Generic Name and Formulations:
Midostaurin 25mg; caps.
Novartis Pharmaceuticals Corp
Indications for RYDAPT:
Treatment of 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. Treatment of 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.
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.
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). Both: monitor for signs/symptoms of interstitial lung disease or pneumonitis; discontinue if pulmonary toxicity develops. Embryo-fetal toxicity. Pregnancy; exclude status within 7 days prior to initiation. Females of reproductive potential and males should use effective contraception during and for at least 4 months after last dose. Nursing mothers: not recommended (during and for at least 4 months after last dose).
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).
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.