Mstarin

BDR Pharma, one of India's leading generic pharmaceutical companies, announced the launch of India's first generic version of Midostaurin - Mstarin, which is indicated for rare and difficult-to-treat cancers.

Instructions for Midostaurin

Trade name: Mstarin

Common name : Midostaurin/Midostaurin

Manufacturer: Indian BDR Pharmaceuticals

Specification: 25mgx28s/box

Indications

Midostaurin is a multi-target protein kinase inhibitor that has been studied for the treatment of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and advanced systemic mastocytosis.

Oral administration

Take twice a day for about 12 hours each time

Give prophylactic antiemetics before treatment to reduce the risk of nausea and vomiting

Swallow capsule whole; Do not open or crush capsules

Consider QT interval assessment by ECG if coadministered with drugs that prolong the QT interval

Missed or vomited dose

Do not take another capsule to make up a dose

Take the next dose at the usual scheduled time

Storage

Store at 25°C (77°F); permitted temperature is 15-30°C (59-86°F)

Store in original packaging to protect against moisture

Acute myeloid leukemia (AML)

Intended for adults with newly diagnosed acute myeloid leukemia (AML) who are FLT3 mutation positive in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation chemotherapy

50 mg orally daily on days 8-21 of induction with cytarabine and daunorubicin 2 times daily (12 hours apart) and on days 8-21 of each cycle after consolidation with high-dose cytarabine

Take before meals

Systemic Mastocytosis (SM)

Indicated for adults with aggressive systemic mastocytosis (ASM), systemic mastocytosis with hematological neoplasms (SM-AHN), or mast cell leukemia (MCL)

100 mg PO Take twice daily (12 hours apart) before meals

Continue treatment until disease progression or unacceptable toxicity

Dose adjustment (ASM, SM-AHN, MCL)

ANC <1 x 10^9/L (no MCL) or ANC <0.5 x 10^9/L, baseline ANC is 0.5-1.5 x 10^9/L

Interrupt dose until ANC ≥1 x 10^9/L, then 50 mg Resume twice daily; if tolerated, increase to 100 mg twice daily

Discontinue if low ANC persists for more than 21 days and is suspected to be related to midostaurin

Platelet count<50 x 10^9/L (no MCL) or <25 x 10^9/L with baseline of 25-75 x 10^9/L

Interrupt dosing until platelet count is ≥50 × 10^9/L, then resume at 50 mg twice daily; If tolerated, increase to 100 mg twice daily

Discontinue use if low platelet count persists for more than 21 days and is suspected to be related to midostaurin

Hemoglobin <8 g/L (no MCL) or life-threatening anemia, baseline 8-10 g/L.

Interrupt dosing until hemoglobin ≥8 g/L, then resume 50 mg twice daily; If tolerated, increase to 100 mg twice daily

Discontinue if low platelet count persists for more than 21 days and is suspected to be related to midostaurin

Grade 3 to 4 nausea and/or vomiting despite optimal antiemetic therapy

Interrupt dosing for 3 days (6 doses), then resume 50 mg twice daily; If tolerated, increase to 100 mg twice daily

Other Grade 3 to 4 nonhematologic toxicities

Interrupt dose until event has resolved to grade ≤ 2, then resume at 50 mg twice daily; if tolerated, increase to 100 mg twice daily

Dosage Considerations

Administer prophylactic antiemetics before treatment to reduce the risk of nausea and vomiting

AML Acute myeloid leukemia

Restrictions of use: Single-agent induction therapy not indicated for AML

Patients selected for treatment of AML based on the presence of FLT3 mutation positivity

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 after treatment

Adverse reactions

> 10% (AML)

Nausea (83%)

Febrile neutropenia (83%)

Hypocalcemia (74%)

Increased ALT, all grades (71%)

Mucositis (66%)

Vomiting (61%)

Headache (46%)

Petechiae (36%)

Musculoskeletal pain (33%)

Estistaxis (28%)

Device-related infection (24%)

Hypernatremia (21%)

Upper respiratory tract infection (20%)

Hyperglycemia (20%)

Increased ALT, grades 3 and 4 (20%)

Hemorrhoids (1 5%)

Arthralgia (14%)

Hyperhidrosis (14%)

Prolonged aPTT (13%)

Renal insufficiency (12%)

Insomnia (12%)

> 10% (SM)

Nausea (82%)

Hyperglycemia (80%)

Vomiting (68%)

Lymphopenia (66%)

Leukopenia (61%)

Anemia (60%)

Diarrhea (54%)

Platelets Hypocalcemia (50%)

Neutropenia (49%)

Eedema (40%)

Increased alkaline phosphatase (39%)

Hypocalcemia (39%)

Increased lipase (37%)

Hyperuricemia (37%)

Increased GGT (35%)

Musculoskeletal pain (35%)

Hyponatremia (34%)

Increased AST (32%)

Increased ALT (31%)

Fatigue (34%)

Abdominal pain (34%)

Upper respiratory tract infection (30%)

Hyperbilirubin Hypoalbuminemia (29%)

Hypoalbuminemia (27%)

Fever (27%)

Constipation (29%)

Headache (26%)

Hypokalemia (25%)

Increased creatinine (25%)

Hyperkalemia (23%)

Hypophosphatemia (22%)

Increased amylase (20%)

Hypomagnesemia (20%)

Joint pain (19%)

Cough (18%)

Urinary tract infection (16%)

Gastrointestinal bleeding (14 %)

Skin rash (14%)

Dizziness (13%)

Pleural effusion (13%)

Epistaxis (12%)

QT prolongation (11%)

Insomnia (11%)

Renal insufficiency (11%)

1-10% (AML)

Hyperuricemia (8%)

Hypertension (8%)

Cellulitis (7%)

Fungal infection (7%)

Dry skin (7%)

Body Weight gain (7%)

Pleural effusion (6%)

Thrombus (5%)

Tremor (4%)

Pericardial effusion (4%)

Hypercalcemia (3%)

Eyelid edema (3%)

1-10% (SM)

Pneumonia (10%)

Herpes virus infection (10%)

Sepsis (9%)

Hypotension (9%)

Febrile neutropenia Oligophobia (8%)

Inability to concentrate (7%)

Tremor (6%)

Hematoma (6%)

Heart failure (6%)

Bronchitis (6%)

Indigestion (6%)

Weight gain (6%)

Contusion (6%)

Cellulitis or erysipelas (5%)

Dizziness (5%)

Chivers (5%)

Oropharyngeal pain (4%)

Myocardial infarction or ischemia (4%)< /p>

Hypersensitivity (4%)

Changes in mental status (4%)

Pulmonary edema (3%)

Gastritis (3%)

Interstitial lung disease or pneumonia (2%)

Contraindications

Hypersensitivity; reactions include anaphylactic shock, difficulty breathing, flushing, chest pain, and angioedema (such as swelling of the airways or tongue, with or without breathing difficulties)

Precautions

Cases of interstitial lung disease and pneumonia, some fatal, have been reported with monotherapy or in combination with chemotherapy; monitor for pulmonary symptoms; discontinue if signs or symptoms of interstitial lung disease or pneumonia occur without an infectious cause

Based on its mechanism of action and the results of animal reproduction studies, midostaurin may cause fetal harm to pregnant women (see Pregnancy)

Drug interactions

Mainly metabolized by CYP3A4

Strong CYP3A4 inhibitors

Coadministration with strong CYP3A inhibitors may increase midostaurin concentrations and risk of toxicity Consider alternative therapies that do not strongly inhibit CYP3A activity

Alternatively, if coadministered, monitoring is not Increased risk of adverse effects, especially during the first week of treatment

Strong CYP3A inducers

Coadministration with strong CYP3A inducers may reduce midostaurin concentrations and reduce efficacy

Avoid coadministration with strong CYP3A inducers