Sunitinib

Oral
Metastatic renal cell carcinoma, Unresectable, metastatic malignant gastrointestinal stromal tumours

Oral
Malignant tumour of endocrine pancreas, advanced

Patients taking strong CYP3A4 inhibitors:
Unresectable, metastatic malignant gastrointestinal stromal tumours; Metastatic renal cell carcinoma: Reduce dose to a Min of 37.5 mg daily.
Advanced pancreatic neuroendocrine tumour Reduce dose to a Min of 25 mg daily.

Patients taking CYP3A4 inducers:
Unresectable, metastatic malignant gastrointestinal stromal tumours; Metastatic renal cell carcinoma: May increase in increments of 12.5 mg to a max of 87.5 mg daily.
Advanced pancreatic neuroendocrine tumour: May increase in increments of 12.5 mg to a max of 62.5 mg daily.

Severe: (Child-Pugh class C): Contraindicated.

May be taken with or without food.

Hypersensitivity to sunitinib. Severe hepatic (Child-Pugh class C) impairment. Lactation.

Patients w/ history of CV events (e.g. heart failure, cardiomyopathy, MI, myocardial ischaemia); history of QT interval prolongation; bradycardia, electrolyte imbalance, thyroid dysfunction, underlying or poorly controlled HTN. Patient undergoing major surgery. Hepatic and renal impairment. Pregnancy. Concomitant use w/ potent CYP3A4 enzyme inhibitors and inducers should be avoided, if not possible, consider dosage adjustment.

Significant: QT prolongation, torsade de pointes, HTN, thyroid dysfunction (e.g. hypo- and hyperthyroidism, thyroiditis), hypoglycaemia, osteonecrosis of the jaw (ONJ), hepatobiliary disorder (e.g. acalculous cholecystitis, emphysematous cholecystitis), adrenal toxicity, hand-foot skin reaction, impaired wound healing or bleeding.
Nervous: Fatigue, asthenia, dizziness, paraesthesia, headache.
CV: Decreased LVEF, peripheral oedema.
GI: GI disturbance, nausea, vomiting, abdominal pain, dyspepsia, diarrhoea, anorexia, taste disturbance, stomatitis, oral mucositis, mouth irritation, pain, or dryness.
Resp: Dyspnoea, cough.
Hepatic: Increased ALT, AST, alkaline phosphatase, and bilirubin.
Genitourinary: Chromaturia, increased creatinine.
Endocrine: Increased amylase and lipase.
Haematologic: Neutropenia, thrombocytopenia, lymphopenia, anaemia.
Musculoskeletal: Arthralgia, myalgia, back and extremity pain.
Dermatologic: Yellow skin discolouration, skin and hair depigmentation, alopecia, dryness, rash, exfoliative dermatitis.
Immunologic: Myelosuppresion.
Others: Electrolyte disturbance (e.g. hypokalemia, hypernatremia), fever.
Potentially Fatal: Heart failure, cardiomyopathy, MI, myocardial ischaemia, tumour lysis syndrome (TLS), thrombotic microangiopathy (i.e. thrombocytopenic purpura, haemolytic uremic syndrome), proteinuria, renal failure, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, haemorrhagic events (e.g. epistaxis, hemoptysis/pulmonary haemorrhage, tumour haemorrhage), infection (e.g. resp infection, UTI, sepsis). Rarely, hepatic failure, GI perforation, pulmonary embolism, pancreatitis, nephrotic syndrome, necrotizing fasciitis, reversible posterior leukoencephalopathy syndrome (RPLS).

PO: D

Monitor LVEF, BP, ECG, adrenal function, CBC w/ differential and platelet, LFTs (prior to and during each cycle of treatment), blood glucose levels, urinalysis, serum chemistries (e.g. Mg, phosphate, K); signs/symptoms of hypoglycaemia, hypothyroidism, hyperthyroidism, or thyroiditis.

Symptoms: Impaired muscle coordination, head shakes, hypoactivity, piloerection, ocular discharge, GI distress. Management: General supportive treatment. Emesis or gastric lavage may be considered to eliminate unabsorbed drug.

Increased plasma concentration w/ potent CYP3A4 enzyme inhibitors (e.g. ketoconazole, erythromycin, ritonavir). Decreased plasma concentration w/ potent CYP3A4 enzyme inducers (e.g. rifampicin, dexamethasone, phenytoin, phenobarbital, carbamazepine).

Increased plasma concentration w/ grapefruit juice. Decrease plasma concentration w/ St John’s wort.

Description: Sunitinib inhibits signal transduction pathways involving multiple receptor tyrosine kinases which are implicated in tumour growth, pathologic angiogenesis and metastatic progression of cancer, including platelet-derived growth factor receptors (i.e. PDGFR-α, PDGFR-β), vascular endothelial growth factor receptors (i.e. VEGFR-1, VEGFR-2, VEGFR-3), stem cell factor receptor (i.e. c-Kit), fms-like tyrosine kinase-3 (Flt-3), colony-stimulating factor receptor type 1 (CSF-1R), and the glial cell-line-derived neurotrophic factor receptor (RET).
Pharmacokinetics:
Absorption: Time to peak plasma concentration: 6-12 hr.
Distribution: Volume of distribution: 2,230 L. Plasma protein binding: Approx 95% (sunitinib); approx 90% (N-desmethyl metabolite).
Metabolism: Metabolised mainly by CYP3A4 enzyme to the primary active N-desmethyl metabolite.
Excretion: Mainly via faeces (approx 61%); urine (approx 16%, as unchanged drug and as N-desmethyl metabolite). Terminal elimination half-life: 40-60 hr (sunitinib); 80-110 hr (N-desmethyl metabolite).

Source: National Center for Biotechnology Information. PubChem Database. Sunitinib, CID=5329102, https://pubchem.ncbi.nlm.nih.gov/compound/Sunitinib (accessed on Jan. 23, 2020)

Store at 25°C. Any unused portions should be disposed of in accordance w/ local requirements. Avoid contact w/ skin or mucous membranes by wearing gloves and protective equipment.

Targeted Cancer Therapy

L01EX01 - sunitinib ; Belongs to the class of other protein kinase inhibitors. Used in the treatment of cancer.

Anon. Sunitinib. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 04/03/2016.

Buckingham R (ed). Sunitinib Malate. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/03/2016.

Joint Formulary Committee. Sunitinib. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 03/05/2017.

McEvoy GK, Snow EK, Miller J et al (eds). Sunitinib Malate. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 04/03/2016.

Sutent Capsule (Pfizer Laboratories Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 04/03/2016.