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…

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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

Adverse reactions reported in ≥10% of patients and ≥2% more frequent with RYDAPT® (midostaurin) capsules in RATIFY1

Adverse Reactions: All Grades Adverse Reactions: All Grades

Adverse Reactions: Grades 3/4 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 Laboratory Abnormality: All Grades and Grades 3/4

ALT, alanine aminotransferase.

  • The most frequent serious adverse reaction (≥10%) in patients in the RYDAPT 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%)

Adverse Events and Specific Populations

Nausea and vomiting1
  • Administer prophylactic antiemetics before treatment with RYDAPT to reduce the risk of nausea and vomiting
  • If a dose of RYDAPT is missed or vomited, the patient should not make up the dose; the next dose should be taken at the usual scheduled time
Females and males of reproductive potential1
  • Pregnancy testing is recommended for females of reproductive potential within 7 days prior to initiating RYDAPT
  • RYDAPT may cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with RYDAPT and for 4 months after the last dose
  • Males with female sexual partners of reproductive potential should use effective contraception during RYDAPT treatment and for at least 4 months after stopping treatment with RYDAPT
  • Based on findings in animals, RYDAPT may impair fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible
Pediatric patients1
  • Safety and effectiveness of RYDAPT have not been established in pediatric patients
Geriatric patients1
  • Clinical studies in AML with RYDAPT did not include sufficient numbers of subjects aged ≥65 years to determine whether they respond differently from younger subjects
  • In general, administration for elderly patients should be cautious, based on patient’s eligibility for concomitant chemotherapy and reflecting the greater frequency of concomitant disease or other drug therapy

 

Reference:
  1. Rydapt [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2018.

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
Embryofetal Toxicity
  • Do not use during pregnancy. Midostaurin caused severe embryofetal 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://psi.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
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 CYP3A4 Inducers: Avoid concomitant use as strong CYP3A4 inducers decrease exposure to midostaurin and may reduce efficacy
  • Strong CYP3A4 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
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%), and upper respiratory tract infection (20%)
  • Most frequent grade 3/4 adverse reactions (≥10%) were febrile neutropenia (84%), device-related infection (16%), and mucositis (11%)
  • Most common (≥10%) lab abnormalities were alanine aminotransferase increase (71%), hypernatremia (21%), and hypocalcemia (74%)

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