Isavuconazole therapy in an FLT3 mutated acute myeloid leukemia patient receiving midostaurin: A case report

Abstract

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.

Keywords

CYP3A4 drug interaction FLT3 positive AML isavuconazole midostaurin

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References

Midostaurin (RYDAPT) (package insert). www.accessdata.fda.gov/drugsatfda_docs/label/2016/208114lbl.pdf (accessed 16 October 2017).

Joseph

Jain

Danziger

. Micafungin: a new echinocandin antifungal. Pharmacotherapy 2007; 27: 53–67.

van Burik

Ratanatharathorn

Stepan

et al.

Micafungin versus fluconazole for prophylaxis against invasive fungal infections during neutropenia in patients undergoing hematopoietic stem cell transplantation. Clin Infect Dis 2004; 39: 1407–1416.

Dutreix

Munarini

Lorenzo

et al.

Investigation into CYP3A4-mediated drug-drug interactions on midostaurin in healthy volunteers. Cancer Chemother Pharmacol 2013; 72: 1223–1234.

Stone

DeAngelo

Klimek

et al.

Patients with acute myeloid leukemia and an activating mutation in FLT3 respond to a small-molecule FLT3 tyrosine kinase inhibitor, PKC412. Blood 2005; 105: 54–60.

Stone

Mandrekar

Sanford

et al.

Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med 2017; 377: 454–464.

Drug interaction results (posaconazole, voriconazole, isavuconazole, midostaurin). Drug facts & comparison. Facts & comparisons eAnswers. Philadelphia, PA: Wolters Kluwer Health, Inc., http://Factsandcomparisons.com (accessed 18 October 2017).

Interaction analysis (posaconazole, voriconazole, isavuconazole, midostaurin). Lexi-interact. Lexicomp. Hudson, OH: Wolters Kluwer Health, Inc., http://Online.lexi.com (accessed 18 October 2017).

Cytochrome P450 drug interactions. Pharmacist’s letter/prescriber’s letter 2006 (full update October 2009); 22: 220233.