Important Safety Information

Boxed Warning/
Hepatotoxicity
  • Hepatotoxicity has been observed in clinical trials and postmarketing experience. Hepatotoxicity may be severe, and in some cases fatal. Monitor hepatic function and interrupt, reduce, or discontinue dosing as recommended
  • Fatal liver failure has been observed. Monitor liver function tests before initiation of treatment, during each cycle of treatment, and as clinically indicated
  • Interrupt SUTENT for Grade 3 or 4 drug-related hepatic adverse reactions and discontinue if there is no resolution
  • Do not restart SUTENT if patients subsequently experience severe changes in liver function tests or have signs and symptoms of liver failure
Cardiovascular events
  • Cardiovascular events, including myocardial ischemia, myocardial infarction, left ventricular ejection fraction declines to below the lower limit of normal, and cardiac failure, including death, have occurred
  • Monitor patients for signs and symptoms of congestive heart failure
  • Discontinue SUTENT for clinical manifestations of congestive heart failure
  • In patients without cardiac risk factors, a baseline evaluation of ejection fraction should be considered. Baseline and periodic evaluations of left ventricular ejection fraction should also be considered while these patients are receiving SUTENT
QT prolongation and
Torsades de Pointes
  • SUTENT can cause QT prolongation in a dose-dependent manner, which may lead to an increased risk for ventricular arrhythmias including Torsades de Pointes, which has been seen in <0.1% of patients
  • Monitor patients who are at higher risk for developing QT interval prolongation, including those with a history of QT interval prolongation, patients who are taking antiarrhythmics, and patients with relevant pre-existing cardiac disease, bradycardia, or electrolyte disturbances. Consider monitoring electrocardiograms and electrolytes
  • Concomitant treatment with strong CYP3A4 inhibitors may increase sunitinib plasma concentrations and dose reduction of SUTENT should be considered
Hypertension
  • Hypertension may occur
  • Monitor blood pressure and treat as needed with standard antihypertensive therapy
  • In cases of severe hypertension, temporary suspension of SUTENT is recommended until hypertension is controlled
Hemorrhagic events
  • Hemorrhagic events, including tumor-related hemorrhage, and viscus perforation (both with fatal events) have occurred
  • These events may occur suddenly, and in the case of pulmonary tumors may present as severe and life-threatening hemoptysis or pulmonary hemorrhage
  • Perform serial complete blood counts (CBCs) and physical examinations
Tumor lysis syndrome (TLS)
  • Cases of TLS (some fatal) have been reported
  • Patients generally at risk of TLS are those with high tumor burden prior to treatment
  • Monitor these patients closely and treat as clinically indicated
Thrombotic
microangiopathy (TMA)
  • TMA, including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, sometimes leading to renal failure or a fatal outcome, has been reported in patients who received SUTENT as monotherapy and in combination with bevacizumab
  • Discontinue SUTENT in patients developing TMA
  • Reversal of the effects of TMA has been observed after treatment was discontinued
Proteinuria
  • Proteinuria and nephrotic syndrome have been reported
  • Some of these cases have resulted in renal failure and fatal outcomes
  • Monitor patients for the development or worsening of proteinuria. Perform baseline and periodic urinalysis during treatment, with follow-up measurement of 24-hour urine protein as clinically indicated
  • Interrupt treatment for 24-hour urine protein ≥3 grams
  • Discontinue for repeat episodes of protein ≥3 grams despite dose reductions or nephrotic syndrome
Dermatologic toxicities
  • Severe cutaneous reactions have been reported, including cases of necrotizing fasciitis, erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), some of which were fatal
  • If signs or symptoms of EM, SJS, or TEN are present, discontinue SUTENT treatment
  • If a diagnosis of SJS or TEN is suspected, treatment must not be restarted
Necrotizing fasciitis
  • Necrotizing fasciitis, including fatal cases, has been reported, including of the perineum and secondary to fistula formation
  • Discontinue SUTENT in patients who develop necrotizing fasciitis
Thyroid dysfunction
  • Thyroid dysfunction may occur
  • Monitor thyroid function in patients with signs and/or symptoms suggestive of thyroid dysfunction, including hypothyroidism, hyperthyroidism, and thyroiditis, and treat per standard medical practice
Hypoglycemia
  • Hypoglycemia may occur
  • SUTENT can result in symptomatic hypoglycemia, which may lead to a loss of consciousness or require hospitalization
  • Reductions in blood glucose levels may be worse in patients with diabetes
  • Check blood glucose levels regularly during and after discontinuation of treatment with SUTENT
  • Assess if antidiabetic drug dosage needs to be adjusted to minimize the risk of hypoglycemia
Osteonecrosis of the jaw (ONJ)
  • ONJ has been reported
  • Consider preventive dentistry prior to treatment with SUTENT
  • If possible, avoid invasive dental procedures, particularly in patients receiving intravenous bisphosphonate therapy
Impaired wound healing
  • Impaired wound healing has occurred with SUTENT
  • Temporary interruption of therapy with SUTENT is recommended in patients undergoing major surgical procedures
  • There is limited clinical experience regarding the timing of reinitiation of therapy following major surgical intervention. Therefore, the decision to resume SUTENT therapy following a major surgical intervention should be based on clinical judgment of recovery from surgery
Embryo fetal toxicity and reproductive potential
  • Females
    • SUTENT can cause fetal harm when administered to pregnant women
    • Advise pregnant women of the potential risk to a fetus
    • Advise females of reproductive potential to use effective contraception during treatment with SUTENT and for 4 weeks following the final dose
  • Males
    • Based on findings in animal reproduction studies, advise male patients with female partners of reproductive potential to use effective contraception during treatment with SUTENT and for 7 weeks after the last dose
  • Male and female infertility
    • Based on findings in animals, male and female fertility may be compromised by treatment with SUTENT
Lactation
  • Because of the potential for serious adverse reactions in breastfed infants from SUTENT, advise a lactating woman not to breastfeed during treatment with SUTENT and for at least 4 weeks after the last dose
Venous thromboembolic events
  • In patients treated with SUTENT (N=7527) for GIST, advanced RCC, pNET, and as adjuvant treatment for RCC, 3.5% of patients experienced a venous thromboembolic event; 2.2% were Grade 3-4
Reversible posterior leukoencephalopathy syndrome (RPLS)
  • There have been (<1%) reports, some fatal, of subjects presenting with seizures and radiological evidence of RPLS
  • Patients with seizures and signs/symptoms consistent with RPLS, such as hypertension, headache, decreased alertness, altered mental functioning, and visual loss, including cortical blindness, should be controlled with medical management including control of hypertension
  • Temporary suspension of SUTENT is recommended; following resolution, treatment may be resumed at the discretion of the treating healthcare provider
Pancreatic function
  • In a trial of patients receiving adjuvant treatment for RCC, 1 patient (<1%) on SUTENT and none on placebo experienced pancreatitis
CYP3A4 Inhibitors and Inducers
  • Dose adjustments are recommended when SUTENT is administered with CYP3A4 inhibitors or inducers
  • During treatment with SUTENT, patients should not drink grapefruit juice, eat grapefruit, or take St. John’s Wort
Most common ARs & most common grade 3/4 ARs (advanced pNET)
  • The most common ARs reported in ≥20% of patients with advanced pNET and more commonly with SUTENT than placebo (all grades, vs placebo) were diarrhea (59% vs 39%), stomatitis/oral syndromes (48% vs 18%), nausea (45% vs 29%), abdominal pain (39% vs 34%), vomiting (34% vs 31%), asthenia (34% vs 27%), fatigue (33% vs 27%), hair color changes (29% vs 1%), hypertension (27% vs 5%), hand-foot syndrome (23% vs 2%), bleeding events (22% vs 10%), epistaxis (21% vs 5%), and dysgeusia (21% vs 5%)
  • The most common grade 3/4 ARs reported in ≥5% of patients with advanced pNET receiving SUTENT (vs placebo) were hypertension (10% vs 1%), hand-foot syndrome (6% vs 0%), stomatitis/oral syndromes (6% vs 0%), abdominal pain (5% vs 10%), fatigue (5% vs 9%), asthenia (5% vs 4%), and diarrhea (5% vs 2%)
Most common grade
3/4 lab abnormalities (advanced pNET)
  • The most common grade 3/4 lab abnormalities (occurring in ≥5% of patients with advanced pNET receiving SUTENT vs placebo) included decreased neutrophils (16% vs 0%), increased glucose (12% vs 18%), increased alkaline phosphatase (10% vs 11%), decreased phosphorus (7% vs 5%), decreased lymphocytes (7% vs 4%), increased creatinine (5% vs 5%), increased lipase (5% vs 4%), increased AST (5% vs 3%), and decreased platelets (5% vs 0%)