Adult: In combination with standard cytarabine and daunorubicin induction and high dose cytarabine consolidation chemotherapy: 50 mg bid on days 8-21 of chemotherapy cycles. Maintenance: As monotherapy for patient in complete response: 50 mg once daily until relapsed for up to 12 cycles of 28 days cycles. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
Adult: 100 mg bid continued until disease progression or unacceptable toxicity occurs. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
Administration
liquid filled cap: Should be taken with food. Take approx 12 hr intervals. Swallow whole, do not open/crush.
Contraindications
Concomitant administration with potent CYP3A4 inducers.
Special Precautions
Patient with cardiac dysfunction, risk of QTc prolongation. Severe renal and hepatic impairment. Pregnancy and lactation.
This drug may cause dizziness and vertigo, if affected do not drive or operate machinery.
Monitoring Parameters
Perform confirmatory test of FLT3 mutation (internal tandem duplication or tyrosine kinase domain) prior to initiation of therapy for acute myeloid leukaemia. Monitor WBC at treatment initiation and regularly thereafter. Assess LVEF at baseline and during treatment or when clinically indicated. Monitor CBC with differential in systemic mastocytosis at least weekly for 4 weeks, then every other week for next 8 weeks, then monthly thereafter or when clinically indicated. Monitor for pulmonary symptoms indicative of ILD or pneumonitis; signs and symptoms of infection. Perform pregnancy test within 7 days of therapy.
Drug Interactions
Increased plasma concentration with strong CYP3A4 inhibitors (e.g. ketoconazole, ritonavir, clarithromycin, nefazodone). Increased risk of QT prolongation with QT prolonging drugs (e.g. chloroquine). Potentially Fatal: Decreased plasma concentration with strong CYP3A4 inducers (e.g. carbamazepine, rifampicin, enzalutamide, phenytoin).
Food Interaction
Increased absorption with food. Decreased serum concentrations with St. John’s wort.
Action
Description: Midostaurin is a multikinase inhibitor effective against tyrosine kinase, protein kinase C family, and multiple receptors including growth factors (e.g. vascular endothelial growth factor, platelet-derived growth factor). It inhibits FLT3 receptor signaling and cell proliferation, inducing apoptosis in mutant expressing leukemic cells and in cells overexpressing wild type FLT3 and PDGFR. It may also inhibit KIT signaling, cell proliferation, and histamine release and induces apoptosis in mast cells. Pharmacokinetics: Absorption: Rapidly absorb from the gastrointestinal tract. Food, particularly high fat meal, increases absorption. Time to peak plasma concentration: 1-3 hours. Distribution: Distributed mainly in plasma. Volume of distribution: 95.2 L. Plasma protein-binding: >99.8% mainly to α1-acid glycoprotein. Metabolism: Metabolised mainly in the liver by CYP3A4 via oxidative pathways to active metabolites, CGP62221 and CGP52421. Excretion: Via urine (5%); faeces (95%, 91% as metabolites, 4% as unchanged drug). Elimination half-life: 19 hours.
Chemical Structure
Midostaurin Source: National Center for Biotechnology Information. PubChem Database. Midostaurin, CID=9829523, https://pubchem.ncbi.nlm.nih.gov/compound/Midostaurin (accessed on Jan. 22, 2020)
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