Drug Detail:Rydapt (Midostaurin [ mye-doe-staw-rin ])
Generic Name: MIDOSTAURIN 25mg
Dosage Form: capsule, liquid filled
Drug Class: Multikinase inhibitors
Patient Selection
Select patients for the treatment of AML with RYDAPT based on the presence of FLT3 mutation positivity [see Clinical Studies (14)]. Information on FDA-approved tests for the detection of FLT3 mutation in AML is available at: http://www.fda.gov/CompanionDiagnostics.
Recommended Dosage in Acute Myeloid Leukemia
The recommended dose of RYDAPT for patients with AML is 50 mg orally twice daily with food on Days 8 to 21 of each cycle of induction with cytarabine and daunorubicin and on Days 8 to 21 of each cycle of consolidation with high-dose cytarabine. For a description of the experience with single-agent treatment with RYDAPT beyond induction and consolidation [see Clinical Studies (14.1)].
Recommended Dosage in ASM, SM-AHN, and MCL
The recommended dose of RYDAPT for patients with ASM, SM-AHN, and MCL is 100 mg orally twice daily with food. Continue treatment until disease progression or unacceptable toxicity occurs. Table 1 provides recommendations for dose modifications of RYDAPT in patients with ASM, SM-AHN, and MCL. Monitor patients for toxicity at least weekly for the first 4 weeks, every other week for the next 8 weeks, and monthly thereafter while on treatment.
| Criteria | RYDAPT Dosing |
|---|---|
| ANC less than 1 x 109/L attributed to RYDAPT in patients without MCL, or ANC less than 0.5 x 109/L attributed to RYDAPT in patients with baseline ANC value of 0.5-1.5 x 109/L | Interrupt RYDAPT until ANC greater than or equal to 1 x 109/L, then resume RYDAPT at 50 mg twice daily, and if tolerated, increase to 100 mg twice daily. Discontinue RYDAPT if low ANC persists for greater than 21 days and is suspected to be related to RYDAPT. |
| Platelet count less than 50 x 109/L attributed to RYDAPT in patients without MCL, or platelet count less than 25 x 109/L attributed to RYDAPT in patients with baseline platelet count of 25-75 x 109/L | Interrupt RYDAPT until platelet count greater than or equal to 50 x 109/L, then resume RYDAPT at 50 mg twice daily, and if tolerated, increase to 100 mg twice daily. Discontinue if low platelet count persists for greater than 21 days and is suspected to be related to RYDAPT. |
| Hemoglobin less than 8 g/dL attributed to RYDAPT in patients without MCL, or life-threatening anemia attributed to RYDAPT in patients with baseline hemoglobin value of 8 to 10 g/dL | Interrupt RYDAPT until hemoglobin greater than or equal to 8 g/dL, then resume RYDAPT at 50 mg twice daily, and if tolerated, increase to 100 mg twice daily. Discontinue if low hemoglobin persists for greater than 21 days and is suspected to be related to RYDAPT. |
| Grade 3/4 nausea and/or vomiting despite optimal anti-emetic therapy | Interrupt RYDAPT for 3 days (6 doses), then resume RYDAPT at 50 mg twice daily, and if tolerated, increase to 100 mg twice daily. |
| Other Grade 3/4 non-hematological toxicities | Interrupt RYDAPT until event has resolved to less than or equal to Grade 2, then resume RYDAPT at 50 mg twice daily, and if tolerated, increase to 100 mg twice daily. |
| Abbreviations: ANC, absolute neutrophil count; MCL, mast cell leukemia. National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) severity: Grade 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms; 4 = life-threatening symptoms. |
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Recommended Administration
- Administer prophylactic anti-emetics before treatment with RYDAPT to reduce the risk of nausea and vomiting.
- Administer RYDAPT orally with food, twice daily at approximately 12-hour intervals [see Clinical Pharmacology (12.3)]. Do not open or crush RYDAPT capsules.
- If a dose of RYDAPT is missed or vomited, do not make up the dose; take the next dose at the usual scheduled time.
- Consider interval assessments of QT by electrocardiogram (ECG) if RYDAPT is taken concurrently with medications that can prolong the QT interval.
