Cases of tumor lysis syndrome (TLS), including fatal cases, have been reported. The patients at risk of TLS are those with tumors having a high proliferative rate or high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken.
In Ph+ CML trials(****), severe (NCI Grades 3/4) lab abnormalities—including neutropenia (3.6%-48%), anemia (1%-42%), thrombocytopenia (<1%-33%), and hepatotoxicity (approx 5%)—and severe adverse experiences (NCI Grades 3/4), including hemorrhage (1.8%-19%), fluid retention (eg, pleural effusion, pulmonary edema, and ascites) (2.5%-11%) and superficial edema (1.5%-6%), and musculoskeletal pain (2%-9%), were reported among patients receiving GLEEVEC. Severe fluid retention appears to be dose-related, was more common in the advanced phase studies (where the dosage was 600 mg/day), and is more common in the elderly.
There have also been reports, including fatalities, of cardiac tamponade, cerebral edema, acute respiratory failure, and gastrointestinal (GI) perforation.
GLEEVEC is metabolized by the CYP3A4 isoenzyme and is an inhibitor of CYP3A4, CYP2D6, and CYP2C9. Significant reductions in imatinib concentrations may occur when GLEEVEC is administered concomitantly with agents that are strong CYP3A4 inducers such as rifampin, St. John's wort, and enzyme-inducing anti-epileptic drugs, eg, phenytoin. The use of concomitant strong CYP3A4 inducers should be avoided. If patients must be administered a strong CYP3A4 inducer, the dosage of GLEEVEC should be increased by at least 50% and clinical response should be carefully monitored. Caution is recommended when GLEEVEC is administered with CYP3A4 inhibitors such as ketoconazole, with CYP2D6 substrates that have a narrow therapeutic window, or with CYP3A4 substrates that have a narrow therapeutic window. Other examples of commonly used drug
|SOURCE Novartis Pharmaceuticals Corporation|
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