Comparative Pharmacology
Head-to-head clinical analysis: AVALIDE versus OLMESARTAN MEDOXOMIL AMLODIPINE AND HYDROCHLOROTHIAZIDE.
Peer-Reviewed Evidence
Head-to-head clinical analysis: AVALIDE versus OLMESARTAN MEDOXOMIL AMLODIPINE AND HYDROCHLOROTHIAZIDE.
AVALIDE vs OLMESARTAN MEDOXOMIL, AMLODIPINE AND HYDROCHLOROTHIAZIDE
Comparing the clinical profiles, pharmacokinetic behaviors, and safety indices of these two therapeutic agents.
Avalide is a combination of an angiotensin II receptor blocker (irbesartan) and a thiazide diuretic (hydrochlorothiazide). Irbesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively antagonizing the AT1 receptor. Hydrochlorothiazide increases sodium and water excretion by inhibiting the Na+/Cl- symporter in the distal convoluted tubule.
Olmesartan medoxomil is an angiotensin II receptor blocker (ARB) that selectively blocks AT1 receptors, inhibiting vasoconstriction and aldosterone secretion. Amlodipine is a dihydropyridine calcium channel blocker that inhibits calcium influx across vascular smooth muscle and cardiac muscle, causing vasodilation. Hydrochlorothiazide is a thiazide diuretic that inhibits sodium reabsorption in the distal convoluted tubule, increasing excretion of sodium and water.
AVALIDE (irbesartan/hydrochlorothiazide) is available as tablets containing 150/12.5 mg, 300/12.5 mg, or 300/25 mg. The typical starting dose is 150/12.5 mg once daily, titrated to 300/12.5 mg once daily as needed. Maximum dose is 300/25 mg once daily.
Oral, one tablet once daily. Initial dose: olmesartan 20 mg/amlodipine 5 mg/hydrochlorothiazide 12.5 mg. Titrate based on response, max dose: olmesartan 40 mg/amlodipine 10 mg/hydrochlorothiazide 25 mg daily.
None Documented
None Documented
Irbesartan: 11-15 h (terminal), HCTZ: 6-15 h (terminal). Clinical context: Steady state reached in 3-5 days; allows once-daily dosing.
Olmesartan: terminal half-life 10-15 hours; supports once-daily dosing. Amlodipine: terminal half-life 30-50 hours; allows once-daily dosing with steady state reached after 7-8 days. Hydrochlorothiazide: terminal half-life 6-15 hours; prolonged in renal impairment.
Renal: HCTZ ~70% unchanged; Irbesartan ~20% unchanged, remainder as metabolites via biliary (60%) and renal (20%). Combined: Renal ~50%, biliary/fecal ~50%.
Olmesartan: ~40% excreted in urine (10-20% unchanged, rest as metabolites), ~60% in feces via bile. Amlodipine: ~60% excreted in urine (10% unchanged), 20-25% in feces. Hydrochlorothiazide: >95% excreted unchanged in urine.
Category C
Category D/X
ARB and Thiazide Diuretic Combination
ARB