european urology supplements 6 (2007) 594–599

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Impact of Tamsulosin OCAS on Energy of Patients

with LUTS/BPH

Mark Speakman *
Taunton and Somerset Hospital, Musgrove Park, Taunton TA1 5DA, United Kingdom

Article info Abstract

Keywords: The impact of nighttime lower urinary tract symptoms suggestive of

Benign prostatic hyperplasia benign prostatic hyperplasia (LUTS/BPH) such as nocturia has long
Energy been underestimated. Lack of sleep because of these symptoms can
Lower urinary tract considerably affect a patient’s performance and his general feeling of
symptoms well-being. Chronic sleep deficit may lead to increased morbidity and
Nocturia mortality. Therefore, it is important that therapies for LUTS/BPH provide
Oral controlled absorption a proper control of nighttime LUTS. Numerous studies in the field of
system sleep disorders have shown that increasing the length and quality of
Sleep sleep (QoS) can result in a significant improvement in energy and quality
Tamsulosin of life (QoL). To relieve nocturnal symptoms of BPH and to improve
Quality of life patients’ QoS and QoL, a new prolonged-release tablet formulation of the
a1-adrenoceptor antagonist tamsulosin using the Oral Controlled
Absorption System (OCAS) technology was recently developed. Tamsu-
losin is slowly released from the OCAS tablet throughout the entire
gastrointestinal tract, including the colon, and thus provides a relatively
stable 24-h plasma concentration of tamsulosin. Due to its advanced
delivery system, tamsulosin OCAS is expected to relieve nighttime
symptoms of LUTS/BPH and to improve QoS and QoL.
# 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.

* Tel. +44 1823342102; Fax: +44 1283343571.

E-mail address: speakmanmj@aol.com.

1. Introduction storage symptoms are usually more bothersome for

Lower urinary tract symptoms suggestive of benign
prostatic hyperplasia (LUTS/BPH) are very prevalent,
particularly among older men. The importance of
the management of LUTS/BPH will increase in the
near future due to the rapidly ageing population in
the Western world [1]. Relief of voiding symptoms
such as slow stream and hesitancy used to be the
primary treatment goal in LUTS/BPH. However,
experts are now becoming increasingly aware that
1569-9056/$ – see front matter # 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.
these patients and can more adversely affect quality
of life (QoL). Especially nocturia, the complaint that
one has to wake up to void several times during the
night, is considered to be extremely bothersome
for men with LUTS/BPH [2]. This was recently
confirmed in a Web survey among 244 practising
urologists attending the European Association of
Urology (EAU) congress [3]. Most respondents of this
survey agreed with the statement that lack of sleep
is the main reason for the inconvenience of nocturia
doi:10.1016/j.eursup.2007.01.003
 european urology supplements 6 (2007) 594–599
and that (new) therapies for LUTS/BPH should be
evaluated for their effects on nocturia, quality of
sleep (QoS), and QoL.
Several studies have shown that lack of sleep
can seriously affect a person’s physical and mental
well-being and impair performance during the next
day [4]. In addition, daytime sleepiness is likely to
reduce alertness and hence increase the risk of falls
and car accidents [5,6]. In the long run, chronic sleep
disorders such as nocturia may even increase the
risk of severe metabolic disorders, such as type 2
diabetes or cardiovascular disease [7,8]. Because bed
partners can have a significant impact on each
other’s sleep, not only the patient with nocturia
but also his partner may suffer from disturbed
sleep and daytime fatigue [9]. Given the potential
consequences of nocturia, questions about sleep
quality and quantity should be an integral part of
every history and physical examination of patients
with LUTS/BPH.
2. Managing sleep disorders: impact on
daily life
Although the association between sleep disorders
on the one hand and daytime sleepiness and QoL on
the other hand is obvious, few clinical data are
available showing that successful treatment of sleep
disorders has an impact on vitality and health. In
the field of LUTS/BPH, several studies showed an
improvement of nocturia after surgical or medical
treatment for LUTS/BPH [10–12]. However, these
studies had rather low power and were not
specifically designed to measure the improvement
of nocturia. Moreover, none of these studies assessed
the impact of nocturia on QoS or QoL. Sleep disorders
other than nocturia that are common in the elderly
include restless leg syndrome and obstructive sleep
apnoea (OSA).
Use of medical therapy to reduce the frequency
of periodic leg movements in patients with restless
leg syndrome has been shown to significantly
increase total sleep time. Various studies in this
field showed that this results in significant improve-
ments in QoS and QoL [13,14]. Leg movements in
these studies were recorded by actigraphy; QoL was
evaluated using modified 50-mm Hamburger Visual
Analogue Scales covering domains on life satisfac-
tion (eg, satisfaction with cognitive performance,
activities of daily living, leisure activities, and
efficacy at work) and burden caused by symptoms
(eg, depression, fatigue, and physical symptoms). In
one of the studies, the standardised sleep inventory
short form-A (SF-A) was used to assess sleep
595
patterns and mood. In another study, QoS was
evaluated using polysomnography (PSG) and sleep
diaries in which symptoms such as sleep latency
and frequency of awakenings were rated. Although
PSG data could not objectively show improved QoS
in this study, the patients reported a subjective
improvement in QoS.
Similarly, treatment of OSA, a condition in which
sleep is disturbed because respiration is decreased
or stopped repeatedly, significantly reduces daytime
sleepiness and improves QoS and QoL of both the
patients and their bed partners [15,16]. For QoS and
QoL assessment in one of these studies, patients and
their bed partners had to complete the Epworth
Sleepiness Scale (ESS) questionnaire, the short
form health survey (SF-36) and the Calgary Sleep
Apnoea Quality of Life Index (SAQLI). Both the
patients and their bed partners reported statistically
significant improvements in total ESS ( p < 0.001 and
p = 0.02, respectively) and SAQLI scores ( p < 0.001
and p = 0.002, respectively) and in the domains of
role-physical, vitality, social functioning, and men-
tal health of the SF-36 questionnaire. In another
study, improvements in QoS were recorded using
somnographic examinations and sleep quality
questionnaires including questions on treatment
effectiveness, daytime tiredness, and improve-
ments in QoS. Overall, the data of these studies
show that improving QoS can have a major impact
on a patient’s and even his partner’s performance
and QoL.
3. Managing nocturia in patients with
LUTS/BPH
3.1. Initial patient evaluation
Lifestyle changes such as reduced fluid intake or
restriction of alcohol or caffeine may help some
patients with nocturia, but successful management
of nocturia usually implies treatment of its under-
lying cause. Therefore, patients with nocturia
should be adequately evaluated to assess the cause
of their complaint. Initial patient screening includes
a detailed history and physical examination [17].
The patients are questioned about timing and
amount of fluid intake, use of medications, and
health problems and undergo physical and neuro-
logic examinations. In addition, the patients have to
complete a 24-h diary including information on
timing and frequency of voiding and urine volume to
distinguish between the different categories of
nocturia, that is, polyuria, nocturnal polyuria, and
reduced bladder capacity [17–19].
596 european urology supplements 6 (2007) 594–599

3.2. Treatment of nocturia due to BPH
Patients with nocturia associated with BPH may
benefit from drugs affecting either prostate volume
or muscle tone in the lower urinary tract (LUT) or
from prostate surgery. Currently, a1-adrenoceptor
(a1-AR) antagonists such as alfuzosin, doxazosin,
and tamsulosin are recommended as first-line
pharmacologic therapy for men with LUTS/BPH
[20]. The a1-AR antagonists improve urinary flow
and other symptoms of BPH by reducing muscle
tone in the bladder neck, the urethra, and the
prostate. Three distinct types of a1-ARs, the a1A-,
a1B-, and the a1D-ARs, exist. Contraction of the
muscles of the human LUT is mainly mediated by
a1A-ARs and a1D-ARs, whereas a1B-ARs are predo-
minantly present in the vasculature. All currently
available a1-AR antagonists are similarly effective in
relieving LUTS/BPH, but tamsulosin differs from the
other agents because of its greater selectivity for the
a1A- and a1D-ARs [21]. Therefore, it is less likely
to cause vasodilatation-associated adverse events
(AEs) such as dizziness and orthostatic hypotension.
Tamsulosin has been available in a modified-release
(MR) capsule formulation for many years and
several clinical studies have assessed its efficacy
and safety versus placebo [22–24]. Drug delivery
systems for a1-AR antagonists such as the MR
capsule were developed to provide a gradual and
continuous drug release but are usually dependent
on the presence of water for drug release [25–27].
Unfortunately, whereas the stomach and the small
intestine contain enough water to allow drug release
in the upper gastrointestinal (GI) tract, water is only

Fig. 1 – (A) The pharmacokinetic (PK) profile of tamsulosin oral controlled absorption system (OCAS) 0.4 mg shows a reduced
Cmax and a consistent and continued 24-h plasma concentration of tamsulosin (mean PK profile of eight subjects).
(B) Scintigraphic analysis shows that tamsulosin is released from the OCAS tablet throughout the entire gastrointestinal
tract, including the colon. Reprinted from Stevens et al [30], with permission from Librapharm Limited.
 european urology supplements 6 (2007) 594–599
scarcely available in the colon. This means that drug
release from these formulations only persists until
arrival in the colon, that is, <24 h. Moreover, release
from these formulations usually also depends on
food intake. Administration of the tamsulosin MR
capsule on an empty stomach increases the max-
imum plasma concentration (Cmax) and the area
under the curve, which might increase the risk of
peak-level associated AEs [28]. Therefore, tamsulo-
sin MR has to be taken after the first meal of the day.
4. Tamsulosin OCAS
Recently, a prolonged-release tablet formulation of
tamsulosin using the Oral Controlled Absorption
System (OCAS) technology was introduced as an
answer to the above-mentioned problems with
current a1-AR antagonist formulations. The OCAS
formulation is composed of an advanced gel layer
that rapidly and completely hydrates during its
passage though the upper GI tract. This hydration
step is crucial to provide sustained drug release
in the colon. Because of its advanced delivery
system, the new tamsulosin tablet formulation
was expected to have a pharmacokinetic (PK) profile
with a lower Cmax and a plasma concentration that is
consistently maintained above the minimum effec-
tive concentration for 24 h, independent of food
intake. This improved PK profile should translate
into a better control of nighttime symptoms of BPH
and a lower risk of peak-associated AEs.
4.1. PK profile and GI transit of tamsulosin OCAS
Two clinical trials provided evidence for the hypoth-
esis that tamsulosin OCAS has an improved PK
profile [29]. As expected, the PK profile was flattened
with a low Cmax and a reduced fluctuation in 24-h
plasma concentrations. Plasma concentrations
were independent of food intake and the elimina-
tion half-life and the time to reach Cmax were
comparable to those of the MR formulation.
The behaviour of tamsulosin OCAS in the GI tract
was recently examined using tandem g-scintigraphy
and PK analysis in a pilot study including eight
healthy men [30]. The participants received a single
radiolabelled tamsulosin OCAS tablet. Scintigraphic
images were taken immediately after dosing, every
15 min until 15 h after dosing and at 24 h after dosing.
Blood samples were collected before dosing, hourly
until 8 h after dosing, and at 12, 15, and 24 h after
dosing. PK data confirmed findings from the above PK
studies and the scintigraphic analysis revealed that
in all cases where release from the radiolabelled
597
tablet core was observed, this occurred within the
colon (Fig. 1). Release time or site from the tablet
core was not affected by individual variations in
gastric residence, small intestinal transit, or colonic
residence. Altogether, the PK and scintigraphic obser-
vations strongly suggest that tamsulosin is slowly
released from the OCAS tablet throughout the entire
GI tract, including the colon, leading to a continuous
and consistent 24-h plasma concentration.
4.2. Effect of tamsulosin OCAS on nocturia, QoS, and QoL
A recently published randomised, double-blind,
placebo-controlled, proof-of-concept study in 117
patients with LUTS/BPH evaluated the influence of
the new tamsulosin OCAS tablet on the severity of
nocturia, QoS, and QoL [31]. The investigators
introduced ‘‘Hours of Undisturbed Sleep’’ (HUS) as
a measure for QoS. The concept of HUS is based on
the finding that not only the number of voiding
episodes but also the time between falling asleep
and the first awakening to void determines perfor-
mance during the next day. Sleep disruption during
slow wave, restorative sleep, which predominates
during the first part of the night, is more likely to
cause daytime sleepiness than sleep disruption later
at night [32].
It was expected that, given its improved PK
profile, the new tamsulosin OCAS tablet would
provide a better relief of nocturia and a better QoS
and QoL (Fig. 2). Indeed, tamsulosin OCAS 0.4 mg
improved nocturia and QoL significantly more than
placebo ( p = 0.028 and p = 0.0087, respectively) and
there was a trend towards an increase in the HUS. In
Fig. 2 – The relationship between behaviour of tamsulosin
oral controlled absorption system in the gastrointestinal
tract (GI) and its impact on quality of sleep and quality of
life. *Not significant versus placebo. HUS = hours of
undisturbed sleep.
598 european urology supplements 6 (2007) 594–599
addition, the investigators found a significant
relation between the reduction in the number of
nocturnal voids on the one hand and the increase in
the HUS and the improvement in QoL on the other
(Spearman coefficient 0.63 and 0.64, respectively).
These findings suggest that improving nocturia
can lead to an improved QoS and overall feeling of
well-being.
5. Conclusions
Nocturia has long been an underestimated symp-
tom of BPH. Only recently, have urologists recog-
nised the great potential impact of nocturia on the
patient’s and his partner’s daily performance and
QoL. Unfortunately, currently available treatments
are not specifically designed to treat nighttime
symptoms of BPH. Most oral drug delivery systems
are dependent on the presence of water for drug
release, but this is only scarcely available in the
colon. The new tamsulosin OCAS tablet formulation
is designed to provide a continued release of
tamsulosin throughout the entire GI tract, including
the colon. This allows a consistent and continued
concentration of tamsulosin over a 24-h period.
Although still relatively limited, clinical data show-
ing the impact of the tamsulosin OCAS tablet on QoS
and QoL are promising. More conclusive data are
expected in the near future from an ongoing study.
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