Angiotensin II-Receptor Antagonists: An Overview

Raquel Dina and Mahtab Jafari


Am J Health Syst Pharm. 2000;57(13) 

In This Article


Irbesartan (Avapro, Bristol-Myers Squibb) is a long-acting nonpeptide AT-II type 1-receptor antagonist with a plasma half-life of 11-15 hours. Irbesartan has no active metabolites and is 90% protein bound. The drug is absorbed rapidly after oral administration and has a bioavailability of 60-80%, the highest in its class.[37] Food intake has no effect on absorption. After oral administration, peak plasma concentrations are achieved in two hours. Irbesartan undergoes hepatic metabolism via glucuronide conjugation and oxidation; no active metabolites have been identified. After administration of a single 150-mg dose of irbesartan, 20% of the dose is excreted renally and about 30% is excreted in the bile.[b] In vitro studies indicate that oxidation of irbesartan occurs primarily via CYP2C9. Warfarin and digoxin appear to have a negligible effect on CYP2C9 metabolism of irbesartan. When potential drug interactions were explored in patients taking warfarin, hydrochlorothiazide, or digoxin concurrently with irbesartan, no changes in the pharmacokinetics of digoxin or the pharmacodynamic effects of warfarin (prothrombin time) were noted.[38]

Antihypertensive effects are seen within two weeks of initiating therapy, with maximum effects occurring at between two and six weeks.[39,40,41] Effects on blood pressure are dose dependent over the range of 75-300 mg.[42,43] However, data from various double-blind, placebo-controlled trials show that daily doses of 150-300 mg, administered once daily or in divided doses, will effectively reduce blood pressure by 3.1-6.1 mm Hg.[42] The addition of hydrochlorothiazide 6.25-25 mg/day to irbesartan 75-300 mg/day further decreases blood pressure [40,44,45] to the same extent as treatment with enalapril 20-40 mg.[46]

In clinical studies of irbesartan there was no relationship between the dosage and the overall frequency of adverse reactions. The rates of serious adverse events were similar for irbesartan (1.0%) and placebo (1.9%).[47] The most common adverse reactions were headache (12% rate for irbesartan, 17% for placebo) and upper-respiratory- tract infection (9.0% for irbesartan, 5.1% for placebo).

The recommended starting dosage of irbesartan is 150 mg once daily; the dosage may be increased to 300 mg once daily with or without food for patients who require further blood pressure reduction. The starting dosage does not need to be reduced in the elderly or in patients with hepatic impairment or mild to severe renal impairment. Hydrochlorothiazide has an additive blood pressure-lowering effect, and the combination of irbesartan and hydrochlorothiazide may be useful when blood pressure is not controlled by irbesartan alone.[40,44,45]

Irbesartan may also be administered with other antihypertensive agents. When irbesartan therapy is discontinued, the dosage does not need to be tapered, regardless of the daily dose administered, because abrupt withdrawal of the drug is not associated with an increase in blood pressure.[40] Likewise, loss of blood pressure regulation should not occur if a dose is missed.

Irbesartan is available as a single-ingredient product and in combination with hydrochlorothiazide (Avalide, Bristol-Myers Squibb; irbesartan 150 mg plus hydrochlorothiazide 12.5 mg and irbesartan 300 mg plus hydrochlorothiazide 12.5 mg). Use of this combination product should be reserved for patients who have not achieved the desired blood pressure-lowering effect with irbesartan monotherapy. It is recommended that this product be started at one tablet once daily. The maximum effect on blood pressure should be attained two to four weeks after therapy begins. No dosage adjustment is necessary in patients with hepatic impairment; however, the combination product is not recommended in patients with renal impairment (CL cr , <30 mL/min).


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