In the presence of clinical manifestations of CHF, discontinuation of SUTENT is recommended. The dose of SUTENT should be interrupted and/or reduced in patients without clinical evidence of CHF but with an ejection fraction <50% and >20% below baseline.

5.3 QT Interval Prolongation
 At approximately twice therapeutic concentrations, SUTENT has been shown to prolong the QTcF interval (see 12.4 Cardiac Electrophysiology). There were no patients on this study with greater than Grade 2 (CTCAE v3.0) QT/QTc interval prolongation. QT interval prolongation may lead to an increased risk for ventricular arrhythmias including torsade de pointes. Torsade de pointe has been observed in <0.1% of SUTENT-exposed patients. SUTENT should be used with caution in patients with a known history of QT interval prolongation, patients who are taking antiarrhythmics, or patients with relevant pre-existing cardiac disease, bradycardia, or electrolyte disturbances. Concomitant treatment with strong CYP3A4 inhibitors, which may increase sunitinib plasma concentrations, should be used with caution and dose reduction of SUTENT should be considered (see 2.2 Dose Modification).

5.4 Hemorrhagic Events
Bleeding events occurred in 37/202 patients (18%) receiving SUTENT in GIST Study A, compared to 17/102 patients (17%) receiving placebo.  In patients receiving SUTENT for treatment-naïve MRCC, 104/375 patients (28%) had bleeding events compared with 25/360 patients (7%) receiving IFN-α; 44/169 patients (26%) receiving SUTENT for cytokine-refractory MRCC experienced bleeding. Epistaxis was the most common hemorrhagic adverse event reported. Less common bleeding events in GIST or MRCC patients included rectal, gingival, upper gastrointestinal, genital, and wound bleeding. In GIST Study A, 14/202 patients (7%) receiving SUTENT and 9/102 patients (9%) on placebo had Grade 3 or 4 bleeding events. In addition, one patient in Study A taking placebo had a fatal gastrointestinal bleeding event during cycle 2. Most events in MRCC patients were Grade 1 or 2; there was one Grade 3 event (bleeding foot wound) in a cytokine-refractory patient  and one Grade 5 event of gastric bleed, unrelated to SUTENT treatment, in a treatment-naïve patient.

Tumor-related hemorrhage has been observed in patients treated with SUTENT. These events may occur suddenly, and in the case of pulmonary tumors may present as severe and life-threatening hemoptysis or pulmonary hemorrhage. Fatal pulmonary hemorrhage occurred in 2 patients receiving SUTENT on a clinical trial of patients with metastatic non-small cell lung cancer (NSCLC). Both patients had squamous cell histology. SUTENT is not approved for use in patients with NSCLC. Treatment-emergent Grade 3 and 4 tumor hemorrhage occurred in 5/202 patients (3%) with GIST receiving SUTENT on Study A. Tumor hemorrhages were observed as early as cycle 1 and as late as cycle 6. One of these five patients received no further drug following tumor hemorrhage. None of the other four patients discontinued treatment or experienced dose delay due to tumor hemorrhage. No patients with GIST in the Study A placebo arm were observed to undergo intratumoral hemorrhage. Tumor hemorrhage has not been observed in patients with MRCC. Clinical assessment of these events should include serial complete blood counts (CBCs) and physical examinations.

Serious, sometimes fatal gastrointestinal comp