Tauritmo

Midostaurin instructions

Common name: Midostaurin

Trade name: Rydapt

All names: Midostaurin, Rydapt, Midostaurin, Tauritmo< /p>

Indications

This product is suitable for the treatment of the following patients:

In combination with standard cytarabine and daunorubicin induction and cytarabine consolidation chemotherapy, it is suitable for adults with newly diagnosed FLT3 mutation-positive acute myeloid leukemia (AML).

Adults with aggressive systemic mastocytosis (ASM), systemic mastocytosis with hematologic neoplasm (SM-AHN), or mast cell leukemia (MCL).

Usage and Dosage

1. Dosage form and specifications
Rydapt is a soft capsule with only one specification. Each capsule contains 25 mg of midostaurin.

2. Recommended dosage and administration

1) AML: During the induction period of two courses of treatment (days 1 to 3), patients receive intravenous bolus injection of daunorubicin hydrochloride and intravenous infusion of cytarabine on days 1 to 7. On days 8 to 21, patients take midostaurin 50 mg with food, twice a day. This is followed by a consolidation treatment period of 4 courses. On days 1, 3 and 5, after intravenous infusion of cytarabine every 12 hours, midostaurin 50 mg is taken twice a day on days 8 to 21. The last is a maintenance treatment period, with a total of 12 courses of treatment. Midostaurin 50 mg is taken twice a day until the disease relapses or the adverse reactions cannot be tolerated.

2) ASM, SM-AHN and MCL: Patients take midostaurin 100mg with food, twice a day, a course of 28 days, until disease recurrence or intolerable adverse reactions. Monitor patients for toxicity at least weekly during the first 4 weeks of treatment, every other week for the next 8 weeks, and monthly as treatment continues.

3. The dosage needs to be adjusted if adverse reactions occur

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

(1) Interrupt dose until ANC ≥1 × 10^9/L, then resume at 50 mg twice daily; if tolerated, increase to 100 mg twice daily

(2) 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, baseline is 25-75 x 10^9/L

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

(2) 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.

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

(2) 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

(1) 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 non-hematologic toxicities

(1) Interrupt the dose until the event has resolved to ≤Grade 2, then resume at 50 mg twice daily; if tolerated, increase to 100 mg twice daily

4. Recommended medication method

To reduce the risk of nausea and vomiting after taking the medication, antiemetics can be taken prophylactically before taking the medication. Midostaurin is taken twice a day, about 12 hours apart; the capsules cannot be opened or crushed and should be swallowed whole. If you miss a dose or vomit after taking the medicine, you cannot make up the dose on the same day. You should take the next dose on the scheduled schedule; if midostaurin is taken with drugs that may prolong the QT interval, an electrocardiogram should be used to evaluate the QT interval.

Adverse reactions

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 Infections (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%)

Nausea (82%)

Hyperglycemia (80%)

Vomiting (68%)

Lymphopenia (66%)

Leukopenia (61%)

Anemia (60%)

Diarrhea (54 %)

Thrombocytopenia (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%)

Hyperbilirubinemia (29%)

Hypoalbuminemia (27%)

Irritability (27%)

Constipation (29%)

Headache (2 6%)

Hypokalemia (25%)

Increased creatinine (25%)

Hyperkalemia (23%)

Dyspnea (23%)

Hypophosphatemia (22%)

Increased amylase (20%)

Low magnesium Bloodemia (20%)

Joint pain (19%)

Cough (18%)

Urinary tract infection (16%)

Gastrointestinal bleeding (14%)

Skin rash (14%)

Dizziness (13%)

Pleural effusion (1 3%)

Epistaxis (12%)

QT prolongation (11%)

Insomnia (11%)

Renal insufficiency (11%)

Hyperuricemia (8%)

Hypertension (8%)

Cellulitis (7%)

Fungal infection (7%)

Dry skin (7%)

Weight gain (7%)

Pleural effusion (6%)

Thrombus formation (5%)

Tremor (4%)

Pericardial effusion (4%)

Hypercalcemia (3%)

Eyelid edema (3%)

Pneumonia (10%)

Herpesvirus infection (10%)

Sepsis (9%)

Hypotension ( 9%)

Febrile neutropenia (8%)

Difficulty concentrating (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%)

Hypersensitivity reaction (4%)

Changes in mental status (4%)

Pulmonary edema (3%)

Gastritis (3%)

Interstitial lung disease or pneumonia (2%)

Precautions

1. Embryo-fetal toxicity: Based on the mechanism of action and findings from animal reproduction studies, midostaurin taken by pregnant women may harm the fetus. Animal studies have shown that midostaurin can cause embryo-fetal toxicity, including late-stage embryo-fetal death and reduced fetal body weight after birth. When doses lower than those recommended for humans are given, fetal development and growth may be delayed. Pregnant women should be advised of the potential risk to the fetus. The pregnancy status of women of reproductive potential should be checked within 7 days before starting midostaurin treatment. Advice: Male partners of women should use effective contraception during midostaurin treatment and for at least 4 months after the last dose.

2. Patients with pulmonary toxicity: Interstitial lung disease and pneumonia have occurred when midostaurin was used alone or in combination with chemotherapy, some of which were fatal. Patients should be monitored for pulmonary symptoms. After experiencing signs or symptoms of interstitial lung disease or pneumonia, use should be discontinued until the etiology of the infection is determined.

3. Medication in children: The safety and effectiveness of midostaurin have not been determined in pediatric patients, and its use is not recommended for the time being.

4. Medication for elderly patients: In a clinical study of midostaurin in the treatment of advanced SM, among 142 patients, 45.1% (64/142) were aged ≥65 years and 11.3% (16/142) were ≥75 years old. No overall differences in safety or response rates were observed between subjects aged ≥65 years and younger subjects, but greater sensitivity in individual older patients cannot be ruled out. Clinical studies of the treatment of AML have not included a sufficient number of subjects aged ≥65 years to determine whether these patients respond differently to younger subjects.

Storage
Store at 25°C (77°F); permitted temperature 15-30°C (59-86°F)
Store in original packaging to protect against moisture.

Treatment Effect

Rydapt is the first drug approved to treat AML in 25 years.

The indication for AML was obtained based on the results of the Phase III PARIFY trial. The trial screened 3,279 patients with FLT3 mutations, of which 717 patients participated. The enrolled patients received Rydapt combined with cytarabine + daunorubicin. The results show that Rydapt combination treatment can significantly improve overall survival time (OS) and reduce the risk of death by 23%.

The median event-free survival time (EFS) of the Rydapt combination treatment group was significantly longer than that of the chemotherapy group (8.2 months vs 3.0 months).

Adverse reactions with an incidence rate of more than 20% include neutropenic fever, nausea, vomiting, mucositis, headache, musculoskeletal pain, petechiae, device-related infections, epistaxis, hyperglycemia, upper respiratory tract infection, etc.

Obtaining indications for SM is based on the results of 2 single-group, open-label, multi-center trials, with effective rates reaching 21% and 17% respectively.