Sunitinib Malate (2 brand names, 1 dosage form, 1 route)
Available dosage forms: CAPSULE.
Routes of administration: ORAL.
Brand Names
- SUNITINIB MALATE
- SUTENT
Boxed Warning
Hepatotoxicity may be severe, and in some cases, fatal. Monitor hepatic function and interrupt, dose reduce, or discontinue SUTENT as recommended [see Warnings and Precautions (5.1)].
Contraindications
None.
Adverse Reactions
The following clinically significant adverse reactions are described elsewhere in the labeling. •Hepatotoxicity [see Warnings and Precautions (5.1)] •Cardiovascular Events [see Warnings and Precautions (5.2)] •QT Interval Prolongation and Torsade de Pointes [see Warnings and Precautions (5.3)] •Hypertension [see Warnings and Precautions (5.4)] •Hemorrhagic Events [see Warnings and Precautions (5.5)] •Tumor Lysis Syndrome [see Warnings and Precautions (5.6)] •Thrombotic Microangiopathy [see Warnings and Precautions (5.7)] •Proteinuria [see Warnings and Precautions (5.8)] •Dermatologic Toxicities [see Warnings and Precautions (5.9)] •Reversible Posterior Leukoencephalopathy Syndrome [see Warnings and Precautions (5.10)] •Thyroid Dysfunction [see Warnings and Precautions (5.11)] •Hypoglycemia [see Warnings and Precautions (5.12)] •Osteonecrosis of the Jaw [see Warnings and Precautions (5.13)] •Impaired Wound Healing [see Warnings and Precautions (5.14)]
Mechanism of Action
Sunitinib is a small molecule that inhibits multiple receptor tyrosine kinases (RTKs), some of which are implicated in tumor growth, pathologic angiogenesis, and metastatic progression of cancer. Sunitinib was evaluated for its inhibitory activity against a variety of kinases (>80 kinases) and was identified as an inhibitor of platelet-derived growth factor receptors (PDGFRα and PDGFRβ), vascular endothelial growth factor receptors (VEGFR1, VEGFR2, and VEGFR3), stem cell factor receptor (KIT), Fms-like tyrosine kinase-3 (FLT3), colony stimulating factor receptor Type 1 (CSF-1R), and the glial cell-line derived neurotrophic factor receptor (RET). Sunitinib inhibition of the activity of these RTKs has been demonstrated in biochemical and cellular assays, and inhibition of function has been demonstrated in cell proliferation assays. The primary metabolite exhibits similar potency compared to sunitinib in biochemical and cellular assays. Sunitinib inhibited the phosphorylation of multiple RTKs (PDGFRβ, VEGFR2, KIT) in tumor xenografts expressing RTK targets in vivo and demonstrated inhibition of tumor growth or tumor regression and/or inhibited metastases in some experimental models of cancer. Sunitinib demonstrated the ability to inhibit growth of tumor cells expressing dysregulated target RTKs (PDGFR, RET, or KIT) in vitro and to inhibit PDGFRβ- and VEGFR2-dependent tumor angiogenesis in vivo.
Overdosage
Treatment of overdose with SUTENT should consist of general supportive measures. There is no specific antidote for overdosage with SUTENT. If indicated, elimination of unabsorbed drug should be achieved by emesis or gastric lavage. Cases of accidental overdose have been reported; these cases were associated with adverse reactions consistent with the known safety profile of SUTENT, or without adverse reactions. In nonclinical studies, mortality was observed following as few as 5 daily doses of 500 mg/kg (3000 mg/m2) in rats. At this dose, signs of toxicity included impaired muscle coordination, head shakes, hypoactivity, ocular discharge, piloerection, and gastrointestinal distress. Mortality and similar signs of toxicity were observed at lower doses when administered for longer durations.