midostaurin

Midostaurin is a prescription anti-cancer drug that acts as a multi-target tyrosine kinase inhibitor. It inhibits several kinases, most notably FLT3 and KIT, along with other kinases in related pathways. It was developed from the earlier compound PKC412 and is marketed in part under the brand name Rydapt.

Indications and use: In the United States, midostaurin is approved for adults with newly diagnosed FLT3-mutated acute myeloid leukemia (AML) in combination with standard induction chemotherapy (cytarabine and daunorubicin) and subsequent consolidation therapy. It is also approved for certain forms of systemic mastocytosis, including aggressive systemic mastocytosis, systemic mastocytosis with associated hematologic neoplasm, and mast cell leukemia, where indicated.

Administration and dosing: For AML, the usual regimen is 50 mg taken orally twice daily on Days 8–21 of each 28-day cycle, in combination with chemotherapy, continuing through consolidation as prescribed. For systemic mastocytosis indications, the dosing is generally higher (commonly 100 mg twice daily) and adjusted for tolerability and indication. Dosing can vary by country and specific approval.

Safety and adverse effects: Common adverse effects include nausea, vomiting, diarrhea, fatigue, edema, rash, and cytopenias. Hepatic enzyme elevations and other laboratory abnormalities may occur. Cardiac rhythm disturbances have been reported. Midostaurin is a substrate of CYP3A4, so strong inhibitors or inducers can affect exposure and may require dose adjustments. It should be used during pregnancy only when clearly needed, due to potential fetal risk.

Pharmacology and history: Midostaurin is metabolized mainly by the liver via CYP3A4. It was originally developed as PKC412 and later approved for FLT3-mutated AML in 2017.