Modern combination therapy of tadalafil and tamsulosin as a new treatment in men with lower urinary tract symptoms Review article
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Published:
Mar 31, 2022
Keywords:
BPH, LUTS, benign prostatic hyperplasia, lower urinary tract symptoms, erectile dysfunction, tadalafil, tamsulosin, combination therapy
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Abstract
Based on the available scientific research, tadalafil administered daily at a dose of 5 mg is safe and effective in the treatment of men with lower urinary tract symptoms and erectile dysfunction, compared to placebo or tamsulosin alone. The combination of 5 mg tadalafil and 0.4 mg tamsulosin daily allows for a better lower urinary tract symptoms improvement compared to monotherapy drugs, even with an increased, but acceptable and tolerable side effects. When tamsulosin or tadalafil is discontinued, lower urinary tract symptoms are significantly worsened compared to baseline in patients previously treated with combination therapy.
Tadalafil 5 mg should be considered as one of the primary treatment options in lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction patients as it has an excellent tolerability, safety, and efficacy profile, both as monotherapy and in combination with 0.4 mg tamsulosin. Better effectiveness in alleviating lower urinary tract symptoms was observed with combination therapy while maintaining sexual function. Continuing to switch to monotherapy maintains lower urinary tract symptoms relief, but only tadalafil is able to maintain erectile dysfunction improvement. Our results support evidence of an increasingly tailored and modular lower urinary tract symptoms treatment.
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Wiatr , T., & Chłosta , P. (2022). Modern combination therapy of tadalafil and tamsulosin as a new treatment in men with lower urinary tract symptoms. Medycyna Faktow (J EBM), 15(1(54), 40-45. https://doi.org/10.24292/01.MF.0122.5
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References
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4. Giuliano F, Uckert S, Maggi M et al. The mechanism of action of phosphodiesterase type 5 inhibitors in the treatment of lower urinary tract symptoms related to benign prostatic hyperplasia. Eur Urol. 2013; 63(3): 506-16.
5. Vignozzi L, Gacci M, Cellai I et al. PDE5 inhibitors blunt inflammation in human BPH: a potential mechanism of action for PDE5 inhibitors in LUTS. Prostate. 2013; 73(13): 1391-402.
6. Morelli A, Sarchielli E, Comeglio P et al. Phosphodiesterase type 5 expression in human and rat lower urinary tract tissues and the effect of tadalafil on prostate gland oxygenation in spontaneously hypertensive rats. J Sex Med. 2011; 8(10): 2746-60.
7. Morelli A, Comeglio P, Filippi S et al. Mechanism of action of phosphodiesterase type 5 inhibition in metabolic syndrome-associated prostate alterations: an experimental study in the rabbit. Prostate. 2013; 73(4): 428-41.
8. Fibbi B, Morelli A, Vignozzi L et al. Characterization of phosphodiesterase type 5 expression and functional activity in the human male lower urinary tract. J Sex Med. 2010; 7(1 Pt 1): 59-69.
9. Morelli A, Filippi S, Sandner P et al. Vardenafil modulates bladder contractility through cGMP-mediated inhibition of RhoA/Rho kinase signaling pathway in spontaneously hypertensive rats. J Sex Med. 2009; 6(6): 1594-608.
10. Filippi S, Morelli A, Sandner P et al. Characterization and functional role of androgen dependent PDE5 activity in the bladder. Endocrinology. 2007; 148(3): 1019-29.
11. 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(5): 994-1003.
12. Gacci M, Salvi M, Sebastianelli A et al. The use of a single daily dose of tadalafil to treat signs and symptoms of benign prostatic hyperplasia and erectile dysfunction. Res Rep Urol. 2013; 5: 99-111.
13. Uckert S, Kuthe A, Jonas U et al. Characterization and functional relevance of cyclic nucleotide phosphodiesterase isoenzymes of the human prostate. J Urol. 2001; 166: 2484-90.
14. Andersson KE, de Groat WC, McVary KT et al. Tadalafil for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia: pathophysiology and mechanism(s) of action. Neurourol Urodyn. 2011; 30: 292-301.
15. Uckert S, Sormes M, Kedia G et al. Effects of phosphodiesterase inhibit ors on tension induced by norepinephrine and accumulation of cyclic nucleotides in isolated human prostatic tissue. Urology. 2008; 71: 526-30.
16. Kedia GT, Uckert S, Jonas U et al. The nitric oxide pathway in the human prostate: clinical implications in men with lower urinary tract symptoms. World J Urol. 2008; 26: 603-9.
17. McVary KT, Roehrborn CG, Kaminetsky JC et al. Tadalafil relieves lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Urol. 2007; 177(4): 1401-7.
18. Roehrborn CG, McVary KT, Elion-Mboussa A et al. Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a dose finding study. J Urol. 2008; 180(4): 1228-34.
19. Egerdie RB, Auerbach S, Roehrborn CG et al. Tadalafil 2.5 or 5 mg administered once daily for 12 weeks in men with both erectile dysfunction and signs and symptoms of benign prostatic hyperplasia: results of a randomized, placebo-controlled, double-blind study. J Sex Med. 2012; 9(1): 271-81.
20. Takeda M, Nishizawa O, Imaoka T et al. Tadalafil for the treatment of lower urinary tract symptoms in Japanese men with benign prostatic hyperplasia: results from a 12-week placebo-controlled dose-finding study with a 42-week open-label extension. Low Urin Tract Symptoms. 2012; 4(3): 110-9.
21. Matsukawa Y, Takai S, Majima T et al. Objective impacts of tadalafil on storage and voiding function in male patients with benign prostatic hyperplasia: 1-year outcomes from a prospective urodynamic study. World J Urol. 2019; 37(5): 867-72.
22. Kim SC, Park JK, Kim SW et al. Tadalafil administered once daily for treatment of lower urinary tract symptoms in Korean men with benign prostatic hyperplasia: results from a placebo-controlled pilot study using tamsulosin as an active control. Low Urin Tract Symptoms. 2011; 3(2): 86-93.
23. Yokoyama O, Yoshida M, Kim SC et al. Tadalafil once daily for lower urinary tract symptoms suggestive of benign prostatic hyperplasia: a randomized placebo and tamsulosin-controlled 12-week study in Asian men. Int J Urol. 2013; 20(2): 193-201.
24. Oelke M, Giuliano F, Mirone V et al. Monotherapy with tadalafil or tamsulosin similarly improved lower urinary tract symptoms suggestive of benign prostatic hyperplasia in an international, randomised, parallel, placebo-controlled clinical trial. Eur Urol. 2012; 61(5): 917-25.
25. Giuliano F, Oelke M, Jungwirth A et al. Tadalafil once daily improves ejaculatory function, erectile function, and sexual satisfaction in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia and erectile dysfunction: results from a randomized, placebo- and tamsulosin. J Sex Med. 2013; 10(3): 857-65.
26. Oelke M, Giuliano F, Baygani SK et al. Treatment satisfaction with tadalafil or tamsulosin vs placebo in men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH): results from a randomized, placebo-controlled study. BJU Int. 2014; 114(4): 568-75.
27. Pogula VR, Kadiyala LS, Gouru VR et al. Tadalafil vs. tamsulosin in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia: a prospective, randomized study. Cent European J Urol. 2019; 72(1): 44-50.
28. Bechara A, Romano S, Casabe 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(9): 2170-8.
29. Regadas RP, Reges R, Cerqueira JBG et al. Urodynamic effects of the combination of tamsulosin and daily tadalafil in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia: a randomized, placebo-controlled clinical trial. Int Urol Nephrol. 2013; 45(1): 39-43.
30. Zhou Z, Zheng X, Wu J et al. Meta-analysis of efficacy and safety of tadalafil plus tamsulosin compared with tadalafil alone in treating men with benign prostatic hyperplasia and erectile dysfunction. Am J Mens Health. 2019; 13(5): 1557988319882597.
31. Sebastianelli A, Spatafora P, Frizzi J et al. Tadalafil 5 mg alone or in combination with tamsulosin 0.4 mg for the management of men with lower urinary tract symptoms and erectile dysfunction: results of a prospective observational trial. J Clin Med. 2019; 8(8): 1126.
32. Sebastianelli A, Spatafora P, Frizzi J et al. Which drug to disconti nue 3 months after combination therapy of tadalafil plus tamsulosin for men with lower urinary tract symptom and erectile dysfunction? Results of a prospective observational trial. Eur Urol Focus. 2019; 7(2): 1-8.
33. Singh DV, Mete UK, Mandal AK 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(1): 187-96.
34. Kim JH, Baek MJ, Sun HY et al. Efficacy and safety of 5 alpha-reductase inhibitor monotherapy in patients with benign prostatic hyperplasia: a meta-analysis. PLoS One. 2018; 13(10): e0203479.
35. Naslund MJ, Miner M. A review of the clinical efficacy and safety of 5alpha-reductase inhibitors for the enlarged prostate. Clin Ther. 2007; 29(1): 17-25.
36. Favilla V, Russo GI, Privitera S et al. Impact of combination therapy 5-alpha reductase inhibitors (5-ARI) plus alpha-blockers (AB) on erectile dysfunction and decrease of libido in patients with LUTS/BPH: a systematic review with meta-analysis. aging male. Aging Male. 2016; 19(3): 175-81.
2. Gravas S, Cornu JN, Gacci M et al. Management of non-neurogenic male LUTS. In: EAU Guidelines 2020. Arnhem, The Netherlands: EAU Guidelines Office; 2020.
3. Mirone V, Sessa A, Giuliano F et al. Current benign prostatic hyperplasia treatment: impact on sexual function and management of related sexual adverse events. Int J Clin Pract. 2011; 65(9): 1005-13.
4. Giuliano F, Uckert S, Maggi M et al. The mechanism of action of phosphodiesterase type 5 inhibitors in the treatment of lower urinary tract symptoms related to benign prostatic hyperplasia. Eur Urol. 2013; 63(3): 506-16.
5. Vignozzi L, Gacci M, Cellai I et al. PDE5 inhibitors blunt inflammation in human BPH: a potential mechanism of action for PDE5 inhibitors in LUTS. Prostate. 2013; 73(13): 1391-402.
6. Morelli A, Sarchielli E, Comeglio P et al. Phosphodiesterase type 5 expression in human and rat lower urinary tract tissues and the effect of tadalafil on prostate gland oxygenation in spontaneously hypertensive rats. J Sex Med. 2011; 8(10): 2746-60.
7. Morelli A, Comeglio P, Filippi S et al. Mechanism of action of phosphodiesterase type 5 inhibition in metabolic syndrome-associated prostate alterations: an experimental study in the rabbit. Prostate. 2013; 73(4): 428-41.
8. Fibbi B, Morelli A, Vignozzi L et al. Characterization of phosphodiesterase type 5 expression and functional activity in the human male lower urinary tract. J Sex Med. 2010; 7(1 Pt 1): 59-69.
9. Morelli A, Filippi S, Sandner P et al. Vardenafil modulates bladder contractility through cGMP-mediated inhibition of RhoA/Rho kinase signaling pathway in spontaneously hypertensive rats. J Sex Med. 2009; 6(6): 1594-608.
10. Filippi S, Morelli A, Sandner P et al. Characterization and functional role of androgen dependent PDE5 activity in the bladder. Endocrinology. 2007; 148(3): 1019-29.
11. 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(5): 994-1003.
12. Gacci M, Salvi M, Sebastianelli A et al. The use of a single daily dose of tadalafil to treat signs and symptoms of benign prostatic hyperplasia and erectile dysfunction. Res Rep Urol. 2013; 5: 99-111.
13. Uckert S, Kuthe A, Jonas U et al. Characterization and functional relevance of cyclic nucleotide phosphodiesterase isoenzymes of the human prostate. J Urol. 2001; 166: 2484-90.
14. Andersson KE, de Groat WC, McVary KT et al. Tadalafil for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia: pathophysiology and mechanism(s) of action. Neurourol Urodyn. 2011; 30: 292-301.
15. Uckert S, Sormes M, Kedia G et al. Effects of phosphodiesterase inhibit ors on tension induced by norepinephrine and accumulation of cyclic nucleotides in isolated human prostatic tissue. Urology. 2008; 71: 526-30.
16. Kedia GT, Uckert S, Jonas U et al. The nitric oxide pathway in the human prostate: clinical implications in men with lower urinary tract symptoms. World J Urol. 2008; 26: 603-9.
17. McVary KT, Roehrborn CG, Kaminetsky JC et al. Tadalafil relieves lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Urol. 2007; 177(4): 1401-7.
18. Roehrborn CG, McVary KT, Elion-Mboussa A et al. Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a dose finding study. J Urol. 2008; 180(4): 1228-34.
19. Egerdie RB, Auerbach S, Roehrborn CG et al. Tadalafil 2.5 or 5 mg administered once daily for 12 weeks in men with both erectile dysfunction and signs and symptoms of benign prostatic hyperplasia: results of a randomized, placebo-controlled, double-blind study. J Sex Med. 2012; 9(1): 271-81.
20. Takeda M, Nishizawa O, Imaoka T et al. Tadalafil for the treatment of lower urinary tract symptoms in Japanese men with benign prostatic hyperplasia: results from a 12-week placebo-controlled dose-finding study with a 42-week open-label extension. Low Urin Tract Symptoms. 2012; 4(3): 110-9.
21. Matsukawa Y, Takai S, Majima T et al. Objective impacts of tadalafil on storage and voiding function in male patients with benign prostatic hyperplasia: 1-year outcomes from a prospective urodynamic study. World J Urol. 2019; 37(5): 867-72.
22. Kim SC, Park JK, Kim SW et al. Tadalafil administered once daily for treatment of lower urinary tract symptoms in Korean men with benign prostatic hyperplasia: results from a placebo-controlled pilot study using tamsulosin as an active control. Low Urin Tract Symptoms. 2011; 3(2): 86-93.
23. Yokoyama O, Yoshida M, Kim SC et al. Tadalafil once daily for lower urinary tract symptoms suggestive of benign prostatic hyperplasia: a randomized placebo and tamsulosin-controlled 12-week study in Asian men. Int J Urol. 2013; 20(2): 193-201.
24. Oelke M, Giuliano F, Mirone V et al. Monotherapy with tadalafil or tamsulosin similarly improved lower urinary tract symptoms suggestive of benign prostatic hyperplasia in an international, randomised, parallel, placebo-controlled clinical trial. Eur Urol. 2012; 61(5): 917-25.
25. Giuliano F, Oelke M, Jungwirth A et al. Tadalafil once daily improves ejaculatory function, erectile function, and sexual satisfaction in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia and erectile dysfunction: results from a randomized, placebo- and tamsulosin. J Sex Med. 2013; 10(3): 857-65.
26. Oelke M, Giuliano F, Baygani SK et al. Treatment satisfaction with tadalafil or tamsulosin vs placebo in men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH): results from a randomized, placebo-controlled study. BJU Int. 2014; 114(4): 568-75.
27. Pogula VR, Kadiyala LS, Gouru VR et al. Tadalafil vs. tamsulosin in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia: a prospective, randomized study. Cent European J Urol. 2019; 72(1): 44-50.
28. Bechara A, Romano S, Casabe 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(9): 2170-8.
29. Regadas RP, Reges R, Cerqueira JBG et al. Urodynamic effects of the combination of tamsulosin and daily tadalafil in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia: a randomized, placebo-controlled clinical trial. Int Urol Nephrol. 2013; 45(1): 39-43.
30. Zhou Z, Zheng X, Wu J et al. Meta-analysis of efficacy and safety of tadalafil plus tamsulosin compared with tadalafil alone in treating men with benign prostatic hyperplasia and erectile dysfunction. Am J Mens Health. 2019; 13(5): 1557988319882597.
31. Sebastianelli A, Spatafora P, Frizzi J et al. Tadalafil 5 mg alone or in combination with tamsulosin 0.4 mg for the management of men with lower urinary tract symptoms and erectile dysfunction: results of a prospective observational trial. J Clin Med. 2019; 8(8): 1126.
32. Sebastianelli A, Spatafora P, Frizzi J et al. Which drug to disconti nue 3 months after combination therapy of tadalafil plus tamsulosin for men with lower urinary tract symptom and erectile dysfunction? Results of a prospective observational trial. Eur Urol Focus. 2019; 7(2): 1-8.
33. Singh DV, Mete UK, Mandal AK 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(1): 187-96.
34. Kim JH, Baek MJ, Sun HY et al. Efficacy and safety of 5 alpha-reductase inhibitor monotherapy in patients with benign prostatic hyperplasia: a meta-analysis. PLoS One. 2018; 13(10): e0203479.
35. Naslund MJ, Miner M. A review of the clinical efficacy and safety of 5alpha-reductase inhibitors for the enlarged prostate. Clin Ther. 2007; 29(1): 17-25.
36. Favilla V, Russo GI, Privitera S et al. Impact of combination therapy 5-alpha reductase inhibitors (5-ARI) plus alpha-blockers (AB) on erectile dysfunction and decrease of libido in patients with LUTS/BPH: a systematic review with meta-analysis. aging male. Aging Male. 2016; 19(3): 175-81.