Angiotensin II-Receptor Antagonists: An Overview

Raquel Dina and Mahtab Jafari


Am J Health Syst Pharm. 2000;57(13) 

In This Article


Valsartan (Diovan, Novartis) was the second nonpeptide AT-II type 1- receptor antagonist available for the treatment of hypertension. Valsartan is rapidly absorbed from the gastrointestinal tract after oral administration and can be administered without regard to food intake.[25] The peak effect of valsartan is evident in two to four hours; the bioavailability is 25%. Valsartan has a half-life of six to nine hours and demonstrates antihypertensive effects for approximately 24 hours. Less than 10% of an orally administered dose of valsartan undergoes biotransformation in the liver; the enzymes responsible for its metabolism are unknown, and no active metabolites have been identified. [26] Elimination occurs primarily in the bile (86%) and to a lesser extent via the kidneys (13%), largely as unchanged drug.[27,28]

Dosages ranging from 80 to 320 mg once daily are effective for controlling blood pressure and are recommended in patients who are not volume depleted. Greater reductions in blood pressure are apparent with incremental increases in the dosage up to 320 mg/day; hence, it is recommended that valsartan be started at 80 mg/day and the dosage adjusted upward until the desired response is reached.[6] No reduction in the starting dosage is required in patients with mild to moderate hepatic or renal insufficiency or in the elderly. The effectiveness of valsartan 80-320 mg/ day in reducing blood pressure was established by a randomized, doubleblind, placebo-controlled trial.[6] In a comparative double-blind trial, valsartan 80 mg/day was as effective as enalapril maleate 20 mg/day and amlodipine 5 mg/day (as the besylate) in lowering the blood pressure of patients with mild to moderate hypertension. [29,30] In addition, valsartan 80 and 160 mg/day was as effective as enalapril 20 mg/day and lisinopril 10 or 20 mg/day in lowering blood pressure in patients with mild to moderate essential hypertension.[31,81] As is the case with other AT-II-receptor antagonists, hydrochlorothiazide acts additively to lower blood pressure in patients who do not achieve adequate blood pressure reduction with valsartan alone.[32,33]

The safety of valsartan has been assessed in various clinical trials.[34,35] Valsartan was well tolerated at dosages of 80-160 mg/day. At higher dosages (320 mg/day), dizziness became more prevalent (9.3% of patients, versus 3.4% for 80-160 mg/day). Headache, upper-respiratory-tract infection, diarrhea, and fatigue occurred most commonly (>1%), but at rates comparable to those in placebo recipients.[34] In one study, dry cough was considerably less common with valsartan (21.4%) than with the ACE inhibitors lisinopril (71.1%).[36] In another study comparing valsartan with an ACE inhibitor (enalapril) and with placebo, <2% of study patients reported cough.[29]

No clinically important pharmacokinetic interactions were reported when valsartan was given with digoxin, warfarin, glyburide, cimetidine, or hydrochlorothiazide. The most important laboratory finding was an increase in serum potassium of >20% in 4.4% of patients taking valsartan versus 2.9% of patients taking placebo; however, no valsartan-treated patients who developed hyperkalemia discontinued the drug.[a]


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