Midostaurin

What it is and how it works

Midostaurin inhibits multiple receptor tyrosine kinases, including wild-type and mutant FLT3 (internal tandem duplication and tyrosine kinase domain mutations) and wild-type and D816V-mutant KIT, as well as PDGFR, VEGFR2 and protein kinase C. This inhibits proliferation and induces apoptosis of leukaemic cells and neoplastic mast cells.

Indications

Newly diagnosed FLT3-mutated acute myeloid leukaemia in adults, in combination with standard induction and consolidation chemotherapy followed by maintenance monotherapy; aggressive systemic mastocytosis, systemic mastocytosis with associated haematological neoplasm and mast cell leukaemia.

Dosage and administration (summary)

AML: 50 mg orally twice daily with food on days 8–21 of induction and consolidation chemotherapy cycles, then as maintenance. Advanced systemic mastocytosis: 100 mg twice daily with food. Prophylactic antiemetics are recommended.

Contraindications

Hypersensitivity to midostaurin or excipients; concomitant use of strong CYP3A4 inducers (e.g. rifampicin, carbamazepine, phenytoin, St John’s wort).

Warnings and precautions

Neutropenia and serious infections may occur; monitor blood counts. Interstitial lung disease and pneumonitis, cardiac dysfunction and QT prolongation have been reported; monitor respiratory symptoms, ECG and cardiac function in at-risk patients. Strong CYP3A4 inhibitors increase exposure and require close monitoring; nausea and vomiting are common.

Pregnancy

May cause fetal harm; avoid in pregnancy and use effective contraception during treatment and for at least 4 months afterwards.

Storage and supply

Store below 30 °C in the original package to protect from moisture.

Source: reference summary prepared from the EU SmPC/EPAR, BNF and WHO Model Formulary. The approved product information in Iran governs.