Tadalafil Relieves Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia

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Chapter 14–BPH 冒 101 䉴 The MTOPS study taught us that over a period of 5 years the alpha-blocker doxazosin does not prevent episodes of acute urinary retention or the need for surgical intervention for BPH in men enrolled in this trial when compared to placebo. Sanofi-Aventis sponsored a 2-year placebo-controlled trial using the alpha-blocker alfuzosin 10 mg once daily in a group of high risk patients who had a PSA greater than 1.5 and presumably a larger prostate gland (ALTESS). The results of this study are similar to those of the MTOPS study and suggest that alfuzosin over 2 years does not prevent the need for BPH-related surgery, but does prevent worsening of symptoms. Compared to the placebo group, there was a 30% reduction in worsening of symptom score, which is analogous to the MTOPS study, and a 26% overall reduced incidence of progression events. However, BPH-related surgery was nearly as common in the alfuzosin treatment group as it was in the placebo group, as was the incidence of acute urinary retention episode. It is always important to confirm findings from one study with another dataset, and the ALTESS study corroborated the findings of the MTOPS study and validated the impression that alpha-blockers indeed do not modify the natural history of the disease or its progression to either acute urinary retention or surgery, at least in those men with increased risk based on serum PSA and/or enlarged prostate gland. C. G. Roehrborn, MD

Tadalafil Relieves Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia McVary KT, Roehrborn CG, Kaminetsky JC, et al (Northwestern Univ, Chicago; Univ of Texas, Dallas; Univ Urology Associates, New York; et al) J Urol 177:1401-1407, 2007 14–13

Purpose.—We assessed the efficacy and safety of tadalafil dosed once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia. Materials and Methods.—Following a 4-week, single-blind, placebo runin 281 men were randomly assigned (1:1) to 5 mg tadalafil for 6 weeks, followed by dose escalation to 20 mg for 6 weeks or 12 weeks of placebo. Results.—Tadalafil significantly improved the mean change from baseline in International Prostate Symptom Score at 6 weeks (5 mg tadalafil ⫺2.8 vs placebo ⫺1.2) and at 12 weeks (5/20 mg tadalafil ⫺3.8 vs placebo ⫺1.7). Larger changes were observed with inclusion of the placebo run-in at 12 weeks (5/20 mg tadalafil ⫺7.1 vs placebo ⫺4.5). Significant improvements were also seen in the International Prostate Symptom Score irritative and obstructive domains, the International Prostate Symptom Score quality of life index, a question about urinary symptom improvement and the Benign Prostatic Hyperplasia Impact Index (significant at 12 weeks) vs placebo. International Prostate Symptom Score and International Index of Erectile Function erectile function domain scores significantly improved in the 56% of men with lower urinary tract symptoms/benign prostatic hyperplasia who

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102 冒 Urology were sexually active and had erectile dysfunction. Changes in uroflowmetry parameters were similar in the placebo and tadalafil groups. Commonly reported (2% or greater) treatment emergent adverse events were “erection increased,” dyspepsia, back pain, headache, nasopharyngitis and upper respiratory tract infection (each 5.1% or less). No change in post-void residual volume was seen with tadalafil treatment. Conclusions.—Tadalafil once daily was well tolerated and demonstrated clinically meaningful and statistically significant symptomatic improvement for lower urinary tract symptoms/benign prostatic hyperplasia. Tadalafil also improved erectile function in men with lower urinary tract symptoms and erectile dysfunction. Hemodynamic interaction study between the alpha1-blocker alfuzosin and the phosphodiesterase-5 inhibitor tadalafil in middle-aged healthy male subjects Giuliano F, Kaplan SA, Cabanis M-J, et al (Raymond Poincare´ Hosp, Garches, France; Cornell Univ, New York; Sanofi-Synthelabo Recherche, Montpellier, France; et al) Urology 67:1199-1204, 2006 14–14

Objectives.—To examine the hemodynamic interactions of the phosphodiesterase type 5 (PDE-5) inhibitor tadalafil with the uroselective alpha1blocker alfuzosin (10 mg daily), commonly prescribed for benign prostatic hyperplasia-related lower urinary tract symptoms. Erectile dysfunction is commonly associated with lower urinary tract symptoms. PDE-5 inhibitors are the first-line treatment of choice for erectile dysfunction. When coadministered with alpha1-blockers, PDE-5 inhibitors could induce orthostatic hypotension. Methods.—During each of the two periods of a randomized, doubleblind, placebo-controlled, crossover study, 18 healthy middle-aged men received alfuzosin 10 mg daily for 7 days and either a single 20-mg dose of tadalafil or placebo on day 7. The blood pressure and heart rate were monitored before and for 24 hours after tadalafil or placebo. Results.—The combination of tadalafil 20 mg with alfuzosin 10 mg daily elicited a maximal decrease in standing systolic blood pressure that was not significantly different from that after placebo (mean difference 4.35 mm Hg, P ⫽ nonsignificant). Analysis of the blood pressure outliers showed that only 1 subject had an asymptomatic standing systolic blood pressure of less than 85 mm Hg. No vasodilatory adverse events were observed with the combined medication. Conclusions.—In healthy, middle-aged men, tadalafil 20 mg showed no clinically relevant hemodynamic interactions with alfuzosin 10 mg daily.

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Chapter 14–BPH 冒 103 The Effects of Tamsulosin and Sildenafil in Separate and Combined Regimens on Detailed Hemodynamics in Patients With Benign Prostatic Enlargement Nieminen T, Tammela TLJ, Ko¨o¨bi T, et al (Univ of Tampere, Finland; Tampere Univ Hosp, Finland) J Urol 176:2551-2556, 2006 14–15

Purpose.—We measured the detailed hemodynamic effects of tamsulosin and sildenafil separately and together in patients with benign prostatic enlargement. Materials and Methods.—The supine effects of and responses to passive orthostasis (60 degrees for 8 minutes) were measured in 16 patients with benign prostatic enlargement with the finger blood pressure method and whole-body impedance cardiography. The medications, 100 mg sildenafil (single doses) and 0.4 mg tamsulosin (once daily for up to 14 days), were administered in a randomized, double-blind, crossover fashion. Results.—Supine systolic arterial pressure decreased with sildenafil (mean ± SEM ⫺11 ± 2 mm Hg) and sildenafil plus tamsulosin (⫺14 ± 2 mm Hg) more than with placebo (⫺2 ± 4 mm Hg, p