Gleevec Film-Coated Tablets 100 mg (Imatinib Mesylate)

Adult dose

Chronic myeloid leukemia (CML), adults For adult patients with Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia, a dose of 400mg once daily is recommended. For adult patients with Philadelphia chromosome-positive accelerated-phase or blast-phase (blast crisis) chronic myeloid leukemia, a dose of 600mg once daily is recommended. In the absence of severe adverse reactions or severe leukemia-unrelated neutropenia or thrombocytopenia, dose escalation may be considered from 400mg to 600mg in adults with chronic-phase disease, or from 600mg to 800mg (400mg twice daily) in adults with accelerated-phase or blast-phase (blast crisis) 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 Gastrointestinal stromal tumor (GIST) For adult patients with Kit (CD 117)-positive, unresectable and/or metastatic malignant gastrointestinal stromal tumors (GIST), a dose of 400mg once daily is recommended. For adult patients receiving this drug as adjuvant therapy after surgical resection of a Kit (CD 117)-positive gastrointestinal stromal tumor, a dose of 400mg once daily is recommended. The optimal duration of administration of this drug as adjuvant therapy has not been established. In a clinical trial comparing treatment with this drug for 1 year and 3 years in patients at high risk of GIST recurrence, a treatment duration of 3 years was recommended. For the following diseases associated with tyrosine kinases sensitive to imatinib, for which prior treatment or therapy has failed or no clinical treatment option with a clear benefit is available: Myelodysplastic syndromes/myeloproliferative diseases: A dose of 400mg once daily is recommended. Hypereosinophilic syndrome/chronic eosinophilic leukemia: A dose of 100mg once daily is recommended. The dose may be increased to 400mg once daily. Recurrent or metastatic dermatofibrosarcoma protuberans: 800mg once daily (400mg twice daily) To minimize the risk of gastrointestinal irritation, take the prescribed dose with a meal and plenty of water. Doses of 400mg or 600mg are taken once daily, and the 800mg dose is taken as 400mg twice daily. For patients unable to swallow film-coated tablets, the tablets may be suspended in water or apple juice. Place the required number of tablets in an appropriate amount of beverage and stir (approximately 50mL of liquid for a 100mg tablet). The suspension of completely disintegrated tablets should be taken immediately. Continue treatment until there is evidence of disease progression or unacceptable toxicity. As the incidence of adverse reactions may increase at higher doses, patients whose dose is increased should be monitored closely. This drug is metabolized mainly in the liver. The minimum recommended dose for patients with mild, moderate, or severe hepatic impairment is 400mg once daily. The dose may be reduced if it is not tolerated. 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 once 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 efficacy is insufficient while the dose is tolerated, it may be increased. 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. In the event of nonhematologic adverse reactions If a severe nonhematologic adverse reaction occurs with this drug, interrupt treatment until the symptoms resolve. Then resume treatment as appropriate, according to the initial severity of the adverse reaction. If the bilirubin level rises to more than 3 times the institutional upper limit of normal (IULN), or liver transaminases rise to more than 5 times the IULN, discontinue treatment until the bilirubin level is 1.5 times the IULN or less and transaminases are less than 2.5 times the 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, In the event of hematologic adverse reactions Dose reduction or interruption of treatment for severe neutropenia and thrombocytopenia is recommended as shown below. 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 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 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, 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 falls again to < 50 × 109/L, repeat step 1 and resume treatment at the reduced dose of 400mg. ANC = absolute neutrophil count Onset after at least 1 month of treatment

Child dose

A dose of 340mg/m2 per day is recommended for patients with Philadelphia chromosome-positive chronic myeloid leukemia in the chronic, accelerated, or blast phase (the total daily dose should not exceed 600mg). The dose may be administered once daily or in 2 divided doses, in the morning and evening. In pediatric patients, this medicine may be administered once daily or, optionally, in 2 divided doses in the morning and evening. Reduce the pediatric dose 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 medicine 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 again falls to < 50 × 109/L, 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) 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, discontinue this medicine until ANC ≥ 1 × 109/L and platelet count ≥ 20 × 109/L, then resume treatment at a dose of 200mg/m2.

This drug should not be administered to patients with hypersensitivity to this drug or other ingredients. Interactions may occur when used with other medications, so caution should be exercised, especially when coadministered with certain medications (dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarbital, St. John's wort). Patients with impaired liver function should use this drug cautiously and monitor liver function closely, as its metabolism primarily occurs in the liver. Patients who have undergone thyroid surgery may experience hypothyroidism, so regular monitoring of thyroid-stimulating hormone levels is necessary. Fluid retention may occur, so regular weight changes should be measured, and sudden weight gain should be reported to a doctor immediately. Patients with a history of heart disease or renal failure should carefully monitor for signs of heart failure or renal failure and seek appropriate treatment if necessary. Due to the risk of gastrointestinal bleeding, any gastrointestinal symptoms should be reported to healthcare personnel immediately, and discontinuation of the drug should be considered if necessary. There is a risk of tumor lysis syndrome, so dehydration must be corrected before administration, and appropriate treatment should be provided if uric acid levels are high. Patients who are carriers of hepatitis B should undergo hepatitis B testing before and during treatment with this drug, and observe for signs of infection activation, consulting a specialist as necessary. Regular blood tests should be conducted to check blood cell counts, and liver and kidney functions should be periodically examined, considering dose adjustment or discontinuation if abnormalities are found. In pediatric patients, growth delays have been reported, so regular monitoring of growth status is necessary. Symptoms such as dizziness, drowsiness, and blurred vision may occur while taking this drug, so caution is advised when driving or operating machinery. During pregnancy, the drug may be harmful to the fetus, so it should be avoided in pregnant women, and women of childbearing potential should undergo pregnancy testing prior to treatment and use effective contraception during therapy. Lactating women should refrain from breastfeeding, as this drug may be excreted in breast milk. In the case of overdose, symptoms like nausea, vomiting, diarrhea, rash, swelling, muscle cramps may occur, and appropriate medical treatment should be sought immediately. This drug must be taken only as directed by a doctor, adhering to the prescribed dosage and method.

Neutropenia, thrombocytopenia, anemia, headache, dyspepsia, edema, weight gain, nausea, vomiting, muscle cramps, musculoskeletal pain, diarrhea, rash, fatigue, abdominal pain, herpes zoster, herpes simplex, nasopharyngitis, pneumonia, sinusitis, sialadenitis, upper respiratory infection, influenza, urethritis, gastroenteritis, septicemia, fungal infection, tumor hemorrhage, tumor necrosis, erythrocytopenia, febrile neutropenia, thrombocytosis, lymphocytopenia, bone marrow suppression, eosinophilia, lymphadenopathy, hemolytic anemia, anorexia, hypokalemia, increased appetite, hypophosphatemia, decreased appetite, dehydration, gout, hypercalciuria, hypercalcemia, hyperglycemia, hyponatremia, hyperkalemia, hypomagnesemia, insomnia, depression, decreased libido, anxiety, confusion, dizziness, paralysis, taste disorder, sensory disturbance, migraine, drowsiness, fainting, peripheral neuropathy, memory impairment, sciatica, restless leg syndrome, tremor, cerebral hemorrhage, hypersomnolence, increased intracranial pressure, convulsion, optic neuritis, eyelid edema, increased lacrimation, conjunctival hemorrhage, conjunctivitis, dry eyes, blurred vision, eye irritation, eye pain, orbital edema, scleral hemorrhage, retinal hemorrhage, blepharitis, macular edema, cataract, glaucoma, papilledema, vitreous hemorrhage, vertigo, tinnitus, hearing loss, palpitations, tachycardia, congestive heart failure, pulmonary edema, heart failure, arrhythmia, atrial fibrillation, cardiac arrest, myocardial infarction, angina, pericardial effusion, flushing, bleeding, hypertension, hematoma, subdural hematoma, peripheral coldness, hypotension, Raynaud's phenomenon, dyspnea, epistaxis, cough, pleural effusion, oropharyngitis, pharyngitis, pleuritic pain, pulmonary fibrosis, pulmonary hypertension, pulmonary hemorrhage, bloating, abdominal distension, gastroesophageal reflux, constipation, thirst, gastritis, stomatitis, oral ulcer, gastrointestinal bleeding, belching, blood in stool, esophagitis, ascites, gastric ulcer, hematemesis, cheilitis, dysphagia, pancreatitis, colitis, diverticulitis, bowel obstruction, inflammatory bowel disease, elevated liver enzymes, hyperbilirubinemia, hepatitis, jaundice, liver failure, hepatic necrosis, periorbital edema, dermatitis, eczema, pruritus, facial edema, xerosis, erythema, alopecia, night sweats, photosensitivity rash, pustular rash, bruise, increased sweating, urticaria, petechial hemorrhage, increased bruising, hypopigmentation, skin pigmentation disorders, exfoliative dermatitis, brittle nails, folliculitis, petechiae, psoriasis, photosensitivity, excessive skin pigmentation, bullous pemphigoid, acute febrile neutrophilic dermatosis, nail discoloration, angioedema, vesicular rash, erythema multiforme, leukocytoclastic vasculitis, Stevens-Johnson syndrome, acute generalized eruptive pustulosis, arthralgia, musculoskeletal pain, limb pain, myalgia, bone pain, spinal pain, joint swelling, joint and muscle rigidity, myasthenia, arthritis, avascular necrosis, renal colic, hematuria, acute renal failure, increased frequency of urination, gynecomastia, erectile dysfunction, menorrhagia, irregular menstruation, sexual dysfunction, mastalgia, breast hypertrophy, scrotal swelling, fluid retention, weakness, fever, generalized edema, chills, rigidity, bleeding, chest pain, lethargy, weight gain, weight loss, increased blood creatinine, increased blood creatine phosphokinase, increased blood lactate dehydrogenase, increased blood alkaline phosphatase, increased blood amylase, reactivation of hepatitis B, thrombotic microangiopathy, cerebral edema, vitreous hemorrhage, pericarditis, cardiac constriction, thrombosis, embolism, anaphylactic shock, acute respiratory failure, interstitial lung disease, colonic obstruction, small bowel obstruction, gastrointestinal perforation, diverticulitis, vascular ectasia of the gastric fundus, hand-foot erythema sensory neuropathy syndrome, panniculitis, lichen planus, pemphigus, toxic epidermal necrolysis, DRESS syndrome, pseudoporphyria, rhabdomyolysis, myopathy, hemorrhagic corpus luteum, hemorrhagic ovarian cyst, tumor lysis syndrome, chronic renal failure, nausea, vomiting, diarrhea, rash, erythema, edema, swelling, fatigue, muscle cramps, thrombocytopenia, erythrocytopenia, abdominal pain, decreased appetite, weakness, myalgia, increased CPK, elevated bilirubin, gastrointestinal pain, fever, facial swelling, increased transaminases, thrombocytopenia, leukopenia, anorexia

This drug is sensitive to air and moisture, so it should be stored in a tightly closed container when in use. Additionally, it is important to store the drug at room temperature between 1°C and 30°C to maintain its efficacy.

Appearance

Dark yellow-brown round film-coated tablets

Package unit

60 tablets (10 tablets/PTP packaging X 6)