Arab Journal of Urology (2013) 11, 142–147 Arab Journal of Urology (Ofﬁcial Journal of the Arab Association of Urology) www.sciencedirect.com STONES/ENDOUROLOGY ORIGINAL ARTICLE Eﬃcacy and safety of tamsulosin vs. alfuzosin as medical expulsive therapy for ureteric stones a, b c Ahmed K. Ibrahim , Isam H. Mahmood , Nada S. Mahmood Urology Division, Department of Surgery, University of Mosul, Mosul, Iraq Department of Pharmacology, College of Pharmacy, University of Mosul, Mosul, Iraq Department of Pharmacology, College of Medicine, University of Mosul, Mosul, Iraq Received 29 December 2012, Received in revised form 18 February 2013, Accepted 22 February 2013 Available online 6 April 2013 KEYWORDS Abstract Objective: To evaluate and compare the efﬁcacy of tamsulosin and alfuz- osin as medical expulsive therapy for ureteric stones. Ureteric stones; Patients and methods: In all, 112 patients with ureteric stones of 610 mm, located Medical expulsive ther- along the ureter, were randomly divided into three groups. In group I, 32 patients apy; received no a-blockers (controls), in group II 40 patients received tamsulosin Tamsulosin; 0.4 mg daily, and in group III 40 patients received alfuzosin 10 mg daily. All patients Alfuzosin were given analgesia and antibiotics when indicated. The follow-up was weekly for 4 weeks. ABBREVIATIONS Results: The mean stone size and age were comparable in the three groups. The MET, medical expulsive stone expulsion rate was 44%, 85% and 75% in groups I, II and III, respectively. therapy; Half of the stones in group II passed within 2 weeks, half in group III passed within US, ultrasonography 3 weeks, while more than half of the stones in group I did not pass even after 4 weeks. The mean number of painful episodes was 2.45, 1.38 and 1.64 in groups Corresponding author. Address: Urology Division, Department of Surgery, College of Medicine, Mosul University, Alshifaa Street, Mosul, Iraq. Tel.: +964 7708224454. E-mail address: firstname.lastname@example.org (A.K. Ibrahim). Peer review under responsibility of Arab Association of Urology. Production and hosting by Elsevier 2090-598X ª 2013 Production and hosting by Elsevier B.V. on behalf of Arab Association of Urology. http://dx.doi.org/10.1016/j.aju.2013.02.003 Efﬁcacy and safety of tamsulosin vs. alfuzosin as medical expulsive therapy for ureteric stones 143 I, II and III, respectively. The drug-related side-effects reported by patients were mild and transient. Conclusion: The use of tamsulosin or alfuzosin as medical expulsive therapy for ureteric stones in the three sections of the ureter (upper, middle and lower) was safe and effective, as shown by the increased overall stone expulsion rate, reduced stone expulsion time and fewer pain episodes. Tamsulosin was associated with a greater rate of stone expulsion than was alfuzosin. ª 2013 Production and hosting by Elsevier B.V. on behalf of Arab Association of Urology. Introduction the highest density in the distal ureter . Stimulation of the receptors increases the force of ureteric contrac- tion and the frequency of ureteric peristalsis, whereas Urinary tract stones are one of the most common uro- antagonism of the receptors has the opposite effects. logical conditions worldwide. The prevalence is esti- The a1-adrenoreceptor antagonists (a1-blockers) inhibit mated to be 1–5% in Asia, 5–9% in Europe and 13% contractions of the ureteric musculature, reduce the ba- in the USA . Ureteric stones represent one of the ma- sal tone, and decrease the peristaltic frequency and colic jor causes for attendance at the emergency and outpa- pain, facilitating the expulsion of ureteric stones . tient departments in urology, and are associated with The aim of the present study was to compare tamsul- considerable morbidity. osin and alfuzosin for their efﬁcacy and safety as MET Current therapeutic options for ureteric stones in- in patients with a symptomatic uncomplicated ureteric clude active intervention and conservative ‘watch and stone that was located in one of the three sections of wait’ approaches. Recent advances in endoscopic stone the ureter. We also assessed the effect of these two drugs management have allowed upper tract stones to be in reducing the pain episodes in these patients. treated using minimally invasive techniques, which have increased the success rates and decreased treatment- Patients and methods related morbidity. These advances include ESWL, uret- eroscopy and percutaneous approaches. Although these procedures are less invasive than traditional open sur- This was a prospective randomised controlled trial. The gery they are more expensive and have inherent risks inclusion criterion was a symptomatic ureteric stone of , but the surgical and anaesthetic risks are not negligi- <10 mm in diameter. The exclusion criteria were acute ble, and serious complications, although rare, are possi- infection, a solitary kidney, elevated levels in renal func- ble . Thus, for many patients, a conservative tional tests at presentation, severe hydronephrosis, bilat- treatment with no invasive procedures is an appealing eral ureteric stones, pregnancy or lactation, current use option. However, watchful waiting does not always re- of a-blockers, calcium-channel blockers or steroids, sult in stone clearance and can be associated with recur- age <18 years, and any allergic reaction to the study rent renal colic . medication. The 2007 Guideline for the Management of Ureteral The study was conducted between July 2012 and Calculi of the AUA , and the European Association December 2012, and was approved by the Department of Urology guideline, recommend watchful waiting with of Surgery and authorities of the Mosul College of medical treatment for patients with a stone of <10 mm Medicine. In all, 112 patients fulﬁlled the above criteria in diameter and with well-controlled pain. and completed the follow-up. All of the eligible patients Medical expulsive therapy (MET) has been investi- had signed an informed consent. gated as a supplement to observation in an effort to im- At the initial visit the patients had a complete history prove spontaneous stone-passage rates, which can be taken, a physical examination, urine analysis, and blood unpredictable. Because ureteric oedema and ureteric urea nitrogen and serum creatinine levels were mea- spasm have been postulated to affect stone passage, sured. All patients were assessed with urinary ultraso- these effects have been targeted by pharmacological nography (US) and a plain abdominal X-ray. IVU or intervention. Therefore, the primary agents that have CT was used in a few patients depending on speciﬁc been evaluated for MET are calcium-channel blockers, indications. steroids, NSAIDs and a1-adrenergic receptor antago- nists . Study design The human ureter contains a-adrenergic receptors along its length, with the highest concentration in the In consultation with a statistician, the sample size was distal ureter. Three subtypes of a1 receptor have been scheduled to be 50 patients in each of three groups, tak- described, i.e., a1a, a1b and a1d, with the last having ing into consideration previous similar studies, and the 144 Ibrahim et al. patients were randomised systematically at a ratio of anova was used to compare between age and ureteric 1:1. The fate of the patients through the various stages stone size among the groups, with differences considered (enrolment, follow-up and analysis) is shown in the con- signiﬁcant at P < 0.05; other data are presented as per- sort chart (Fig. 1). centages or proportions if the totals were small. Accordingly, the patients were divided into three groups, i.e. group I (control, 32 patients, no a-blockers), Results group II, (40 patients) taking a tamsulosin capsule of 0.4 mg daily, group III (40 patients) receiving alfuzosin The three groups were matched for age and stone size 10 mg daily. The patients were followed-up weekly for (Table 1). Most stones were in the lower ureter 4 weeks, and every visit comprised a focused history, a (Fig. 2). Among the 40 patients in group II, 34 (85%) physical examination and urinary US, with pain episodes successfully passed the stone spontaneously, and in and any drug-related side-effects also reported. Signiﬁ- group III, 30 (75%) did so, whereas in group I only 14 cant pain episodes were deﬁned as an acute pain episode (44%) patients passed the stone spontaneously. The that necessitated the use of parenteral analgesia and/or differential rate of stone passage for each part of the hospitalisation. (All the patients were given diclofenac ureter is shown in Table 2; the difference was signiﬁcant potassium orally 50 mg and/or diclofenac sodium as an for the lower ureteric stones and overall stone passage. intramuscular injection of 75 mg on demand). The date The stone expulsion time is also shown in Table 2, of stone passage (if any) was recorded. where half the stones in group II passed within 2 weeks, The criteria for treatment discontinuation and the half in group III passed within 3 weeks, but more than need for intervention (ESWL or endoscopy) were half of the stones in group I did not pass even after uncontrolled pain, fever, severe hydronephrosis, or lack 4 weeks. The mean number of painful episodes was of successful stone expulsion after 4 weeks. 2.45, 1.38 and 1.64 for groups I, II and III, respectively. Assessed for eligibility (n= 164) Not meeting inclusion criteria (n= 12) Enrollment Other reasons (n=2) Randomization Alfuzosin group Tamsulosin group Control group (n=50) (n = 50) (n= 50) Follow up Excluded from study (n=7) Excluded from study (n=8) Excluded from study (n= 8) Lost from follow - up (n=3) "Lost from follow - up (n=10) Lost from follow - up (n= 2) Analysis Analyzed (n=32) Analyzed (n=40) Analyzed (n=40) Figure 1 The consort chart. Efﬁcacy and safety of tamsulosin vs. alfuzosin as medical expulsive therapy for ureteric stones 145 Table 1 The patients’ characteristics. Mean (SD) or n (%)variable Group I (Control) II (Tamsulosin) III (Alfuzosin) P Age (years) 36.71 (11.64) 38.17 (14.54) 36.5 (11.54) 0.819 Stone size (mm) 5.65 (1.25) 5.58 (0.93) 5.94 (1.66) 0.441 Sex M 25 (78) 32 (80) 34 (85) F 7 (22) 8 (20) 6 (15) Total 32 40 40 Figure 2 The distribution of the ureteric stones within the ureter in the three groups. Table 2 Location and rate of the spontaneous passage of stones, and the duration before passage. n/N (%) or n/N at location Group III P III P Upper Passed 1/4 8/12 0.192 5/10 0.406 Not passed 3/4 4/12 5/10 5/10 Mid Passed 1/5 2/2 0.143 3/4 0.167 Not passed 4/5 –/– 1/4 Lower Passed 12/23 (52) 24/26 (92) 0.002 22/26 (85) 0.014 Not passed 11/23 (48) 2/26 (8) 4/26 (15) Total passed 14/32 (44) 34/40 (85) 0.002 30/40 (75) 0.007 Not passed 18/32 (56) 6/40 (15) 10/40 (25) Weeks to stone passage, n (%) 1 2 (6) 12 (30) – 11 (28) 2 4 (13) 9 (23) – 8 (20) 3 6 (19) 8 (20) – 7 (18) 4 2 (6) 5 (13) – 4 (10) 146 Ibrahim et al. Of those patients in whom the stone failed to pass reported that 25 of 29 patients in a tamsulosin group after 4 weeks, 12 (from all groups) who had an upper (86%), 23 of 30 in an alfuzosin group (77%), and 14 ureteric stone were managed successfully with ESWL, of 28 in a control group (50%) expelled the stones by two of seven patients on a-blockers (groups II and the end of the study, results similar to those in the pres- III) needed more than one session, while two of ﬁve ent study. A recent Korean study  showed that calcu- in the control group needed more than one session. li passed through the ureter spontaneously in 32 patients Five patients had mid-ureteric stones, three of whom (78% of the group) treated with tamsulosin 0.2 mg, in 23 were managed successfully with two sessions of ESWL, (77%) treated with tamsulosin 0.4 mg, in 27 (75%) trea- and the remaining two (from the control group) were ted with alfuzosin 10 mg, and in 16 (47%) treated with treated with ureteroscopy and lithotripsy, respectively. trospium chloride. Comparison between the two tamsul- Finally, 17 patients had lower ureteric stones, and all osin doses and the 10 mg alfuzosin dose showed no sig- were treated successfully with ureteroscopy and niﬁcant differences in expulsion rate or expulsion time lithotripsy. for lower ureteric calculi. Side-effects were reported in ﬁve patients in group II The present study showed that treatment with an (13%), including retrograde ejaculation in three and a-blocker gave better results than in the control group. postural hypotension in two. In group III, six patients Stone size, location and symptom duration are the most reported side-effects (15%), two complaining of retro- important variables for predicting spontaneous stone grade ejaculation, three of postural hypotension and expulsion, in addition to patient-dependent factors such one had nasal congestion. None of these patients as pain tolerance and the development of infection, that stopped the MET because of the side-effects. determine the need for active stone removal or decom- pression of the renal collecting system . Miller and Discussion Kane  reported that the mean time to spontaneous stone passage of stones of 62 mm, 2–4 mm and 4–6 mm was 8.2, 12.2 and 22.1 days, respectively, and Tamsulosin is the most commonly used a-blocker for 95% of those that passed did so by 31, 40 and 39 days, the medical treatment of ureteric stones, because of its respectively. Coll et al.  reported that the spontane- excellent tolerability, the lack of need for dose titration ous passage rate for stones of 1 mm in diameter was on initiation of treatment (which allows a fully effective 87%, for 2–4 mm was 76%, for 5–7 mm was 60%, for dose to be administered immediately) and its uroselec- 7–9 mm was 48% and for stones of >9 mm was 25%. tivity for a1a and a1d. This results in relaxation of the The spontaneous passage rate as a function of stone smooth muscles of the lower ureter, facilitating stone location was 48% for those in the proximal ureter, passage and relieving pain . However, other 60% for mid-ureteric stones, 75% for distal stones and a-blockers were also found to be effective in promoting 79% for stones at the vesico-ureteric junction. the expulsion of ureteric stones. Yilmaz et al.  showed In the present study we included patients with ure- that tamsulosin, terazosin and doxazosin were equally teric stones in the upper, middle and lower ureter; both effective in increasing the frequency of spontaneous pas- tamsulosin and alfuzosin facilitated the expulsion of ure- sage of ureteric calculi. Wang et al.  showed that tam- teric stones from all parts of the ureter, and tamsulosin sulosin was associated with an expulsive rate of 81%, was slightly better. The two treatments had a better and terazosin of 78%. Another study from China  effect than in the control group. A review of previous reported that MET using alfuzosin slow-release 10 mg reports showed that most studies tested the effects of daily was effective in increasing the spontaneous passage a-blockers as MET when the stones were in the distal rate of ureteric stones (81.8%) and reducing analgesic ureter. Ahmed and Al-Sayed  and Agrawal et al. use. Those authors concluded that MET with an  compared the effects of tamsulosin and alfuzosin a-blocker was safe and effective, as shown by the in- in patients with ureteric stones in the distal ureter, and creased stone expulsion rate and reduced expulsion time, Yilmaz et al.  compared the effects of tamsulosin, and the reduced need for analgesics. terazosin and doxazosin on lower ureteric stones. The present study showed that tamsulosin was asso- Al-Ansari et al.  assessed the effect of tamsulosin ciated with an overall spontaneous expulsion rate of on the spontaneous passage rate of distal ureteric stones. 85%, greater than with alfuzosin (75%) or in the control However, Chau et al.  used alfuzosin for upper ure- group (44%). The efﬁcacy of tamsulosin or alfuzosin has teric stones, with a spontaneous passage rate of 72.7% been studied in many previous trials. Agrawal et al.  vs. 21.4% for the control. In the present study the compared the efﬁcacy of tamsulosin and alfuzosin for respective rates of spontaneous stone passage for upper treating ureteric stones and reported expulsion rates of ureteric stones were one of four in the control, 8/12 for 82.3%, 70.5% and 35.2% for tamsulosin, alfuzosin tamsulosin and 5/10 for alfuzosin. and a control group, values lower than the rates An additional beneﬁt to the use of a-blockers in pa- obtained in the present study. Ahmed and Al-Sayed  tients with ureteric stones, especially those who are can- Efﬁcacy and safety of tamsulosin vs. alfuzosin as medical expulsive therapy for ureteric stones 147  Sigala S, Dellabella M, Milanese G, Fornari S, Faccoli S, didates for surgical intervention, is the emerging role of Palazollo F, et al. Evidence for the presence of alpha1 these drugs in relieving symptoms related to an indwell- adrenoceptor subtypes in the human ureter. Neurourol Urodyn ing JJ stent, as reported by other studies [17,18]. 2005;24:142–8. In the present study there were minor therapy-related  Seitz C. Medical expulsive therapy of ureteral calculi and side-effects in ﬁve patients taking tamsulosin and in six supportive therapy after extracorporeal shock wave lithotripsy. Eur Urol 2010(Suppl.);807–13. taking alfuzosin. The side-effects were mild and did  Ahmed AA, Al-Sayed AS. Tamsulosin versus alfuzosin in the not require the withdrawal of treatment in any patient. treatment of patients with distal ureteral stones: prospective, The side-effects included retrograde ejaculation, randomized, comparative study. Korean J Urol 2010;51:193–7. postural hypotension and nasal congestion. Previous  Yilmaz E, Batislam E, Basar MM, Tuglu D, Ferhat M, Basar H. reports also showed that treatment with tamsulosin or The comparison and efﬁcacy of three different alpha1-adrenergic blockers for distal ureteral stones. Int J Urol 2005;173:2010–2. alfuzosin produced no or only mild adverse effects  Wang CJ, Huang SW, Chang CH. Efﬁcacy of an alpha1 blocker [7,10,19]. Furthermore, a recent study by Mokhless in expulsive therapy of lower ureteral stones. J Endourol et al.  showed that tamsulosin is a safe and effective 2008;22:41–6. treatment option for lower ureteric stones in children.  Chau L, Tai D, Fung B, Man Li J, Fan C, Wah Li M. Medical The limitations of the present study were the rela- expulsive therapy using alfuzosin for patient presenting with ureteral stone less than 10 mm: a prospective randomized tively few patients, which should be increased in future controlled trial. Int J Urol 2011;18:510–4. studies, and the absence of a placebo arm.  Agrawal M, Gupta M, Gupta A, Agrawal A, Sarkari A, Lavania In conclusion, the use of tamsulosin 0.4 mg or P. Prospective randomized trial comparing efﬁcacy of alfuzosin alfuzosin 10 mg as MET for ureteric stones in all three and tamsulosin in management of lower ureteral stones. Urology sections of the ureter was safe and effective, as shown 2009;73:706–9.  Cha WH, Choi JD, Kim KH, Seo YJ, Lee K. Comparison and by the increased overall stone expulsion rate, reduced efﬁcacy of low-dose and standard-dose tamsulosin and alfuzosin stone expulsion time and fewer pain episodes. 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Arab Journal of Urology
– Taylor & Francis
Published: Jun 1, 2013
Keywords: Ureteric stones; Medical expulsive therapy; Tamsulosin; Alfuzosin; MET, medical expulsive therapy; US, ultrasonography