Efficacy and safety of the coadministration of tadalafil once daily with finasteride for 6 months in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia.

Casabé A et al.

The Journal of Urology. 2014 Mar; 191(3):727-733

https://doi.org/10.1016/j.juro.2013.09.059PMID: 24096118

PURPOSE: Medical treatment for men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia is 5α-reductase inhibitor monotherapy or coadministration with an α-blocker. We assessed the effects of tadalafil 5 mg coadministered with finasteride 5 mg during 26 weeks on lower urinary tract symptoms and sexual symptoms.

MATERIALS AND METHODS: In an international, randomized, double-blind, parallel study of men 45 years old or older who were 5α-reductase inhibitor naïve and had an I-PSS (International Prostate Symptom Score) of 13 or greater and prostate volume 30 ml or greater, 350 were treated with placebo/finasteride and 345 received tadalafil/finasteride for 26 weeks. Changes in lower urinary tract symptoms secondary to benign prostatic hyperplasia were assessed with the I-PSS, erectile dysfunction improvements were assessed with the IIEF-EF (International Index of Erectile Function-Erectile Function) in sexually active men and safety was assessed by evaluating adverse events.

RESULTS: Least squares mean changes from baseline in I-PSS after 4, 12 and 26 weeks of tadalafil/finasteride coadministration were -4.0, -5.2 and -5.5, respectively. Corresponding values for placebo/finasteride coadministration were -2.3, -3.8 and -4.5 (p ≤ 0.022 at all visits favoring tadalafil/finasteride coadministration). I-PSS subscores (storage and voiding) and quality of life index were also numerically improved with tadalafil/finasteride coadministration. Least squares mean changes from baseline in IIEF-EF with tadalafil/finasteride coadministration were 3.7 after 4 weeks, and 4.7 after 12 and 26 weeks. Corresponding values for placebo/finasteride coadministration were -1.1, 0.6 and -0.0 (p < 0.001 at all visits favoring tadalafil/finasteride coadministration). Tadalafil/finasteride coadministration was well tolerated and most adverse events were mild/moderate.

CONCLUSIONS: The coadministration of tadalafil/finasteride provides early improvement in lower urinary tract symptoms in men with benign prostatic hyperplasia and prostatic enlargement. Tadalafil/finasteride coadministration also improves erectile function in men who have comorbid erectile dysfunction.

Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Casabé A ¹,
Roehrborn CG ²,
Da Pozzo LF ³,
Zepeda S ⁴,
Henderson RJ ⁵,
Sorsaburu S ⁶,
Henneges C ⁷,
Wong DG ⁶,
Viktrup L ⁸

Affiliations

¹ Instituto Médico Especializado, Buenos Aires, Argentina
² University of Texas Southwestern Medical Center, Dallas, Texas
³ Department of Urology, Ospedale Papa Giovanni XXIII-Bergamo, Bergamo, Italy
⁴ Saltillo University Hospital, Saltillo, Mexico
⁵ Regional Urology LLC, Shreveport, Louisiana
⁶ Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana
⁷ Global Statistical Sciences, Lilly Deutschland GmbH, Bad Homburg, Germany
⁸ Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana. viktrup_lars@lilly.com

Classifications

New Finding

Evaluations

Good

15 Nov 2013

Francisco Cruz

+ -1 Evaluators

This randomized controlled trial (RCT) investigated an innovative combination therapy for lower urinary tract symptom (LUTS) treatment in men with an enlarged prostate gland: finasteride plus tadalafil. The control arm received finasteride alone. Finasteride is indicated to treat male LUTS, prevent benign prostatic hyperplasia (BPH) progression, and reduce the risk of BPH-related surgery. Typically, improvements occur after a minimum period of 6-12 months, and improvement is more evident in prostates above 40ml. Tadalafil is also approved for LUTS treatment in men with BPH and erectile dysfunction. The effects with tadalafil can be detected within the first weeks after the onset of treatment. The combination has, in addition, the potential advantage of preventing the sexual dysfunction that is often seen with finasteride treatment. The RCT enrolled men ≥45 years of age with BPH-LUTS for >6 months, a prostate volume ≥ 30ml, a total International Prostate Symptom Score (IPSS) ≥13, and a Qmax between 4-15ml/sec, who were naïve to 5-alpha reductase inhibitor (5-ARI) therapy. The trial lasted 26 weeks, with visits at 4 and 12 weeks. The primary objective was the changes in total IPSS score at 12 weeks. Secondary outcomes included IPSS subscores and erectile function at 4, 12 and 26 weeks. A total of 695 patients (mean age 63.7±7.7 years and mean prostate volume 49.4±20.4ml) were randomized and 659 patients completed 12 weeks of therapy (329 in the combination arm and 330 in the finasteride-alone arm). The combination was superior to finasteride alone in improving the total IPSS score (mean change from baseline was -4.0, -5.2 and -5.5 in the combination arm and -2.3, -3.8, and -4.5 in the finasteride-alone arm; p<0.022 at all visits, favoring combination). Improvement in sexual function (among patients with sexual dysfunction) was superior in the combination arm. No serious adverse events were observed with the combination therapy. The combination of tadalafil and finasteride provides early BPH/LUTS improvement. However, since the effect of finasteride is known to occur after 24-52 weeks, the long-term advantage of the tadalafil-finasteride combination remains unclear. This is a smart combination, but longer follow up is necessary.