Comparative Pharmacology
Head-to-head clinical analysis: EXFORGE HCT versus RAUVAL.
Peer-Reviewed Evidence
Head-to-head clinical analysis: EXFORGE HCT versus RAUVAL.
EXFORGE HCT vs RAUVAL
Comparing the clinical profiles, pharmacokinetic behaviors, and safety indices of these two therapeutic agents.
EXFORGE HCT is a combination of amlodipine (a dihydropyridine calcium channel blocker), valsartan (an angiotensin II receptor blocker), and hydrochlorothiazide (a thiazide diuretic). Amlodipine inhibits calcium ion influx across cardiac and vascular smooth muscle cells, leading to vasodilation. Valsartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II. Hydrochlorothiazide increases excretion of sodium and water by inhibiting the Na+/Cl- symporter in the distal convoluted tubule.
Rauval (rauwolfia serpentina alkaloids) depletes catecholamines and serotonin from peripheral sympathetic nerve endings and the brain by binding to and inhibiting vesicular monoamine transporters (VMAT), thus reducing sympathetic outflow. This leads to vasodilation, decreased peripheral vascular resistance, and reduced blood pressure.
One tablet orally once daily. Initial dose based on previous antihypertensive therapy; maximum dose is one tablet of 10 mg amlodipine/320 mg valsartan/25 mg hydrochlorothiazide per day.
1.5 mg orally once daily, increased to 3 mg per day if needed. Maximum dose 6 mg per day.
None Documented
None Documented
Valsartan: 6 hours (terminal). Amlodipine: 30-50 hours (terminal), permits once-daily dosing. Hydrochlorothiazide: 6-15 hours (terminal).
Terminal elimination half-life is 7-10 hours in normal renal function; prolonged to 14-20 hours in renal impairment, requiring dose adjustment.
Valsartan: 13% excreted unchanged in urine, 83% in feces via biliary secretion. Amlodipine: 10% excreted unchanged in urine, 60% as metabolites in urine, 20-25% in feces. Hydrochlorothiazide: ≥95% excreted unchanged in urine.
Renal excretion of unchanged drug accounts for 60-70% of elimination; biliary/fecal excretion accounts for 20-30%.
Category C
Category C
Antihypertensive
Antihypertensive