Leukemias, lymphomas, and other hematologic cancers:

Indications for: RYDAPT

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.

Adult Dosage:

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 Dosage:

Not established.

RYDAPT 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 Classification:

Kinase inhibitor.

RYDAPT 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.

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.

Note:

Register pregnant patients exposed to Rydapt by calling (888) 669-6682.

Metabolism:

  • CYP3A4.

Drug Elimination:

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

Generic Drug Availability:

NO

How Supplied:

Caps—56, 112