Extended-release alfuzosin hydrochloride: a new alpha-adrenergic receptor antagonist for symptomatic benign prostatic...

Extended-release (ER) alfuzosin hydrochloride is the most recently approved alpha-adrenergic receptor antagonist (AARA) for the management of symptomatic benign prostatic hyperplasia (BPH). Although new to the United States, alfuzosin has been available in immediate-release (IR) and sustained-release (SR) formulations in other countries for many years.

This article reviews data on the pharmacodynamics, pharmacokinetics, efficacy, tolerability, drug-interaction potential, and dosing of alfuzosin ER.

Relevant articles were identified through MEDLINE, EMBASE, and International Pharmaceutical Abstracts searches of the English-language literature published between 1986 and September 2003 using the terms alfuzosin, alpha-adrenergic receptor antagonists, and quinazolines. The reference lists of identified articles were also searched, as were abstracts from annual meetings of the American Urological Association for the past 5 years. Data regarding the ER formulation were emphasized, and data involving the IR/SR formulations were included only when data for the ER formulation were not available or as needed for clarification.

In comparative trials with its IR counterpart (alfuzosin ER 10 mg QD vs alfuzosin IR 2.5 mg TID), alfuzosin ER was an equieffective once-daily AARA. No comparative trials of alfuzosin ER with the SR (BID) formulation or with other AARAs were identified. Food has been found to exert a clinically important effect by enhancing the bioavailability of the ER formulation; thus, the drug should be taken on a full stomach. Hepatic impairment has been found to significantly delay the elimination of alfuzosin IF, which constitutes a contraindication to use of the ER formulation. Renal impairment does not appear to exert clinically important effects on the pharmacokinetics of alfuzosin ER. Adverse events with alfuzosin ER include dizziness, upper respiratory tract infection, headache, and fatigue, with hypotension and syncope reported rarely. Concurrent use of inhibitors of the cytochrome P450 3A4 isozyme (eg, ketoconazole, diltiazem, cimetidine, atenolol) can significantly elevate serum concentrations of alfuzosin and enhance its pharmacodynamic effects.

In the absence of direct head-to-head comparative trials, the role of alfuzosin ER in the management of symptomatic BPH relative to that of other AARAs is unclear. Because the effect size (drug response minus placebo response) of alfuzosin ER is comparable to that of other AARAs, marked differences in efficacy are unlikely. Extrapolating from direct comparative trials between these agents and alfuzosin IR/SR, alfuzosin ER would be expected to have better cardiovascular tolerability (eg, in terms of dizziness and orthostasis) than prazosin, terazosin, or doxazosin, and to have similar tolerability to tamsulosin. However, the existing data do not suggest that alfuzosin ER is likely to represent a significant advance over tamsulosin.