Korean J Urol.  2006 Sep;47(9):1001-1006. 10.4111/kju.2006.47.9.1001.

Drug Interaction Study of Vardenafil 20mg and Doxazosin 4mg or Tamsulosin 0.2mg in Patients with Benign Prostatic Hyperplasia and Erectile Dysfunction to Evaluate Changes in Blood Pressure

• Lee SY
• Kim SC
• Kim HW

• KMID: 2294099
• DOI: http://doi.org/10.4111/kju.2006.47.9.1001

Abstract

Purpose
This study aimed at evaluating the expected additive blood pressure (BP) lowering effect of vardenafil when administered in the background of chronic alpha1-blocker therapy.
Materials and Methods
Patients (n=90) with symptomatic benign prostatic hypertrophy (BPH) and erectile dysfunction (ED) took vardenafil 20mg in the morning following repeated doxazosin gastrointestinal therapeutic system (GITS) 4mg (n=60) or tamsulosin 0.2mg (n=30) HS a day for 30 days. The standing and sitting BP at baseline, before taking the vardenafil and 30 minutes and 1 hour post vardenafil were measured 3 consecutive times. The data were analyzed by Student's t-test (paired), repeated measures of two-way ANOVA, chi-square tests and Pearson correlation analysis.
Results
Doxazosin produced a significant reduction in systolic/diastolic BP ( 12.3/ 6.7mmHg), but tamsulosin did not. In the doxazosin group, the average reductions in BP from baseline ( 24.7/ 15.8mmHg) were significantly higher than that for the tamsulosin group ( 14.6/ 7.5mmHg). However, the average BP change was not different in both group ( 12.4/ 9.1mmHg in the doxazosin group and 11.3/ 6.4mmHg in the tamsulosin group) following a single dose of 20mg vardenafil. The higher the BP was at baseline, the more the reduction in BP was in both the doxazosin and tamsulosin groups. Two patients of tamsulosin showed a sitting systolic BP <85mmHg, but they didn't experience dizziness.
Conclusions
We recommend starting Vardenafil treatment in the background of chronic aalpha1 blocker therapy, including tamsulosin, with a low dose and to increase the dose by monitoring the BP, particularly for the patients with hypertension.

Keyword

Doxazosin; Tamsulosin; Vardenafil; Blood pressure

MeSH Terms

Blood Pressure*
Dizziness
Doxazosin*
Drug Interactions*
Erectile Dysfunction*
Humans
Hypertension
Male
Prostatic Hyperplasia*
Vardenafil Dihydrochloride
Doxazosin

Reference

1. Cha JS, Park JK. Association between lower urinary tract symptoms and erectile dysfunction. Korean J Urol. 2005. 46:1023–1027.

2. Burchardt M, Burchardt T, Baer L, Kiss AJ, Pawar RV, Shabsigh A, et al. Hypertension is associated with severe erectile dysfunction. J Urol. 2000. 164:1188–1191.

3. McVary KT. Erectile dysfunction and lower urinary tract symptoms secondary to BPH. Eur Urol. 2005. 47:838–845.

4. McVary KT, McKenna KF. The relationship between erectile dysfunction and lower urinary tract symptoms: epidemiological, clinical, and basic science evidence. Curr Urol Rep. 2004. 5:251–257.

5. van Moorselaar RJ, Hartung R, Emberton M, Harving N, Matzkin H, Elhilali M, et al. Alfuzosin 10mg once daily improves sexual function in men with lower urinary tract symptoms and concomitant sexual dysfunction. BJU Int. 2005. 95:603–608.

6. Sairam K, Kulinskaya E, McNicholas TA, Boustead GB, Hanbury DC. Sildenafil influences lower urinary tract symptoms. BJU Int. 2002. 90:836–839.

7. Gillenwater JY, Conn RL, Chrysant SG, Roy J, Gaffney M, Ice K, et al. Doxazosin for treatment of benign prostatic hyperplasia in patients with mild to moderate essential hypertension: a double-blind, placebo-controlled, dose-response multicenter study. J Urol. 1995. 154:110–115.

8. Kaplan SA, Meade-D'Alisera P, Quinones S, Soldo KA. Doxazosin in physiologically and pharmacologically normotensive men with benign prostatic hyperplasia. Urology. 1995. 46:512–517.

9. Nieminen T, Ylitalo R, Koobi T, Ylitalo P, Kahonen M. The vasodilatory effect of alfuzosin and tamsulosin in passive orthostasis: a randomised, double-blind, placebo-controlled study. Eur Urol. 2005. 47:340–345.

10. Pomara G, Morelli G, Pomara S, Taddei S, Ghiadoni L, Dinelli N, et al. Cardiovascular parameter changes in patients with erectile dysfunction using PDE-5 inhibitors: a study with sildenafil and vardenafil. J Androl. 2004. 25:625–629.

11. Kloner RA. Cardiovascular effects of the 3 phosphodiesterase-5 inhibitors approved for the treatment of erectile dysfunction. Circulation. 2004. 110:3149–3155.

12. Kostis JB, Jackson G, Rosen R, Barrett-Connor E, Billups K, Burnett AL, et al. Sexual dysfunction and cardiac risk (the Second Princeton Consensus Conference). Am J Cardiol. 2005. 96:313–321.

13. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003. 289:2560–2572.

14. Fulton B, Wagstaff AJ, Sorkin EM. Doxazosin. An update of its clinical pharmacology and therapeutic applications in hypertension and benign prostatic hyperplasia. Drugs. 1995. 49:295–320.

15. de Mey C. Cardiovascular effects of alpha-blockers used for the treatment of symptomatic BPH: impact on safety and well-being. Eur Urol. 1998. 34:Suppl 2. 18–28.

16. Mazzu A, Sundaresan P, Xia C. An interaction study to evaluate changes in blood pressure and pulse rate following vardenafil compared to placebo treatment on the background of the alpha-blockers, tamsulosin and terazosin, in separate cohorts of patients with benign prostatic hyperplasia. Bayer Pharmaceutical data file. 2003.

17. Spera P, Dabiri G, Ilson B, Montague T, Patel B, Diringer K. A radnomized, double-blind, placebo-controlled, two-part, three period crossover drug interaction study of vardenafil (10mg and 20mg) and tamsulosin (0.4mg) in healthy males aged 45 to 75 to evaluate changes in blood pressure. Bayer Pharmaceutical data file. 2003.

18. Cases A. Doxazosin in a gastrointestinal therapeutic system formulation. Drugs Today (Barc). 2000. 36:679–688.

19. Chapple CR, Carter P, Christmas TJ, Kirby RS, Bryan J, Milroy EJ, et al. A three month double-blind study of doxazosin as treatment for benign prostatic bladder outlet obstruction. Br J Urol. 1994. 74:50–56.

20. Fawzy A, Braun K, Lewis GP, Gaffney M, Ice K, Dias N. Doxazosin in the treatment of benign prostatic hyperplasia in normotensive patients: a multicenter study. J Urol. 1995. 154:105–109.

21. Kloner RA, Mohan P, Segerson T, Thibonnier M, Norenberg C, Padma-Nathan H. Cardiovascular safety of vardenafil in patients receiving antihypertensive medication: a post-hoc analysis of five placebo-controlled clinical trials. J Am Coll Cardiol. 2003. 41:276A.

22. Cheitlin MD, Hutter AM Jr, Brindis RG, Ganz P, Kaul S, Russell RO Jr, et al. ACC/AHA expert concensus document use of sildenafil (Viagra) in patients with cardiovascular disease. J Am Coll Cardiol. 1999. 33:273–282.

23. Kloner RA, Mitchell M, Emmick JT. Cardiovascular effects of tadalafil. Am J Cardiol. 2003. 92:37M–46M.

24. Auerbach SM, Gittelman M, Mazzu A, Cihon F, Sundaresan P, White WB. Simultaneous administration of vardenafil and tamsulosin does not induce clinically significant hypotension in patients with benign prostatic hyperplasia. Urology. 2004. 64:998–1003.