Results of Switching Terazosin and Doxazosin in the Treatment of Bph

Kocatepe Tip Dergisi (2002),2, 119-130 The Medical Journal ofKocatepe • 2002, Afyon Kocatepe Oniversitesi RESULTS OF SWITCHING TERAZOSIN AND DOXAZOSIN IN THE TREATMENT OF BPH

Murat SAM LI, Cetin DiN<;EL

Afyon Kocatepe University. Faculty of Medicine. Department Of Urology. Afyon

ABSTRACT:Objective: Medical treatment of the BPH is one of the alternatives among a variety of therapeutic options. Doxazosin and terazosin are the most widely used molecules in the treatment of BPH . We compared the effectivity of these molecules by switching the drug in those who did not benefit from the first drug. Methods: This was a prospective randomized study. Patients in the study were similar in age, prostatic weight, International Prostatic Symptom Score (I-PSS), uroflow parameters and PSA levels. Fifty men (mean age 59.4 years, SD 7.6, range 48-78) received either doxazosin (25 men), or terazosin (25 men), once daily at night. Patients were evaluated at one, 2 and 3 month s. Improvement in I-PSS and the maximal flow rate (Qmax) by minimum 20% was accepted as improvement. Patients who showed improvement in Hone of the parameters have switched the drug and these patients were followed in the next 3 months. Results: Of the 25 men using doxazosin, I I (44%) showed improve ment both in I-PSS and Qmax at 3 month s. Of the 25 men using terazosin, 10 (40%) showed improvement both in I-PSS and Qmax at 3 months (p>0.05). After 3 months of treatment, the peak urinary flow rate increas ed significantly (p< 0.001) for both doxazosin (+4.5 mLls) and terazosin (+3.1 mLls) groups. The International Prostatic Symptom Score improved significantly (P< 0.01) with both alpha-blockers after 3 month s of treatment in these groups. Nineteen patients, who did not show improve ment in any of the parameters, switched the drug. Of the patients who switched the drug, 2 (4%) showed improvement both in I-PSS and in the peak urinary flow rate, 2 (4%) showed improvement only in I-PSS but not in the peak urinary flow rate and 15 (30%) did not show improvement in any of the parameters. Conclusion: These results suggest that alpha blockade with either doxazosin or terazosin is effective in men with symptomatic BPH . Two of the alpha-blocking molecules showed equal effectivity in the treatment of BPH. If one of the molecules is ineffective in the treatment of BPH , then the other molecule will probably be ineffective. [Key Words: terazosin, doxazosin, benign prostatic hyperplasia, drug switch]

INTRODUCTION In the I970s, the pioneering work of Caine led to the discovery of alpha-J­ Men over the age of 50 will probable have adrenoceptor predominance in the prostatic benign prostatic hyperplasia (BPH) at a rate of stroma and capsule. This finding triggered the about 85%. Also 50% of the men will require search for a-receptor blocking agents in treatment at their eighties [1]. Medical patients with lower urinary tract symptoms treatment of the BPH is one of the alternatives sugges tive of bladder outflow obstruction [2]. among a variety of therapeutic options. The initial agents were derived from Various types of surgery, medical treatment antihyper tensive drugs because of the a­ with alpha- l-u drenergic antagonists or 5-alpha­ receptor blocking capability [3]. Recently, reductase inhibitors are included in the options severa l investigations have detected of treatment. significantly more alpha- l-adre nergic receptors

119 in hypertrophic prostatic tissue than in normal agents are similar, this may not prove the tissue [4, 5, 6) and that blocking urethral alpha­ effectiveness of the agents are similar. We l- adrenoceptors causes the prostatic urethra to investigated whether one of the alpha- I­ relax [7). More recently, several prostate blockers is not effective; is it rational to expect ­, specific drugs have been introduced. During some improvement with another alpha- I­ II the last 2 decades, the therapeutic efficacy of blocker. these drugs has been clearl y demonstrated in f several clini cal trials, and today alpha- l ­ MATERIAL AND METHODS adrenocept or blockers are the first line medical treatment for lower urinary tract symptoms This is a two-armed, randomized study suggestive of bladder outlet obstruction [8). and lasted about 1,5 year. The pretrial The alpha- l -blockers are valued for rapid onset assess ment and establishing a baseline to of action, effectiveness independent of prostate evaluate the effect of treatment required each . size, minimal influence on sexual function and patient to undergo a history and symptom good therapeutic profile [9]. assessment, digital rectal examination (ORE), We searched the literature for doxazosin transrectal ultrasound (TRUS), and and terazosin switch or conversion protocols. uroflowmet ric analysis. The severi ty of One of the 2 studies we found in the literature symptoms was assesse d subjectively using the that investigated both drugs looked at which Intern ational Prostatic Symptom Score (I-PSS) dosage of each agent control blood pressure (maximum 35 points). Objective symptoms of [10]. This study also did not provide an BPH were evaluated by uroflowmetry [12]. appropriate conversion dosage for patients with Inclusion criteria of the study can be seen in benign prostatic hyperplasia. The other study Table (I ). Parameters of the patients enrolled in the literature reported the conversion of in the study are listed in Tabl e (2). Patients doxazosin to terazosin to determine whether were excluded if they had urinary tract the switch would lead to differences in BPH infection (> 10 white blood cell/hi gh power symptoms, blood pressure or adverse effects field), prostate cancer, had any other [II]. medication that would interfere with doxazosin In this study, we planned to investigate and terazosin or underwent prostatic surgery. 1­ whether different types of alpha-I-blockers PSS and quality of life scores (QOL score) may have different clini cal responses. However were evaluated by the same physician. the molecular structures of the alpha- I-blocker

Table 1. Inclusi on criteria

Parameter Value Qma x <15 mLis I-PSS score 28 PSA <4.0 ng/mL ORE No sign of malignancy TR US Any volume of prostate

120 Table 2. General parameters of the patients

Age (yea rs) Prostate Vol. (mL) I-PSS score QOL score Qmax verage flow rate mean±S.D. 59,4±7,6 9, 1± 16,5 14,1±5,4 3,7±1,l min-max 14-83 8-28 2-6

Fifty patients with symptomatic BPH the treatment period was the maximum urinary study randomly assigned to terazosin (n = 25) or flow rates (Qmax). Improvement was defined 'al doxazosin (n = 25). Terazosin 10 mg and as a 20% decrease from baseline in I-PSS and doxazosin 8 mg once daily was administered 20% increase from baseline in Qmax. for 12 weeks. Symptoms were evaluated using Increasing QOL score by I point was detected, the International Prostate Symptom Sco re (I­ but it was not accepted as one of the PSS), and quality of life score (QOL) was improvement criteria (Table 3). Advers e assessed subjec tively before treatment , and reactions potentially related to the study drugs again after four, 8 and 12 weeks of treatment. were recorded throughout the treatment period. Objective measurement taken before and after

Table 3. The criteria for evaluating treatment efficacy

favorabl Parameter unfavorable e I-PSS score; after treatment to baseline ~20 % < 20% [(before treatment)-(after treatment)]/[before treatment] Qmax (mLlsec) ; after treatment to baseline ~20 % <20% [(after treatment)-(before treatment)]/[before treatment]

The following protocol was used in drug evaluated every 4 weeks and reassessment was dose regimen; in the doxazosin group, patients employed with I-PSS, uroflowmetry and PSA started from 1mg and increased to 8mg, and in measurements. At the end of the 12 weeks of the terazosin group, patients started from 1mg treatment Qmax, I-PSS score were assessed and increased to 10mg. Patients switched whether to continue the drug or switch the drug doxazosin to terazosin or terazosin to with the other one. Ten patients on terazosin doxazosin with the following protocol; arm and nine patients on doxazosin arm did not doxazosin 8 mg to 10 mg terazosin, and 10 mg show improvement in I-PSS score and Qmax, terazosin to 8 mg doxazosin. so they had their drug switched with the other Treatment and follow-up flowchart was one after 2 weeks of washout period . These represented in Fig. (I). Twenty-five patients in patients were followed-up for more 3 months each arm of the treatment scheme were to evaluate effectiveness of the switched drug. randomized for the each drug. Patients were

121 BPH Symptoms IPSS Uroflowmelry n=50 TRUS,PSA,DRE

no FOll OW-Up

Medical lreatment n=25 n=25 Randomization for Doxazosin vs Terazosin

Doxazosin; Terazosm: Evaluation at 1, 2, 3 mos. Evaluation at 1, 2, 3 mos. IPSS, Uroflow ., PSA IPSS, Uroflow., PSA artial Success With Drug

yes yes

n=11 n=10 (44%) (40%)

cont. drug cont. drug n=9 n=10 no no (36%) (40%)

Change Drug Doxazosin toTerazosin Terazosi n to Doxazosin

n=10 n=9 ..

Doxazosin; Terazosin; Evaluation at 1,2, 3 mos. Evaluation at 1, 2, 3 mos. IPSS, Uroflow.. PSA IPSS, Uroflow.. PSA

artial Succe ss With 1 Drug n= l n=1 (11 %) (10%) yes yes

n=7 (70%) n=8 (88%)

no no

Other Modes of Treatmen t

Fig. 1. Treatment and follow-up scheme

122 Statistical Analysis improvement in Qmax value or I-PSS score (4 Changes in urodynamic parameters, I-PSS showed improvement in I-PSS and 1 in Qmax and QOL scores between baseline and, 3- and value in the doxazosin arm, and 3 showed 6-month follow-up were determin ed, and p improvement in I-PS S and 2 in Qmax value in values were calc ulated with the Wilcoxon the terazosin arm). These patients were not signed-rank test. Chi-square test with Yates' included in the switching the drug program. correction for co ntinuity is applied to analyze Nine patients (36 %) using doxazosin and 10 the percent ages on the treatment scheme. patients (40%) using terazosin did not show Friedman test for several related samples was any improve ment in those parameters. These used to analyze the values of a parameter, patients had their drug sw itched; nine patient s measured during the study at different times. began to use terazosin instead of doxazosin and Improvement s with drugs were eva luated with 10 patients began to use doxazosin instead of Kolm ogorov-Smi rnov test. terazosin. These patients were in follow-up for more 3 month s du ration. The results of the RESULTS patients who swi tched the drug were as follows; out of 10 patients who switched Patients characteristics at baseline are terazosin-to-doxazosin; 1 (10 %) showed presented in Table (4). Patients in the both arm improvement in both parameters, 7 (70 %) did of the treatment were homogenous. There was not show improvement in any of the no statistical difference between the ages of the parameters and 2 (20%) showe d imp rovement patients, prostate volume, I-PS S sco re, QOL only in I-PSS score. On the other hand, out of score, Qmax values and PSA levels of the nine patients who switched doxazosin-to­ groups. terazosin; one ( 11%) showed improvement in Fig. (I) represents the treatment and both parameters and 8 (88%) did not show follow-up of the patients. There were twenty­ improvement in any of the parameters. None of five patient s on each arm of the treatment the patients showe d improve ment in Qmax and program. Of these 11 (44% ) patients on the in I-PSS score. Statistical analyses of the doxazosin arm and 10 (40 %) patient s on the percents on eac h branch of the treatment arms terazosin arm showed improvement in both were statistically insignificant (Chi-square test Qmax value and I-PS S sco re. Five patients on with Yates' correction for con tinuity is applied ; each of the treatment arms showed either p>0.05).

Table 4. Predru g assess ment of the patients in eac h gro up.

Pts. Age (years) Prostate vol (mL) I-PSS score QOL score PSA (ng/mL) Qmax (mLisec)

Doxazosin l\IeantS.D. 58,7±8,7 ~7 ,4± 15, 2 14,4±6,2 3,7±1,2 2,5±2 ,1 10,8±2,7 Min.-max. 148-78 14-83 8-28 2-6 0,60-1,1 5-14 Terazosin MeantS.D. 60±6,3 50,8± 17,9 13,8±4,4 3,8± 1,1 2,3±1,1 11,5±1,9 Min.-max. 149-71 2 1-83 8-2 1 2-6 0,4 3-3,9 8- 14

~Iann Wh itney-U test; p>0.05 for all parameters.

123 Tab le (5) shows that the effec tive ness of test for several related samples was applied to the drugs was equal in patients who respo nd analyze the difference betw een base line, three favorably to the trea tment. Graphic and 6 mo nths' values of I-PSS score, QOL prese ntation on Fig (2) is an alternative method score and Qmax value for the eac h treatment for eva luating the improvement of alpha- l ­ arms . However, statist ical differences were blockers advocated by The International detected betwee n baseline and at 3 and 6 Consultation on BPH (ICBPH) rI 3]. It is easy month values, improvement of the parameters to eva luate the percen t of patients who were not equal or more than 20%, so the achieved some change in the I-PSS score. As patient s were acce pted as unres ponsive to the an example, if change in the I-PSS score (- 3) treatment. Moreover, no statistical diffe rence was accepted as a reference then as it could be was detected between QOL score and Qmax seen on the graph, more than 60% of patients value in the terazosin arm. showed improvement. No statistical difference Table (7) shows the changes in the PSA between the efficacies of the drugs was value of the patients during 6-mo nth follow-up. detected (Kolmogorov-S mirnov test; p=0.99) However a decrease in the level of PSA co uld Tab le (6) represents the outcome of the be seen, the difference was not statistically patie nts afte r 6 months of treatment who did significant (Friedman test for several related not improve after 3 months of treatment of one samples, p>0.05). drug and swi tched to the other drug. Friedma n

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I-PSS Changes

Fig. 2. Cumulative freq uency distribution of impro veme nt for doxazosin and terazosin for patients after 3 months of treatmen t. Kolmogorov-Smirnov test; p=0.99

124 o Table 5. Clinical and urodynamic outcomes of patients who showed favorab le results after 3 months of treatment with one of the alpha l-blockers

Doxazosin Terazosin p* Qmax l 3.l i 3.1 l 2.9i 2.3 >0.05 I-PSS 8.2i3.7 8.3i 4.2 >0.05 QOL 2.7iO.97 2.8iO .95 >0.05

"Mann Whitney-U test

Table 6. Clinical and urodynamic outcomes of patients who had their drug switched

i I l-PSS I I-PSS I r.rss I p* I QOL :I QOL I QOL I p* I Qma x I Qmax I Qma x p* i Baseline At 3 mo At 6 1110 Baseline At 3 mo At 6 mo Baseline At 3 mo Al 6 mo l>oxazosin arm r.t ean:!S.D 1 13.3±4, 3 1 1I .5±3.7 1 10.3±3.4 1<0.0 5 13.6±0.8 I 3.3±0.8 1 2.9±0.7 I<0.05 I 12. 1+1.6 I 11.4+ 1.3 I 13.3+1.6 <0.05 :rerazosin arm l\kan- S.D 1 10.+3.9 1 9.7+3.2 I 8.9+2.7 1 <0.0513.2+0.6 13 .2+0.61 2.5+1.2 1>0.05 1 11.5+2 111 .3+2.211 2.4 +2.4 >0.05

"Friedman Test for severa l related samples

Table 7. PSA changes of the patients shows the changes in the PSA value of the patients during 6 month follow-up.

i' PSA base line PSA at 31h month PSA at 6t h mon th p* Doxazosin arm Me.m±S.D. 2.5i2.l 1.9i O.6 1.3i O.8 >0.05 Terazosin arm "Iean.::S.D. 2.3il l.7iO.7 1.6i O.9 >0.05

-Friedman Test for several related samples

In our group of patients, one patient in the DISCUSSION ~ arm complained of dizziness, but did not c:.sed him to give up taking the drug. The other Multiple methods of minimally invasive JIIieol on the terazosin arm complained of erectile surgical therapies have been introduced in the ~ and caused him to give up taking the last decade. These methods include balloon ~ This patient showed only improvement in the 1­ dilatation, temporary and permanent urethral I5SSOJe. stents, various laser techn iques, microwave Fifte:en patients did not benefit from both of the thermotherapy, transurethral needle ablation, ....l-bkxkers, Transurethral endoscopic surgery electrovaporization, and high-int ensity focused ...pbmerl for these patients. Endoscopicevaluation ultrasound. Alpha- J-receptor blockers to .*:se (l!lients revealed minimal urethral stricturein reduce the sympathetic tone of the prostate are 2p11il::ols and bladder neck contracture in 3 patients. considered as first-line therapy to relieve the .... \U ot 15 patients did not show additional symptoms of benign prostatic hyperplasia 114J . ~. a 0 for unresponsiveness to both of the alpha­ The rationale for selective alpha- I-blockade in LiiJtXexs. Transurethral resection of the prostatic benign prostatic hyperplasia (BPH) is based ~.a; ~Iied to these patients. upon the observations that the prostate

125 adenoma contains betw een 20% and 40% Another published data by Kapl an et al smooth muscle and the co ntractile properties of suggested that efficacy of terazosin and prostatic smoot h muscle are mediated by the doxazosin was not affected by the dosin g alpha-l -adre noce ptor [15J. Selective alpha- l­ schedule. Adverse eve nts were also receptor block ers . relax prostatic smoo th significantly decreased by dosing in the muscle, relieve bladd er outlet obstruction, and evening period [21, 22 J. enhance urine flow with fewer side effects. Literature about the side effect of these Several alpha-blockers are available for drugs reports dizziness, headach e, postura l treatment of ben ign prostatic hyperpl asia, hypoten sion, and retrograde ejaculation [16J. including alfuzosi n, tarnsulosin, terazos in, and The most co mmon adverse events of terazosin doxazosin. Different meta-an alyses have and doxazosin resul ting in premature shown these age nts to be comparable in terms term ination were dizziness (6.7-10.7%), of efficacy in improving symptom score and asthenia (3.8-7.5% ), peripheral edema (4.0%) increasing urinary flow rates [16J. and somnolence (2.0%) [22, 23 , 24J. However, In this study, we planned to compare the publi cations proposed the alpha-blockers has efficacy of doxazosin and tera zosin by not been associated with an incre ased switching the drug on the same patient who did incidence of erect ile dysfun ction as a side not show improvement with the prev ious drug. effect [25], some authors published erectile Patients were selected randoml y to prescribe dysfunction (3-7%) as an adverse drug reaction one of the drug and followed during the first 3 of alpha- l -blocking drugs. [26, 27J months' dur ation . The dru g was switched if the Under the light of these studies, patients evaluation of the patient show ed unfavorable in the doxazosin arm received 8 mg and in the result s at the end of the 3'd month. Patient s who terazosin arm received 10 mg da ily at night and switched the drug were also followed for more the follow-up period was limi ted to 3 months 3 months' duration and evaluated wh ether they duration to evaluate the efficacy of the drug. show improvement in the same parameters. Patients on the both treatment arm co nsumed In the literature, a dose of 8 mg. the drug in a titrated way from I mg to 8 mg in doxazosin was found to be more efficacious the doxazosin arm and I mg to 10 mg in the than 4 mg. and the side effects associated with terazosin arm within a week period. Patients both dosages appeared to be similar. who consumed their drug in this schedule were MacDi armid et al co ncluded that the 8 mg. not affected seriously by side effects. Onl y one dose sho uld be tried in patient s who have not patient in the doxazosin arm reported dizziness achie ved an adeq uate therapeuti c response to 4 (4%) and another patient in the terazosin arm mg. and are tolerating the med ication [17J. reported erectile dysfun ction (4%). Kaplan reported that 10mg of terazosi n and The efficacy of the alph a-f-blocker age nt 8mg of doxazosin result in superior subjective in the treatment of benign pros tatic hyperpla sia and objective results versus the lower doses were represe nted between 15% and 30% [18J. Fawzy et al showed in a mult icenter study change from baselin e after 3 months of that steady-s tate peak and trough plasma treatment [22, 23, 28, 29 J. Djavan et al doxazosin concentrations were ach ieved by 6 reported imp rovement in total symptom score weeks of therapy [ 19J. As symptom relief is by 30-40 % and Qmax by 16-25% [8J. the primary goa l of therapy in BPH, We accepted favo rable response to doxazosin's effects are rapid in onset [8, 20J. therapy, defined as any reduction in sym ptom On the other hand , the effec t of terazosin on score and maximu m flow rate by 20%. If the the peak urinary flow rate was apparent in patient did not respond to the therapy by 20% studies as short as 8 wee ks [20, 2 1J. on both param eters than it was accepted as Improvements were includ ed both in symptom partial response to the therapy. These patients score and in the peak flow rate. These data were dropp ed from follow-up. were also remarkabl y consistent among the Most importantl y, the effec t of terazosin vario us alpha- I-blocki ng age nts. on symptoms and peak urinary flow rate was

126

: indepe nde nt of the baseline prostate size for preferable to search o ther options of treat men t the range of pros tate volumes report ed [30] . for the pa tient. How ever literature rep ort ed the efficacy of the However , the nu mb er of the patients incl uded alpha- I- bloc ker therap y was not infl uence d in this st udy is low and the res ult ca n be with prostate vo lume, our patients we re suggested, it is one of the rare studies in the ho mogenou s on prostate volumes with addition literature documenting the subject. to other pa rameters. In our gro up of patien ts improvement was REFERENCES achi eved on doxazosin and terazosin ann of the treatment group by 44 % and 40% res pec tively . 1. Coffey DS , W alsh PC: Clinica l and Twent y percent of patients on eac h treatment experime ntal studies of ben ign prostatic arm showed part ial improvem en t. T hirty-six hyperpl asia. Urol Clin North Am. 1990; percent of the patien ts on the doxazo sin arm 17:461- 475. and 40 % of the patients on the terazo sin did 2. Ca ine M , Raz S, Zeigler M: Adrenergic not sho w imp ro vem ent in any of the and cholinergic receptors in the hu man parameters. T he efficacy of the doxazo sin and prostate, prostatic ca ps ule and bladder terazosin in our group of patients agreed with neck. Br J Urol 1975; 47 : 193. the literatu re. Since qu alit y of life score (QOL 3. Lepor H, Meretyk S, Kn app-Malon ey G: score) was a relative parameter so it was not Th e safety, efficacy and comp liance of accepted as the parameter of improvem en t in terazosin therapy for ben ign prostatic the treatment ar ms . hyper plasia. J Uro11992; 147: 1554 . Patients who did not respond to the first 4. Lepor H, Gu p Dr , Bauma nn M, S hapiro E: line med ical treatmen t had thei r dru g swi tched Co mparison of alpha I adrenoceptors in with the other one. Ni ne patient s (36 %) in the the prostate adenoma and prostate ca psule doxazosin arm and 10 pat ients (40 %) in the of me n wit h sy mp tomatic and jerazosin ann did not show improveme nt. asy mptomatic beni gn prostatic funhermore, 7 out of 10 patient s (70 %) in the hyp erplasia. Br J Urol 1991 ; 67 : 493 8. ~o sin-t o- d o x a zo sin arm and 8 out of 9 5. Shapiro E, Hartanto V, Lep or H: The parients (88 %) in the doxazosin-to-terazosin respon se to alpha bloc kade in beni gn .m did not also repre sent further prostatic hyperplasia is related to the improvement. Ho wever, cha nge in I-P SS sco re percent area den sity of prostatic smooth .ct in the flow rate was stat istica lly muscle. Prostate 1992 ; 2 1: 297 -30 7. ~iicanl. non e of these patients achieved 6. Kob ayashi S, Tang R, Shapiro E, Lepor H : iIIIprovement by 20 % or more. Change in the Charac teri zation and locali zation of PS...-\ valu es of these pa tients did not show prostatic alpha I adrenocepto rs using -.istical differen ce during 6- mo nth follow-up. radioliga nd receptor bindin g on slide mo unted tissue section. J Uro l 1993; 150: CONCLUSION 2002-26 . 7. Kunish ima Y, Kawabe K, Ni iji ma Tel: A Subjective and objective impro vemen ts ph armacologic al study of alpha adrenergic a.id be achiev ed with the use of alpha- l ­ receptor subtypes in smooth muscle of IIIID.:Ur therapy in BPH sy mptom s. If the hu man urinary bladder base and prostatic • '-on does not improve in I-PSS sco re and in urethra. J Uro l 1985; 134 : 396-8 . * fkm rate with the use of one alpha- J­ 8. Djavan B, Marberger M: A meta-analysis ~. ch angin g the molecul e does not show on the efficacy and tolerabil ity of a 1­ ~ improv em ent. adrenoceptor antagonis ts in patien ts wi th If on e type of mo lec ule is ineffective to lower urinary tract sy mptoms suggestive .usymptoms then it will be better not to test of benign prostat ic obs truction. Eur Urol ...~ alpha-I-blockin g molecul e. It is 1999; 36:1.

127 9. Kirby RS: Clinical pharmacology of a 1­ doxazosin concentrations in the treatment adrenoceptor anta goni sts. Em Uro l, of benign pro static hyperpl asia. suppl.1999; 36: 48. Mult icenter Stud y Group. Urology 1999 10. Hayduk K, Schn eider HT: Feb;53(2):329-35. Antihypertensive effects of doxazosin in 20. Mobley OF, Kaplan S, Ice K, Gaffney M, systemic hypertension and comparison Dias N: Effect of doxazosin on the with terazosin. Am J Cardiol 1987; symptoms of benign prostatic hyperplasia: 59:95G-8G . results from three doubl e-bl ind placebo­ 1I. Jansen OJ Jr, Resch NO, Hoffm an RM : controlled studies. Int J Clin Pract 1997 Doxazosin-t o-terazosin switch for benign Jul-Au g;51(5):282-8. pro static hyp erpl asia. Am J Health Syst 21. Kaplan SA , Soldo KA, Olsson CA : Pharm 1999 Jul I; 56(13): 1351. Terazosin and doxazosin in norm otensive 12. Cocke tt ATK, Aso Y, Chatelain Cet: men with symptomatic prostatism: a pilot Recommendations of the international study to determine the effect of dosing con sensus committee. In Coc kett ATK, regimen on efficac y and safety. Em Urol Aso Y, Chatelain C, ed, The 2nd 1995;28(3):223-8. Internati onal Co nsultation of Benign 22. Kaplan SA, Te AE, Ikeguch i E, Santarosa, Prostatic Hyperpl asia. Paris: Pitie RP: The treatment of benign prostatic Salapatiere, 1993 : 533-64. hyperplasia with alpha blocke rs in men 13. Deni s L, Griffiths K, Khoury S, Cockett over the age of 80 years. Br J Urol 1997 ATK , McC onnell J, Chatelain C, Murphy Dec;80(6):875-9 . G, Yoshid a 0 (eds.): The Fourth 23. Lepor H: Long-term efficacy and safety of Intern ational Consultation on Benign terazosin in patients with benign prostatic Prostatic Hyperpla sia (BPH), Paris, July hyper plasia. Terazosin Research Group . 2-5 , 1997. Health Publi cation LTD ., 1998, Urology 1995 Mar;45(3):406-13. pp 63-8 1. 24. McK iern an JM , Lowe FC: Side effects of 14. Akduman B, Crawford ED : Terazosin, terazosin in the treatment of symptomatic doxazosin, and prazosin: current clinical benign prostatic hyperpl asia. South Med J experience. Urology 2001 Dec;58(6 1997 May;90(5):509- I3. Suppl 1):49-54. 25. Mikh ailidi s DP, Khan MA, Milionis HJ, 15. Lepor H, Laddu A: Terazosin in the Morgan RJ: The treatment of hypertension treatment of benign prostat ic hype rplasia: in patients with erectile dysfun ction . Curr the United States experience. Br J Urol Med Res Opin 2000; 16 Suppl 1:s31-6. 1992 Nov;70 Suppl 1:2-9. 26. Lepor H, Knapp-Malone y G, Sun shin e H: 16. Debruyne FM : Alpha blockers: are all A dose titration study evaluating created equal? Urology 2000 Nov 1;56(5 terazosin , a selective, once-a-day alpha 1­ Suppl 1):20-2. blocker for the treatment of symptomatic 17. MacDiarm id SA , Emery RT, Ferguson SF, benign prostatic hyperplasia. J Urol 1990 McGuirt-Franklin R, McIntyre WJ , Dec;144(6):1393-7; discussion 1397- 8. John son DE: A randomized doubl e-blind 27. Uyg ur MC, Gur E, Arik AI, Altug U, Erol study assessing 4 versus 8 mg. doxazosin 0 : Erectile dysfunction following for benign prostati c hyperplasia. J Uro l treatment s of benign prostatic hyperpl asia : 1999 Nov; I62(5):I629 -32. a prospective study. Andrologia 1998 18. Kapl an SA: Uroselective alpha- blockade Feb-Mar;30( I):5- IO. for benign prostatic hyperplasia:c1 inically 28. Gillenw ater JY, Fawzy A, Klimberg I: For significant or marketing sav vy? Urol ogy the Multi cent er Study Group : Doxazosin 1999; 54 :776 -779 . for the treatment of benign prostatic 19. Fawzy A, Vashi V, Chung M, Dias N, hyperpl asia in patients with mild to Gaffney M: Clinical correlation of moderate esse ntial hypertension : a maxim al urinary flow rate and plasma double-blind placebo-cont rolled dose­

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response multice nter study. J Urol 1995; AUTHORS: 154:110-11 5. M. SA MLI: MD , Afyon Kocatepe Unive rsity, 29. Janknegt RA, Chap ple CR : Efficacy and Faculty of Medicine, Department Of Urology, safety of the alpha-I-blocker doxa zosin in Afyon the treatm ent of benign prostatic C; . DiNC; EL: MD , Afyon Kocatepe Unive rsity, hyperplasia. Analysis of 5 studies . Eur Fac ulty of Med icine, Department Of Urology, Uro l 1993; 24:3 19-326. Afyon 30. Boy le P, Robertson C, Man ski R, Padl ey RJ, Roehrborn CG: Meta-a nalysis of ADDRESS FORCORRESPONDENCE: rand omi zed trials of terazosin in the M. Murat Samli, MD. treatm ent of ben ign pros tatic hyperplasia. Kocatepe mah. Umit Yapi Sitesi A Blok No: Il/IO Urology 200 1 Nov; 58(5): 7 17-22. 03200 Afyon Turkey PHONE: +90-543-605 47 40 FAX: +90-272-217 2029 E-MA IL:[email protected]

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