© The Canadian Journal of Urology™; 19(Supplement 1); October 2012
BPH/LUTS
Silodosin (Rapaflo)
Dr. Kapoor provides an overviewof themanagement of
benign prostatic hyperplasia (BPH)/LUTS elsewhere
in this supplement.
3
The choice of one of the two most
commonly acceptedmedical therapies for BPH is based
on prostate volume and symptom severity (degree
of bother) that the patient is reporting. For patients
with small prostates and moderate symptoms, alpha
blockers are most often indicated. Investigators have
determined that there are three main alpha receptors:
α
1
A,
α
1
B, and
α
1
D. It appears that
α
1
A receptors are
more specific for smooth muscle in the urinary tract,
whereas
α
1
B receptors are more often found in blood
vessels.
5
Since the early 1990s when patients whowere being
treated with the non-selective alpha blocker terazosin
for hypertension reported an improvement in their
urinary flow and BPH symptoms, there has been a
quest to develop a more uro-selective alpha blocker
to mitigate vascular side effects such as orthostatic
hypotension and nasal stuffiness, which are commonly
reported by patients.
6
Tamsulosin is one of the most
prescribed uro-selective alpha blockers.
In Canada, the selective alpha blocker silodosinwas
recently approved for the treatment of BPH/LUTS.
Dr. Kapoor describes the indications and advantages
of silodosin in an article in this supplement.
3
In vitro
experiments have demonstrated that silodosin’s
α
1
A-
to-
α
1
B binding ratio is extremely high (162:1), whereas
tamsulosin’s
α
1
A-to-
α
1
B binding ratio is only 50:1.
7
The European clinical study led by Chapple that
compared tamsulosin to silodosin to placebo with
the aim of demonstrating non-inferiority showed
some interesting results.
8
Most notably, silodosin was
proven to be non-inferior to tamsulosin and better than
placebo for the reduction of International Prostate
Symptom Score (IPSS) and improvement in quality
of life. It was also slightly better than tamsulosin in
improving Qmax response and in possibly reducing
nocturia episodes. The major difference was in the
reported incidence of ejaculatory dysfunction: 14%
with silodosin versus only 2% with tamsulosin.
However, the rates of withdrawal from the study due
to this side effect were virtually identical for both
alpha blockers.
Daily tadalafil (Cialis)
A new approval/indication for an “old” drug
became a reality in Canada recently, when 5 mg daily
tadalafil was approved for men with ED and LUTS,
secondary to BPH. This approval had been predicted
in a previous article,
1
in which Barkin had discussed
guidelines for the management of patients with BPH,
which recommend stratifying patients by symptoms
and prostate size. Men with small prostates (< 30 cc)
and moderate symptoms should be offered an alpha
blocker, whereas men with enlarged prostates (> 30 cc)
and moderate symptoms should be offered the
combination of an alpha blocker and a 5-alpha
reductase inhibitor (5-ARI) from day one. This
provides the greatest reduction in the risks of clinical
progression, acute urinary retention, and need for
surgery.
1
Some men who are receiving combination therapy
may still have LUTS or may experience ED as a side
effect of the 5-ARI. EDhas been shown to be associated
with more severe LUTS, where the degree of LUTS is
a risk factor for ED.
9
To treat ED, 5 mg daily tadalafil
represents a paradigm shift from on-demand PDE-5
inhibitors. A 1 year, open-label study reported that
patients who were treated with 5 mg daily tadalafil
had improved International Prostate Symptom Score
(
IPSS) results, quality of life, and International Index
of Erectile Dysfunction (IIEF) scores.
10
Daily tadalafil is now approved as monotherapy for
men who have ED and BPH/LUTS, simultaneously.
In my opinion, it should also be indicated for men
with enlarged prostates, ideally given in combination
with the 5-ARI (if they have stopped the alpha blocker
because of side effects or lack of efficacy).
1
Ureteral stones
Silodosin (Rapaflo)
For many years, research suggested that there are alpha
receptors in the human ureter. This theory was tested
clinically to determine if the use of alpha blockers
might encourage the passage of ureteral stones.
11
Recently, a Japanese study of 187 patients looked
at ureteral stone management and compared the
standard approach of high fluid intake and watchful
waiting (control group) versus high fluid intake and
use of silodosin (sildosin group).
12
This was the first
published study to report the efficacy and potential
utilization of silodosin in the management of ureteral
stones. The results were very encouraging. Overall,
the stone expulsion rate was 50.0% (92 patients) in
the control group versus 66.3% (89 patients) in the
silodosin group (p = 0.056). The mean expulsion times
were 15.19 ± 7.14 days in the control group versus
10.27
± 8.35 days in the silodosin group, (p = 0.0058).
The study stratified the stones into six categories
depending on their size and location. For stones in the
distal ureter that were 6 mm to 9 mm in diameter, the
BARKIN AND FOLIA
50
