Alfuzosin Hydrochloride for the Treatment of Benign Prostatic Hyperplasia

Mary Lee

Disclosures

Am J Health Syst Pharm. 2003;60(14) 

In This Article

Place in Therapy

Drug therapy for BPH can be categorized into two groups: agents that interfere with testosterone's stimulatory effect on prostate enlargement and agents that relax prostatic smooth muscle. Of the agents that interfere with testosterone's stimulatory effect on prostate size, finasteride, a 5-α-reductase inhibitor, is the only one with FDA-approved labeling for BPH treatment. Alpha-1-adrenergic antagonists relax prostatic smooth muscle, but do not reduce prostate size.

Alpha-adrenergic antagonists work best in patients with BPH symptoms caused by excessive adrenergic tone in the prostatic stroma. However, it is impossible to identify patients with excessive adrenergic tone, as no convenient, noninvasive test is available to assess this problem.[33]

When selecting drug therapy for moderate to severe BPH, the choice of a particular agent depends on actual or patient-perceived effectiveness of therapy, onset of action, convenience of the dosing regimen, adverse effects, potential for drug interactions, and cost. Clinically, most physicians prescribe an α-adrenergic antagonist as first-line therapy because these agents are more effective than finasteride, onset of action is quicker than that of finasteride (symptomatic relief occurs sooner), and the cost of single-source (nongeneric) α1-adrenergic antagonists is comparable with that of finasteride.[33,59] These benefits outweigh the more frequent cardiovascular adverse effects of α-adrenergic antagonists when compared with finasteride. Alpha-1 adrenergic antagonists are also the first-line treatment for moderate to severe BPH in patients whose prostate is less than 40 g in size. Finasteride has been found to be useful in patients with significantly enlarged prostates (more than 40 g in size).[87]

Drug therapy for BPH should begin with a single agent, most likely an α1-adrenergic antagonist. Adding finasteride to a failing α1-adrenergic antagonist regimen offers no benefit, except possibly in patients with prostates at least 40-50 g in size.[68] If patients do not respond to treatment with an α1-adrenergic antagonist, surgery is recommended.

Patients should be informed that symptom improvement will continue only as long as the drug is continued.[31] This applies to both finasteride and α-adrenergic antagonists. When used to treat severe BPH, α1-adrenergic antagonists should be viewed as interim treatment only (i.e., they may control symptoms and delay the eventual need for surgical intervention). It is unclear if such drug therapy halts BPH progression. Thus, despite continuation of treatment, BPH may progress and the patient may require another form of treatment (e.g., surgery).

All α1-adrenergic antagonists are equally effective in treating the voiding symptoms of BPH and in improving a patient's quality of life.[5] However, they do differ in their potential to cause adverse effects. Approximately 10-12% of patients discontinue second-generation α1-adrenergic antagonists because of cardiovascular adverse effects; therefore, agents less likely to produce adverse effects would be advantageous in selected patients.[88,89] Of the α1-adrenergic antagonists available on the U.S. market, tamsulosin is the least likely to cause hypotension and other cardiovascular adverse effects and is the preferred agent for patients with poorly controlled angina, patients with serious cardiac arrhythmias, patients with reduced circulating volume, and patients taking multiple antihypertensives.[35,90] It is unknown whether the once-a-day alfuzosin formulation has a cardiovascular adverse effect profile similar to that of tamsulsosin.

It is estimated that 30-50% of patients with BPH have essential hypertension.[91,92] Souverein et al.[93] conducted an epidemiologic study of 6249 patients with BPH who had recently started taking α1-adrenergic antagonists. According to the results, cardiovascular diseases (e.g., heart diseases, acute myocardial infarction, angina pectoris, arrhythmias, congestive heart failure, and cerebrovascular accidents) were twice as common among these patients than agematched population controls. Patients with hypertension who are beginning treatment with α1-adrenergic antagonists may be more likely to experience cardiovascular adverse effects, since they may be taking antihypertensive medications. For such patients, it was once thought that second-generation α1-adrenergic antagonists might be good choices as they are effective antihypertensives and may ameliorate the symptoms of BPH. However, clinical opinion does not support the use of one α1-adrenergic antagonist to treat both BPH and hypertension if the patient is already responding well to an existing antihypertensive regimen for a variety of reasons: (1) additive hypotensive adverse effects of combination therapy are unpredictable, (2) the U.S. Joint National Committee on the Detection and Evaluation of High Blood Pressure does not support the use of α1-adrenergic antagonists as first-line treatment for essential hypertension,[94] (3) urologists treating BPH are uncomfortable modifying the antihypertensive drug therapy of patients, which was likely initiated by another physician, and (4) discontinuation of some antihypertensives (when starting an α1-adrenergic antagonist) can result in rebound hypertension. In patients with moderate to severe BPH and essential hypertension who are being treated with one or more antihypertensive agents, it is more convenient for physicians to choose a treatment for BPH which will not interfere with the other medications taken by the patient. Presently, tamsulosin is the most commonly used α1-adrenergic antagonist in these patients.

Conclusion

IR alfuzosin is similar to all other second-generation α1-adrenergic antagonists in mechanism, clinical efficacy, and adverse effects. No dosage titration is needed for ER alfuzosin, and its onset of peak action is within days of the start of treatment.

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