Angina, transient ischemic attack, MI, and ischemic stroke observed (use with caution in patients with history of or increased risk for these events; use in patients with recent arteriothrombotic event [within 6 months] not recommended). Perforation and fistula (including fatal) have been reported (monitor for symptoms of gastrointestinal perforation and fistula). Hemorrhagic events (including fatal) have been reported (use not recommended in patients with history of hemoptysis, cerebral hemorrhage or clinically significant gastrointestinal hemorrhage within 6 months). Severe and fatal hepatotoxicity (transaminase and bilirubin elevations) has been reported (monitor hepatic function; may require dosage interruption, reduction, or discontinuation; not recommended in patients with pre-existing severe hepatic impairment). May cause and/or worsen hypertension (monitor for hypertension; antihypertensive therapy should be used if needed and dosage reduction may be necessary for persistent hypertension (despite antihypertensive therapy); discontinue for severe and persistent hypertension which is refractory to dose reduction and antihypertensive therapy). Proteinuria has been observed (obtain baseline and periodic urinalysis; discontinue for grade 4 proteinuria). QTc prolongation, including torsade de pointes, has occurred (use caution in patients with history of QTc prolongation, with medications known to prolong the QT interval, or with pre-existing cardiac disease; obtain baseline and periodic 12-lead ECGs, correct electrolyte (potassium, calcium, and magnesium) abnormalities prior to and during treatment). Hypothyroidism has been reported (monitor thyroid function tests). VEGF receptor inhibitors are associated with impaired wound healing (discontinue treatment at least 7 days prior to scheduled surgery; treatment reinitiation should be guided by clinical judgment; discontinue if wound dehiscence occurs). Gilbert’s syndrome, mild indirect (unconjugated) hyperbilirubinemia, may occur (monitor ALT elevation; dosage modification recommended in patients with known Gilbert’s syndrome, mild indirect bilirubin elevation and ALT >3 times ULN).