Resinib

Sunitinib is a small molecule that blocks several receptor tyrosine kinases (RTKs). Some of these receptors play a part in tumour growth, the abnormal formation of new blood vessels, and the spread of cancer to other parts of the body. When sunitinib was tested against a large number of kinases (more than 80), it was found to inhibit a number of them. These include the platelet-derived growth factor receptors (PDGFRα and PDGFRβ), the vascular endothelial growth factor receptors (VEGFR1, VEGFR2 and VEGFR3), the stem cell factor receptor (KIT), Fms-like tyrosine kinase-3 (FLT3), the colony stimulating factor receptor type 1 (CSF-1R), and the glial cell-line derived neurotrophic factor receptor (RET).

Sunitinib has been shown to block the activity of these RTKs in both laboratory (biochemical) tests and tests on cells. Its effect on function has also been seen in cell proliferation tests, where it slows cell growth. The main metabolite of sunitinib is about as potent as sunitinib itself in both kinds of laboratory tests.

Sunitinib can cause harm to a developing fetus when given to a pregnant woman. There is currently no data available on pregnant women to determine this drug-related risk. If a patient uses it during pregnancy, or becomes pregnant while on this medicine, she should be informed of the potential danger to the unborn baby. It is not known whether Sunitinib or its breakdown products pass into human breast milk. Because Sutinib may cause serious adverse effects in a breastfed infant, a breastfeeding mother should be advised not to breastfeed while being treated with Sutinib and for at least 4 weeks after her final dose.

Pediatric use: The pharmacokinetics of Sunitinib have not been evaluated in pediatric patients.

Renal insufficiency: After a single dose, systemic exposure to Sunitinib was similar in patients with severe renal impairment (CLcr <30 mL/min) and in patients with normal renal function (CLcr >80 mL/min). Sunitinib was not eliminated through hemodialysis. Even so, systemic exposure was 47% lower in patients with ESRD on hemodialysis than in patients with normal renal function.

Hepatic insufficiency: Again after a single dose, systemic exposures were similar in patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment and in patients with normal hepatic function.

Cardiac electrophysiology: Sunitinib can cause QT interval prolongation, and the effect depends on the dose. This may raise the risk of ventricular arrhythmias, including Torsade de Pointes.

If someone takes too much Sutinib, treatment is general supportive care. There is no specific antidote for Sutinib overdose. Where it is indicated, drug that has not yet been absorbed should be removed by inducing vomiting or by gastric lavage.

Cases of accidental overdose have been reported. Some of these were linked to adverse reactions that matched the known safety profile of Sutinib, and some had no adverse reactions at all. One person took 1500 mg of Sutinib in an attempted suicide and had no adverse reaction.

In nonclinical studies, rats died after as few as 5 daily doses of 500 mg/kg (3000 mg/m2). At this dose the signs of toxicity were impaired muscle coordination, head shakes, hypoactivity, ocular discharge, piloerection and gastrointestinal distress. Deaths and similar signs of toxicity also occurred at lower doses when the doses were given over longer periods.

Store Sunitinib at 25°C in a cool, dry place, away from light. Keep it out of the reach of children.