n on IFN-α (2%) experienced declines in LVEF to >20% below baseline and to below 50%. Left ventricular dysfunction was reported in four patients (1%) and CHF in two patients (<1%) who received SUTENT.
In the Phase 3 pNET study, cardiac failure leading to death was reported in 2/83 (2%) patients on SUTENT and no patients on placebo.
Patients who presented with cardiac events within 12 months prior to SUTENT administration, such as myocardial infarction (including severe/unstable angina), coronary/peripheral artery bypass graft, symptomatic CHF, cerebrovascular accident or transient ischemic attack, or pulmonary embolism were excluded from SUTENT clinical studies. It is unknown whether patients with these concomitant conditions may be at a higher risk of developing drug-related left ventricular dysfunction. Physicians are advised to weigh this risk against the potential benefits of the drug. These patients should be carefully monitored for clinical signs and symptoms of CHF while receiving SUTENT. Baseline and periodic eva luations of LVEF should also be considered while these patients are receiving SUTENT. In patients without cardiac risk factors, a baseline eva luation of ejection fraction should be considered.
5.4QT Interval Prolongation and Torsade de Pointes
SUTENT has been shown to prolong the QT interval in a dose dependent manner, which may lead to an increased risk for ventricular arrhythmias including Torsade de Pointes. Torsade de Pointes has been observed in <0.1% of SUTENT-exposed patients.
SUTENT should be used with caution in patients with a history of QT interval prolongation, patients who are taking antiarrhythmics, or patients with relevant pre-existing cardiac disease, bradycardia, or electrolyte disturbances. When using SUTENT, periodic monitoring with on-treatment electrocardiograms and electrolytes (magnesium, potassium) should be considered. 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 Dosage and Administration (2.2)].
5.5Hypertension
Patients should be monitored for hypertension and treated as needed with standard anti-hypertensive therapy. In cases of severe hypertension, temporary suspension of SUTENT is recommended until hypertension is controlled.
Of patients receiving SUTENT for treatment-naïve RCC, 127/375 patients (34%) receiving SUTENT compared with 13/360 patients (4%) on IFN-α experienced hypertension. Grade 3 hypertension was observed in 50/375 treatment-naïve RCC patients (13%) on SUTENT compared to 1/360 patients (<1%) on IFN-α. While all-grade hypertension was similar in GIST patients on SUTENT compared to placebo, Grade 3 hypertension was reported in 9/202 GIST patients on SUTENT (4%), and none of the GIST patients on placebo. Of patients receiving SUTENT in the Phase 3 pNET study, 22/83 patients (27%) on SUTENT and 4/82 patients (5%) on placebo experienced hypertension. Grade 3 hypertension was reported in 8/83 pNET patients (10%) on SUTENT, and 1/82 patient (1%) on placebo. No Grade 4 hypertension was reported. SUTENT dosing was reduced or temporarily delayed for hypertension in 21/375 patients (6%) on the treatment-naive RCC study and 7/83 pNET patients (8%). Four treatment-naïve RCC patients, including one with malignant hypertension, one patient with pNET, and no GIST patients discon |
