Medical Therapy

Medical therapy of BPH can be broadly divided into antiadrenergic and antiandrogenic approaches. The α1-adrenergic receptor antagonists (alpha-blockers) and 5-alpha reductase inhibitors (5-ARIs) are well-established representatives of the two approaches.

  • α1-Adrenergic receptor antagonists are effective in reducing the dynamic component of BPH, as they reduce prostatic smooth muscle tone, relieving bladder outlet obstruction12
  • 5-ARIs based on androgen deprivation therapy have been shown to be effective in addressing the static component of BPH by reducing the physical size of the prostate12 
  • Combination therapy with α1-adrenergic receptor antagonists and 5-ARIs has been shown to be more effective in providing symptom relief and preventing BPH progression than monotherapy with either type of agent in certain patient populations12

α1-Adrenergic receptor antagonists

The α1-adrenergic receptor antagonists, or alpha-blockers, are considered first-line medical therapy for treating symptomatic BPH. These agents work by binding to α1-adrenergic receptors in the bladder neck and prostate and preventing sympathetic activation of these receptors by the neurotransmitter norepinephrine. This action relaxes the bladder and prostate smooth muscle tissue, decreasing urethral resistance, improving urine flow, and reducing BPH symptoms.12

The alpha-blockers used in the treatment of BPH include: alfuzosin, doxazosin, terazosin, tamsulosin, and silodosin (RAPAFLO®). Meta-analyses of data from studies of alfuzosin, doxazosin, terazosin, and tamsulosin indicate that they are similarly effective in relieving symptoms. However, the adverse event profile of these agents is slightly different.12

The most common side effects of alpha-blockers include dizziness, orthostatic hypotension, nasal congestion, and ejaculatory problems.12

Learn more about RAPAFLO®'s selectivity profile.

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5-alpha reductase inhibitors

5-ARIs inhibit the production of dihydrotestosterone, the primary androgen regulating growth of the prostate. 5-ARIs address the static component of BPH and relieve mechanical obstruction of the bladder by shrinking the prostate, but they have no effect on smooth muscle tone. Although 5-ARIs reduce the size of the prostate by ~25% in 3 to 6 months, they are less effective than alpha-blockers in relieving BPH symptoms, particularly in men without prostatic enlargement.12  In clinical trials significant symptom relief did not become apparent for 6 months.33

These agents are indicated for patients with particularly large prostates, in whom prostate size may contribute to the severity of symptoms. 5-ARI therapy is not appropriate for men with BPH symptoms who do not have evidence of prostate enlargement.12

Patients should be informed of the sexual side effects of 5-ARIs before starting treatment so that they can make an informed decision.12

Currently available 5-α reductase inhibitors include finasteride and dutasteride. Finasteride selectively inhibits the type 2 form of 5-α reductase whereas dutasteride inhibits both type 1 and type 2 isoforms. Although dutasteride therapy results in lower serum DHT levels, it is not clear whether there are significant differences in their clinical profile.33

The most commonly reported adverse events associated with 5-α reductase inhibitors are sexual side effects, including impotence, ejaculatory disorders, and decreased libido.33

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Combination therapy

Combination therapy with an α1-adrenergic receptor antagonist and 5-ARI addresses both the static and dynamic components of BPH. The α1-adrenergic receptor antagonist relaxes the smooth muscle of the prostate and urethra, while the 5-ARI reduces the size of the prostate. Patients with severe symptoms, large prostates and high PSA values who are at highest risk of disease progression are thought to benefit most from combination therapy with an α1-adrenergic receptor antagonist and 5-ARI.12

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References
  1. Fenter TC, Naslund MJ, Shah MB, et al. The cost of treating the 10 most prevalent diseases in men 50 years of age or older. Am J Manag Care. 2006;12(4 suppl):S90-S98.
  2. RAPAFLO® (silodosin) Capsules full Prescribing Information, November 2009.
  3. Marks LS, Gittelman MC, Hill LA, Volinn W, Hoel G. Rapid efficacy of the highly selective α1A-adrenoceptor antagonist silodosin in men with signs and symptoms of benign prostatic hyperplasia: pooled results of 2 phase 3 studies. J Urol. 2009;181:2634-2640.
  4. National Institute of Diabetes and Digestive and Kidney Diseases. Prostate enlargement: benign prostatic hyperplasia. NIH Publication No. 07-3012. June 2006.
  5. Bruskewitz RC. Quality of life and sexual function in patients with benign prostatic hyperplasia. Rev Urol. 2003;5:72-80.
  6. Roberts RO, Jacobsen SJ, Rhodes T, et al. Natural history of prostatism: impaired health status in men with lower urinary tract symptoms. J Urol. 1997;157:1711-1717.
  7. http://www.dictionary.com
  8. Atlas of Human Anatomy, Frank H. Netter, MD, Ciba-Geigy Corporation, Summit, NJ, 1989.
  9. Data on file, Watson Laboratories, Inc.
  10. Marks LS, Gittelman MC, Hill LA, Volinn W, Hoel G. Silodosin in the treatment of the signs and symptoms of benign prostatic hyperplasia: a 9-month, open-label extension study. Urology. 2009;74:1318-1322.
  11. Agency for Healthcare Quality and Research (U.S. Dept Health and Human Services): Quick Tips When Talking With Your Doctor. Available at: http://www.ahrq.gov/consumer/quicktips/doctalk.htm. Accessed July 28, 2010.
  12. American Urological Association. AUA guideline on management of benign prostatic hyperplasia (2003). Chapter 1: Diagnosis and treatment recommendations. J Urol. 2003;170:530-547.
  13. Fagelman E, Lowe FC. Herbal medications in the treatment of benign prostatic hyperplasia (BPH). Urol Clin N Am. 2002;29:23-29, vii.
  14. National Institute on Aging: Talking With Your Doctor: A Guide For Older People. NIH Publication No. 05-3452. August 2005 (Reprinted April 2010). Available at: http://www.nia.nih.gov/NR/rdonlyres/90DF996C-DF5F-4245-B7CA-B2E1B993D8C7/0/TWYD_0521_web.pdf. Accessed July 29, 2010.
  15. Medline Plus Medical Encyclopedia from NIH: Enlarged Prostate. Available at: http://www.nlm.nih.gov/medlineplus/ency/article/000381.htm. Accessed July 29, 2010.
  16. Shvartzman P, Borkan JM, Stoliar L, et al. Second-hand prostatism: effects of prostatic symptoms on spouses’ quality of life, daily routines and family relationships. Family Pract. 2001;18:610-613.
  17. Kuritzky L. A primary care physician’s perspective on benign prostatic hyperplasia. Rev Urol. 2003;5(suppl 5):S42-S48.
  18. Wolters R, et al: Lower urinary tract symptoms: social influence is more important than symptoms in seeking medical care. BJU Int. 2002;90:655–661.
  19. Rosen RC, Giuliano F, Cason CC. Sexual dysfunction and lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Eur Urol. 2005;47:824–837.
  20. Ponholzer A, Madersbacher S. Lower urinary tract symptoms and erectile dysfunction; links for diagnosis, management and treatment. Int J Impot Res. 2007;19:544-550.
  21. MacDiarmid SA, Hill LA, Volinn W, Hoel G. 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;75:520-525.
  22. Marks LS. Reply to editorial comment. Urology. 2009;74:1323-1324.
  23. Schwinn DA, Roehrborn CG. α1-Adrenoceptor subtypes and lower urinary tract symptoms. Int J Urol. 2008;15:193-199.
  24. Straus SM, Kors JA, De Bruin ML, et al. Prolonged QTc interval and risk of sudden cardiac death in a population of older adults. J Am Coll Cardiol. 2006;47:362-367.
  25. Carbone DJ, Hodges S. Medical therapy for benign prostatic hyperplasia: sexual dysfunction and impact on quality of life. Int J Impot Res. 2003;15:299-306.
  26. Nomiya M, Yamaguchi O. A quantitative analysis of mRNA expression of alpha 1 and beta-adrenoceptor subtypes and their functional roles in human normal and obstructed bladders. J Urol. 2003;170(2 Pt 1):649-653.
  27. Murata S, Taniguchi T, Takahashi M, et al. Tissue selectivity of KMD-3213, an α1-adrenoreceptor antagonist, in human prostate and vasculature. J Urol. 2000;164:578-583.
  28. Stafford-Smith M, Bartz R, Wilson K, et al. Alpha-adrenergic mRNA subtype expression in the human nasal turbinate. Can J Anesth. 2007;54:549-555.
  29. Wei JT, Calhoun E, Jacobsen SJ. Urologic Diseases in America Project: benign prostatic hyperplasia. J Urol. 2008;179(5 Suppl.):S75-S80.
  30. Issa MM, Regan T. Medical therapy for benign prostatic hyperplasia—present and future impact. Am J Manag Care. 2007;13:S4-S9.
  31. Berry SJ, Coffey DS, Walsh PC, et al. The development of human benign prostatic hyperplasia with age. J Urol. 1984;132:474.
  32. Nickel JC. Comparison of clinical trials with finasteride and dutasteride. Rev Urol. 2004;6 Suppl 9:S31-39.
  33. Hernández C, Estivill E, Prieto M, et al. Nocturia in Spanish patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH). Curr Med Res Opin. 2008;24:1033-1038.

RAPAFLO® is indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH). RAPAFLO® is not indicated for the treatment of hypertension.

Important Safety Information

RAPAFLO® is contraindicated in patients with severe renal impairment (CCr <30 mL/min), severe hepatic impairment (Child-Pugh score ≥10), and with use of strong CYP3A4 inhibitors. Postural hypotension with or without symptoms (eg, dizziness) may develop when beginning treatment with RAPAFLO®. As with all alpha-blockers, there is a potential for syncope. Patients should be warned of the possible occurrences of such events and should avoid situations where injury could result. RAPAFLO® should be used with caution in patients with moderate renal impairment. Patients should be assessed to rule out the presence of prostate cancer prior to starting treatment with RAPAFLO®. Patients planning cataract surgery should inform their ophthalmologist that they are taking RAPAFLO®.

The most common side effects are retrograde ejaculation, dizziness, diarrhea, orthostatic hypotension, headache, nasopharyngitis, and nasal congestion.