Imatinate Capsule

Imatinib is a kinase inhibitor indicated for the treatment of: - Newly diagnosed adult and pediatric patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase - Patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in blast crisis (BC), accelerated phase (AP), or in chronic phase (CP) after failure of interferon-alpha therapy - Adult patients with relapsed or refractory Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) - Pediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) in combination with chemotherapy - Adult patients with myelodysplastic/myeloproliferative diseases (MDS/MPD) associated with platelet-derived growth factor receptor (PDGFR) gene re-arrangements. - Adult patients with aggressive systemic mastocytosis (ASM) without the D816V c-Kit mutation or with c-Kit mutational status unknown - Adult patients with hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL) who have the FIP1L1-PDGFRα fusion kinase (mutational analysis or fluorescence in situ hybridization [FISH] demonstration of CHIC2 allele deletion) and for patients with HES and/or CEL who are FIP1L1-PDGFRα fusion kinase negative or unknown. - Adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans (DFSP) - Patients with Kit (CD117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumors (GIST). - Adjuvant treatment of adult patients following resection of Kit (CD117) positive GIST. Newly Diagnosed Philadelphia Positive Chronic Myeloid Leukemia (Ph+ CML). Ph+ CML in Blast Crisis (BC), Accelerated Phase (AP) or Chronic Phase (CP) After Interferon-alpha (IFN) Therapy Patients with Philadelphia chromosome positive chronic myeloid leukemia in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha therapy. Adult Patients With Ph+ Acute Lymphoblastic Leukemia (ALL) Adult patients with relapsed or refractory Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Abridged from the full prescribing information.

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Source: US FDA prescribing information, via openFDA. Provided for general information only — it is not a substitute for your doctor's or pharmacist's advice. Always follow your prescriber's instructions.

• Edema and severe fluid retention have occurred. Weigh patients regularly and manage unexpected rapid weight gain by drug interruption and diuretics. - Cytopenias, particularly anemia, neutropenia, and thrombocytopenia, have occurred. Manage with dose reduction, dose interruption, or discontinuation of treatment. Perform complete blood counts weekly for the first month, biweekly for the second month, and periodically thereafter. - Severe congestive heart failure and left ventricular dysfunction have been reported, particularly in patients with comorbidities and risk factors. Monitor and treat patients with cardiac disease or risk factors for cardiac failure. - Severe hepatotoxicity, including fatalities may occur. Assess liver function before initiation of treatment and monthly thereafter or as clinically indicated. Monitor liver function when combined with chemotherapy known to be associated with liver dysfunction. - Grade 3/4 hemorrhage has been reported in clinical studies in patients with newly diagnosed CML and with GIST. GI tumor sites may be the source of GI bleeds in GIST. - Gastrointestinal (GI) perforations, some fatal, have been reported. - Cardiogenic shock/left ventricular dysfunction has been associated with the initiation of Imatinib in patients with conditions associated with high eosinophil levels (e.g., HES, MDS/MPD, and ASM). - Bullous dermatologic reactions (e.g., erythema multiforme and Stevens-Johnson syndrome) have been reported with the use of Imatinib. - Hypothyroidism has been reported in thyroidectomy patients undergoing levothyroxine replacement. Closely monitor TSH levels in such patients. - Fetal harm can occur when administered to a pregnant woman. Apprise women of the potential harm to the fetus, and to use effective contraception. - Growth retardation occurring in children and pre-adolescents receiving Imatinib has been reported. Close monitoring of growth in children under Imatinib treatment is recommended. - Tumor Lysis Syndrome. Close monitoring is recommended. - Reports of motor vehicle accidents have been received in patients receiving Imatinib. Caution patients about driving a car or operating machinery. - Renal Toxicity. A decline in renal function may occur in patients receiving Imatinib tablets. Evaluate renal function at baseline and during therapy, with attention to risk factors for renal dysfunction. Fluid Retention and Edema Imatinib is often associated with edema and occasionally serious fluid retention. Weigh and monitor patients regularly for signs and symptoms of fluid retention. Investigate unexpected rapid weight gain carefully and provide appropriate treatment. Abridged from the full prescribing information.

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Source: US FDA prescribing information, via openFDA. Provided for general information only — it is not a substitute for your doctor's or pharmacist's advice. Always follow your prescriber's instructions.

The following serious adverse reactions are described elsewhere in the labeling: Fluid Retention and Edema Hematologic Toxicity Congestive Heart Failure and Left Ventricular Dysfunction Hepatotoxicity Hemorrhage Gastrointestinal Disorders Hypereosinophilic Cardiac Toxicity Dermatologic Toxicities Hypothyroidism Growth Retardation in Children and Adolescents Tumor Lysis Syndrome Impairments Related to Driving and Using Machinery Renal Toxicity The most frequently reported adverse reactions (greater than or equal to 30%) were edema, nausea, vomiting, muscle cramps, musculoskeletal pain, diarrhea, rash, fatigue and abdominal pain. Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Chronic Myeloid Leukemia The majority of Imatinib-treated patients experienced adverse reactions at some time. Imatinib was discontinued due to drug-related adverse reactions in 2.4% of patients receiving Imatinib in the randomized trial of newly diagnosed patients with Ph+ CML in chronic phase comparing Imatinib versus IFN+Ara-C, and in 12.5% of patients receiving Imatinib in the randomized trial of newly diagnosed patients with Ph+ CML in chronic phase comparing Imatinib and nilotinib. Imatinib was discontinued due to drug-related adverse reactions in 4% of patients in chronic phase after failure of interferon-alpha therapy, in 4% of patients in accelerated phase and in 5% of patients in blast crisis. The most frequently reported drug-related adverse reactions were edema, nausea and vomiting, muscle cramps, musculoskeletal pain, diarrhea and rash (Table 2 and Table 3 for newly diagnosed CML, Table 4 for other CML patients). Edema was most frequently periorbital or in lower limbs and was managed with diuretics, other supportive measures, or by reducing the dose of Imatinib. The frequency of severe superficial edema was 1.5% to 6%. A variety of adverse reactions represent local or general fluid retention, including pleural effusion, ascites, pulmonary edema, and rapid weight gain with or without superficial edema. These reactions appear to be dose related, were more common in the blast crisis and accelerated phase studies (where the dose was 600 mg/day), and are more common in the elderly. Abridged from the full prescribing information.

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Source: US FDA prescribing information, via openFDA. Provided for general information only — it is not a substitute for your doctor's or pharmacist's advice. Always follow your prescriber's instructions.