Uses of Sunitix 37.5: - Kidney cancer - Gastrointestinal stromal tumour Leukemia, Renal cell carcinoma, Gastrointestinal stromal tumor, Meningioma Hypersensitivity, Renal impairment

Targeted Cancer Therapy

Sunitinib inhibits cellular signaling by targeting multiple receptor tyrosine kinases (RTKs).These include all receptors for platelet-derived growth factor (PDGF-Rs) and vascular endothelial growth factor receptors (VEGFRs), which play a role in both tumor angiogenesis and tumor cell proliferation. The simultaneous inhibition of these targets therefore reduces tumor vascularization and triggers cancer cell apoptosis and thus results in tumor shrinkage.Sunitinib also inhibits CD117 (c-KIT), the receptor tyrosine kinase that (when improperly activated by mutation) drives the majority of gastrointestinal stromal cell tumors. It has been recommended as a second-line therapy for patients whose tumors develop mutations in c-KIT that make them resistant to imatinib, or who the cannot tolerate the drug.In addition, sunitinib binds other receptors. These include: RET, CD114, CD135. The fact that sunitinib targets many different receptors, leads to many of its side effects such as the classic hand-foot syndrome, stomatitis, and other dermatologic toxicities.

How to use Sunitinib: Take this medicine in the dose and duration as advised by your doctor. Do not chew, crush or break it. Sunitinib may be taken with or without food, but it is better to take it at a fixed time. Administration: May be taken with or without food. Adult Dose: Hepatic Impairment Mild to moderate impairment: Dose adjustment not necessary for initial dose; monitor subsequent doses Severe impairment: Not studied Child Dose: Safety and efficacy not established Renal Dose: Renal Impairment No dose adjustment necessary

Increased plasma conc w/ strong CYP3A4 inhibitors (eg ketoconazole, ritonavir, itraconazole, erythromycin, clarithromycin, grapefruit juice). Decreased plasma conc w/ strong CYP3A4 inducers [eg rifampin, dexamethasone, phenytoin, carbamazepine, phenobarb, St. John's wort (Hypericum perforatum)]. Anticoagulants eg warfarin, acenocoumarol (periodically monitor platelets, prothrombin time/INR & physical exam).

Hypersensitivity, Renal impairment

Common - Nausea - Vomiting - Weakness - Rash - Abdominal pain - Indigestion - Discoloration of skin - Fatigue - Fever - Dry skin - High blood pressure - Diarrhea - Constipation - Painful blisters on hands and feet - Stomatitis (Inflammation of the mouth) - Hair discoloration - Pain in extremity - Back pain - Headache - Joint pain - Weight loss - Cough - Taste change - Breathlessness >10% Dyspepsia (MRCC 46%),Altered taste (MRCC 43%; GIST 21%),Fatigue (GIST 42%; MRCC 74%),Diarrhea (GIST 40%; MRCC 55%),Rash (MRCC 38%; GIST 14%),Vomiting (MRCC 37%; GIST 24%),Constipation (MRCC 34%; GIST 20%),Skin discoloration (MRCC 33%; GIST 30%),Abdominal pain (GIST 33%; MRCC 20%),Nausea (GIST 31%; MRCC 54%),Anorexia (MRCC 31%; GIST 33%),Mucositis/stomatitis (GIST 29%; MRCC 53%),Dyspnea (MRCC 28%; GIST 10%),HTN (MRCC 28%; GIST 15%),Arthralgia (MRCC 28%; GIST 12%),Bleeding (MRCC 26%; GIST 18%),Headache (MRCC 25%; GIST 13%),Asthenia (GIST 22%),Lymphopenia (MRCC 21%),Fever (GIST 18%; MRCC 15%),Limb pain (MRCC 18%),Back pain (MRCC 17%; GIST 11%),Myalgia (MRCC 17%; GIST 14%),Cough (MRCC 17%; GIST 8%),Dry skin (17%),Hair color changes (17%),Neutropenia (MRCC 13%; GIST 11%),Alopecia (MRCC 12%),Hand-foot syndrome (MRCC 12%; GIST 14%),Dehydration (MRCC 11%) 1-10% Venous thrombotic events,Hemorrhoids,Pancreatitis,Flu-like syndrome <1% Hepatotoxicity,Acute renal failure,Adrenal dysfunction

Pregnancy Category D. There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Precaution: CHF, HTN, history of QT interval prolongation, patients taking antiarrhythmics or w/ preexisting cardiac disease, bradycardia or electrolyte disturbances, hemorrhagic events, hypothyroidism. Perform CBC & physical exam. May affect ability to drive or operate machinery. Pregnancy.

Treatment of overdose with Sunitinib should consist of general supportive measures. There is no specific antidote for overdosage with Sunitinib. 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 Sunitinib, or without adverse reactions. A case of intentional overdose involving the ingestion of 1,500 mg of Sunitinib in an attempted suicide was reported without adverse reaction. In non-clinical 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.

Targeted Cancer Therapy

Multikinase inhibitor (including VEGF & PDGF receptor tyrosine kinases) some of which are implicated in tumor growth, angiogenesis, and metastasis.

Pregnancy Category D. There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.