Tofacitinib Dosing in Dialysis Patients
For patients with end-stage renal disease on hemodialysis, tofacitinib should be dosed at 5 mg once daily (if the standard dose would be 5 mg twice daily) or 5 mg once daily (if the standard dose would be 10 mg twice daily), administered after the dialysis session on dialysis days. 1
Dosing Algorithm for Dialysis Patients
Standard Dose Reduction Requirements
If the patient's usual dose is 10 mg twice daily: Reduce to 5 mg twice daily for moderate-to-severe renal impairment, then further reduce to 5 mg once daily for hemodialysis patients 1
If the patient's usual dose is 5 mg twice daily: Reduce directly to 5 mg once daily for hemodialysis patients 1
If using extended-release formulations (XELJANZ XR): Patients on 22 mg once daily should reduce to 11 mg once daily for renal impairment, then switch to immediate-release XELJANZ 5 mg once daily for hemodialysis 1
Critical Timing Considerations
Administer the dose after the dialysis session on dialysis days to avoid removal of the drug during dialysis 1
If a dose was inadvertently taken before dialysis: Do not give a supplemental dose after dialysis, as this would result in overdosing 1
On non-dialysis days: Continue the once-daily dosing schedule 1
Pharmacokinetic Rationale
The dose reduction is necessary because tofacitinib exposure (AUC) increases significantly with declining renal function. In patients with end-stage renal disease on non-dialysis days, the AUC is approximately 40% greater than in patients with normal renal function and similar to those with moderate renal impairment 2. While dialysis can remove tofacitinib with a dialyzer efficiency of approximately 73%, the extensive non-renal clearance of the drug means that dialysis does not result in clinically significant elimination 2.
Additional Monitoring Requirements
Hematologic Monitoring
Lymphocyte counts: Discontinue tofacitinib if lymphocyte count falls below 500 cells/mm³ (confirmed by repeat testing) 1
Absolute neutrophil count (ANC): Interrupt dosing if ANC is 500-1000 cells/mm³; discontinue if ANC falls below 500 cells/mm³ 1
Hemoglobin: Interrupt dosing if hemoglobin drops below 8 g/dL or decreases by more than 2 g/dL until values normalize 1
Infection Risk
Dialysis patients receiving tofacitinib face heightened infection risk due to both uremia-related immune dysfunction and JAK inhibition. Serious infections including pneumonia, opportunistic infections (tuberculosis, cryptococcosis, herpes zoster), and sepsis have been reported 1. Close monitoring for signs of infection is mandatory, and tofacitinib should be interrupted if serious infection develops 1.
Common Pitfalls to Avoid
Do not use the standard twice-daily dosing in dialysis patients: This will result in drug accumulation and increased toxicity risk 1, 2
Do not give supplemental doses after dialysis: Despite dialyzer removal, the extensive non-renal clearance means supplementation is unnecessary and potentially harmful 1, 2
Do not forget to adjust for drug interactions: If the patient is also receiving strong CYP3A4 inhibitors (e.g., ketoconazole) or moderate CYP3A4 plus strong CYP2C19 inhibitors (e.g., fluconazole), further dose reduction may be necessary 1