Indicated for the treatment of:

Newly Diagnosed Philadelphia Positive Chronic Myeloid Leukemia (Ph+ CML):

• Newly diagnosed adult and pediatric patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase.

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). 

Pediatric patients with Ph+ Acute Lymphoblastic Leukemia (ALL):

• Pediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) in combination with chemotherapy.

Myelodysplastic/Myeloproliferative Diseases (MDS/MPD):

• Adult patients with myelodysplastic/myeloproliferative diseases associated with PDGFR (platelet-derived growth factor receptor) gene rearrangements.

Aggressive Systemic Mastocytosis (ASM):

• Adult patients with aggressive systemic mastocytosis without the D816V c-Kit mutation or with c-Kit mutational status unknown.

Hypereosinophilic Syndrome (HES) and/or Chronic Eosinophilic Leukemia (CEL):

• Adult patients with hypereosinophilic syndrome and/or chronic eosinophilic leukemia who have the FIP1L1-PDGFRα fusion kinase (mutational analysis or FISH demonstration of CHIC2 allele deletion) and for patients with HES and/or CEL who are FIP1L1-PDGFRα fusion kinase negative or unknown.

Dermatofibrosarcoma Protuberans (DFSP):

• Adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans.

Kit+ Gastrointestinal Stromal Tumors (GIST):

• Patients with Kit (CD117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumors.

Adjuvant Treatment of GIST:

• Adjuvant treatment of adult patients following complete gross resection of Kit (CD117) positive GIST.

All doses of Gleevec should be taken with a meal and a large glass of water. Doses of 400 mg or 600 mg should be administered once daily, whereas a dose of 800 mg should be administered as 400 mg twice a day.

Treatment may be continued as long as there is no evidence of progressive disease or unacceptable toxicity.

Reports of motor vehicle accidents have been received in patients receiving Gleevec. Caution patients about driving a car or operating machinery.

Treatment with Gleevec is associated with anemia, neutropenia, and thrombocytopenia. Perform complete blood counts weekly for the first month, biweekly for the second month, and periodically thereafter as clinically indicated.

Hemorrhage and gastric antral vascular ectasia has been reported in postmarketing experience.

Congestive heart failure and left ventricular dysfunction have been reported in patients taking Gleevec.

Gleevec is often associated with edema and occasionally serious fluid retention.

Clinical cases of hypothyroidism have been reported in thyroidectomy patients undergoing levothyroxine replacement during treatment with Gleevec.

In patients with hypereosinophilic syndrome with occult infiltration of HES cells within the myocardium, cases of cardiogenic shock/left ventricular dysfunction have been associated with HES cell degranulation upon the initiation of Gleevec therapy. The condition was reported to be reversible with the administration of systemic steroids, circulatory support measures and temporarily withholding Gleevec.

Cases of fatal liver failure and severe liver injury requiring liver transplants have been reported with both short-term and long-term use of Gleevec.

If elevations in bilirubin greater than 3 times the institutional upper limit of normal (IULN) or in liver transaminases greater than 5 times the IULN occur, Gleevec should be withheld until bilirubin levels have returned to a less than 1.5 times the IULN and transaminase levels to less than 2.5 times the IULN. In adults, treatment with Gleevec may then be continued at a reduced daily dose (i.e., 400 mg to 300 mg, 600 mg to 400 mg or 800 mg to 600 mg). In children, daily doses can be reduced under the same circumstances from 340 mg/m²/day to 260 mg/m²/day.

A decline in renal function may occur in patients receiving Gleevec. Evaluate renal function prior to initiating Gleevec and monitor during therapy, with attention to risk factors for renal dysfunction such as pre-existing renal impairment, diabetes mellitus, hypertension, and congestive heart failure.

Patients with moderate renal impairment (CrCL=20–39 mL/min) should receive a 50% decrease in the recommended starting dose and future doses can be increased as tolerated. Doses greater than 600 mg are not recommended in patients with mild renal impairment (CrCL=40–59 mL/min). For patients with moderate renal impairment doses greater than 400 mg are not recommended.

Imatinib should be used with caution in patients with severe renal impairment. A dose of 100 mg/day was tolerated in two patients with severe renal impairment.

Cases of Tumor Lysis Syndrome (TLS), including fatal cases, have been reported in patients with CML, GIST, ALL and eosinophilic leukemia receiving Gleevec.

Growth retardation has been reported in children and pre-adolescents receiving Gleevec.

Bullous dermatologic reactions, including erythema multiforme and Stevens Johnson syndrome, have been reported with use of Gleevec.

Musculoskeletal and Connective Tissue Disorders: avascular necrosis/hip osteonecrosis, rhabdomyolysis/myopathy, growth retardation in children, musculoskeletal pain upon treatment discontinuation (including myalgia, pain in extremity, arthralgia, bone pain).

The use of concomitant strong CYP3A4 inducers should be avoided (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, phenobarbital). If patients must be co-administered a strong CYP3A4 inducer, based on pharmacokinetic studies, the dosage of Gleevec should be increased by at least 50%, and clinical response should be carefully monitored.

Concomitant administration of Gleevec and strong CYP3A4 inhibitors may result in a significant imatinib exposure increase. Grapefruit juice may also increase plasma concentrations of imatinib; avoid grapefruit juice.

Gleevec will increase plasma concentration of CYP3A4 metabolized drugs (e.g., triazolo benzodiazepines, dihydropyridine calcium channel blockers, certain HMG CoA reductase inhibitors, etc.). Use caution when administering Gleevec with CYP3A4 substrates that have a narrow therapeutic window.

Because warfarin is metabolized by CYP2C9 and CYP3A4, use low-molecular weight or standard heparin instead of warfarin in patients who require anticoagulation.

Gleevec can cause fetal harm when administered to a pregnant woman. Advise sexually active female patients of reproductive potential to use effective contraception (methods that result in less than 1% pregnancy rates) when using Gleevec and for 14 days after stopping Gleevec.

Imatinib and its active metabolite are excreted into human milk. Because of the potential for serious adverse reactions in breastfed infants from Gleevec, advise a lactating woman not to breastfeed during treatment and for 1 month after the last dose.

GoToSource

• Use in patients under the age of 1 year. GoToSource

• Long term use for pulmonary arterial hypertension. GoToSource

• Regression of type 2 diabetes. GoToSource

• Rosai-dorfman disease. GoToSource

• Brainstem and recurrent malignant gliomas. GoToSource

• Metastatic medullary thyroid carcinoma. GoToSource

• Adjunctive therapy for hydroxyurea in patients with progressive/recurrent low-grade glioma. GoToSource

• Unresectable hepatocellular carcinoma. GoToSource

• Prostate cancer with evidence of biochemical relapse after definitive radical retropubic prostatectomy or radiotherapy. GoToSource

• Adjunctive therapy for pretreated progressive glioblastoma multiforme. GoToSource

• AIDS-related kaposi’s sarcoma. GoToSource

• Adjunctive therapy for metastatic breast cancer. GoToSource

• Advanced chordoma. GoToSource

• Adenoid cystic carcinoma of the salivary glands. GoToSource

• Thymic carcinoma with overexpression of mutated KIT. GoToSource

• Refractory metastatic pilocytic astrocytoma. GoToSource

• Adjunctive therapy for untreated extensive-stage small cell lung cancer. GoToSource

• Adjunctive therapy for prostate cancer with bone metastases. GoToSource

• Adjunctive therapy for bone pain due to androgen-independent prostate cancer. GoToSource

• Improve recovery in spinal cord injury. GoToSource

• Prevention of atherosclerosis. GoToSource 

• Melanomas harboring mutationally activated or amplified KIT arising on mucosal, acral, and chronically sun-damaged skin. GoToSource

Cardiotoxicity, heart failure, myocardial infarction, hypophosphatemia with associated bone and mineral metabolic changes (deficiency of phosphates in the blood), gynecomastia (male breast enlargement), hypothyroidism, cutaneous reactions including stevens-johnson syndrome, liver damage, interstitial lung disease and myeloid malignancies. GoToSource

Kidney failure. GoToSource

Fluid retention, increased risk of infection and thrombocytopenia (deficiency of platelets in the blood). GoToSource

Sensorineural hearing loss. GoToSource

Periorbital edema (swelling around the eyes), epiphora (excessive eye watering), retinal hemorrhage and neovascularization (abnormal blood vessel formation). GoToSource 

Growth failure in children. GoToSource

Tumor lysis syndrome (potentially life-threatening metabolic disorder). GoToSource 

Fetal harm. GoToSource

Subdural hematoma. GoToSource

Upper gastrointestinal hemorrhage. GoToSource

Gastric antral vascular ectasia (condition in which the lining of the stomach bleeds). GoToSource

Lawsuits filed for heart failure.