells/mm 3, ANC < 1,000 cells/mm 3, or hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL. b Tofacitinib PK was evaluated in subjects with varying degrees of renal impairment, where the severity of renal impairment was defined based on creatinine clearance (CLcr) estimated using the Cockcroft-Gault equation: CLcr > 80 mL/min (normal renal function); CLcr > 50 and ≤ 80 mL/min (mild renal impairment); ≥ 30 and ≤ 50 mL/min (moderate renal impairment); < 30 mL/min (severe renal impairment). Table 4 Dosage Modifications of Tofacitinib TabletsDue to Drug Interactions and for Lymphopenia, Neutropenia or Anemia in Adults with Ulcerative Colitis Adults Tofacitinib Tablets Dosage Modifications with Concomitant Use of CYP3A4 and/or CYP2C19 Inhibitor(s) Strong CYP2C19 inhibitor(s) No dosage modification is recommended. Moderate CYP2C19 inhibitor(s) Moderate CYP3A4 inhibitor(s) Moderate CYP3A4 inhibitor(s) with strong CYP2C19 inhibitor(s) (e.g., fluconazole) Induction: 5 mg twice daily for at least 8 weeks; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed continue 5 mg twice daily for a maximum of 16 weeks. Discontinue 5 mg twice daily after 16 weeks if adequate therapeutic response is not achieved. Strong CYP3A4 inhibitor(s) Maintenance: 5 mg once daily. For patients with loss of response during maintenance treatment, may consider a dosage of 5 mg twice daily (limited to the shortest duration), with careful consideration of the benefits and risks for the individual patient. Use the lowest effective dosage needed to maintain response. Dosage Modifications for Lymphopenia, Neutropenia, or Anemia Lymphocyte count less than 500 cells/mm 3, confirmed by repeat testing Discontinue dosing. ANC less than 500 cells/mm 3 Discontinue dosing. ANC 500 to 1,000 cells/mm 3 If taking: ● 10 mg twice daily, reduce to 5 mg twice daily. When ANC is greater than 1,000, increase to 10 mg twice daily based on clinical response. ● 5 mg twice daily, interrupt dosing. When ANC is greater than 1,000, resume 5 mg twice daily. Hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL Interrupt dosing until hemoglobin values have normalized. Switching from Tofacitinib Tablets to XELJANZ XR Extended-Release Tablets Patients treated with tofacitinib 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 tofacitinib tablets 5 mg. 10 mg twice daily may be switched to XELJANZ XR extended-release tablets 22 mg once daily the day following the last dose of tofacitinib tablets 10 mg.