Tofacitinib
Quoted from the FDA label. Product labels differ by manufacturer and change over time; confirm against the label for the product you are using. Not yet reviewed by a ClinDose pharmacist.
Dosing in kidney impairment
Renal Impairment Moderate and Severe Renal Impairment XELJANZ-treated patients with moderate renal impairment (RI) (CLcr ≥ 30 and ≤ 50 mL/minute) or severe RI (< 30 mL/minute) had greater tofacitinib blood concentrations than XELJANZ-treated patients with normal renal function (CLcr > 80 mL/minute). The recommended dosage of tofacitinib extended-release tablets in patients with moderate or severe RI (including those with severe RI who are undergoing hemodialysis) is lower than the recommended dosage in patients with normal renal function [see Dosage and Administration (2.3 , 2.5) ] .
Mild Renal Impairment The recommended dosage in patients with mild RI (CLcr > 50 and ≤ 80 mL/minute) is the same as patients with normal renal function.
| Adults | Tofacitinib extended-release tablets |
|---|---|
| Patients with Normal Renal and Hepatic FunctionExcludes patients who concomitantly use XELJANZ tablets/tofacitinib extended-release 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/mm3, ANC < 1000 cells/mm3, or hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL. | 11 mg once daily |
| Recommended Dosage in Patients with Renal Impairment (RI)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). | |
| Mild RI (CLcr > 50 and ≤ 80 mL/min) | 11 mg once daily |
| Moderate RI (CLcr ≥ 30 and ≤ 50 mL/min) | XELJANZ tablets 5 mg once daily |
| Severe RI (CLcr < 30 mL/min) | XELJANZ tablets 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) | 11 mg once daily |
| Moderate HI (Child-Pugh B) | XELJANZ tablets 5 mg once daily |
| Severe HI (Child-Pugh C) | Use of XELJANZ tablets/tofacitinib extended-release tablets is not recommended. |
| Dosage Modifications with Concomitant Use of CYP3A4 and/or CYP2C19 Inhibitor(s) | |
| Strong CYP2C19 inhibitor(s) | 11 mg once daily |
| Moderate CYP2C19 inhibitor(s) | |
| Moderate CYP3A4 inhibitor(s) | |
| Moderate CYP3A4 inhibitor(s) with strong CYP2C19 inhibitor(s) (e.g., fluconazole) | XELJANZ tablets 5 mg once daily |
| Strong CYP3A4 inhibitor(s) | |
| Dosage Modifications for Lymphopenia, Neutropenia, or Anemia | |
| Patients with lymphocyte count less than 500 cells/mm3, confirmed by repeat testing | Discontinue dosing. |
| Patients with ANC less than 500 cells/mm3 | Discontinue dosing. |
| Patients with ANC 500 to 1,000 cells/mm3 | Interrupt dosing. When ANC is greater than 1,000, resume 11 mg once 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. |
| Adults | Tofacitinib Extended Release Tablets |
| Patients with Normal Renal and Hepatic FunctionExcludes patients who concomitantly use tofacitinib extended-release 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/mm3, ANC < 1,000 cells/mm3, or hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL. | 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, may consider a dosage of 22 mg once daily (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. |
| Recommended Dosage in Patients with Renal Impairment (RI)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). | |
| Mild RI (CLcr > 50 and ≤ 80 mL/min) | Same as patients with normal renal function. |
| Moderate RI (CLcr ≥ 30 and ≤ 50 mL/min) | Induction: 11 mg once daily for atleast 8 weeks; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed continue 11 mg once daily for a maximum of 16 weeks. Discontinue 11 mg once daily after 16 weeks if adequate therapeutic response is not achieved. Maintenance: Tofacitinib extended release tablets is not recommended. See Maintenance Dosage for XELJANZ tablets for Moderate or Severe RI. 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. |
| Severe RI (CLcr < 30 mL/min) | |
| 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: 11 mg once daily for at least 8 weeks; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed continue 11 mg once daily for a maximum of 16 weeks. Discontinue 11 mg once daily after 16 weeks if adequate therapeutic response is not achieved. Maintenance: Tofacitinib extended release tablets is not recommended. See Maintenance Dosage for XELJANZ tablets for Moderate HI. |
| Severe HI (Child-Pugh C) | Use of tofacitinib extended release tablets is not recommended. |
Dosing in liver impairment
Hepatic Impairment Severe Hepatic Impairment Tofacitinib extended-release tablets has not been studied in patients with severe hepatic impairment (HI) (Child-Pugh C); therefore, use of tofacitinib extended-release tablets in patients with severe HI is not recommended. Moderate Hepatic Impairment XELJANZ-treated patients with moderate hepatic impairment (Child-Pugh B) had greater tofacitinib blood concentration than XELJANZ-treated patients with normal hepatic function [see Clinical Pharmacology ].
Higher blood concentrations may increase the risk of some adverse reactions. The recommended tofacitinib extended-release tablets dosage in patients with moderate HI is lower than the recommended dosage in patients with normal hepatic function [see Dosage and Administration (2.3 , 2.5) ] . Mild Hepatic Impairment The recommended dosage of tofacitinib extended-release tablets in patients with mild hepatic impairment (Child-Pugh A) is the same as patients with normal hepatic function.
Hepatitis B or C Serology The safety and efficacy of tofacitinib extended-release tablets have not been studied in patients with positive hepatitis B virus or hepatitis C virus serology.
| Adults | Tofacitinib extended-release tablets |
|---|---|
| Patients with Normal Renal and Hepatic FunctionExcludes patients who concomitantly use XELJANZ tablets/tofacitinib extended-release 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/mm3, ANC < 1000 cells/mm3, or hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL. | 11 mg once daily |
| Recommended Dosage in Patients with Renal Impairment (RI)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). | |
| Mild RI (CLcr > 50 and ≤ 80 mL/min) | 11 mg once daily |
| Moderate RI (CLcr ≥ 30 and ≤ 50 mL/min) | XELJANZ tablets 5 mg once daily |
| Severe RI (CLcr < 30 mL/min) | XELJANZ tablets 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) | 11 mg once daily |
| Moderate HI (Child-Pugh B) | XELJANZ tablets 5 mg once daily |
| Severe HI (Child-Pugh C) | Use of XELJANZ tablets/tofacitinib extended-release tablets is not recommended. |
| Dosage Modifications with Concomitant Use of CYP3A4 and/or CYP2C19 Inhibitor(s) | |
| Strong CYP2C19 inhibitor(s) | 11 mg once daily |
| Moderate CYP2C19 inhibitor(s) | |
| Moderate CYP3A4 inhibitor(s) | |
| Moderate CYP3A4 inhibitor(s) with strong CYP2C19 inhibitor(s) (e.g., fluconazole) | XELJANZ tablets 5 mg once daily |
| Strong CYP3A4 inhibitor(s) | |
| Dosage Modifications for Lymphopenia, Neutropenia, or Anemia | |
| Patients with lymphocyte count less than 500 cells/mm3, confirmed by repeat testing | Discontinue dosing. |
| Patients with ANC less than 500 cells/mm3 | Discontinue dosing. |
| Patients with ANC 500 to 1,000 cells/mm3 | Interrupt dosing. When ANC is greater than 1,000, resume 11 mg once 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. |
| Adults | Tofacitinib Extended Release Tablets |
| Patients with Normal Renal and Hepatic FunctionExcludes patients who concomitantly use tofacitinib extended-release 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/mm3, ANC < 1,000 cells/mm3, or hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL. | 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, may consider a dosage of 22 mg once daily (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. |
| Recommended Dosage in Patients with Renal Impairment (RI)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). | |
| Mild RI (CLcr > 50 and ≤ 80 mL/min) | Same as patients with normal renal function. |
| Moderate RI (CLcr ≥ 30 and ≤ 50 mL/min) | Induction: 11 mg once daily for atleast 8 weeks; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed continue 11 mg once daily for a maximum of 16 weeks. Discontinue 11 mg once daily after 16 weeks if adequate therapeutic response is not achieved. Maintenance: Tofacitinib extended release tablets is not recommended. See Maintenance Dosage for XELJANZ tablets for Moderate or Severe RI. 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. |
| Severe RI (CLcr < 30 mL/min) | |
| 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: 11 mg once daily for at least 8 weeks; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed continue 11 mg once daily for a maximum of 16 weeks. Discontinue 11 mg once daily after 16 weeks if adequate therapeutic response is not achieved. Maintenance: Tofacitinib extended release tablets is not recommended. See Maintenance Dosage for XELJANZ tablets for Moderate HI. |
| Severe HI (Child-Pugh C) | Use of tofacitinib extended release tablets is not recommended. |
Preparation and administration
Important Administration Instructions Tofacitinib extended-release tablets are not substitutable with XELJANZ (tablets and oral solution). Switching between XELJANZ and tofacitinib extended-release tablets should be made by the healthcare provider. Dose interruption is recommended for management of lymphopenia, neutropenia, and anemia [see Warnings and Precautions and Adverse Reactions ] .
Interrupt use of tofacitinib extended-release tablets if a patient develops a serious infection until the infection is controlled [see Warnings and Precautions ]. Take tofacitinib extended-release tablets with or without food [see Clinical Pharmacology ] . Swallow tofacitinib extended-release tablets whole and intact. Do not crush, split, or chew the extended-release tablets [see Clinical Pharmacology ].