le to reliably estimate their frequency or establish a causal relationship to drug exposure.
Cases of serious infection (with or without neutropenia), in some cases with fatal outcome, have been reported.
Cases of myopathy and/or rhabdomyolysis with or without acute renal failure, in some cases with fatal outcome, have been reported. Patients with signs or symptoms of muscle toxicity should be managed as per standard medical practice.
Thrombotic microangiopathy has been reported in patients on SUTENT. Suspension of SUTENT is recommended; following resolution, treatment may be resumed at the discretion of the treating physician.
Cases of fatal hemorrhage associated with thrombocytopenia have been reported.
Pulmonary embolism, in some cases with fatal outcome, has been reported.
Cases of renal impairment and/or failure, in some cases with fatal outcome, have been reported.
Cases of proteinuria and rare cases of nephrotic syndrome have been reported. Baseline urinalysis is recommended, and patients should be monitored for the development or worsening of proteinuria. The safety of continued SUTENT treatment in patients with moderate to severe proteinuria has not been systematically eva luated. Discontinue SUTENT in patients with nephrotic syndrome.
Hypersensitivity reactions, including angioedema, have been reported.
Cases of fistula formation, sometimes associated with tumor necrosis and/or regression, in some cases with fatal outcome, have been reported.
Cases of arterial thromboembolic events, sometimes fatal, have been reported in patients treated with SUTENT. The most frequent events included cerebrovascular accident, transient ischemic attack and cerebral infarction.
7DRUG INTERACTIONS
7.1CYP3A4 Inhibitors
Strong CYP3A4 inhibitors such as ketoconazole may increase sunitinib plasma concentrations. Selection of an alternate concomitant medication with no or minimal enzyme inhibition potential is recommended. Concurrent administration of SUTENT with the strong CYP3A4 inhibitor, ketoconazole, resulted in 49% and 51% increases in the combined (sunitinib + primary active metabolite) Cmax and AUC0–∞ values, respectively, after a single dose of SUTENT in healthy volunteers. Co-administration of SUTENT with strong inhibitors of the CYP3A4 family (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) may increase sunitinib concentrations. Grapefruit may also increase plasma concentrations of sunitinib. A dose reduction for SUTENT should be considered when it must be co-administered with strong CYP3A4 inhibitors [see Dosage and Administration (2.2)].
7.2CYP3A4 Inducers
CYP3A4 inducers such as rifampin may decrease sunitinib plasma concentrations. Selection of an alternate concomitant medication with no or minimal enzyme induction potential is recommended. Concurrent administration of SUTENT with the strong CYP3A4 inducer, rifampin, resulted in a 23% and 46% reduction in the combined (sunitinib + primary active metabolite) Cmax and AUC0–∞ values, respectively, after a single dose of SUTENT in healthy volunteers. Co-administration of SUTENT with inducers of the CYP3A4 family (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, St. John's Wort) may decrease sunitinib concentrations. St. John' |
