Skip to main content
SpringerLink
Log in

Tadalafil

In the Treatment of Signs and Symptoms of Benign Prostatic Hyperplasia with or without Erectile Dysfunction

  • Adis Drug Profile
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Abstract

Tadalafil is a selective cyclic guanosine monophosphate-specific phosphodiesterase type 5 inhibitor. Once-daily tadalafil 5 mg was effective in treating the signs and symptoms of benign prostatic hyperplasia (BPH). In phase III trials in men with BPH, the mean change from baseline to week 12 in the total International Prostate Symptom Score (IPSS; primary endpoint) was significantly greater in those treated with once-daily tadalafil 5 mg than with placebo. Improvements in total IPSS that occurred over the initial 12 weeks of tadalafil treatment were maintained with continued treatment over a 1-year period in an open-label extension study. Moreover, tadalafil was effective in treating both erectile dysfunction (ED) and the signs and symptoms of BPH in a phase III trial that specifically enrolled men with both indications. Both the International Index of Erectile Function-Erectile Function domain score and the total IPSS (co-primary endpoints) were significantly improved from baseline to week 12 after treatment with once-daily tadalafil 5 mg compared with placebo. Tadalafil was generally well tolerated (for a period of up to 1 year) in patients with BPH, including those with ED, with adverse events being of mild to moderate intensity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. McVary KT, Roehrborn CG, Avins AL, et al. American Urological Association guideline: management of benign prostatic hyperplasia (BPH) [online]. 2012. http://www.auanet.org. Accessed 21 May 2012.

  2. Oelke M, Bachmann A, Descazeaud A, et al. Guidelines on the treatment of non-neurogenic male LUTS [online]. 2012. http://www.uroweb.org. Accessed 8 May 2012.

  3. Abrams P, Cardozo L, Fall M, et al. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Am J Obstet Gynecol. 2002;187(1):116–26.

    Article  PubMed  Google Scholar 

  4. 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(6):637–49.

    Article  PubMed  Google Scholar 

  5. Rosen RC, Wei JT, Althof SE, et al. Association of sexual dysfunction with lower urinary tract symptoms of BPH and BPH medical therapies: results from the BPH Registry. Urology. 2009;73(3):562–6.

    Article  PubMed  Google Scholar 

  6. 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(3):292–301.

    Article  PubMed  CAS  Google Scholar 

  7. Gomelsky A, Dmochowski RR. Urodynamic effects of once-daily tadalafil in men with LUTS secondary to clinical BPH. Curr Urol Rep. 2010;11(4):254–60.

    Article  PubMed  Google Scholar 

  8. Uckert S, Kuczyk MA. Cyclic nucleotide metabolism including nitric oxide and phosphodiesterase-related targets in the lower urinary tract. Handb Exp Pharmacol. 2011;202:527–42.

    Article  PubMed  Google Scholar 

  9. Wright PJ. Comparison of phosphodiesterase type 5 (PDE5) inhibitors. Int J Clin Pract. 2006;60(8):967–75.

    Article  PubMed  CAS  Google Scholar 

  10. Uckert S, Oelke M. Phosphodiesterase (PDE) inhibitors in the treatment of lower urinary tract dysfunction. Br J Clin Pharmacol. 2011;2(2):197–204.

    Article  Google Scholar 

  11. Curran M, Keating G. Tadalafil. Drugs. 2003;63(20):2203–12. (discussion 13–4).

    Article  PubMed  CAS  Google Scholar 

  12. Eli Lilly and Company. Cialis (tadalafil) tablets, for oral use [online]. 2011. http://pi.lilly.com. Accessed 8 May 2012.

  13. Blount MA, Beasley A, Zoraghi R, et al. Binding of tritiated sildenafil, tadalafil, or vardenafil to the phosphodiesterase-5 catalytic site displays potency, specificity, heterogeneity, and cGMP stimulation. Mol Pharmacol. 2004;66(1):144–52.

    Article  PubMed  CAS  Google Scholar 

  14. Corbin JD, Francis SH, Webb DJ. Phosphodiesterase type 5 as a pharmacologic target in erectile dysfunction. Urology. 2002;60(2 Suppl. 2):4–11.

    Article  PubMed  Google Scholar 

  15. Uckert S, Stief CG, Mayer M, et al. Distribution and functional significance of phosphodiesterase isoenzymes in the human lower urinary tract. World J Urol. 2005;23(6):368–73.

    Article  PubMed  Google Scholar 

  16. 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(6):2484–90.

    Article  PubMed  CAS  Google Scholar 

  17. 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.

    Article  PubMed  CAS  Google Scholar 

  18. Tinel H, Stelte-Ludwig B, Hutter J, et al. Pre-clinical evidence for the use of phosphodiesterase-5 inhibitors for treating benign prostatic hyperplasia and lower urinary tract symptoms. BJU Int. 2006;98(6):1259–63.

    Article  PubMed  CAS  Google Scholar 

  19. Truss MC, Uckert S, Stief CG, et al. Cyclic nucleotide phosphodiesterase (PDE) isoenzymes in the human detrusor smooth muscle: I. Identification and characterization. Urol Res. 1996;24(3):123–8.

    Article  PubMed  CAS  Google Scholar 

  20. 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.

    Article  PubMed  CAS  Google Scholar 

  21. Waldkirch E, Uckert S, Yildirim H, et al. Cyclic AMP-specific and cyclic GMP-specific phosphodiesterase isoenzymes in human cavernous arteries—immunohistochemical distribution and functional significance. World J Urol. 2005;23(6):405–10.

    Article  PubMed  CAS  Google Scholar 

  22. Kuthe A, Wiedenroth A, Magert HJ, et al. Expression of different phosphodiesterase genes in human cavernous smooth muscle. J Urol. 2001;165(1):280–3.

    Article  PubMed  CAS  Google Scholar 

  23. Porst H. IC351 (tadalafil, Cialis): update on clinical experience. Int J Impot Res. 2002;14(Suppl. 1):S57–64.

    Article  PubMed  Google Scholar 

  24. Weeks JL, Zoraghi R, Beasley A, et al. High biochemical selectivity of tadalafil, sildenafil and vardenafil for human phosphodiesterase 5A1 (PDE5) over PDE11A4 suggests the absence of PDE11A4 cross-reaction in patients. Int J Impot Res. 2005;17(1):5–9.

    Article  PubMed  CAS  Google Scholar 

  25. Taylor J, Baldo OB, Storey A, et al. Differences in side-effect duration and related bother levels between phosphodiesterase type 5 inhibitors. BJU Int. 2009;103(10):1392–5.

    Article  PubMed  CAS  Google Scholar 

  26. Uckert S, Sormes M, Kedia G, et al. Effects of phosphodiesterase inhibitors on tension induced by norepinephrine and accumulation of cyclic nucleotides in isolated human prostatic tissue. Urology. 2008;71(3):526–30.

    Article  PubMed  Google Scholar 

  27. Zhao C, Kim SH, Lee SW, et al. Activity of phosphodiesterase type 5 inhibitors in patients with lower urinary tract symptoms due to benign prostatic hyperplasia. BJU Int. 2011;107(12):1943–7.

    Article  PubMed  Google Scholar 

  28. Uckert S, Hedlund P, Waldkirch E, et al. Interactions between cGMP- and cAMP-pathways are involved in the regulation of penile smooth muscle tone. World J Urol. 2004;22(4):261–6.

    Article  PubMed  Google Scholar 

  29. Oger S, Behr-Roussel D, Gorny D, et al. Combination of alfuzosin and tadalafil exerts an additive relaxant effect on human detrusor and prostatic tissues in vitro. Eur Urol. 2010;57(4):699–707.

    Article  PubMed  CAS  Google Scholar 

  30. 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.

    Article  PubMed  CAS  Google Scholar 

  31. Minagawa T, Aizawa N, Igawa Y, et al. Inhibitory effects of phosphodiesterase 5 inhibitor, tadalafil, on mechanosensitive bladder afferent nerve activities of the rat, and on acrolein-induced hyperactivity of these nerves. BJU Int. 2012. doi:10.1111/j.1464-410X.2012.11255.x.

    PubMed  Google Scholar 

  32. 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. 2010;183(3):1092–7.

    Article  PubMed  CAS  Google Scholar 

  33. 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.

    Article  PubMed  CAS  Google Scholar 

  34. Porst H, Kim ED, Casabe AR, et al. Efficacy and safety of tadalafil once daily in the treatment of men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia: results of an international randomized, double-blind, placebo-controlled trial. Eur Urol. 2011;60(5):1105–13.

    Article  PubMed  CAS  Google Scholar 

  35. 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.

    Article  PubMed  CAS  Google Scholar 

  36. 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.

    Article  PubMed  CAS  Google Scholar 

  37. Martinez-Salamanca JI, Carballido J, Eardley I, et al. Phosphodiesterase type 5 inhibitors in the management of non-neurogenic male lower urinary tract symptoms: critical analysis of current evidence. Eur Urol. 2011;60(3):527–35.

    Article  PubMed  CAS  Google Scholar 

  38. Taie K, Moombeini H, Khazaeli D, et al. Improvement of urodynamic indices by single dose oral tadalafil in men with supra sacral spinal cord injury. Urol J. 2010;7(4):249–53.

    PubMed  Google Scholar 

  39. Kloner RA, Mitchell M, Emmick JT. Cardiovascular effects of tadalafil. Am J Cardiol A. 2003;92(9):37m–46m.

    Article  CAS  Google Scholar 

  40. Beasley CM Jr, Mitchell MI, Dmitrienko AA, et al. The combined use of ibutilide as an active control with intensive electrocardiographic sampling and signal averaging as a sensitive method to assess the effects of tadalafil on the human QT interval. J Am Coll Cardiol. 2005;46(4):678–87.

    Article  PubMed  CAS  Google Scholar 

  41. Kloner RA, Hutter AM, Emmick JT, et al. Time course of the interaction between tadalafil and nitrates. J Am Coll Cardiol. 2003;42(10):1855–60.

    Article  PubMed  CAS  Google Scholar 

  42. Guillaume M, Lonsdale F, Darstein C, et al. Hemodynamic interaction between a daily dosed phosphodiesterase 5 inhibitor, tadalafil, and the alpha-adrenergic blockers, doxazosin and tamsulosin, in middle-aged healthy male subjects. J Clin Pharmacol. 2007;47(10):1303–10.

    Article  PubMed  CAS  Google Scholar 

  43. Giuliano F, Kaplan SA, Cabanis MJ, et al. Hemodynamic interaction study between the α1-blocker alfuzosin and the phosphodiesterase-5 inhibitor tadalafil in middle-aged healthy male subjects. Urology. 2006;67(6):1199–204.

    Article  PubMed  Google Scholar 

  44. MacDiarmid SA, Hill LA, Volinn W. Lack of pharmacodynamic interaction of silodosin, a highly selective α1a-adrenoceptor antagonist, with the phosphodiesterase-5 inhibitors sildenafil and tadalafil in healthy men. Urology. 2010;75(10):520–5.

    Article  PubMed  Google Scholar 

  45. Goldfischer E, Kowalczyk JJ, Clark WR, et al. Hemodynamic effects of once-daily tadalafil in men with signs and symptoms of benign prostatic hyperplasia on concomitant α1-adrenergic antagonist therapy: results of a multicenter randomized, double-blind, placebo-controlled trial. Urology. 2012;79(4):875–82.

    Article  PubMed  Google Scholar 

  46. Lee JY, Park SY, Jeong TY, et al. Combined tadalafil and α-blocker therapy for benign prostatic hyperplasia in patients with erectile dysfunction: a multicenter, prospective study. J Androl. 2012;33(3):397–403.

    Article  PubMed  CAS  Google Scholar 

  47. Forgue ST, Patterson BE, Bedding AW, et al. Tadalafil pharmacokinetics in healthy subjects. Br J Clin Pharmacol. 2006;61(3):280–8.

    Article  PubMed  CAS  Google Scholar 

  48. Wrishko R, Sorsaburu S, Wong D, et al. Safety, efficacy, and pharmacokinetic overview of low-dose daily administration of tadalafil. J Sex Med. 2009;6(7):2039–48.

    Article  PubMed  CAS  Google Scholar 

  49. Troconiz IF, Tillmann C, Staab A, et al. Tadalafil population pharmacokinetics in patients with erectile dysfunction. Eur J Clin Pharmacol. 2007;63(6):583–90.

    Article  PubMed  CAS  Google Scholar 

  50. Eli Lilly and Company. A study of tadalafil in benign prostatic hyperplasia [ClinicalTrials.gov identifier NCT01183650]. US National Institutes of Health, ClinicalTrials.gov 2012. http://www.clinicaltrials.gov. Accessed 23 May 2012.

  51. Forgue ST, Phillips DL, Bedding AW, et al. Effects of gender, age, diabetes mellitus and renal and hepatic impairment on tadalafil pharmacokinetics. Br J Clin Pharmacol. 2007;63(1):24–35.

    Article  PubMed  CAS  Google Scholar 

  52. Donatucci CF, Brock GB, Goldfischer ER, et al. Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a 1-year, open-label extension study. BJU Int. 2011;107(7):1110–6.

    Article  PubMed  Google Scholar 

  53. Broderick GA, Brock GB, Roehrborn CG, et al. Effects of tadalafil on lower urinary tract symptoms secondary to benign prostatic hyperplasia in men with or without erectile dysfunction. Urology. 2010;75(6):1452–7.

    Article  PubMed  Google Scholar 

  54. Porst H, McVary KT, Montorsi F, et al. Effects of once-daily tadalafil on erectile function in men with erectile dysfunction and signs and symptoms of benign prostatic hyperplasia. Eur Urol. 2009;56(4):727–36.

    Article  PubMed  CAS  Google Scholar 

  55. Porst H, Rajfer J, Casabe A, et al. Long-term safety and efficacy of tadalafil 5 mg dosed once daily in men with erectile dysfunction. J Sex Med. 2008;5(9):2160–9.

    Article  PubMed  CAS  Google Scholar 

  56. Washington SL 3rd, Shindel AW. A once-daily dose of tadalafil for erectile dysfunction: compliance and efficacy. Drug Des Devel Ther. 2010;4:159–71.

    PubMed  CAS  Google Scholar 

  57. Donatucci CF, Wong DG, Giuliano F, et al. Efficacy and safety of tadalafil once daily: considerations for the practical application of a daily dosing option. Curr Med Res Opin. 2008;24(12):3383–92.

    Article  PubMed  CAS  Google Scholar 

  58. Seftel AD, Farber J, Fletcher J, et al. A three-part study to investigate the incidence and potential etiologies of tadalafil-associated back pain or myalgia. Int J Impot Res. 2005;17(5):455–61.

    Article  PubMed  CAS  Google Scholar 

  59. McGwin G Jr, Vaphiades MS, Hall TA, et al. Non-arteritic anterior ischaemic optic neuropathy and the treatment of erectile dysfunction. Br J Ophthalmol. 2006;90(2):154–7.

    Article  PubMed  Google Scholar 

  60. Hazell L, Cornelius V, Wilton LV, et al. The safety profile of tadalafil as prescribed in general practice in England: results from a prescription-event monitoring study involving 16 129 patients. BJU Int. 2009;103(4):506–14.

    Article  PubMed  Google Scholar 

  61. Bella AJ, Brant WO, Lue TF, et al. Non-arteritic anterior ischemic optic neuropathy (NAION) and phosphodiesterase type-5 inhibitors. Can J Urol. 2006;13(5):3233–8.

    PubMed  Google Scholar 

  62. Maddox PT, Saunders J, Chandrasekhar SS. Sudden hearing loss from PDE-5 inhibitors: a possible cellular stress etiology. Laryngoscope. 2009;119(8):1586–9.

    Article  PubMed  CAS  Google Scholar 

  63. McGwin G. Phosphodiesterase type 5 inhibitor use and hearing impairment. Arch Otolaryngology Head Neck Surg. 2010;136(5):488–92.

    Article  Google Scholar 

  64. Lowe G, Costabile RA. 10-Year analysis of adverse event reports to the Food and Drug Administration for phosphodiesterase type-5 inhibitors. J Sex Med. 2012;9(1):265–70.

    Article  PubMed  Google Scholar 

  65. King SH, Hallock M, Strote J, et al. Tadalafil-associated priapism. Urology. 2005;66(2):432.

    Article  PubMed  Google Scholar 

  66. van Dijk MM, de la Rosette JJ, Michel MC. Effects of α1-adrenoceptor antagonists on male sexual function. Drugs. 2006;66(3):287–301.

    Article  PubMed  Google Scholar 

  67. 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 alpha-blockers for lower urinary tract symptoms due to benign prostatic hyperplasia. Eur Urol. 2012;61(5):994–1003.

    Article  PubMed  CAS  Google Scholar 

  68. Liguori G, Trombetta C, De Giorgi G, et al. Efficacy and safety of combined oral therapy with tadalafil and alfuzosin: an integrated approach to the management of patients with lower urinary tract symptoms and erectile dysfunction; preliminary report. J Sex Med. 2009;6(2):544–52.

    Article  PubMed  CAS  Google Scholar 

  69. Cordell WH, Maturi RK, Costigan TM, et al. Retinal effects of 6 months of daily use of tadalafil or sildenafil. Arch Ophthalmol. 2009;127(4):367–73.

    Article  PubMed  CAS  Google Scholar 

  70. Hellstrom WJ, Gittelman M, Jarow J, et al. An evaluation of semen characteristics in men 45 years of age or older after daily dosing with tadalafil 20 mg: results of a multicenter, randomized, double-blind, placebo-controlled, 9-month study. Eur Urol. 2008;53(5):1058–65.

    Article  PubMed  CAS  Google Scholar 

  71. Hellstrom WJ, Overstreet JW, Yu A, et al. Tadalafil has no detrimental effect on human spermatogenesis or reproductive hormones. J Urol. 2003;170(3):887–91.

    Article  PubMed  CAS  Google Scholar 

  72. Wrishko RE, Dingemanse J, Yu A, et al. Pharmacokinetic interaction between tadalafil and bosentan in healthy male subjects. J Clin Pharmacol. 2008;48(5):610–8.

    Article  PubMed  CAS  Google Scholar 

  73. Spence R, Mandagere A, Harrison B, et al. No clinically relevant pharmacokinetic and safety interactions of ambrisentan in combination with tadalafil in healthy volunteers. J Pharm Sci. 2009;98(12):4962–74.

    Article  PubMed  CAS  Google Scholar 

  74. Eli Lilly and Company. A study of tadalafil in men with benign prostatic hyperplasia [ClinicalTrials.gov identifier NCT00970632]. US National Institutes of Health, ClinicalTrials.gov. 2012. http://www.clinicaltrials.gov. Accessed 14 Jun 2012.

Download references

Disclosure

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the author on the basis of scientific and editorial merit.

Author information

Authors and Affiliations

  1. Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore, 0754, Auckland, New Zealand

    Monique P. Curran

Authors
  1. Monique P. Curran
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Monique P. Curran.

Additional information

The manuscript was reviewed by: M. Gacci, Department of Urology, University of Florence, Florence, Italy; H. Porst, Private Practice of Urology and Andrology, Hamburg, Germany.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Curran, M.P. Tadalafil. Drugs Aging 29, 771–781 (2012). https://doi.org/10.1007/s40266-012-0010-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40266-012-0010-7

Keywords

Search

Navigation