RYDAPT Dosage & Rx Info | Uses, Side Effects

Rydapt Generic Name & Formulations

Legal Class

General Description

Midostaurin 25mg; caps.

Pharmacological Class

Kinase inhibitor.

How Supplied

Caps—56, 112

Manufacturer

Novartis Pharmaceuticals Corp

Generic Availability

Mechanism of Action

Midostaurin demonstrated the ability to inhibit FLT3 receptor signaling and cell proliferation, and it induced apoptosis in leukemic cells expressing ITD and TKD mutant FLT3 receptors or overexpressing wild type FLT3 and PDGF receptors. Midostaurin also demonstrated the ability to inhibit KIT signaling, cell proliferation and histamine release and induce apoptosis in mast cells.

Rydapt Indications

Indications

In adults with newly diagnosed FLT3 mutation-positive acute myeloid leukemia (AML) as detected by an FDA-approved test, in combination with standard cytarabine and daunorubicin induction + cytarabine consolidation. In adults with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL).

Limitations of Use

Not for use as single-agent induction therapy for AML.

Rydapt Dosage and Administration

Adult

Swallow whole. Take with food approx. 12hrs apart. Give prophylactic antiemetics prior to initiation. AML: 50mg twice daily on Days 8–21 of each induction cycle with cytarabine and daunorubicin, and on Days 8–21 of each consolidation cycle with high-dose cytarabine. ASM, SM-AHN, MCL: 100mg twice daily until disease progression or unacceptable toxicity. Dose modifications: see full labeling.

Children

Not established.

Rydapt Contraindications

Not Applicable

Rydapt Boxed Warnings

Not Applicable

Rydapt Warnings/Precautions

Warnings/Precautions

For ASM, SM-AHN, MCL: monitor for toxicity at least weekly for first 4 weeks, every other week for next 8 weeks, and monthly thereafter. Discontinue if low ANC, platelet count, or hemoglobin persists >21 days. Interrupt dose if Grade 3/4 nausea and/or vomiting despite antiemetics or other Grade 3/4 non-hematological toxicities; resume at reduced dose and increase if tolerated (see full labeling). For all: monitor patients for pulmonary symptoms; discontinue if signs/symptoms of interstitial lung disease or pneumonitis occurs without an infectious etiology. Embryo-fetal toxicity. Advise females of reproductive potential and males (w. female partners) to use effective contraception during and for at least 4 months after the last dose. Pregnancy: exclude status within 7 days prior to initiation. Nursing mothers: not recommended (during and for at least 4 months after the last dose).

Rydapt Pharmacokinetics

Absorption

Time to maximal concentrations occurred between 1 to 3 hours in the fasted state.

Distribution

>99.8% plasma protein bound.
Estimated geometric mean volume of distribution: 95.2 L.

Metabolism

CYP3A4.

Elimination

Fecal (95%), renal (5%). Half-life: 19 hours.

Rydapt Interactions

Interactions

Concomitant drugs that prolong QT interval; monitor EKG periodically. Potentiated by strong CYP3A inhibitors (eg, boceprevir, clarithromycin, cobicistat, conivaptan, danoprevir/ritonavir, diltiazem, elvitegravir/ritonavir, grapefruit juice, idelalisib, indinavir/ritonavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, paritaprevir/ritonavir and [ombitasvir and/or dasabuvir], posaconazole, ritonavir, saquinavir/ritonavir, tipranavir/ritonavir, troleandomycin, voriconazole); consider alternatives; if co-administration needed, monitor for increased adverse reactions. Avoid concomitant strong CYP3A inducers (eg, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John's wort). Concomitant sensitive CYP2B6, BCRP or OATP1B1 substrates may need dose adjustment of these substrates. Risk of prolonged Grade 4 neutropenia, thrombocytopenia in pediatrics treated with combination chemotherapy (including anthracyclines, fludarabine, cytarabine); see full labeling.

Rydapt Adverse Reactions

Adverse Reactions

AML: Febrile neutropenia, nausea, mucositis, vomiting, headache, petechiae, musculoskeletal pain, epistaxis, device-related infection, hyperglycemia, upper respiratory tract infection. ASM, SM-AHN, MCL: also diarrhea, edema, abdominal pain, fatigue, constipation, pyrexia, dyspnea; pulmonary toxicity.

Rydapt Clinical Trials

See Literature

Rydapt Note

Notes

Rydapt Patient Counseling