Carevec 400 Milligrams (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 or 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 tumor (GIST) - A dose of 400mg daily is recommended for adult patients with Kit (CD 117)-positive unresectable and/or metastatic malignant gastrointestinal stromal tumors (GIST). - A dose of 400mg daily is recommended for adult patients receiving this medicine as adjuvant therapy following surgical resection of Kit (CD 117)-positive gastrointestinal stromal tumors. The optimal duration of administration of this medicine as adjuvant therapy has not been established. In a clinical trial comparing administration of this medicine for 1 year and 3 years in patients at high risk of GIST recurrence, a treatment duration of 3 years was recommended. 3. The following diseases associated with tyrosine kinases sensitive to imatinib, for which existing medicines or treatment regimens have failed or no treatment method with a clear clinical benefit is available: - Myelodysplastic/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) The prescribed dose should be taken with a meal and plenty of water to minimize the risk of gastrointestinal irritation. Doses of 400mg or 600mg are taken once daily, and the 800mg dose is taken as 400mg twice daily. 4) Treatment should continue 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 has been increased should be closely monitored. 6) This medicine is metabolized mainly in the liver, and 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 medicine and its metabolites is minimal. The minimum recommended starting dose for patients with renal impairment or patients receiving hemodialysis is 400mg daily. However, caution is required when administering it to patients with renal impairment. If the dose is not tolerated, it may be reduced; if it is tolerated but efficacy is insufficient, the dose may be increased. 8) No specific pharmacokinetic studies of this medicine 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. 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 use of this medicine, interrupt treatment until the symptoms resolve. Treatment may then be resumed as appropriate, depending on the initial severity of the adverse reaction. If the bilirubin level increases to more than 3 times the upper limit of normal (IULN: Institutional Upper Limit of Normal), or liver transaminases increase to more than 5 times the upper limit of normal (IULN), treatment should be interrupted until the bilirubin level is 1.5 times the upper limit of normal (IULN) or lower and transaminases are less than 2.5 times the 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. Hypereosinophilic syndrome and chronic eosinophilic leukemia (starting dose 100mg) 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 with this medicine at the previous dose (the dose before the severe adverse reaction occurred). Chronic-phase chronic myeloid leukemia, myelodysplastic/myeloproliferative diseases, gastrointestinal stromal tumors (starting 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 medicine until ANC ≥ 1.5 × 109/L and platelet count ≥ 75 × 109/L. 2. Resume treatment with this medicine 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 (starting 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 medicine 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 medicine until ANC ≥ 1 × 109/L and platelet count ≥ 20 × 109/L, and then resume treatment at a dose of 300mg. Dermatofibrosarcoma protuberans (starting dose 800mg) 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 with this medicine 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

2) Pediatric patients - A dose of 340mg/m2 per day based on body surface area is recommended for pediatric patients with Philadelphia chromosome-positive chronic myeloid leukemia in the chronic, accelerated, or blast phase (the total daily dose should not exceed 600mg). It may be administered once daily or divided into 2 doses per day, in the morning and evening. 4. Other 2) In pediatric patients, this drug may be taken once daily or, at the patient's option, the daily dose may be divided into 2 doses, in the morning and evening. 5. Dose adjustment 1) In the event of nonhematologic adverse reactions The pediatric dose should be reduced from 340mg/m2 to 260mg/m2, or from 260mg/m2 to 200mg/m2. 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 drug until ANC ≥ 1.5 × 109/L and platelet count ≥ 75 × 109/L. 2. Resume treatment at the 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- 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 drug 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, discontinue this drug until ANC ≥ 1 × 109/L and platelet count ≥ 20 × 109/L, then resume treatment at a dose of 200mg/m2.

This medication should not be used by patients allergic to this drug or other components. Women who are pregnant or may become pregnant should not take this medication, as it could harm the fetus. Breastfeeding women are also advised not to take this medication. Patients with impaired liver or kidney functions should be monitored closely when taking this medication. Patients with a history of heart disease or heart failure, and renal failure also require caution, and any abnormal symptoms should be treated immediately. In patients with hypereosinophilia with cardiac infiltration, issues with heart function may arise after taking this medication, so consultation with a specialist is advised, and steroid treatment may be necessary. Patients taking levothyroxine after thyroid surgery should undergo regular thyroid function tests. In pediatric patients, long-term use of this medication may result in growth delays, necessitating close monitoring of growth status. As there is a risk of tumor lysis syndrome, dehydration should be corrected prior to administration, and treatment is needed if uric acid levels are high. Hepatitis B virus carriers should consult a specialist before and during treatment to closely monitor for hepatitis reactivation. While taking this medication, neutropenia, thrombocytopenia, anemia, headaches, dyspepsia, edema, weight gain, nausea, vomiting, muscle cramps, pain, diarrhea, rash, fatigue, and abdominal pain may commonly occur as side effects. If these side effects are severe, dose adjustment or discontinuation may be necessary.

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

This medication should be stored in a tightly sealed container to protect from air and moisture. It is recommended to keep the storage temperature between 1 to 30 degrees Celsius (room temperature).

Appearance

Oval film-coated tablets, deep yellow to brown in color

Package unit

30 tablets (6 tablets/PTPX5)