Sunitinib; Uses, Dosage, Side Effects, Interactions, Pregnancy Sunitinib is an indolinone derivative and tyrosine kinase inhibitor with potential antineoplastic activity. Sunitinib blocks the tyrosine kinase activities of vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor b (PDGFRb), and c-kit, thereby inhibiting angiogenesis and cell proliferation. This agent also inhibits the phosphorylation of Fms-related tyrosine kinase 3 (FLT3), another receptor tyrosine kinase expressed by some leukemic cells. Sunitinib is a selective tyrosine kinase receptor inhibitor that is used in the therapy of gastrointestinal stromal tumors and advanced renal cell carcinoma. Sunitinib therapy is associated with transient elevations in serum aminotransferase and bilirubin levels and rare instances of clinically apparent acute liver injury. Sunitinib inhibits cellular signaling by targeting multiple RTKs. These include all platelet-derived growth factor receptors (PDGF-R) and vascular endothelial growth factor receptors (VEGF-R). Sunitinib also inhibits KIT (CD117), the RTK that drives the majority of GISTs. In addition, sunitinib inhibits other RTKs including RET, CSF-1R, and flt3. Mechanism of Action of Sunitinib Sunitinib is a small molecule that inhibits multiple 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 (PDGFRa and PDGFRb), 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. or Sunitinib malate, an inhibitor of multiple receptor tyrosine kinases, is an antineoplastic agent. Receptor tyrosine kinases (RTKs) are involved in the initiation of various cascades of intracellular signaling events that lead to cell proliferation and/or influence processes critical to cell survival and tumor progression (eg, angiogenesis, metastasis, inhibition of apoptosis), based on the respective kinase. Although the exact mechanism of antineoplastic activity of sunitinib has not been fully elucidated, data from biochemical and cellular assays indicate that sunitinib may inhibit signal transduction pathways involving multiple receptors (ie, cell surface) tyrosine kinases, including platelet-derived growth factor receptors (ie, PDGFR-alpha, PDGFR-beta), vascular endothelial growth factor receptors (ie, VEGFR-1, VEGFR-2, VEGFR-3), stem cell factor receptor (ie, c-Kit), forms-like tyrosine kinase 3 (Flt-3), colony stimulating factor receptor type 1 (CSF-1R), and the glial cell line-derived neurotrophic factor receptor (RET). Sunitinib-induced inhibition of signal transduction pathways involving PDGFR-beta, VEGFR-2, and c-Kit has been confirmed in tumor xenografts expressing receptor tyrosine kinase targets in vivo. Sunitinib has been shown to inhibit the growth of tumor cells expressing dysregulated target receptor tyrosine kinases (ie, PDGFR, RET, c-Kit) in vitro; the drug also has been shown to inhibit PDGFR-beta- and VEGFR-2-dependent tumor angiogenesis in vivo. You Might Also Read Terbinafine, Uses, Dosage, Side Effects, InteractionIndications of Sunitinib Renal Cell Carcinoma Gastrointestinal Stromal Tumor Pancreatic Cancer Advanced Renal Cell Carcinoma Soft Tissue Sarcoma Thyroid Cancers Gastrointestinal stromal tumor Sutent is indicated for the treatment of unresectable and/or metastatic malignant gastrointestinal stromal tumor (GIST) in adults after a failure of imatinib treatment due to resistance or intolerance. Metastatic renal cell carcinoma Sutent is indicated for the treatment of advanced/metastatic renal cell carcinoma (MRCC) in adults. Pancreatic neuroendocrine tumors Sutent is indicated for the treatment of unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumors with disease progression in adults. Experience with Sutent as first-line treatment is limited. Metastatic Pancreatic Neuroendocrine Tumors Refractory Gastrointestinal stromal tumor Unresectable, locally advanced Pancreatic Neuroendocrine Tumors For the treatment of advanced renal cell carcinoma as well as the treatment of gastrointestinal stromal tumor after disease progression on or intolerance to imatinib mesylate. Contra Indication of Sunitinib Diabetes High cholesterol Low amount of magnesium in the blood Low amount of phosphate in the blood Low amount of calcium in the blood Low amount of sodium in the blood HThe high amount of potassium in the blood Low amount of potassium in the blood Anemia Decreased Blood Platelets Decreased Neutrophils a Type of White Blood Cell High blood pressure Very Rapid Heartbeat – Torsades de Pointes prolonged QT interval on EKG Abnormal EKG with QT changes from Birth Hardening of the arteries due to plaque buildup Liver problems High Amount of Bilirubin in the Blood High Blood Sugar Abnormal liver function tests Pregnancy A mother who is producing milk and breastfeeding Relapse of Hepatitis B Infection Symptoms Pancreatitis past history of complete removal of the stomach You Might Also Read Dapsone 5% Tropical Gel - Uses, Dosage, Side EffectsDosages of Sunitinib Strengths: 12.5 mg; 25 mg; 37.5 mg; 50 mg Renal Cell Carcinoma 50 mg orally once daily on a schedule of 4 weeks on treatment followed by 2 weeks off Gastrointestinal Stromal Tumor 50 mg orally once daily on a schedule of 4 weeks on treatment followed by 2 weeks off Pancreatic Cancer 37.5 mg orally once daily Side Effects of Sunitinib The most common chest pain certainly hair loss a headache joint painPain dizziness nausea and vomiting Severe stomach ache epigastric pain, diarrhoea, anorexia, flatulence, a headache, dizziness, fainting, fast or pounding heartbeats. More common Fast or irregular heartbeat appetite loss changes in nails constipation fatigue fever Back pain dizziness a headache increased cough Acid or sour stomach decreased appetite Agitation chest congestion chest pain cold sweats confusion decreased sexual ability or desire stomach or abdominal cramps, gas, or pain trouble sleeping Less common bleeding gums blood in the urine or stools chest pain diarrhea Burning, crawling, itching, numbness, prickling, “pins and needles“, or tingling feelings difficulty in moving muscle stiffness redness of the face, neck, arms and occasionally, upper chest lack or loss of strength muscle spasm difficult or labored breathing dry mouth a headache irritability lack or loss of strength loose stools loss of interest or pleasure muscle stiffness night sweats passing gas stomach discomfort, upset, or pain swollen joints trouble concentrating increased blood pressure Drug Interactions of Sunitinib Sunitinib may interact with following drugs, supplements & may change the efficacy of drugs alpha blockers (e.g., alfuzosin, doxazosin, silodosin, tamsulosin) anticancer medications (e.g., cabazitaxel, docetaxel, doxorubicin, etoposide, ifosfamide, irinotecan, vincristine) “azole” antifungal medications (e.g., fluconazole, itraconazole, ketoconazole) beta-blockers (e.g., atenolol, propranolol, metoprolol) barbiturates (e.g., butalbital, pentobarbital, phenobarbital) benzodiazepines (e.g., chlordiazepoxide, clonazepam, diazepam, lorazepam) calcium channel blockers (e.g., nifedipine, diltiazem, verapamil, amlodipine, carbamazepine chloroquine corticosteroids (e.g., dexamethasone, prednisone, methylprednisolone) cyclosporine dantrolene “gliptin” diabetes medications (e.g., linagliptin, saxagliptin, sitagliptin) HIV protease inhibitors (e.g., atazanavir, indinavir, ritonavir, saquinavir) losartan macrolide antibiotics (e.g., azithromycin, clarithromycin, erythromycin) metronidazole mirtazapine montelukast norfloxacin ondansetron carbamazepine phenytoin progestins (e.g., dienogest, levonorgestrel, medroxyprogesterone, norethindrone) proton pump inhibitors (PPIs; e.g., esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole) selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, duloxetine, fluoxetine,paroxetine, sertraline) sildenafil “statin” anticholesterol medications (e.g., atorvastatin, lovastatin, simvastatin) tadalafil tetracycline theophylline tolterodine tramadol other selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, fluoxetine, sertraline) 5-HT3 antagonists (e.g., granisetron, ondansetron) tamsulosin tapentadol thiazide diuretics (e.g., hydrochlorothiazide, indapamide) tramadol tricyclic antidepressants (e.g., nortriptyline, amitriptyline, imipramine, other tyrosine kinase inhibitors (e.g., dasatinib, imatinib, nilotinib, sunitinib) tetracycline tocilizumab vandetanib vemurafenib trimethoprim warfarin You Might Also Read Type II Collagen - Uses, Dosage, Side Effects, InteractionsPregnancy & Lactation FDA Pregnancy Category D Pregnancy This medication should not be used during pregnancy. If you become pregnant while taking this medication, contact your doctor immediately. Lactation It is not known if sunitinib passes into breast milk. If you are a breastfeeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding. The safety and effectiveness of using this medication have not been established for children. References DrugBank http://www.drugbank.ca/drugs/DB01268 http://www.drugbank.ca/drugs/DB01268#targets http://www.drugbank.ca/drugs/DB01268#enzymes http://www.drugbank.ca/drugs/DB01268#transporters https://www.drugs.com/cdi/sunitinib.html https://www.drugs.com/sutent.html Human Metabolome Database (HMDB) http://www.hmdb.ca/metabolites/HMDB0015397 ClinicalTrials.gov https://clinicaltrials.gov/ DailyMed https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=SUNITINIB+MALATE https://www.webmd.com/drugs/2/drug-94971/sunitinib-oral/details/list-contraindications https://online.epocrates.com/u/1034321/Sutent/Contraindications+Cautions FDA Pharm Classes https://www.accessdata.fda.gov/spl/data/175e4912-3580-442a-bda0-e9cc4de181e2/175e4912-3580-442a-bda0-e9cc4de181e2.xml https://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/ucm162549.htm LiverTox https://livertox.nlm.nih.gov/Sunitinib.htm NCIT https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=NCI_Thesaurus&code=C71622 FDA/SPL Indexing Data https://www.fda.gov/ForIndustry/DataStandards/SubstanceRegistrationSystem-UniqueIngredientIdentifierUNII/ EU Community Register of Medicinal Products https://ec.europa.eu/health/documents/community-register/html/h347.htm HSDB https://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@rn+@rel+557795-19-4 WHO ATC https://www.whocc.no/atc/ https://www.whocc.no/atc_ddd_index/ European Chemicals Agency (ECHA) https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/171284 https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/210743 European Chemicals Agency – ECHA https://www.echa.europa.eu/web/guest/information-on-chemicals/cl-inventory-database/-/discli/details/171284 https://www.echa.europa.eu/web/guest/information-on-chemicals/cl-inventory-database/-/discli/details/210743 FDA Medication Guides https://www.fda.gov/downloads/Drugs/DrugSafety/UCM219111.pdf FDA Orange Book https://www.fda.gov/Drugs/InformationOnDrugs/ucm129662.htm NCI Cancer Drugs https://www.cancer.gov/about-cancer/treatment/drugs/sunitinibmalate PubMed Health http://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0012268/ Springer Nature Read more … Wikipedia https://en.wikipedia.org/wiki/Sunitinib Show More