fedratinib and Kidney-Failure--Chronic

Fedratinib is an oral, selective Janus kinase 2 inhibitor that is approved in the United States for the treatment of patients with intermediate-2 or high-risk myelofibrosis. Pharmacokinetics and tolerability of fedratinib in subjects with renal impairment (RI) and hepatic impairment (HI) were evaluated in two separate studies.. In the renal study, male and female subjects with stable, chronic mild, moderate, and severe RI, as well as those with end-stage renal disease, were included. The hepatic study included subjects with stable, chronic mild HI. Both were phase 1, multicenter, open-label, single-dose studies, and included matched healthy subjects. Subjects received a single oral dose of fedratinib 300 mg on day 1, were discharged on day 4, returned for clinical visits on days 5-12, and had their end-of-study visit between days 14 and 16.. Thirty-six and 17 subjects were included in the renal and hepatic studies, respectively. In the renal study, fedratinib area under the plasma concentration-time curve from time 0 to infinity (AUC. Mild RI and HI do not necessitate fedratinib dosage adjustments. Subjects with moderate RI should be monitored (with dosage adjustments made as necessary), whereas those with severe RI should receive a daily dose of 200 mg, reduced from the indicated dose of 400 mg.

Topics: Adolescent; Adult; Aged; Area Under Curve; Case-Control Studies; Female; Follow-Up Studies; Humans; Janus Kinase 2; Kidney Failure, Chronic; Liver Diseases; Male; Maximum Tolerated Dose; Middle Aged; Prognosis; Pyrrolidines; Sulfonamides; Survival Rate; Tissue Distribution; Young Adult