SUTENT has been associated with hepatotoxicity, which may result in liver failure or death. Liver failure has been observed in clinical trials (7/2281 [0.3%]) and post-marketing experience. Liver failure signs include jaundice, elevated transaminases and/or hyperbilirubinemia in conjunction with encephalopathy, coagulopathy, and/or renal failure. Monitor liver function tests (ALT, AST, bilirubin) before initiation of treatment, during each cycle of treatment, and as clinically indicated. SUTENT should be interrupted for Grade 3 or 4 drug-related hepatic adverse events and discontinued if there is no resolution. Do not restart SUTENT if patients subsequently experience severe changes in liver function tests or have other signs and symptoms of liver failure.
Safety in patients with ALT or AST >2.5 × ULN or, if due to liver metastases, >5.0 × ULN has not been established.
5.2Pregnancy
SUTENT can cause fetal harm when administered to a pregnant woman. As angiogenesis is a critical component of embryonic and fetal development, inhibition of angiogenesis following administration of SUTENT should be expected to result in adverse effects on pregnancy. In animal reproductive studies in rats and rabbits, sunitinib was teratogenic, embryotoxic, and fetotoxic. There are no adequate and well-controlled studies of SUTENT in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with SUTENT.
5.3Left Ventricular Dysfunction
In the presence of clinical manifestations of congestive heart failure (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.
Cardiovascular events, including heart failure, myocardial disorders and cardiomyopathy, some of which were fatal, have been reported through post-marketing experience. For GIST and RCC, more patients treated with SUTENT experienced decline in left ventricular ejection fraction (LVEF) than patients receiving either placebo or interferon-α (IFN-α). In the double-blind treatment phase of GIST Study A, 22/209 patients (11%) on SUTENT and 3/102 patients (3%) on placebo had treatment-emergent LVEF values below the lower limit of normal (LLN). Nine of 22 GIST patients on SUTENT with LVEF changes recovered without intervention. Five patients had documented LVEF recovery following intervention (dose reduction: one patient; addition of antihypertensive or diuretic medications: four patients). Six patients went off study without documented recovery. Additionally, three patients on SUTENT had Grade 3 reductions in left ventricular systolic function to LVEF <40%; two of these patients died without receiving further study drug. No GIST patients on placebo had Grade 3 decreased LVEF. In the double-blind treatment phase of GIST Study A, 1 patient on SUTENT and 1 patient on placebo died of diagnosed heart failure; 2 patients on SUTENT and 2 patients on placebo died of treatment-emergent cardiac arrest.
In the treatment-naïve RCC study, 103/375 (27%) and 54/360 (15%) patients on SUTENT and IFN-α, respectively, had an LVEF value below the LLN. Twenty-six patients on SUTENT (7%) and seve |
