: •with moderate or severe renal insufficiency
•with moderate hepatic impairment
•receiving potent inhibitors of Cytochrome P450 3A4 (CYP3A4) (e.g., ketoconazole)
•receiving one or more concomitant medications that result in both moderate inhibition of CYP3A4 and potent inhibition of CYP2C19 (e.g., fluconazole).
2.2 General Considerations for Administration
■XELJANZ should not be used in patients with severe hepatic impairment.
■It is recommended that XELJANZ not be initiated in patients with a lymphocyte count less than 500 cells/mm3, an absolute neutrophil count (ANC) less than 1000 cells/mm3, or who have hemoglobin levels less than 9 g/dL.
■Coadministration of XELJANZ with potent inducers of CYP3A4 (e.g., rifampin) may result in loss of or reduced clinical response to XELJANZ.
2.3 Dosage Modifications
XELJANZ treatment should be interrupted if a patient develops a serious infection until the infection is controlled.
Table 1: Dose Adjustments for Lymphopenia
Low Lymphocyte Count [see Warnings and Precautions (5.4)]
Lab Value
(cells/mm3)
Recommendation
Lymphocyte count greater than or equal to 500
Maintain dose
Lymphocyte count less than 500
Discontinue XELJANZ
(Confirmed by repeat testing)
Table 2: Dose Adjustments for Neutropenia
Low ANC [see Warnings and Precautions (5.4)]
Lab Value
(cells/mm3)
Recommendation
ANC greater than 1000
Maintain dose
ANC 500–1000
For persistent decreases in this range, interrupt dosing until ANC is greater than 1000
When ANC is greater than 1000, resume XELJANZ 5 mg twice daily
ANC less than 500
Discontinue XELJANZ
(Confirmed by repeat testing)
Table 3: Dose Adjustments for Anemia
Low Hemoglobin Value [see Warnings and Precautions (5.4)]
Lab Value
(g/dL)
Recommendation
Less than or equal to 2 g/dL decrease and greater than or equal to 9.0 g/dL
Maintain dose
Greater than 2 g/dL decrease or less than 8.0 g/dL
Interrupt the administration of XELJANZ until hemoglobin values have normalized
(Confirmed by repeat testing)
3 DOSAGE FORMS AND STRENGTHS
XELJANZ is provided as 5 mg tofacitinib (equivalent to 8 mg tofacitinib citrate) tablets: White, round, immediate-release film-coated tablets, debossed with "Pfizer" on one side, and "JKI 5" on the other side.
4 CONTRAINDICATIONS
None
5 WARNINGS AND PRECAUTIONS
5.1 Serious Infections
Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported in rheumatoid arthritis patients receiving XELJANZ. The most common serious infections reported with XELJANZ included pneumonia, cellulitis, herpes zoster and urinary tract infection [see Adverse Reactions (6.1)]. Among opportunistic infections, tuberculosis and other mycobacterial infections, cryptococcus, esophageal candidiasis, pneumocystosis, multidermatomal herpes zoster, cytomegalovirus, and BK virus were reported with XELJANZ. Some patients have presented with disseminated rather than localized disease, and were often taking concomitant immunomodulating agents such as methotrexate or corticosteroids.
Other serious infections that were not reported in clinical studies may also occur (e.g., histoplasmosis, coccidioidomycosis, and listeriosis).
XELJANZ should n |
