JT-Nib Tablets 400 mg (Imatinib Mesylate)

Adult dosage

1. Chronic myeloid leukemia (CML) 1) Adults - A dose of 400mg once daily is recommended for adult patients with Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia. - A dose of 600mg once daily is recommended for adult patients with Philadelphia chromosome-positive accelerated-phase or blast-phase (blast crisis) chronic myeloid leukemia. 3) In the absence of severe adverse reactions and severe leukemia-unrelated neutropenia or thrombocytopenia, an increase from 400mg to 600mg in adult patients with chronic-phase disease, or from 600mg to 800mg (400mg twice daily) in adult patients with accelerated-phase or blast-phase (blast crisis) disease, may be considered in the following cases: (1) Disease progression (at any time) (2) Failure to achieve a satisfactory hematologic response after at least 3 months of treatment (3) Failure to achieve a cytogenetic response after 6-12 months of treatment (4) Loss of a previously achieved hematologic or cytogenetic response 2. Gastrointestinal stromal tumor (GIST) - A dose of 400mg daily is recommended for adult patients with Kit (CD 117)-positive, unresectable and/or metastatic malignant gastrointestinal stromal tumor (GIST). - A dose of 400mg daily is recommended for adult patients receiving this drug as adjuvant therapy after resection of Kit (CD 117)-positive gastrointestinal stromal tumor. 3. The following diseases associated with tyrosine kinases sensitive to imatinib, for which previous medications or treatment regimens have failed or for which no clinical treatment with a clear benefit is available: - Myelodysplastic syndromes/myeloproliferative diseases: A dose of 400mg daily is recommended. - Hypereosinophilic syndrome/chronic eosinophilic leukemia: A dose of 100mg daily is recommended. The dose may be increased up to 400mg daily. - Recurrent or metastatic dermatofibrosarcoma protuberans: 800mg daily (400mg twice daily) 4. Other 1) To minimize the risk of gastrointestinal irritation, take the prescribed dose with a meal and plenty of water. The 400mg or 600mg dose is taken once daily, and the 800mg dose is taken as 400mg twice daily. 4) Continue treatment until there is evidence of disease progression or unacceptable toxicity. 5) Since the incidence of adverse reactions may increase at higher doses, patients whose dose is increased should be monitored closely. 6) This drug is metabolized mainly in the liver. The minimum recommended dose for patients with mild, moderate, or severe hepatic impairment is 400mg daily. The dose may be reduced if it is not tolerated. 7) Renal excretion of this drug and its metabolites is minimal. The minimum recommended starting dose for patients with renal impairment or those receiving hemodialysis is 400mg daily. However, caution is required when administering this drug to patients with renal impairment. If the dose is not tolerated, it may be reduced; if it is tolerated but efficacy is inadequate, the dose may be increased. 8) No specific pharmacokinetic studies of this drug have been conducted in elderly patients; however, no significant age-related pharmacokinetic differences were observed in approximately 20% of patients aged 65 years or older who participated in clinical trials. There is no specific recommended dose for elderly patients. 5. Dose adjustment 1) In the event of nonhematologic adverse reactions If a severe nonhematologic adverse reaction occurs with use of this drug, interrupt treatment until the symptoms resolve. Then resume treatment as appropriate, according to the initial severity of the adverse reaction. If bilirubin levels rise to more than 3 times the institutional upper limit of normal (IULN), or liver transaminases rise to more than 5 times the institutional upper limit of normal (IULN), treatment should be interrupted until bilirubin levels are 1.5 times or less the institutional upper limit of normal (IULN) and transaminases are less than 2.5 times the institutional upper limit of normal (IULN). Treatment may then be continued at a reduced daily dose. The adult dose should be reduced from 400mg to 300mg, from 600mg to 400mg, or from 800mg to 600mg, 2) In the event of hematologic adverse reactions Dose reduction or interruption of treatment for severe neutropenia and thrombocytopenia is recommended as shown in the table below. Table 1. Dose adjustment for neutropenia and thrombocytopenia Hypereosinophilic syndrome and chronic eosinophilic leukemia (initial dose 100mg) ANC < 1.0 × 109/L and/or platelets < 50 × 109/L 1. Interrupt treatment with this drug until ANC ≥ 1.5 × 109/L and platelet count ≥ 75 × 109/L. 2. Resume treatment with this drug at the previous dose (the dose before the onset of the severe adverse reaction). Chronic-phase chronic myeloid leukemia, myelodysplastic syndromes/myelodysplastic proliferative disease, gastrointestinal stromal tumor (initial dose 400mg) Hypereosinophilic syndrome/chronic eosinophilic leukemia (dose 400mg) ANC < 1.0 × 109/L and/or platelets < 50 × 109/L 1. Interrupt treatment with this drug until ANC ≥ 1.5 × 109/L and platelet count ≥ 75 × 109/L. 2. Resume treatment with this drug at the original starting dose of 400mg. 3. If ANC < 1.0 × 109/L and/or platelet count < 50 × 109/L occurs again, repeat step 1 and resume treatment at the reduced dose of 300mg. Accelerated-phase or blast-phase chronic myeloid leukemia (initial dose 600mg) ANC < 0.5 × 109/L and/or platelets < 10 × 109/L 1. Determine whether the cytopenia is related to leukemia (bone marrow aspiration or biopsy). 2. If the cytopenia is not related to leukemia, reduce the dose of this drug to 400mg. 3. If the cytopenia persists for 2 weeks, reduce the dose further to 300mg. 4. If the cytopenia persists for 4 weeks and is still not related to leukemia, interrupt this drug until ANC ≥ 1 × 109/L and platelet count ≥ 20 × 109/L, then resume treatment at a dose of 300mg. Dermatofibrosarcoma protuberans (initial dose 800mg) ANC < 1.0 × 109/L and/or platelets < 50 × 109/L 1. Interrupt treatment with this drug until ANC ≥ 1.5 × 109/L and platelet count ≥ 75 × 109/L. 2. Resume treatment with this drug at 600mg. 3. If ANC < 1.0 × 109/L and/or platelet count < 50 × 109/L occurs again, repeat step 1 and resume treatment at the reduced dose of 400mg. ANC = absolute neutrophil count 1) Occurring after at least 1 month of treatment

Children's dosage

1. Chronic myeloid leukemia (CML) 2) Pediatric patients - For patients with chronic, accelerated, or blast-phase chronic myeloid leukemia who are Philadelphia chromosome-positive, a dose of 340mg/m2 per day based on body surface area is recommended (the total daily dose must not exceed 600mg). The dose may be administered once daily or divided into 2 doses per day, in the morning and evening. 4. Other 2) Pediatric patients may take this medicine once daily or, optionally, divide the daily dose into 2 doses, in the morning and evening. 5. Dose adjustment 1) In the event of nonhematologic adverse reactions Reduce the pediatric dose from 340mg/m2 to 260mg/m2, or from 260mg/m2 to 200mg/m2. 2) In the event of hematologic adverse reactions Pediatric chronic-phase chronic myeloid leukemia (starting dose 340mg/m2) ANC < 1.0 × 109/L and/or platelets < 50 × 109/L 1. Interrupt treatment with this medicine until ANC ≥ 1.5 × 109/L and platelet count ≥ 75 × 109/L. 2. Resume treatment at the original previous dose (before the severe adverse reaction occurred). 3. If ANC < 1.0 × 109/L and/or platelet count < 50 × 109/L recurs, repeat step 1 and resume treatment at the reduced dose of 260mg/m2. Pediatric accelerated-phase or blast-phase chronic myeloid leukemia (starting dose 340mg/m2) 1) ANC < 0.5 × 109/L and/or platelets < 10 × 109/L 1. Determine whether the cytopenia is related to leukemia (bone marrow aspiration or biopsy). 2. If the cytopenia is not related to leukemia, reduce the dose of this medicine to 260mg/m2. 3. If the cytopenia persists for 2 weeks, further reduce the dose to 200mg/m2. 4. If the cytopenia persists for 4 weeks and is still not related to leukemia, interrupt this medicine until ANC ≥ 1 × 109/L and platelet count ≥ 20 × 109/L, and then resume treatment at a dose of 200mg/m2.

This medication should not be administered to patients with hypersensitivity to this drug or any of its components. Women who are pregnant or may become pregnant should not take this medication, and it should also not be given to breastfeeding women. Caution is required when administering to patients with impaired liver or renal function, and patients with a history of heart disease or heart failure should be closely monitored for their cardiac condition. In patients with hypereosinophilia, rare adverse reactions may occur, so cardiac assessment before administration is recommended, and steroid therapy may be used if necessary. Since it may affect thyroid function, regular thyroid function tests should be performed. In pediatric patients prior to puberty, growth delays may occur, so growth status should be periodically monitored. Tumor lysis syndrome may occur, so dehydration should be corrected before administration, and appropriate treatment should be provided if uric acid levels are high. For carriers of hepatitis B, there is a risk of hepatitis reactivation before and during administration of this medication, so consultation with specialists and regular liver function tests are necessary. Common adverse effects during the use of this medication include decreased blood cell counts, headache, dyspepsia, edema, weight gain, nausea, vomiting, muscle cramps, diarrhea, rash, and fatigue; if serious side effects occur, immediate consultation with healthcare professionals is necessary. Depending on the severity of adverse reactions, dose adjustment or discontinuation may be required.

• Neutropenia
• thrombocytopenia
• anemia
• headache
• dyspepsia
• edema
• weight gain
• nausea
• vomiting
• muscle cramps

This medication should be stored in a tightly sealed container to prevent exposure to air or moisture. The recommended storage temperature is room temperature between 1 to 30 degrees Celsius.

Appearance

Dark yellow to brown rectangular film-coated tablets

Package unit

30 tablets (10 tablets/PTP×3)