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Introduction: 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., Case Report: 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., Discussion: 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.

Midostaurin is a multitargeted tyrosine kinase inhibitor approved by the Food and Drug Administration for FMS-related tyrosine kinase 3-positive acute myeloid leukemia in combination with standard daunorubicin and cytarabine induction and high-dose cytarabine consolidation. The pharmacokinetics of midostaurin 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. Midostaurin is primarily metabolized by the liver through the CYP3A4 enzyme with fecal excretion accounting for 95% of the dose (4% recovered as unchanged drug). Only 5% of the parent drug is found in the urine. This is the first case report documenting the administration of midostaurin in two patients with end-stage renal disease on HD. Given the limited excretion of both active and inactive metabolites of midostaurin in the urine, one does not expect an increase in toxicity related to impaired drug excretion. Although this report describes the likely successful utilization of midostaurin, caution should be exercised when administering in patient populations with end organ disease. Medical history, concomitant comorbidities, and goals of therapy should be taken into account.

Midostaurin is the first approved FMS-related tyrosine kinase 3 (FLT3) inhibitor indicated for FLT3 mutated acute myeloid leukemia. Midostaurin is a major cytochrome P450 3A4 (CYP3A4) substrate. Coadministration with a strong CYP3A4 inhibitor or inducer can lead to a potential increase or decrease in midostaurin exposure. This report describes a 43-year-old patient with FLT3-internal tandem duplication (FLT3-ITD) positive acute myeloid leukemia who initially presented with leukocytosis and concern for acute leukemia. Following the initiation of induction chemotherapy, the patient developed lung nodules concerning for a fungal infection. Isavuconazole, a moderate CYP3A4 inhibitor, was successfully initiated and maintained, while midostaurin therapy was also administered. Clinicians should be aware and exercise caution when using midostaurin with CYP3A4 inhibitors and inducers.