Table 2.

Practice points on clinical pharmacology of selected targeted agents.

	Pazopanib	Sunitinib	Sorafenib	Axitinib	Everolimus	Temsirolimus
Dose	800 mgs/day 1 h before 2 h after food	50 mgs/day 4week on 2 week off or 2week on 1 week off	400 mgs BD	5 mgs BD without food ↑ to 7 mgs BD then to 10 mgs BD every 2 weeks	10 mgs OD	25 mgs/wkly IV
Dose modification protocol	400 mgs/day then in 200 mgs steps	12.5 mgs decrements	400 mgs OD then to alternate day	3 mgs or 2 mgsBD	2.5 mgs OD then ↑ to 5 mgs OD	Restart at 5 mgs/wk increase to 15 mgs/wk
Interactions
CYP3A4 inhibitors	↓dose to 400 mgs	37.5mgs	↓ dose	5 mgs BD	↓ dose	12.5 mgs/wk
CYP3A4 inducers		87.5 mgs				50 mgs /wk
Renal dysfunction	No dose reduction till Cr clearance <30 ml/min	None even in severe impairment	None required	None required	None	Stop therapy
Hepatic dysfunction
Child A	No change	No change	No change	No change	↓ dose	↓dose
Child B	200 mgs/day	No change	No change	50% ↓
Cardiac dysfunction	Stop if LVEF ↓ >15% cQT interval >50 msec	Stop if LVEFR >15% cQT interval >50 msec	Cardiac ischemia/ CCF	None required	None required	None required
Monitoring therapy	BP-weekly LFT Bi weekly LVEF TFT Urine protein	BP-weekly LFT each cycle LVEF TFT	BP-weekly LFT Biweekly LVEF TFT Urine protein	BP-weekly LFT 2weekly TFT Urine protein	CBC weekly RFT Lipid Glucose Bi weekly	CBC weekly RFT, LFT Glucose, lipid profile levels Bi weekly CXR
Comments	PPI ↓absorption by 40%	Caution in bleeding or perforation	Caution in bleeding or perforation risk risk hypoglycemia	Avoid in GI bleed or perforation risk	Watch for pnemonitis and infections	Watch for interstitial lung disease, bowel perforations, and infections