Glinib Tablet 200 mg (Imatinib Mesylate)

Adult dose

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 chronic myeloid leukemia. 3) In the absence of severe adverse reactions and severe leukemia-unrelated neutropenia or thrombocytopenia, dose escalation may be considered 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 disease, 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 Tumors (GIST) - A dose of 400mg daily is recommended for adults with Kit(CD 117)-positive, unresectable and/or metastatic malignant gastrointestinal stromal tumors (GIST). - A dose of 400mg daily is recommended for adults receiving this drug as adjuvant therapy following resection of Kit(CD 117)-positive gastrointestinal stromal tumors. The optimal duration of administration of this drug as adjuvant therapy has not been established. A clinical trial comparing administration of this drug for 1 year and 3 years in patients at high risk of GIST recurrence recommended a treatment duration of 3 years. 3. The following diseases associated with tyrosine kinases sensitive to imatinib, for which prior treatment or therapy has failed or for which no clinical treatment option 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 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 closely monitored. 6) This drug is primarily metabolized by the liver. The minimum recommended dose for patients with mild, moderate, or severe hepatic impairment is 400mg daily. The dose may be reduced if the patient does not tolerate it. * Classification of hepatic impairment Liver function test Mild Total bilirubin: = 1.5 ULN AST: > ULN (may be normal or below ULN if total bilirubin is greater than ULN) Moderate Total bilirubin: > 1.5-3.0 ULN AST: Not applicable Severe Total bilirubin: > 3-10 ULN AST: Not applicable - ULN: upper limit of normal - AST: aspartate aminotransferase 7) Renal excretion of this drug and its metabolites is minimal. The minimum recommended starting dose for patients with renal impairment or those undergoing hemodialysis is 400mg daily. However, caution is required when administering this drug to patients with renal impairment. If the patient does not tolerate the dose, it may be reduced; if 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, among the approximately 20% of patients aged 65 years or older enrolled in clinical trials, there were no significant age-related pharmacokinetic differences. No specific dose is recommended for elderly patients. 5. Dose Adjustment 1) In the event of nonhematologic adverse reactions If a severe nonhematologic adverse reaction occurs with the use of this drug, discontinue treatment until the symptoms resolve. Then resume treatment as appropriate, based on the initial severity of the adverse reaction. If bilirubin rises to more than 3 times the institutional upper limit of normal (IULN) or hepatic transaminases rise to more than 5 times the institutional upper limit of normal (IULN), interrupt treatment until bilirubin is at or below 1.5 times the institutional upper limit of normal (IULN) and transaminases are below 2.5 times the institutional upper limit of normal (IULN). Treatment may then be continued at a reduced daily dose. Reduce the adult dose from 400mg to 300mg, from 600mg to 400mg, or from 800mg to 600mg, 2) In the event of hematologic adverse reactions Dose reduction or treatment interruption is recommended for severe neutropenia and thrombocytopenia, 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 severe adverse reaction occurred). Chronic-phase chronic myeloid leukemia, myelodysplastic syndromes/myelodysplasia, gastrointestinal stromal tumors (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 falls again to < 50 × 109/L, 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, further reduce the dose to 300mg. 4. If the cytopenia persists for 4 weeks and is still not related to leukemia, discontinue 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 falls again to < 50 × 109/L, 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

Child dose

1. Chronic myeloid leukemia (CML) 2) Pediatric patients - For pediatric patients with Philadelphia chromosome-positive chronic-, accelerated-, or blast-phase chronic myeloid leukemia, a dose of 340mg/m2 per day based on body surface area is recommended (not exceeding a total daily dose of 600mg). The dose may be given once daily or divided into 2 doses, in the morning and evening. 4. Other 2) In pediatric patients, this drug may be taken once daily or, optionally, the daily dose may be divided into 2 doses, in the morning and evening. 5. Dosage adjustment 1) If nonhematologic adverse reactions occur Reduce the pediatric dose from 340mg/m2 to 260mg/m2, or from 260mg/m2 to 200mg/m2. 2) If hematologic adverse reactions occur Pediatric chronic-phase chronic myeloid leukemia (initial dose 340mg/m2) ANC < 1.0 × 109/L and/or platelets < 50 × 109/L 1. Interrupt treatment with this drug until ANC ≥ 1.5 × 109/L and the platelet count ≥ 75 × 109/L. 2. Resume treatment at the previous dose (before the severe adverse reaction occurred). 3. If ANC falls again to < 1.0 × 109/L and/or the platelet count falls again to < 50 × 109/L, repeat step 1 and resume treatment at the reduced dose of 260mg/m2. Pediatric accelerated- or blast-phase chronic myeloid leukemia (initial 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 drug to 260mg/m2. 3. If the cytopenia persists for 2 weeks, reduce the dose further to 200mg/m2. 4. If the cytopenia persists for 4 weeks and is still not related to leukemia, discontinue this drug until ANC ≥ 1 × 109/L and the platelet count ≥ 20 × 109/L, then resume treatment at a dose of 200mg/m2.

This drug should not be administered to individuals who have had allergic reactions to this drug or any of its components. Women who are pregnant or may become pregnant should not use this drug, nor should nursing mothers. Moreover, patients with impaired liver or kidney function need to exercise caution when using this drug. Patients with a history of heart disease or heart failure, as well as renal failure, must seek immediate diagnosis and treatment if symptoms or signs develop while using this drug. Especially for patients with hypereosinophilia, cardiac problems may arise, so it is advisable to thoroughly assess cardiac status before administration and, if necessary, to conduct steroid therapy alongside it. Thyroid function may also be affected, so thyroid levels should be checked regularly. In children before puberty, growth delays have been reported upon administration, hence growth status should be monitored periodically. While taking this drug, it is recommended to prevent dehydration and to pre-treat if uric acid levels are high. Additionally, hepatitis B virus carriers should consult a specialist and regularly monitor liver conditions as there is a risk of hepatitis reactivation before and during treatment with this drug. Common side effects during the use of this drug may include decreased blood cell count, headache, dyspepsia, edema, weight gain, nausea, vomiting, muscle cramps, musculoskeletal pain, diarrhea, rash, fatigue, abdominal pain, etc. Most are mild to moderate in severity. If side effects are severe, dose adjustments or discontinuation may be needed, so consult a healthcare professional if abnormal symptoms occur.

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

This drug is sensitive to air and moisture, so it must be stored in a tightly sealed container. It is advisable to store it at room temperature, between 1 to 30 degrees Celsius. This helps to maintain the efficacy of the drug for a longer period.

Appearance

Oval film-coated tablet of dark yellow-brown color

Package unit

60 tablets/PTP