For:
Advanced Systemic Mastocytosis*
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 for the treatment of adult patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL).

Mechanism of Action

Mechanism of Action

KIT is a driver of systemic mastocytosis (SM)1,2

  • The KIT D816V mutation is the most common mutation, occurring in ~90% of patients with SM3

RYDAPT is the first FDA-approved multitargeted inhibitor of D816V mutant and wild-type KIT for advanced systemic mastocytosis (SM)1*

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

  • RYDAPT® (midostaurin) capsules inhibits KIT signaling, cell proliferation, and histamine release, as well as induces apoptosis in mast cells1
  • RYDAPT also inhibits the activity of several other receptor tyrosine kinases, such as FLT3 and PDGFRα/β, as well as members of the serine/threonine kinase PKC family1

Mechanism of action in advanced SM1

RYDAPT® (midostaurin) capsules mechanism of action

FLT3, FMS-like tyrosine kinase 3; MOA, mechanism of action; PDGFRα/β, platelet-derived growth factor receptor α/β; PKC, protein kinase C.

References:
  1. Rydapt [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2021.
  2. Pardanani A. Systemic mastocytosis in adults: 2017 update on diagnosis, risk stratification and management. Am J Hematol. 2016;91(11):1146-1159.
  3. Garcia-Montero AC, Jara-Acevedo M, Teodosio C, et al. KIT mutation in mast cells and other bone marrow hematopoietic cell lineages in systemic mast cell disorders: a prospective study of the Spanish Network on Mastocytosis (REMA) in a series of 113 patients. Blood. 2006;108(7):2366-2372.
  4. Gotlib J, Kluin-Nelemans HC, George TI, et al. Efficacy and safety of midostaurin in advanced systemic mastocytosis. N Engl J Med. 2016;374(26):2530-2541.

INDICATION for RYDAPT® (midostaurin) capsules

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).

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
Aggressive Systemic Mastocytosis (SM), SM With Associated Hematologic Neoplasm, Mast Cell Leukemia
  • Most common adverse reactions (≥20%) excluding laboratory terms were nausea (82%), vomiting (68%), diarrhea (54%), edema (40%), musculoskeletal pain (35%), abdominal pain (34%), fatigue (34%), upper respiratory tract infection (30%), constipation (29%), pyrexia (27%), headache (26%), and dyspnea (23%)
  • Grade ≥3 adverse reactions (≥5%) excluding laboratory terms were fatigue (9%), sepsis (9%), gastrointestinal hemorrhage (9%), pneumonia (8%), diarrhea (8%), febrile neutropenia (8%), edema (7%), dyspnea (7%), nausea (6%), vomiting (6%), abdominal pain (6%), and renal insufficiency (5%)
  • Most common (≥10%) nonhematologic grade ≥3 laboratory abnormalities were hyperglycemia (nonfasting) (18%), lipase increase (18%), and hyperuricemia (11%)
  • Most common (≥20%) hematologic grade ≥3 laboratory abnormalities were lymphopenia (42%), anemia (38%), thrombocytopenia (27%), and neutropenia (22%)

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).