Angiotensin II-Receptor Antagonists: An Overview

Raquel Dina and Mahtab Jafari

Am J Health Syst Pharm. 2000;57(13)

Drug Interactions

Of the AT-II-receptor antagonists, only candesartan has any clinically important interactions with digoxin, warfarin, and hydrochlorothiazide. Candesartan may increase serum concentrations of digoxin and may decrease warfarin concentrations; however, there is no apparent change in the International Normalized Ratio.

Losartan is metabolized by the CYP isoenzyme system; however, the effects of potent inhibitors of CYP3A4 and CYP2C9 on losartan pharmacokinetics have not been clinically studied. When administered with losartan, phenobarbital causes a 20% reduction in serum concentrations of losartan and its metabolite, thus reducing its effectiveness. Eprosartan, candesartan, irbesartan, valsartan, and telmisartan are not metabolized by the CYP system.

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Table 1. Comparison of Angiotensin II-Receptor Antagonists
Drug	Active Metabolite	Bioavailability (%)	Daily Dose (mg)	Half-life (hr)	Cost ($)a
Losartan	Yes	33	25-100	2 (losartan) 6-9 (EXP-3174)	38
Valsartan	No	25	80-320	6	36
Irbesartan	No	60-80	150-300	11-15	36
Candesartan	No	42	8-32	3-4 3-11	36
Eprosartan	No	13	600-800	5-9	37
Telmisartan	No	42-58	20-80	24	39

a Estimated cost, based on average wholesale price (Drug Topics Red Book, 1999), to the pharmacist for a one-month supply at the usual starting dosage.

Table 2. Clinical Trials Comparing Angiotensin-II-Receptor Antagonists with Angiotensin-Converting-Enzyme Inhibitors a
a	Losartan dosages are expressed in terms of losartan potassium, and candesartan dosages are expressed in terms of candesartan cilexetil. BP = blood pressure, SBP = systolic blood pressure, DBP = diastolic blood pressure, NR = not reported, HCTZ = hydrochlorothiazide.
b	Primary efficacy variable was assessed after eight weeks of therapy.

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Angiotensin II-Receptor Antagonists: An Overview

Drug Interactions

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