effects of Alfuzosin 10 mg once daily on sexual function in men treated for symptomatic benign prostatic hyperplasia

We evaluated the effects of extended-release Alfuzosin HCl 10 mg once daily (q.d.) on sexual function in men with lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH). In a randomized, double-blind, placebo-controlled study of men aged > or = 50 years, after a 28-day placebo run-in period, patients were randomized to receive Alfuzosin 10 mg q.d. or matching placebo for 28 days. The mean change from baseline (day 1) in sexual function on day 29 was assessed using the Danish Prostate Symptom Score Sex (DAN-PSSsex) questionnaire. A total of 372 patients were randomized to receive Alfuzosin (n=186) or placebo (n=186), with 355 completing the study. At baseline, 64% of the patients reported erectile dysfunction (ED) and 63% reported ejaculatory dysfunction (EjD). For the 320 patients who completed the DAN-PSSsex, Alfuzosin treatment was associated with a significant improvement in the mean change from baseline in erectile function on day 29 compared with placebo (P=0.02). No significant difference was observed between the two treatment groups in the mean change from baseline in ejaculatory function on day 29. For patients with ED at baseline, a marginal improvement in erectile function was demonstrated with Alfuzosin treatment (P=0.09 vs placebo). For patients with EjD at baseline, the mean change from baseline in ejaculatory function with Alfuzosin was comparable to that with placebo. Dizziness was the most common adverse event with Alfuzosin treatment (5 vs 0% with placebo), with other adverse events reported with comparable frequency in both treatment groups. After 1 month of treatment, Alfuzosin 10 mg q.d. significantly improved erectile function in men with lower urinary tract symptoms/ benign prostatic hypertrophy and had no adverse effect on ejaculatory function.

three months treatment with the α1 blocker Alfuzosin does not affect total or transition zone volume of the prostate

Treatment with α1-adrenergic receptor blockers improves lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia. This study was conducted to test the hypothesis that induction of apoptosis in prostate tissue could be a mechanism underlying the observed clinical benefit. This placebo-controlled, double-blind, randomized trial enrolled 536 men with LUTS who were treated with Alfuzosin (10 or 15 mg) once daily or placebo for 3 months. Total prostate and transition zone volume was measured by standardized transrectal ultrasound measurements at baseline and 3 months. Total prostate volume increased by 0.4 ml from baseline in placebo patients but decreased by −0.25 ml in the combined Alfuzosin groups. Percentage change was not statistically significantly different between the placebo and Alfuzosin groups. Changes in transition zone volumes from baseline were similar in both treatment arms; percentage change was not statistically significantly different between the placebo and Alfuzosin groups. Volume changes did not correlate with prostate volumes at baseline. Overall, neither total prostate nor transition zone volume increased or decreased systematically within the 3-month treatment period. If Alfuzosin-induced apoptosis in prostate tissue, it was not evident by a measurable change in prostate volume after 3 months’ treatment. Further analysis at 1 and 2 years will determine the effect of longer-term treatment.

Alfuzosin 10 mg once daily prevents overall clinical progression of benign prostatic hyperplasia but not acute urinary retention results of a 2 year placebo controlled study

OBJECTIVES

To evaluate the effect of Alfuzosin 10 mg once daily administered for 2 years on progression events in men with lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH).

PATIENTS AND METHODS

In all, 1522 men at risk of having progression events from LUTS/BPH were randomized to receive Alfuzosin 10 mg once daily (759) or placebo (763) for 2 years. Endpoints assessed were the occurrence of a first episode of acute urinary retention (AUR; primary) and the need for BPH-related surgery. Post hoc analyses included a deterioration in the International Prostate Symptom Score (IPSS) of ≥ 4 points and overall clinical progression of BPH (occurrence of AUR and/or surgery and/or symptom deterioration).

RESULTS

Over 2 years, symptom deterioration was the most common progression event (14.3%), followed by BPH-related surgery (5.8%) and AUR (2.0%). Alfuzosin did not reduce the risk of AUR (Alfuzosin 2.1% vs placebo 1.8%, P = 0.82) but tended to reduce the risk of surgery (5.1% vs 6.5%, P = 0.18); the reduction in risk (RR) and 95% confidence interval with Alfuzosin was 22 (−18 to 48)%; and significantly reduced the risk of symptom deterioration (11.7% vs 16.8%; P = 0.0013); the RR was 30 (10–46)%. The overall clinical progression of BPH was significantly lower with Alfuzosin than with placebo (16.3% vs 22.1%, P < 0.001); RR 26 (9–40)%. Alfuzosin also significantly improved the IPSS (P = 0.017), quality of life (P < 0.001) and peak flow rate (P = 0.001) compared with placebo. Baseline levels of prostate-specific antigen (PSA) predicted both AUR and BPH-related surgery events, while the baseline postvoid residual urine volume predicted symptom deterioration. The incidence of adverse events with Alfuzosin was comparable to that with placebo.

CONCLUSIONS

Alfuzosin 10 mg once daily prevents the overall clinical progression of BPH, defined by the occurrence of a deterioration in IPSS of ≥ 4 points and/or AUR and/or BPH-related surgery, but does not reduce the primary occurrence of AUR. Alfuzosin significantly improves LUTS and quality of life over 2 years, and is well tolerated.

clinical uroselectivity evidence from patients treated with slow release Alfuzosin for symptomatic benign prostatic obstruction

Objective

 To assess the safety profile of slow-release (SR) Alfuzosin in the treatment of benign prostatic obstruction (BPO), with special attention to orthostatic blood pressure changes, postural symptoms and efficacy.

Patients and methods

Two placebo-controlled studies involving 588 patients (292 receiving SR Alfuzosin 5 mg twice daily and 296 a placebo) were pooled; 51% of the patients were ≥65 years of age and 43% had associated cardiovascular disease including hypertension and/or were receiving concomitant antihypertensive drugs.

Results

SR Alfuzosin was very well tolerated with an overall incidence of adverse events similar to that of placebo (18.5% and 15.8% of patients, respectively) and an overall incidence of withdrawal from therapy for adverse events lower than that of placebo (3.4% and 5.7%, respectively). Adverse events potentially related to vasodilatation were infrequent with SR Alfuzosin (the same incidence as with placebo, i.e. 2.7% of patients) and these adverse events occurred mainly during the first month of Alfuzosin treatment. The effect on supine blood pressure was minimal. In the subgroups of elderly and hypertensive patients treated with SR Alfuzosin, the cumulative incidence of asymptomatic orthostatic hypotension during the first month of treatment was slightly higher than with placebo with no objective consequences on the incidence of adverse events. The clinical efficacy of SR Alfuzosin was confirmed by a significant improvement in urinary symptoms and a significant increase in maximum flow rates.

Conclusion

SR Alfuzosin (10 mg/day) can be administered safely without titration in patients with BPO, even in elderly and hypertensive patients. Its favourable benefit/risk ratio allows Alfuzosin to be classified as a clinically uroselective α1-blocker. Specific analysis of orthostatic changes in blood pressure is important when assessing the safety profile of an α1-blocker in patients with BPO.

efficacy and safety of sustained release Alfuzosin 5 mg in patients with benign prostatic hyperplasia algebi study group

OBJECTIVES: To assess the efficacy and safety of a sustained-release (SR) formulation of Alfuzosin, a selective alpha(1)-blocker, in patients with symptomatic benign prostatic hyperplasia (BPH). METHODS: A total of 390 men were randomly assigned to receive SR-Alfuzosin (n = 194), 5 mg twice daily without dose titration, or placebo (n = 196) for 12 weeks. Of the patients included, 47% had concomitant cardiovascular disease, mainly hypertension or coronary heart disease. RESULTS: SR-Alfuzosin significantly improved urinary symptoms versus placebo assessed using the I-PSS (-31 vs. -18%, p = 0.007) and Boyarsky (-30 vs. -16%, p < 0.001) scores, with a direct correlation between both scores. Maximum flow rate increased significantly with SR-Alfuzosin (+2.4 ml/s, i.e. +29%) compared with placebo (+1.1 ml/s, i.e. +14%, p = 0.006). Residual urine was also significantly reduced with SR-Alfuzosin. Overall, SR-Alfuzosin was as well tolerated as placebo. Nine patients dropped out for adverse events with SR-Alfuzosin (4.6%) and 14 (7.1%) with placebo. The incidence of vasodilation-related events (dizziness, postural symptoms, headache) with SR-Alfuzosin (3.1%) was similar to that of placebo (3.6%). No first-dose effect was observed compared with placebo. The reduction in supine blood pressure with SR-Alfuzosin was minor (< or = 5 mm Hg), both in normotensive and hypertensive patients. CONCLUSION: SR-Alfuzosin is an effective treatment of symptoms related to BPH that shows a good safety profile in normotensive and hypertensive patients, without the need of dose titration.

urinary flow rates in patients with benign prostatic hypertrophy following treatment with Alfuzosin

Summary— In order to document further the onset of action of Alfuzosin, a selective alpha-1 blocker, 93 symptomatic patients with benign prostatic hypertrophy were randomly allocated to a single oral dose of either Alfuzosin 1.25 mg or 2.5 mg, or placebo, after a 1-week placebo lead-in period. The effects on flow rates were assessed 1 h 30 min after administration. Peak and mean flow rates were significantly increased in the Alfuzosin groups, as compared with placebo, in a dose-dependent manner. After a single intake of placebo, the mean values of these 2 parameters showed little change. The effect on the cardiovascular system (heart rate and blood pressure) was mild. This study indicates that the action of Alfuzosin is already present 1 h 30 min after administration.

combination of Alfuzosin and tadalafil exerts an additive relaxant effect on human detrusor and prostatic tissues in vitro

Abstract Background Lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) and erectile dysfunction (ED) are highly prevalent in aging men and are strongly linked. Alpha 1 -blockers such as Alfuzosin are effective monotherapies for LUTS. Phosphodiesterase type 5 (PDE5) inhibitors such as tadalafil are the first-line treatment for ED. Both drugs act by two different mechanisms of action on common urogenital target organs and, thus, may have additive effects. Objectives We evaluated in vitro the effects of Alfuzosin, tadalafil, and the combination of both on human detrusor and prostatic smooth muscle. Design, setting, and participants Prostatic and bladder tissue were obtained from patients ( n =20 and n =17, respectively) undergoing cystoprostatectomy for bladder cancer. Measurements In organ baths, isolated prostatic strips and isolated bladder strips were incubated with vehicle, tadalafil (10 −6 M and 10 −5 M), Alfuzosin (3×10 −8 M or 10 −6 M and 10 −5 M) or a combination. Concentration-response curves (CRCs) to norepinephrine were generated on prostatic strips and detrusor strips precontracted with carbachol. Strips were also submitted to electrical field stimulation (EFS). Results and limitations When Alfuzosin and tadalafil were combined, the maximal relaxation to norepinephrine on carbachol-precontracted detrusor strips was significantly increased compared with tadalafil alone, and EFS-induced detrusor contractions were better inhibited compared with each compound alone. Tadalafil significantly inhibited norepinephrine-induced prostatic strip contractions by reducing the maximal effect, whereas Alfuzosin shifted the CRC of norepinephrine to the right. Combining both tadalafil and Alfuzosin resulted in a greater relaxant effect. Likewise, the combination was more effective at reducing EFS-induced contractions compared with each compound alone. Conclusions The combination of Alfuzosin and tadalafil exerts an additive effect of inhibiting adrenergic smooth muscle tone of prostatic tissue and EFS-induced detrusor contractions and conversely, of enhancing adrenergic relaxation of detrusor precontracted with carbachol. These experiments provide experimental support for the clinical investigation of the combination of α1-blockers and PDE5 inhibitors in the treatment of LUTS.

combination of Alfuzosin and tadalafil exerts in vitro an additive relaxant effect on human corpus cavernosum

ABSTRACT Introduction Phosphodiesterase type 5 (PDE5) inhibitors, such as tadalafil, are a first-line treatment for erectile dysfunction (ED). Nevertheless, some patients do not respond to this treatment. Clinical data suggest that the addition of α1-adrenoceptor blocker, such as Alfuzosin, commonly prescribed for lower urinary tract symptoms suggestive of benign prostatic hyperplasia, may be of benefit. Aim Evaluation of the effect of Alfuzosin, tadalafil or the combination of both on human corpus cavernosum. Methods Human cavernosal tissues were obtained from 10 patients undergoing penile surgery. Strips contractility was studied in organ baths. Concentration–response curves to tadalafil were generated on norepinephrine (NE, 1–10 µM)-precontracted strips in the presence of Alfuzosin or vehicle. Frequency–response curves (FRC) to electrical field stimulation (EFS, 0–64 Hz, 3 ms, 10 seconds, 300 mA) were generated in the presence of vehicle, Alfuzosin, tadalafil, or both drugs combined. EFS (20 Hz, 1 ms, 10 seconds, 300 mM)-induced nitrergic relaxation on NE-precontracted strips was studied in the presence of vehicle, Alfuzosin, tadalafil, or both drugs combined. Main Outcome Measures Functional measurement of cavernosal smooth muscle relaxation in the presence of tadalafil and Alfuzosin. Results The relaxation induced by tadalafil (10 −10 to 10 −5  M) on precontracted strips was enhanced by Alfuzosin at both 10 −8 and 10 −7  M. The combination of Alfuzosin (3.10 −8  M) and tadalafil (10 −7  M) was more efficient to inhibit FRC-induced contractions than each compound alone. The combination of tadalafil (10 −6  M) and Alfuzosin (10 −8  M) increased the relaxation induced by EFS and its effect was greater than tadalafil alone. In addition, the combination of tadalafil (10 −6  M) and Alfuzosin (10 −7  M) prolonged EFS-induced relaxation to a greater extent than each compound alone. Conclusions In vitro, the combination of Alfuzosin and tadalafil is more efficient than each compound alone to relax adrenergic tone or to enhance nitrergic relaxation of the human corpus cavernosum. Such a combination deserves further investigation in placebo-controlled studies to evaluate its benefit in ED patients who are not sufficiently improved by PDE5 inhibitors. Oger S, Behr-Roussel D, Gorny D, Tremeaux JC, Combes M, Alexandre L, and Giuliano F. Combination of Alfuzosin and tadalafil exerts in vitro an additive relaxant effect on human corpus cavernosum.