For:
Newly Diagnosed FLT3+ Acute Myeloid Leukemia (AML)
Important Safety Information:

CONTRAINDICATIONS
Do not use in patients with hypersensitivity to midostaurin or its excipients. Hypersensitivity reactions have included anaphylactic shock, dyspnea, flushing, chest pain, and angioed…

See More

Indication: 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 an FDA-approved test.

Limitations of Use
RYDAPT is not indicated as a single-agent induction therapy for the treatment of patients with AML.

Safety Profile

Adverse Reactions

Safety Profile Comparable to Standard Chemotherapy Plus Placebo

Common adverse reactions reported in ≥10% of patients and ≥2% more frequent with RYDAPT in RATIFY1

Adverse Reactions: All Grades
Adverse Reactions: Grades 3/4

aFor trial sites in North America, only grades 3 and 4 were collected.

bBased on grouping of individual patients; upper respiratory tract infections: eg, nasopharyngitis, upper respiratory tract infections, sinusitis; mucositis: eg, radiation mucositis, stomatitis, laryngeal pain; musculoskeletal pain: eg, back pain, bone pain, pain in extremity; renal insufficiency: eg, blood creatinine increased, renal failure, acute kidney injury; hyperglycemia: mainly hyperglycemia.


Laboratory Abnormalities

New or worsening laboratory abnormalities reported in ≥10% of patients and ≥2% more frequent with RYDAPT in RATIFY1

Laboratory Abnormality: All Grades and Grades 3/4

ALT, alanine aminotransferase.

  • The most frequent serious adverse reaction (≥10%) in patients in the RYDAPT® (midostaurin) capsules plus chemotherapy arm was febrile neutropenia (16%), which occurred at a similar rate in the placebo arm (16%)
  • Discontinuation due to any adverse reaction occurred in 9% of patients in the RYDAPT arm vs 6% in the placebo arm. The most frequent (>1%) grade 3/4 adverse reaction leading to discontinuation in the RYDAPT arm was renal insufficiency (1%)

Postconsolidation Phase Tolerability

Tolerability for patients who remained in remission following completion of consolidation therapy1

  • In the pivotal study, 205 patients (RYDAPT n=120, placebo n=85) who remained in remission following completion of consolidation continued to receive either single-agent RYDAPT or placebo for a median of 11 months (range 0.5-17 months); 120 patients (RYDAPT n=69, placebo n=51) completed 12 treatment cycles
  • Common adverse reactions reported during the postconsolidation phase with ≥5% difference between the RYDAPT and placebo arms, respectively, included nausea (47% vs 18%), hyperglycemia (20% vs 13%), and vomiting (19% vs 5%)

 

Reference:
  1. Rydapt [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2021.

INDICATION for RYDAPT® (midostaurin) capsules

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 an FDA-approved test.

Limitations of Use
RYDAPT is not indicated as a single-agent induction therapy for the treatment of patients with AML.

IMPORTANT SAFETY INFORMATION for RYDAPT® (midostaurin) capsules

CONTRAINDICATIONS
  • Do not use in patients with hypersensitivity to midostaurin or its excipients. Hypersensitivity reactions have included anaphylactic shock, dyspnea, flushing, chest pain, and angioedema
WARNINGS AND PRECAUTIONS
Embryo-Fetal Toxicity
  • Do not use during pregnancy. Midostaurin caused severe embryo-fetal abnormalities and death in animal studies
  • Verify pregnancy status of females of reproductive potential within 7 days prior to initiating RYDAPT
  • Advise females of reproductive potential to use effective contraception during treatment and for at least 4 months after the last dose
  • Males taking RYDAPT should use effective contraception with females of reproductive potential and pregnant women and for at least 4 months after the last dose
  • Pregnancy exposure registry to monitor pregnancy outcomes: Females who may have been exposed to RYDAPT during pregnancy, directly or through a male partner receiving RYDAPT, should contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 and/or at https://report.novartis.com/
Pulmonary Toxicity
  • Cases of interstitial lung disease and pneumonitis, some fatal, have occurred in patients treated with RYDAPT as monotherapy or with chemotherapy
  • Monitor patients for pulmonary symptoms. Discontinue RYDAPT in patients who experience signs or symptoms of interstitial lung disease or pneumonitis without an infectious etiology
Risk of Prolonged Severe Neutropenia and Thrombocytopenia in Pediatric Patients Treated With Combination Chemotherapy
  • Prolonged (≥44 days) grade 4 neutropenia and thrombocytopenia were reported in 2 pediatric patients with FLT3 mutation-positive AML treated with midostaurin and combination chemotherapy. An azole antifungal (a strong CYP3A4 inhibitor) was coadministered which may increase midostaurin concentrations and risk of toxicity
  • The safety and effectiveness of RYDAPT in pediatric patients have not been established
ADDITIONAL CONSIDERATIONS
Lactation
  • Because of the potential for serious adverse reactions in breastfed infants from RYDAPT, advise women not to breastfeed during treatment with RYDAPT and for at least 4 months after the last dose
Infertility
  • Based on findings in animals, RYDAPT may impair fertility in females and males of reproductive potential. It is unknown whether these effects on fertility are reversible
Drug Interactions
  • Strong CYP3A Inducers: Avoid concomitant use as strong CYP3A4 inducers decrease exposure to midostaurin and may reduce efficacy
  • Strong CYP3A Inhibitors: Coadministration with strong CYP3A4 inhibitors may increase midostaurin concentrations and may increase the risk of toxicity. Monitor patients for increased risk of adverse reactions, especially during the first week of RYDAPT use in each chemotherapy cycle and the first week of consecutive RYDAPT administration. Consider alternative therapies that do not strongly inhibit CYP3A4 activity
  • CYP2B6, BCRP, OATP1B1 Substrates: RYDAPT decreased the systemic exposure of a sensitive CYP2B6 substrate. Coadministration of RYDAPT increased the exposure of a breast cancer resistance protein (BCRP) and organic anion transporter polypeptide (OATP)1B1 substrate. Dose adjustments for coadministered CYP2B6, BCRP, or OATP1B1 substrates may be necessary with RYDAPT
ADVERSE REACTIONS
Acute Myeloid Leukemia
  • Most common adverse reactions (≥20%) were febrile neutropenia (83%), nausea (83%), mucositis (66%), vomiting (61%), headache (46%), petechiae (36%), musculoskeletal pain (33%), epistaxis (28%), device-related infection (24%), hyperglycemia (20%), upper respiratory tract infection (20%), and electrocardiogram QT prolonged (20%)
  • Most frequent grade 3/4 adverse reactions (≥10%) were febrile neutropenia (84%), device-related infection (16%), and mucositis (11%)
  • Most common (≥10%) laboratory abnormalities were hypolcalcemia (74%), alanine aminotransferase increase (71%), and hypernatremia (21%)

Please see full Prescribing Information for RYDAPT® (midostaurin) capsules.

*Aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL) are collectively referred to as advanced systemic mastocytosis (SM).