Gilteritinib administration in a hemodialysis patient

Gilteritinib is a multitargeted tyrosine kinase inhibitor (TKI) approved by the Food and Drug Administration (FDA) for acute myeloid leukemia (AML) with a FMS-related tyrosine kinase 3 (FLT3) mutation. The pharmacokinetics of gilteritinib in the setting of severe renal impairment (creatinine clearance [CrCl] 15-29 mL/min utilizing Cockcroft-Gault method) and end-stage renal disease are unknown. Gilteritinib is primarily metabolized by the liver through the CYP3A4 enzyme and is eliminated in both the feces and urine. Its excretion is primarily through the fecal route, accounting for 64.5% of the recovered dose. Only about 16.4% of the recovered dose has been detected in the urine of human subjects.

We describe our patient case documenting the administration of gilteritinib in the setting of end-stage renal disease (ESRD) and hemodialysis (HD).Management and Outcomes: Our patient was initiated on single agent gilteritinib 120 mg by mouth once daily for relapse FLT3-TDK positive AML. Treatment course was complicated by pancytopenia, neutropenic fever, and staphylococcus lugdunensis bacteremia requiring temporary interruption of therapy.

Given that gilteritinib is metabolized by the liver and eliminated primarily in the feces, one does not expect an increase in toxicity related to impaired renal function. Although this report describes the successful utilization of gilteritinib, caution should be exercised when administering in patient populations with end organ disease, and patient comorbidities should be taken into account.