Tofacitinib Dose Adjustment in Renal Impairment

Introduction to Tofacitinib Dosing

The American College of Rheumatology recommends that for patients with severe renal impairment (CrCl <30 mL/min), tofacitinib dose should be reduced to 5 mg once daily 1

Tofacitinib is primarily metabolized by hepatic CYP3A4 pathway (70%), with approximately 30% renal excretion 2, 3, 1

For patients with mild to moderate renal impairment (CrCl 30-80 mL/min), no dose adjustment is required, and standard dosing can be maintained: 5 mg twice daily for rheumatoid arthritis/psoriatic arthritis or 10 mg twice daily for ulcerative colitis 3, 1, 2, 4

The European Renal Association recommends monitoring renal function periodically during treatment, as well as complete blood count with differential, due to the increased risk of cytopenias in patients with renal impairment 5, 6, 7, 8
The American Academy of Dermatology suggests checking hemoglobin levels regularly and interrupting dosing if hemoglobin decreases by >2 g/dL or falls below 8 g/dL 8
It is recommended to monitor for infections more closely in patients with impaired renal function, as they may have a higher risk of serious infections 9
Consider checking lipid levels approximately 3 months after starting treatment, as recommended by the American College of Cardiology 5, 10

Tofacitinib is contraindicated in patients with severe active infections, according to the Infectious Diseases Society of America 1, 8
Patients with renal impairment may have a higher risk of serious infections, particularly with higher doses, as stated by the National Kidney Foundation 1
The American College of Clinical Pharmacy recommends considering drug interactions that may further affect tofacitinib metabolism, such as reducing the dose to 5 mg once daily when used with potent CYP3A4 inhibitors (e.g., ketoconazole) or medications that result in both moderate CYP3A4 inhibition and potent CYP2C19 inhibition (e.g., fluconazole) 7, 8
The European Association for the Study of the Liver advises avoiding the use of tofacitinib in patients with severe hepatic impairment (Child-Pugh C) regardless of renal function 1, 8