Acute myeloid leukemia (AML) — newly diagnosed, FLT3 mutation-positive, in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation; Aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL)
AML: 50 mg orally twice daily on Days 8-21 of each cycle of induction and consolidation, then as single-agent maintenance 50 mg BID for up to 12 cycles (28-day cycles)
ASM/SM-AHN/MCL: 100 mg orally twice daily
Take with food
Administer antiemetic 30 minutes before each dose
Capsules: 25 mg soft gelatin
Hypersensitivity to midostaurin or excipients.
AML (with chemo): Febrile neutropenia (83%), nausea (83%), mucositis (66%), vomiting (61%), headache (46%), petechiae (36%), musculoskeletal pain (33%), epistaxis (28%), device-related infection (24%), hyperglycemia (20%)
ASM/SM-AHN/MCL: Nausea (82%), vomiting (68%), diarrhea (72%), edema (40%), musculoskeletal pain (35%), abdominal pain (34%), fatigue (28%), upper respiratory tract infection (26%)
Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.
Consult the complete prescribing information for drug interactions, including effects on CYP enzymes, transporters, and concomitant medications that may require dose adjustments or monitoring.
Consult the full prescribing information for pregnancy-related considerations.
Refer to prescribing information for lactation guidance.
Pediatric safety and efficacy information is detailed in the full label.
Dose modifications for organ impairment are specified in the complete prescribing information.
Midostaurin is a multi-kinase inhibitor that inhibits multiple receptor tyrosine kinases including wild-type and mutated FLT3 (ITD and TKD mutations), KIT (wild-type and D816V mutant), PDGFR-α/β, VEGFR2, and members of the serine/threonine kinase protein kinase C (PKC) family. In AML, it inhibits FLT3 receptor signaling. In systemic mastocytosis, it inhibits KIT D816V-driven mast cell proliferation and survival.
Tmax: 1-3 hours. Half-life: 21 hours (active metabolites: 32-482 hours). Protein binding: 94% (midostaurin and metabolites). Metabolized by CYP3A4. Fecal excretion (78%), urinary excretion (4%).
Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.
Rydapt has FDA-approved indications across the following cancer types covered on PipelineEvidence: