8.1 Pregnancy
8.2 Lactation
8.3 Females and Males of Reproductive Potential
8.4 Pediatric Use
8.5 Geriatric Use
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
14 CLINICAL STUDIES
14.1 Acute Myeloid Leukemia
14.2 Systemic Mastocytosis
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
* Sections or subsections omitted from the full prescribing information are not listed.
1 INDICATIONS AND USAGE
1.1 Acute Myeloid Leukemia
RYDAPT is indicated, in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation chemotherapy, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) who are FLT3 mutation-positive, as detected by a FDA approved test [see Dosage and Administration (2.1), Clinical Studies (14.1)].
Limitations of Use
RYDAPT is not indicated as a single-agent induction therapy for the treatment of patients with AML.
1.2 Systemic Mastocytosis
RYDAPT is indicated for the treatment of adult patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL).
2 DOSAGE AND ADMINISTRATION
2.1 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.
2.2 Recommended Dosage in Acute Myeloid Leukemia
The recommended dose of RYDAPT for patients with acute myeloid leukemia 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 [see Clinical Studies (14.1)]. For a description of the experience with single-agent treatment with RYDAPT beyond induction and consolidation, see Clinical Studies (14.1).
2.3 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.
Table 1: RYDAPT Dose Modifications for Patients with Systemic Mastocytosis
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 > 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 RYDA |
