Tauritmo midostaurin RYDAPT

Product Name: Midostaurin

Manufacturer: Novartis Pharmaceuticals (India)

Specification: 25 mg × 112 capsules/box

Shelf Life: 24 months

Acute Myeloid Leukemia (AML) is the most common type of leukemia in adults. Developed by Novartis, Midostaurin is the only approved targeted kinase inhibitor for the clinical treatment of AML. Midostaurin is a small-molecule inhibitor of multiple tyrosine kinase receptors. *In vitro* biochemical or cellular assays have demonstrated that Midostaurin—along with its major active human metabolites, CGP62221 and CGP52421—inhibits the activity of wild-type FLT3, FLT3-ITD mutations, tyrosine kinase domain (TKD) mutations, wild-type and D816V mutant forms of the tyrosine-protein kinase KIT, platelet-derived growth factor receptors α/β (PDGFRα/β), vascular endothelial growth factor receptor-2 (VEGFR-2), and members of the serine/threonine protein kinase C (PKC) family.

Indications for Midostaurin (Tauritmo/midostaurin)

1. In combination with chemotherapy (standard cytarabine and daunorubicin induction chemotherapy followed by cytarabine consolidation chemotherapy) for the treatment of newly diagnosed patients with FLT3-mutated Acute Myeloid Leukemia (AML). Midostaurin (Tauritmo/midostaurin) is not indicated as a single-agent induction therapy for AML.

2. Aggressive Systemic Mastocytosis (ASM), Systemic Mastocytosis with Associated Hematological Neoplasm (SM-AHN), or Mast Cell Leukemia (MCL). Mechanism of Action of Midostaurin (Tauritmo)

The active substance in Midostaurin (Tauritmo)—midostaurin—is a kinase inhibitor that blocks several enzymes responsible for promoting cell growth, thereby achieving its therapeutic effect [2,4].

Midostaurin (Tauritmo) inhibits the FLT3 receptor signaling pathway, thereby suppressing cancer cell proliferation. In leukemia cells harboring FLT3 receptors with ITD and TKD mutations, or those overexpressing wild-type FLT3 and PDGF receptors, Midostaurin (Tauritmo) also induces apoptosis. Furthermore, Midostaurin (Tauritmo) inhibits the KIT signaling pathway, suppresses histamine release, and induces apoptosis in mast cells.

Dosage and Administration of Midostaurin (Tauritmo)

The standard dosage for the treatment of Acute Myeloid Leukemia (AML) is:

• 50 mg (2 capsules) per dose, twice daily, taken orally with food.

For the treatment of Aggressive Systemic Mastocytosis (ASM), Systemic Mastocytosis with Associated Hematological Neoplasm (SM-AHN), or Mast Cell Leukemia (MCL), the standard dosage is:

• 100 mg (4 capsules) per dose, twice daily, taken orally with food. Common Adverse Reactions

For patients with Acute Myeloid Leukemia (AML), common adverse reactions include [1]:

• Low white blood cell count

• Fever (Febrile Neutropenia)

• Nausea

• Inflammation of the mucous membranes (Mucositis)

For patients with Aggressive Systemic Mastocytosis (ASM), Systemic Mastocytosis with Associated Hematological Neoplasm (SM-AHN), or Mast Cell Leukemia (MCL), the most common adverse reactions (≥20%) include:

• Nausea

• Vomiting

• Diarrhea

• Edema

• Musculoskeletal pain and abdominal pain

Use in Specific Populations

Midostaurin (Tauritmo) poses a fatal risk to the fetus; therefore, it is recommended to avoid pregnancy and breastfeeding while taking this medication.

For a complete list of adverse reactions, please refer to the official prescribing information.

Clinical Trials

A clinical trial confirmed the safety and efficacy of Midostaurin (Tauritmo) for the treatment of patients with Acute Myeloid Leukemia (AML); this trial enrolled a total of 717 patients with newly diagnosed AML who had not received prior treatment. The study found that patients receiving Midostaurin (Tauritmo) in combination with chemotherapy had longer survival times compared to those receiving chemotherapy alone. Additionally, for patients receiving Midostaurin (Tauritmo) plus chemotherapy, the median event-free survival was 8.2 months (where an "event" was defined as: failure to achieve complete remission within 60 days of treatment initiation, disease progression, or death); in comparison, the median event-free survival for patients receiving chemotherapy alone was 3 months [2,3].

Another study confirmed the safety and efficacy of Midostaurin (Tauritmo) for the treatment of patients with Advanced Systemic Mastocytosis (SM). This study enrolled 116 adult patients with relapsed or refractory systemic mastocytosis (SM). Enrolled patients had either received no prior treatment or had undergone 1–2 previous treatment regimens. Following treatment with midostaurin (Tauritmo), the response status of 89 patients was evaluable [1,3]. Among these 89 patients, 21% achieved a complete response (CR) or partial response (iCR) within 6 treatment cycles; the estimated median duration of response was 35.4 months (range: 6.6+ to 65.8+). The median time required to achieve a complete or partial response was 0.5 months (range: 0.1 to 3.0).

Product Specifications

Product Name: Indian Novartis Edition Tauritmo (Midostaurin) 25 mg Capsules, 112-Count (RYDAPT / PKC412)

Common Name: Midostaurin

Active Ingredient: Midostaurin

Dosage Form: Soft Capsules

Specification: 25 mg × 112 capsules per box

Manufacturer: Novartis Pharmaceuticals (India)

Indications:

1. In combination with chemotherapy (standard cytarabine and daunorubicin induction chemotherapy, followed by cytarabine consolidation chemotherapy) for the treatment of newly diagnosed adult patients with *FLT3*-mutated acute myeloid leukemia (AML). Midostaurin (Tauritmo) is not indicated as a single-agent induction therapy for AML.

2. Aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL).

Dosage and Administration: • 50 mg (2 capsules) per dose, twice daily, taken orally with food. For the treatment of aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL), the standard dosage is:

• 100 mg (4 capsules) per dose, twice daily, taken orally with food.