Efficacy and Safety of a Fixed-Dose Combination Therapy of Tamsulosin and Tadalafil for Patients With Lower Urinary Tract Symptoms and Erectile Dysfunction: Results of a Randomized, Double-Blinded, Active-Controlled Trial



      Phosphodiesterase type 5 inhibitors and α-adrenergic blocking agents (α-blockers) are widely used for the treatment of erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH).


      To assess the efficacy and safety of fixed-dose combinations (FDCs) of tamsulosin and tadalafil compared with tadalafil monotherapy in patients with comorbid BPH-associated LUTS and ED.


      A randomized, double-blinded, active-controlled trial was conducted of 510 men with BPH-associated LUTS and ED. Patients were treated with FDCs of tamsulosin 0.4 mg plus tadalafil 5 mg (FDC 0.4/5 mg), tamsulosin 0.2 mg plus tadalafil 5 mg (FDC 0.2/5 mg), or tadalafil 5 mg for a 12-week treatment period. For a subsequent 12-week extension period, the patients were administered FDC 0.4/5 mg.


      The primary outcomes were changes from baseline in total International Prostate Symptom Score (IPSS) and International Index of Erectile Function erectile function domain (IIEF-EF) score at week 12 to prove superiority and non-inferiority of FDCs compared with tadalafil 5 mg. The safety assessments were adverse reactions, laboratory test results, and vital signs at week 24.


      The mean changes in total IPSS and IIEF-EF scores were −9.46 and 9.17 for FDC 0.4/5 mg and −8.14 and 9.49 for tadalafil 5 mg, respectively, which indicated superiority in LUTS improvement (P = .0320) and non-inferiority in ED treatment with FDC 0.4/5 mg compared with tadalafil 5 mg. However, the results from FDC 0.2/5 mg failed to demonstrate superiority in LUTS improvement. No clinically significant adverse events regarding the investigational products were observed during the 24-week period.

      Clinical Implications

      The FDC 0.4/5 mg is the first combined formulation of an α-blocker and a phosphodiesterase type 5 inhibitor that offers benefits in patient compliance and as add-on therapy in patients with comorbid BPH-associated LUTS and ED.

      Strengths and Limitations

      The study clearly demonstrated the advantage of FDC 0.4/5 mg. The main advantage of FDC 0.4/5 mg was the enhanced efficacy on BPH-associated LUTS comorbidity with ED, the lower incidence of side effects, and the simplification and convenience of therapy, which led to better overall patient compliance. However, the lack of a tamsulosin monotherapy control group was a limitation of this study.


      The FDC 0.4/5 mg therapy was safe, well tolerated, and efficacious, indicating that combination therapy could provide clinical benefits for patients with BPH-associated LUTS complaints and ameliorate the comorbidity of ED.
      Kim SW, Park NC, Lee SW, et al. Efficacy and Safety of a Fixed-Dose Combination Therapy of Tamsulosin and Tadalafil for Patients With Lower Urinary Tract Symptoms and Erectile Dysfunction: Results of a Randomized, Double-Blinded, Active-Controlled Trial. J Sex Med 2017;14:1018–1027.

      Key Words

      To read this article in full you will need to make a payment
      ISSM Member Login
      Login with your ISSM username and password.
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Purchase one-time access:

      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Seftel A.D.
        • de la Rosette J.
        • Birt J.
        • et al.
        Coexisting lower urinary tract symptoms and erectile dysfunction: a systematic review of epidemiological data.
        Int J Clin Pract. 2013; 67: 32-45
        • Shiri R.
        • Hakkinen J.T.
        • Hakama M.
        • et al.
        Effect of lower urinary tract symptoms on the incidence of erectile dysfunction.
        J Urol. 2005; 174: 205-209
        • Barbosa J.A.
        • Muracca E.
        • Nakano É.
        • et al.
        Interactions between lower urinary tract symptoms and cardiovascular risk factors determine distinct patterns of erectile dysfunction: a latent class analysis.
        J Urol. 2013; 190: 2177-2182
        • Li M.K.
        • Garcia L.
        • Patron N.
        • et al.
        An Asian multinational prospective observational registry of patients with benign prostatic hyperplasia, with a focus on comorbidities, lower urinary tract symptoms and sexual function.
        BJU Int. 2008; 101: 197-202
        • Rosen R.
        • Altwein J.
        • Boyle P.
        • et al.
        Lower urinary tract symptoms and male sexual dysfunction: The Multinational Survey of the Aging Male (MSAM-7).
        Eur Urol. 2003; 44: 637-649
        • Hashimoto M.
        • Hashimoto K.
        • Ando F.
        • et al.
        Prescription rate of medications potentially contributing to lower urinary tract symptoms and detection of adverse reactions by prescription sequence symmetry analysis.
        J Pharm Health Care Sci. 2015; 15: 7-15
        • Turnheim K.
        Drug therapy in the elderly.
        Exp Gerontol. 2004; 39: 1731-1738
        • Salwe K.J.
        • Kalyansundaram D.
        • Bahurupi Y.
        A study on polypharmacy and potential drug-drug interactions among elderly patients admitted in department of medicine of a tertiary care hospital in Puducherry.
        J Clin Diagn Res. 2016; 10: FC06-FC10
        • Lonsdale D.O.
        • Baker E.H.
        Understanding and managing medication in elderly people.
        Best Pract Res Clin Obstet Gynaecol. 2013; 27: 767-788
        • Karami H.
        • Hassanzadeh-Hadad A.
        • Fallah-Karkan M.
        Comparing monotherapy with tadalafil or tamsulosin and their combination therapy in men with benign prostatic hyperplasia: a randomized clinical trial.
        Urol J. 2016; 13: 2920-2926
        • Gacci M.
        • Corona G.
        • Salvi M.
        • et al.
        A systematic review and meta-analysis on the use of phosphodiesterase 5 inhibitors alone or in combination with α-blockers for lower urinary tract symptoms due to benign prostatic hyperplasia.
        Eur Urol. 2012; 61: 994-1003
        • Wang X.H.
        • Wang X.
        • Shi M.J.
        • et al.
        Systematic review and meta-analysis on phosphodiesterase 5 inhibitors and α-adrenoceptor antagonists used alone or combined for treatment of LUTS due to BPH.
        Asian J Androl. 2015; 17: 1022-1032
        • Gratzke C.
        • Bachmann A.
        • Descazeaud A.
        • et al.
        EAU guidelines on the assessment of non-neurogenic male lower urinary tract symptoms including benign prostatic obstruction.
        Eur Urol. 2015; 67: 1099-1109
        • Gravas S.
        • Bach T.
        • Bachmann A.
        • et al.
        Guidelines on the management of non-neurogenic male lower urinary tract symptoms (LUTS), incl. benign prostatic obstruction (BPO). EAU guidelines.
        (Available at:) (Published 2015. Accessed May 23, 2017)
        • Singh D.V.
        • Mete U.K.
        • Mandal A.K.
        • et al.
        A comparative randomized prospective study to evaluate efficacy and safety of combination of tamsulosin and tadalafil vs. tamsulosin or tadalafil alone in patients with lower urinary tract symptoms due to benign prostatic hyperplasia.
        J Sex Med. 2014; 11: 187-196
        • Kloner R.A.
        • Jackson G.
        • Emmick J.T.
        • et al.
        Interaction between the phosphodiesterase 5 inhibitor, tadalafil and 2 alpha-blockers, doxazosin and tamsulosin in healthy normotensive men.
        J Urol. 2004; 172: 1935-1940
        • Kloner R.A.
        Cardiovascular effects of the 3 phosphodiesterase-5 inhibitors approved for the treatment of erectile dysfunction.
        Circulation. 2004; 110: 3149-3155
        • Yan H.
        • Zong H.
        • Cui Y.
        • et al.
        The efficacy of PDE5 inhibitors alone or in combination with alpha-blockers for the treatment of erectile dysfunction and lower urinary tract symptoms due to benign prostatic hyperplasia: a systematic review and meta-analysis.
        J Sex Med. 2014; 11: 1539-1545
        • Fusco F.
        • D’Anzeo G.
        • Sessa A.
        • et al.
        BPH/LUTS and ED: common pharmacological pathways for a common treatment.
        J Sex Med. 2013; 10: 2382-2393
        • Hutchison A.
        • Farmer R.
        • Chapple C.
        • et al.
        Characteristics of patients presenting with LUTS/BPH in six European countries.
        Eur Urol. 2006; 50: 555-561
        • Husson N.
        • Watfa G.
        • Laurain M.C.
        • et al.
        Characteristics of polymedicated (≥ 4) elderly: a survey in a community-dwelling population aged 60 years and over.
        J Nutr Health Aging. 2014; 18: 87-91
        • Grundy S.M.
        Drug therapy of the metabolic syndrome: minimizing the emerging crisis in polypharmacy.
        Nat Rev Drug Discov. 2006; 5: 295-309
        • Grundy S.M.
        Metabolic syndrome: a multiplex cardiovascular risk factor.
        J Clin Endocrinol Metab. 2007; 92: 399-404
        • Regadas R.P.
        • Reges R.
        • Cerqueira J.B.
        • et al.
        The association of tamsulosin and daily tadalafil for the treatment of lower urinary tract symptoms is safe and effective?.
        J Urol. 2012; 187: e507
        • Bechara A.
        • Romano S.
        • Casabé A.
        • et al.
        Comparative efficacy assessment of tamsulosin vs. tamsulosin plus tadalafil in the treatment of LUTS/BPH. Pilot study.
        J Sex Med. 2008; 5: 2170-2178
        • Strittmatter F.
        • Gratzke C.
        • Stief C.G.
        • et al.
        Current pharmacological treatment options for male lower urinary tract symptoms.
        Expert Opin Pharmacother. 2013; 14: 1043-1054
        • Silva J.
        • Silva C.M.
        • Cruz F.
        Current medical treatment of lower urinary tract symptoms/BPH: do we have a standard?.
        Curr Opin Urol. 2014; 24: 21-28
        • Tewari A.
        • Narayan P.
        Alpha-adrenergic blocking drugs in the management of benign prostatic hyperplasia: interactions with antihypertensive therapy.
        Urology. 1999; 53 (discussion 41-2): 14-20
        • White W.B.
        • Moon T.
        Treatment of benign prostatic hyperplasia in hypertensive men.
        J Clin Hypertens (Greenwich). 2005; 7: 212-217
        • Roehrborn C.G.
        • Siami P.
        • Barkin J.
        • et al.
        The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT study.
        Eur Urol. 2010; 57: 123-131
        • Michel M.C.
        • de la Rosette J.J.
        • Piro M.
        • et al.
        Cardiovascular safety of tamsulosin modified release in the fasted and fed state in elderly healthy subjects.
        Eur Urol. 2005; 4: 9-14
        • McVary K.T.
        • Roehrborn C.G.
        • Kaminetsky J.C.
        • et al.
        Tadalafil relieves lower urinary tract symptoms secondary to benign prostatic hyperplasia.
        J Urol. 2007; 177: 1401-1407
        • Roehrborn C.G.
        • Kaminetsky J.C.
        • Auerbach S.M.
        • et al.
        Changes in peak urinary flow and voiding efficiency in men with signs and symptoms of benign prostatic hyperplasia during once daily tadalafil treatment.
        BJU Int. 2010; 105: 502-507
        • Dmochowski R.
        • Roehrborn C.
        • Klise S.
        • et al.
        Urodynamic effects of once daily tadalafil in men with lower urinary tract symptoms secondary to clinical benign prostatic hyperplasia: a randomized, placebo controlled 12-week clinical trial.
        J Urol. 2013; 189: S135-S140