ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS
1.
Silodyx 4 mg hard capsules
Each hard capsule contains 4 mg silodosin.
For a full list of excipients, see section 6.1.
3.
Hard capsule.
Yellow, opaque, hard gelatin capsule, size 3.
4.
Treatment of the signs and symptoms of benign prostatic hyperplasia (BPH).
The recommended dose is one capsule of Silodyx 8 mg daily. For special patient populations, one
capsule of Silodyx 4 mg daily is recommended (see below).
Elderly patients
No dose adjustment is required in the elderly (see section 5.2).
Renal impairment
No dose adjustment is required for patients with mild renal impairment (CL
CR
≥50 to ≤80 ml/min).
A starting dose of 4 mg once daily is recommended in patients with moderate renal impairment (CL
CR
≥30 to <50 ml/min), which may be increased to 8 mg once daily after one week of treatment,
depending on the individual patient’s response. The use in patients with severe renal impairment
(CL
CR
<30 ml/min) is not recommended (see sections 4.4 and 5.2).
Hepatic impairment
No dose adjustment is required for patients with mild to moderate hepatic impairment.
As no data are available, the use in patients with severe hepatic impairment is not recommended (see
sections 4.4 and 5.2).
Children and adolescents
There is no relevant indication for use of Silodyx in children and adolescents.
Method of administration
The capsule should be taken with food, preferably at the same time every day. The capsule should not
be broken or chewed but swallowed whole, preferably with a glass of water.
Hypersensitivity to the active substance or to any of the excipients.
2
Intraoperative Floppy Iris Syndrome (IFIS)
IFIS (a variant of small pupil syndrome) has been observed during cataract surgery in some patients on
α
1
-blockers or previously treated with α
1
-blockers. This may lead to increased procedural
complications during the operation.
The initiation of therapy with Silodyx is not recommended in patients for whom cataract surgery is
scheduled. Discontinuing treatment with an α
1
-blocker 1-2 weeks prior to cataract surgery has been
recommended, but the benefit and duration of stopping the therapy prior to cataract surgery has not yet
been established.
During pre-operative assessment, eye surgeons and ophthalmic teams should consider whether patients
scheduled for cataract surgery are being or have been treated with Silodyx, in order to ensure that
appropriate measures will be in place to manage IFIS during surgery.
Orthostatic effects
The incidence of orthostatic effects with Silodyx is very low. However, a reduction in blood pressure
can occur in individual patients, leading in rare cases to syncope. At the first signs of orthostatic
hypotension (such as postural dizziness), the patient should sit or lie down until the symptoms have
disappeared. In patients with orthostatic hypotension, treatment with Silodyx is not recommended.
Renal impairment
The use of Silodyx in patients with severe renal impairment (CL
CR
<30 ml/min) is not recommended
(see sections 4.2 and 5.2).
Hepatic impairment
Since no data are available in patients with severe hepatic impairment, the use of Silodyx in these
patients is not recommended (see sections 4.2 and 5.2).
Carcinoma of the prostate
Since BPH and prostate carcinoma may present the same symptoms and can co-exist, patients thought
to have BPH should be examined prior to starting therapy with Silodyx, to rule out the presence of
carcinoma of the prostate. Digital rectal examination and, when necessary, determination of prostate
specific antigen (PSA) should be performed before treatment and at regular intervals afterwards.
Treatment with Silodyx leads to a decrease in the amount of semen released during orgasm that may
temporarily affect male fertility. This effect disappears after discontinuation of Silodyx (see
section 4.8).
Silodosin is metabolised extensively, mainly via CYP3A4, alcohol dehydrogenase and UGT2B7.
Silodosin is also a substrate for P-glycoprotein. Substances that inhibit or induce these enzymes and
transporters may affect the plasma concentrations of silodosin and its active metabolite.
Alpha-blockers
There is inadequate information about the safe use of silodosin in association with other
α-adrenoreceptor antagonists. Consequently, the concomitant use of other α-adrenoreceptor
antagonists is not recommended.
CYP3A4 inhibitors
In an interaction study, a 3.7-fold increase in maximum silodosin plasma concentrations and a 3.1-fold
increase in silodosin exposure (i.e. AUC) were observed with concurrent administration of a potent
CYP3A4 inhibitor (ketoconazole 400 mg). Concomitant use with potent CYP3A4 inhibitors (such as
ketoconazole, itraconazole or ritonavir) is not recommended.
When silodosin was co-administered with a CYP3A4 inhibitor of moderate potency such as diltiazem,
an increase in silodosin AUC of approximately 30 % was observed, but C
max
and half-life were not
affected. This change is clinically not relevant and no dose adjustment is required.
3
PDE-5 inhibitors
Minimal pharmacodynamic interactions have been observed between silodosin and maximum doses of
sildenafil or tadalafil. In a placebo-controlled study in 24 subjects 45-78 years of age receiving
Silodyx, the co-administration of sildenafil 100 mg or tadalafil 20 mg induced no clinically
meaningful mean decreases in systolic or diastolic blood pressure, as assessed by orthostatic tests
(standing versus supine). In the subjects over 65 years, the mean decreases at the various time points
were between 5 and 15 mmHg (systolic) and 0 and 10 mmHg (diastolic). Positive orthostatic tests
were only slightly more common during co-administration; however, no symptomatic orthostasis or
dizziness occurred. Patients taking PDE-5 inhibitors concomitantly with Silodyx should be monitored
for possible adverse reactions.
Antihypertensives
In the clinical study program, many patients were on concomitant antihypertensive therapy (mostly
agents acting on the renin-angiotensin system, beta-blockers, calcium antagonists and diuretics)
without experiencing an increase in the incidence of orthostatic hypotension. Nevertheless, caution
should be exercised when starting concomitant use with antihypertensives and patients should be
monitored for possible adverse reactions.
Digoxin
Steady state levels of digoxin, a substrate of P-glycoprotein, were not significantly affected by
co-administration with silodosin 8 mg once daily. No dose adjustment is required.
Fertility
In clinical studies, the occurrence of ejaculation with reduced or no semen has been observed during
treatment with Silodyx (see section 4.8), due to the pharmacodynamic properties of silodosin. Before
starting treatment, the patient should be informed that this effect may occur, temporarily affecting
male fertility.
No studies on the effects on the ability to drive and use machines have been performed. However,
patients should be informed about the possible occurrence of symptoms related to postural
hypotension (such as dizziness) and should be cautioned about driving or operating machines until
they know how Silodyx will affect them.
The safety of Silodyx has been evaluated in four double-blind controlled clinical studies (with
931 patients receiving silodosin 8 mg once daily and 733 patients receiving placebo) and in two long-
term open-label extension phase studies. In total, 1,581 patients have received silodosin at a dose of
8 mg once daily, including 961 patients exposed for at least 6 months and 384
patients exposed for
1 year.
The most frequent adverse reactions reported with silodosin in placebo controlled clinical studies and
during long-term use were ejaculatory disorders such as retrograde ejaculation and anejaculation
(ejaculatory volume reduced or absent), with a frequency of 23 %. This may temporarily affect male
fertility. It is reversible within a few days upon discontinuation of treatment (see section 4.4).
In the table below, adverse reactions reported in all clinical studies and for which a reasonable causal
relationship exists are listed by MedDRA system organ class and frequency: very common (≥1/10);
common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare
4
(<1/10,000), not known (frequency cannot be estimated from available data). Within each frequency
grouping the observed adverse reactions are presented in order of decreasing seriousness.
Very common
Common
Uncommon
Not known
Psychiatric
disorders
Libido decreased
Nervous system
disorders
Dizziness
Syncope
Vascular disorders
Orthostatic
hypotension
Respiratory,
thoracic and
mediastinal
disorders
Nasal congestion
Gastrointestinal
disorders
Diarrhoea
Nausea
Dry mouth
Reproductive system
and breast disorders
Retrograde
ejaculation
Anejaculation
Erectile dysfunction
Injury, poisoning
and procedural
complication
Intraoperative
Floppy Iris
Syndrome
Orthostatic hypotension
: the incidence of orthostatic hypotension in placebo-controlled clinical studies
was 1.2 % with silodosin and 1.0 % with placebo. Orthostatic hypotension may occasionally lead to
syncope (see section 4.4).
Intraoperative Floppy Iris Syndrome (IFIS)
: IFIS has been reported during cataract surgery (see
section 4.4).
Silodosin was evaluated at doses of up to 48 mg/day in healthy male subjects. The dose-limiting
adverse reaction was postural hypotension. If ingestion is recent, induction of vomiting or gastric
lavage may be considered. Should overdose of Silodyx lead to hypotension, cardiovascular support
has to be provided. Dialysis is unlikely to be of significant benefit since silodosin is highly (96.6 %)
protein bound.
5.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Urologicals, alpha-adrenoreceptor antagonists, ATC code:
G04CA04.
Mechanism of action
Silodosin is highly selective for α
1A
-adrenoreceptors that are primarily located in the human prostate,
bladder base, bladder neck, prostatic capsule and prostatic urethra. Blockade of these
α
1A
-adrenoreceptors causes smooth muscle in these tissues to relax, thus decreasing bladder outlet
resistance, without affecting detrusor smooth muscle contractility. This causes an improvement of both
5
storage (irritative) and voiding (obstructive) symptoms (Lower urinary tract symptoms, LUTS)
associated with benign prostatic hyperplasia.
Silodosin has a substantially lower affinity for the α
1B
-adrenoreceptors that are primarily located in the
cardiovascular system. It has been demonstrated
in vitro
that the α
1A
:α
1B
binding ratio of silodosin
(162:1) is extremely high.
Clinical studies
In a Phase II dose-finding, double-blind, placebo-controlled clinical study with silodosin 4 or 8 mg
once daily, a greater improvement in American Urologic Association (AUA) symptom index score
was observed with silodosin 8 mg (-6.8±5.8, n=90; p=0.0018) and silodosin 4 mg (-5.7±5.5, n=88;
p=0.0355) as compared to placebo (-4.0±5.5, n=83).
Over 800 patients with moderate to severe symptoms of BPH (International Prostate Symptom Score,
IPSS, baseline value ≥13) received silodosin 8 mg once daily in two Phase III placebo-controlled
clinical studies conducted in the United States and in one placebo- and active-controlled clinical study
conducted in Europe. In all studies, patients who did not respond to placebo during a 4-week placebo
run-in phase were randomised to receive the study treatment. In all studies, patients treated with
silodosin had a greater decrease in both storage (irritative) and voiding (obstructive) symptoms of
BPH as compared to placebo as assessed after 12 weeks of treatment. Data observed in the Intent-to-
treat populations of each study are shown below:
IPSS
Total Score
IPSS
Irritative symptoms
IPSS
Obstructive
symptoms
Treatment
arm
No. of
patients
Baseline
Value
(±SD)
Study
Change
from
baseline
Difference
(95
%
CI)
vs
placebo
Change
from
baseline
Difference
(95
%
CI)
vs
placebo
Change
from
baseline
Difference
(95
%
CI)
vs
placebo
Silodosin
233
228
22 ± 5
21± 5
-6.5
-3.6
-2.8*
(-3.9, -1.7)
-2.3
-1.4
-0.9*
(-1.4, -0.4)
-4.2
-2.2
-1.9*
(-2.6, -1.2)
US-1
Placebo
Silodosin
233
229
21 ± 5
21 ± 5
-6.3
-3.4
-2.9*
(-4.0, -1.8)
-2.4
-1.3
-1.0*
(-1.5, -0.6)
-3.9
-2.1
-1.8*
(-2.5, -1.1)
US-2
Placebo
Silodosin
371
19 ± 4
-7.0
-2.3*
(-3.2, -1.4)
-2.0*
(-2.9, -1.1)
-2.5
-0.7°
(-1.1, -0.2)
-0.6°
(-1.1, -0.2)
-4.5
-1.7*
(-2.2, -1.1)
-1.4*
(-2.0, -0.8)
Europe
Tamsulosin
376
19 ± 4
-6.7
-2.4
-4.2
Placebo
185
19 ± 4
-4.7
-1.8
-2.9
* p<0.001 vs Placebo; ° p =0.002 vs Placebo
In the active-controlled clinical study conducted in Europe, silodosin 8 mg once daily was shown to be
non inferior to tamsulosin 0.4 mg once daily: the adjusted mean difference (95 % CI) in the IPSS Total
Score between treatments in the per-protocol population was 0.4 (-0.4 to 1.1). The responder rate (i.e.
improvement in the IPSS total score by at least 25 %) was significantly higher in the silodosin (68 %)
and tamsulosin group (65 %), as compared to placebo (53 %).
In the long-term open-label extension phase of these controlled studies, in which patients received
silodosin for up to 1 year, the symptom improvement induced by silodosin at week 12 of treatment
was maintained over 1 year.
6
No significant reduction in supine blood pressure was observed in all clinical studies conducted with
silodosin.
Silodosin 8 mg and 24 mg daily had no statistically significant effect on ECG intervals or cardiac
repolarisation relative to placebo.
Paediatric population
The European Medicines Agency has waived the obligation to submit the results of studies with
Silodyx in all subsets of the paediatric population in BPH (see section 4.2 for information on
paediatric use).
5.2 Pharmacokinetic properties
The pharmacokinetics of silodosin and its main metabolites have been evaluated in adult male subjects
with and without BPH after single and multiple administrations with doses ranging from 0.1 mg to
48 mg per day. The pharmacokinetics of silodosin is linear throughout this dose range.
The exposure to the main metabolite in plasma, silodosin glucuronide (KMD-3213G), at steady-state
is about 3-fold that of the parent drug. Silodosin and its glucuronide reach steady-state after 3 days and
5 days of treatment, respectively.
Absorption
Silodosin administered orally is well absorbed and absorption is dose proportional. The absolute
bioavailability is approximately 32 %.
An
in vitro
study with Caco-2 cells showed that silodosin is a substrate for P-glycoprotein.
Food decreases C
max
by approximately 30 %, increases t
max
by approximately 1 hour and has little
effect on AUC.
In healthy male subjects of the target age range (n=16, mean age 55±8 years) after once-a-day oral
administration of 8 mg immediately after breakfast for 7 days, the following pharmacokinetic
parameters were obtained: C
max
87±51 ng/ml (sd), t
max
2.5 hours (range 1.0-3.0), AUC
433±286 ng • h/ml.
Distribution
Silodosin has a volume of distribution of 0.81 l/kg and is 96.6 % bound to plasma proteins. It does not
distribute into blood cells.
Protein binding of silodosin glucuronide is 91 %.
Biotransformation
Silodosin undergoes extensive metabolism through glucuronidation (UGT2B7), alcohol and aldehyde
dehydrogenase and oxidative pathways, mainly CYP3A4. The main metabolite in plasma, the
glucuronide conjugate of silodosin (KMD-3213G), that has been shown to be active
in vitro
, has an
extended half-life (approximately 24 hours) and reaches plasma concentrations approximately four
times higher than those of silodosin.
In vitro
data indicate that silodosin does not have the potential to
inhibit or induce cytochrome P450 enzyme systems.
Elimination
Following oral administration of
14
C-labelled silodosin, the recovery of radioactivity after 7 days was
approximately 33.5 % in urine and 54.9 % in faeces. Body clearance of silodosin was approximately
0.28 l/h/kg. Silodosin is excreted mainly as metabolites, very low amounts of unchanged drug are
recovered in urine. The terminal half-life of parent drug and its glucuronide is approximately 11 hours
and 18 hours, respectively.
Special populations
Geriatric
Exposure to silodosin and its main metabolites does not change significantly with age, even in subjects
of age over 75 years.
7
Paediatric
Silodosin has not been evaluated in patients less than 18 years of age.
Hepatic impairment
In a single-dose study, the pharmacokinetics of silodosin was not altered in nine patients with
moderate hepatic impairment (Child-Pugh scores 7 to 9), compared to nine healthy subjects. Results
from this study should be interpreted with caution, since enrolled patients had normal biochemistry
values, indicating normal metabolic function, and they were classified as having moderate liver
impairment based on ascites and hepatic encephalopathy.
The pharmacokinetics of silodosin in patients with severe hepatic impairment has not been studied.
Renal impairment
In a single-dose study, exposure to silodosin (unbound) in subjects with mild (n=8) and moderate renal
impairment (n=8) resulted, on average, in an increase of C
max
(1.6-fold ) and AUC (1.7-fold ) relative
to subjects with normal renal function (n=8). In subjects with severe renal impairment (n=5) increase
of exposure was 2.2-fold for C
max
and 3.7-fold for AUC. Exposure to the main metabolites, silodosin
glucuronide and KMD3293, was also increased.
Plasma level monitoring in a Phase III clinical study showed that levels of total silodosin after 4 weeks
of treatment did not change in patients with mild impairment (n=70), compared to patients with
normal renal function (n=155), while the levels were doubled on average in patients with moderate
impairment (n=7).
A review of safety data of patients enrolled in all clinical studies does not indicate that mild renal
impairment (n=487) poses an additional safety risk during silodosin therapy (such as an increase in
dizziness or orthostatic hypotension) as compared to patients with normal renal function (n=955).
Accordingly, no dose adjustment is required in patients with mild renal impairment. Since only limited
experience exists in patients with moderate renal impairment (n=35), a lower starting dose of 4 mg is
recommended. In patients with severe renal impairment administration of Silodyx is not
recommended.
5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety
pharmacology, carcinogenic, mutagenic and teratogenic potential. Effects in animals (affecting the
thyroid gland in rodents) were observed only at exposures considered sufficiently in excess of the
maximum human exposure, indicating little relevance to clinical use.
In male rats, decreased fertility was observed from exposures which were approximately twice the
exposure at the maximum recommended human dose. The observed effect was reversible.
6.
6.1 List of excipients
Capsule content
Starch, pregelatinised (maize)
Mannitol (E421)
Magnesium stearate
Sodium laurilsulfate
Capsule shell
Gelatin
Titanium dioxide (E171)
Yellow iron oxide (E172)
6.2 Incompatibilities
Not applicable.
8
6.3 Shelf life
2 years.
6.4 Special precautions for storage
Do not store above 30°C.
Store in the original package in order to protect from light and moisture.
6.5 Nature and contents of container
The capsules are provided in PVC/PVDC/aluminium foil blisters, packed in carton packs.
Packs of 5, 10, 20, 30, 50, 90, 100 capsules.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
7.
Recordati Ireland Ltd.
Raheens East
Ringaskiddy Co. Cork
Ireland
8.
EU/1/09/607/001
EU/1/09/607/002
EU/1/09/607/003
EU/1/09/607/004
EU/1/09/607/005
EU/1/09/607/006
EU/1/09/607/007
9.
29/01/2010
Detailed information on this medicinal product is available on the website of the European Medicines
Agency (EMEA) http://www.emea.europa.eu/.
9
1.
Silodyx 8 mg hard capsules
2.
Each hard capsule contains 8 mg silodosin.
For a full list of excipients, see section 6.1.
3.
Hard capsule.
White, opaque, hard gelatin capsule, size 0.
4.
Treatment of the signs and symptoms of benign prostatic hyperplasia (BPH).
The recommended dose is one capsule of Silodyx 8 mg daily. For special patient populations, one
capsule of Silodyx 4 mg daily is recommended (see below).
Elderly patients
No dose adjustment is required in the elderly (see section 5.2).
Renal impairment
No dose adjustment is required for patients with mild renal impairment (CL
CR
≥50 to ≤80 ml/min).
A starting dose of 4 mg once daily is recommended in patients with moderate renal impairment (CL
CR
≥30 to <50 ml/min), which may be increased to 8 mg once daily after one week of treatment,
depending on the individual patient’s response. The use in patients with severe renal impairment
(CL
CR
<30 ml/min) is not recommended (see sections 4.4 and 5.2).
Hepatic impairment
No dose adjustment is required for patients with mild to moderate hepatic impairment.
As no data are available, the use in patients with severe hepatic impairment is not recommended (see
sections 4.4 and 5.2).
Children and adolescents
There is no relevant indication for use of Silodyx in children and adolescents.
Method of administration
The capsule should be taken with food, preferably at the same time every day. The capsule should not
be broken or chewed but swallowed whole, preferably with a glass of water.
Hypersensitivity to the active substance or to any of the excipients.
10
Intraoperative Floppy Iris Syndrome (IFIS)
IFIS (a variant of small pupil syndrome) has been observed during cataract surgery in some patients on
α
1
-blockers or previously treated with α
1
-blockers. This may lead to increased procedural
complications during the operation.
The initiation of therapy with Silodyx is not recommended in patients for whom cataract surgery is
scheduled. Discontinuing treatment with an α
1
-blocker 1-2 weeks prior to cataract surgery has been
recommended, but the benefit and duration of stopping the therapy prior to cataract surgery has not yet
been established.
During pre-operative assessment, eye surgeons and ophthalmic teams should consider whether patients
scheduled for cataract surgery are being or have been treated with Silodyx, in order to ensure that
appropriate measures will be in place to manage IFIS during surgery.
Orthostatic effects
The incidence of orthostatic effects with Silodyx is very low. However, a reduction in blood pressure
can occur in individual patients, leading in rare cases to syncope. At the first signs of orthostatic
hypotension (such as postural dizziness), the patient should sit or lie down until the symptoms have
disappeared. In patients with orthostatic hypotension, treatment with Silodyx is not recommended.
Renal impairment
The use of Silodyx in patients with severe renal impairment (CL
CR
<30 ml/min) is not recommended
(see sections 4.2 and 5.2).
Hepatic impairment
Since no data are available in patients with severe hepatic impairment, the use of Silodyx in these
patients is not recommended (see sections 4.2 and 5.2).
Carcinoma of the prostate
Since BPH and prostate carcinoma may present the same symptoms and can co-exist, patients thought
to have BPH should be examined prior to starting therapy with Silodyx, to rule out the presence of
carcinoma of the prostate. Digital rectal examination and, when necessary, determination of prostate
specific antigen (PSA) should be performed before treatment and at regular intervals afterwards.
Treatment with Silodyx leads to a decrease in the amount of semen released during orgasm that may
temporarily affect male fertility. This effect disappears after discontinuation of Silodyx (see
section 4.8).
Silodosin is metabolised extensively, mainly via CYP3A4, alcohol dehydrogenase and UGT2B7.
Silodosin is also a substrate for P-glycoprotein. Substances that inhibit or induce these enzymes and
transporters may affect the plasma concentrations of silodosin and its active metabolite.
Alpha-blockers
There is inadequate information about the safe use of silodosin in association with other
α-adrenoreceptor antagonists. Consequently, the concomitant use of other α-adrenoreceptor
antagonists is not recommended.
CYP3A4 inhibitors
In an interaction study, a 3.7-fold increase in maximum silodosin plasma concentrations and a 3.1-fold
increase in silodosin exposure (i.e. AUC) were observed with concurrent administration of a potent
CYP3A4 inhibitor (ketoconazole 400 mg). Concomitant use with potent CYP3A4 inhibitors (such as
ketoconazole, itraconazole or ritonavir) is not recommended.
When silodosin was co-administered with a CYP3A4 inhibitor of moderate potency such as diltiazem,
an increase in silodosin AUC of approximately 30 % was observed, but C
max
and half-life were not
affected. This change is clinically not relevant and no dose adjustment is required.
11
PDE-5 inhibitors
Minimal pharmacodynamic interactions have been observed between silodosin and maximum doses of
sildenafil or tadalafil. In a placebo-controlled study in 24 subjects 45-78 years of age receiving
Silodyx, the co-administration of sildenafil 100 mg or tadalafil 20 mg induced no clinically
meaningful mean decreases in systolic or diastolic blood pressure, as assessed by orthostatic tests
(standing versus supine). In the subjects over 65 years, the mean decreases at the various time points
were between 5 and 15 mmHg (systolic) and 0 and 10 mmHg (diastolic). Positive orthostatic tests
were only slightly more common during co-administration; however, no symptomatic orthostasis or
dizziness occurred. Patients taking PDE-5 inhibitors concomitantly with Silodyx should be monitored
for possible adverse reactions.
Antihypertensives
In the clinical study program, many patients were on concomitant antihypertensive therapy (mostly
agents acting on the renin-angiotensin system, beta-blockers, calcium antagonists and diuretics)
without experiencing an increase in the incidence of orthostatic hypotension. Nevertheless, caution
should be exercised when starting concomitant use with antihypertensives and patients should be
monitored for possible adverse reactions.
Digoxin
Steady state levels of digoxin, a substrate of P-glycoprotein, were not significantly affected by
co-administration with silodosin 8 mg once daily. No dose adjustment is required.
Fertility
In clinical studies, the occurrence of ejaculation with reduced or no semen has been observed during
treatment with Silodyx (see section 4.8), due to the pharmacodynamic properties of silodosin. Before
starting treatment, the patient should be informed that this effect may occur, temporarily affecting
male fertility.
No studies on the effects on the ability to drive and use machines have been performed. However,
patients should be informed about the possible occurrence of symptoms related to postural
hypotension (such as dizziness) and should be cautioned about driving or operating machines until
they know how Silodyx will affect them.
The safety of Silodyx has been evaluated in four double-blind controlled clinical studies (with
931 patients receiving silodosin 8 mg once daily and 733 patients receiving placebo) and in two long-
term open-label extension phase studies. In total, 1,581 patients have received silodosin at a dose of
8 mg once daily, including 961 patients exposed for at least 6 months and 384
patients exposed for
1 year.
The most frequent adverse reactions reported with silodosin in placebo controlled clinical studies and
during long-term use were ejaculatory disorders such as retrograde ejaculation and anejaculation
(ejaculatory volume reduced or absent), with a frequency of 23 %. This may temporarily affect male
fertility. It is reversible within a few days upon discontinuation of treatment (see section 4.4).
In the table below, adverse reactions reported in all clinical studies and for which a reasonable causal
relationship exists are listed by MedDRA system organ class and frequency: very common (≥1/10);
common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare
12
(<1/10,000), not known (frequency cannot be estimated from available data). Within each frequency
grouping the observed adverse reactions are presented in order of decreasing seriousness.
Very common
Common
Uncommon
Not known
Psychiatric
disorders
Libido decreased
Nervous system
disorders
Dizziness
Syncope
Vascular disorders
Orthostatic
hypotension
Respiratory,
thoracic and
mediastinal
disorders
Nasal congestion
Gastrointestinal
disorders
Diarrhoea
Nausea
Dry mouth
Reproductive system
and breast disorders
Retrograde
ejaculation
Anejaculation
Erectile dysfunction
Injury, poisoning
and procedural
complication
Intraoperative
Floppy Iris
Syndrome
Orthostatic hypotension
: the incidence of orthostatic hypotension in placebo-controlled clinical studies
was 1.2 % with silodosin and 1.0 % with placebo. Orthostatic hypotension may occasionally lead to
syncope (see section 4.4).
Intraoperative Floppy Iris Syndrome (IFIS)
: IFIS has been reported during cataract surgery (see
section 4.4).
Silodosin was evaluated at doses of up to 48 mg/day in healthy male subjects. The dose-limiting
adverse reaction was postural hypotension. If ingestion is recent, induction of vomiting or gastric
lavage may be considered. Should overdose of Silodyx lead to hypotension, cardiovascular support
has to be provided. Dialysis is unlikely to be of significant benefit since silodosin is highly (96.6 %)
protein bound.
5.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Urologicals, alpha-adrenoreceptor antagonists, ATC code:
G04CA04.
Mechanism of action
Silodosin is highly selective for α
1A
-adrenoreceptors that are primarily located in the human prostate,
bladder base, bladder neck, prostatic capsule and prostatic urethra. Blockade of these
α
1A
-adrenoreceptors causes smooth muscle in these tissues to relax, thus decreasing bladder outlet
resistance, without affecting detrusor smooth muscle contractility. This causes an improvement of both
13
storage (irritative) and voiding (obstructive) symptoms (Lower urinary tract symptoms, LUTS)
associated with benign prostatic hyperplasia.
Silodosin has a substantially lower affinity for the α
1B
-adrenoreceptors that are primarily located in the
cardiovascular system. It has been demonstrated
in vitro
that the α
1A
:α
1B
binding ratio of silodosin
(162:1) is extremely high.
Clinical studies
In a Phase II dose-finding, double-blind, placebo-controlled clinical study with silodosin 4 or 8 mg
once daily, a greater improvement in American Urologic Association (AUA) symptom index score
was observed with silodosin 8 mg (-6.8±5.8, n=90; p=0.0018) and silodosin 4 mg (-5.7±5.5, n=88;
p=0.0355) as compared to placebo (-4.0±5.5, n=83).
Over 800 patients with moderate to severe symptoms of BPH (International Prostate Symptom Score,
IPSS, baseline value ≥13) received silodosin 8 mg once daily in two Phase III placebo-controlled
clinical studies conducted in the United States and in one placebo- and active-controlled clinical study
conducted in Europe. In all studies, patients who did not respond to placebo during a 4-week placebo
run-in phase were randomised to receive the study treatment. In all studies, patients treated with
silodosin had a greater decrease in both storage (irritative) and voiding (obstructive) symptoms of
BPH as compared to placebo as assessed after 12 weeks of treatment. Data observed in the Intent-to-
treat populations of each study are shown below:
IPSS
Total Score
IPSS
Irritative symptoms
IPSS
Obstructive
symptoms
Treatment
arm
No. of
patients
Baseline
Value
(±SD)
Study
Change
from
baseline
Difference
(95
%
CI)
vs
placebo
Change
from
baseline
Difference
(95
%
CI)
vs
placebo
Change
from
baseline
Difference
(95
%
CI)
vs
placebo
Silodosin
233
228
22 ± 5
21± 5
-6.5
-3.6
-2.8*
(-3.9, -1.7)
-2.3
-1.4
-0.9*
(-1.4, -0.4)
-4.2
-2.2
-1.9*
(-2.6, -1.2)
US-1
Placebo
Silodosin
233
229
21 ± 5
21 ± 5
-6.3
-3.4
-2.9*
(-4.0, -1.8)
-2.4
-1.3
-1.0*
(-1.5, -0.6)
-3.9
-2.1
-1.8*
(-2.5, -1.1)
US-2
Placebo
Silodosin
371
19 ± 4
-7.0
-2.3*
(-3.2, -1.4)
-2.0*
(-2.9, -1.1)
-2.5
-0.7°
(-1.1, -0.2)
-0.6°
(-1.1, -0.2)
-4.5
-1.7*
(-2.2, -1.1)
-1.4*
(-2.0, -0.8)
Europe
Tamsulosin
376
19 ± 4
-6.7
-2.4
-4.2
Placebo
185
19 ± 4
-4.7
-1.8
-2.9
* p<0.001 vs Placebo; ° p =0.002 vs Placebo
In the active-controlled clinical study conducted in Europe, silodosin 8 mg once daily was shown to be
non inferior to tamsulosin 0.4 mg once daily: the adjusted mean difference (95 % CI) in the IPSS Total
Score between treatments in the per-protocol population was 0.4 (-0.4 to 1.1). The responder rate (i.e.
improvement in the IPSS total score by at least 25 %) was significantly higher in the silodosin (68 %)
and tamsulosin group (65 %), as compared to placebo (53 %).
In the long-term open-label extension phase of these controlled studies, in which patients received
silodosin for up to 1 year, the symptom improvement induced by silodosin at week 12 of treatment
was maintained over 1 year.
14
No significant reduction in supine blood pressure was observed in all clinical studies conducted with
silodosin.
Silodosin 8 mg and 24 mg daily had no statistically significant effect on ECG intervals or cardiac
repolarisation relative to placebo.
Paediatric population
The European Medicines Agency has waived the obligation to submit the results of studies with
Silodyx in all subsets of the paediatric population in BPH (see section 4.2 for information on
paediatric use).
5.2 Pharmacokinetic properties
The pharmacokinetics of silodosin and its main metabolites have been evaluated in adult male subjects
with and without BPH after single and multiple administrations with doses ranging from 0.1 mg to
48 mg per day. The pharmacokinetics of silodosin is linear throughout this dose range.
The exposure to the main metabolite in plasma, silodosin glucuronide (KMD-3213G), at steady-state
is about 3-fold that of the parent drug. Silodosin and its glucuronide reach steady-state after 3 days and
5 days of treatment, respectively.
Absorption
Silodosin administered orally is well absorbed and absorption is dose proportional. The absolute
bioavailability is approximately 32 %.
An
in vitro
study with Caco-2 cells showed that silodosin is a substrate for P-glycoprotein.
Food decreases C
max
by approximately 30 %, increases t
max
by approximately 1 hour and has little
effect on AUC.
In healthy male subjects of the target age range (n=16, mean age 55±8 years) after once-a-day oral
administration of 8 mg immediately after breakfast for 7 days, the following pharmacokinetic
parameters were obtained: C
max
87±51 ng/ml (sd), t
max
2.5 hours (range 1.0-3.0), AUC
433±286 ng • h/ml.
Distribution
Silodosin has a volume of distribution of 0.81 l/kg and is 96.6 % bound to plasma proteins. It does not
distribute into blood cells.
Protein binding of silodosin glucuronide is 91 %.
Biotransformation
Silodosin undergoes extensive metabolism through glucuronidation (UGT2B7), alcohol and aldehyde
dehydrogenase and oxidative pathways, mainly CYP3A4. The main metabolite in plasma, the
glucuronide conjugate of silodosin (KMD-3213G), that has been shown to be active
in vitro
, has an
extended half-life (approximately 24 hours) and reaches plasma concentrations approximately four
times higher than those of silodosin.
In vitro
data indicate that silodosin does not have the potential to
inhibit or induce cytochrome P450 enzyme systems.
Elimination
Following oral administration of
14
C-labelled silodosin, the recovery of radioactivity after 7 days was
approximately 33.5 % in urine and 54.9 % in faeces. Body clearance of silodosin was approximately
0.28 l/h/kg. Silodosin is excreted mainly as metabolites, very low amounts of unchanged drug are
recovered in urine. The terminal half-life of parent drug and its glucuronide is approximately 11 hours
and 18 hours, respectively.
Special populations
Geriatric
Exposure to silodosin and its main metabolites does not change significantly with age, even in subjects
of age over 75 years.
15
Paediatric
Silodosin has not been evaluated in patients less than 18 years of age.
Hepatic impairment
In a single-dose study, the pharmacokinetics of silodosin was not altered in nine patients with
moderate hepatic impairment (Child-Pugh scores 7 to 9), compared to nine healthy subjects. Results
from this study should be interpreted with caution, since enrolled patients had normal biochemistry
values, indicating normal metabolic function, and they were classified as having moderate liver
impairment based on ascites and hepatic encephalopathy.
The pharmacokinetics of silodosin in patients with severe hepatic impairment has not been studied.
Renal impairment
In a single-dose study, exposure to silodosin (unbound) in subjects with mild (n=8) and moderate renal
impairment (n=8) resulted, on average, in an increase of C
max
(1.6-fold ) and AUC (1.7-fold ) relative
to subjects with normal renal function (n=8). In subjects with severe renal impairment (n=5) increase
of exposure was 2.2-fold for C
max
and 3.7-fold for AUC. Exposure to the main metabolites, silodosin
glucuronide and KMD3293, was also increased.
Plasma level monitoring in a Phase III clinical study showed that levels of total silodosin after 4 weeks
of treatment did not change in patients with mild impairment (n=70), compared to patients with
normal renal function (n=155), while the levels were doubled on average in patients with moderate
impairment (n=7).
A review of safety data of patients enrolled in all clinical studies does not indicate that mild renal
impairment (n=487) poses an additional safety risk during silodosin therapy (such as an increase in
dizziness or orthostatic hypotension) as compared to patients with normal renal function (n=955).
Accordingly, no dose adjustment is required in patients with mild renal impairment. Since only limited
experience exists in patients with moderate renal impairment (n=35), a lower starting dose of 4 mg is
recommended. In patients with severe renal impairment administration of Silodyx is not
recommended.
5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety
pharmacology, carcinogenic, mutagenic and teratogenic potential. Effects in animals (affecting the
thyroid gland in rodents) were observed only at exposures considered sufficiently in excess of the
maximum human exposure, indicating little relevance to clinical use.
In male rats, decreased fertility was observed from exposures which were approximately twice the
exposure at the maximum recommended human dose. The observed effect was reversible.
6.
6.1 List of excipients
Capsule content
Starch, pregelatinised (maize)
Mannitol (E421)
Magnesium stearate
Sodium laurilsulfate
Capsule shell
Gelatin
Titanium dioxide (E171)
6.2 Incompatibilities
Not applicable.
16
6.3 Shelf life
2 years.
6.4 Special precautions for storage
Do not store above 30°C.
Store in the original package in order to protect from light and moisture.
6.5 Nature and contents of container
The capsules are provided in PVC/PVDC/aluminium foil blisters, packed in carton packs.
Packs of 5, 10, 20, 30, 50, 90, 100 capsules.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
7.
Recordati Ireland Ltd.
Raheens East
Ringaskiddy Co. Cork
Ireland
8.
EU/1/09/607/008
EU/1/09/607/009
EU/1/09/607/010
EU/1/09/607/011
EU/1/09/607/012
EU/1/09/607/013
EU/1/09/607/014
9.
29/01/2010
Detailed information on this medicinal product is available on the website of the European Medicines
Agency (EMEA) http://www.emea.europa.eu/.
17
ANNEX II
A. MANUFACTURING AUTHORISATION HOLDER
RESPONSIBLE FOR BATCH RELEASE
B. CONDITIONS OF THE MARKETING AUTHORISATION
18
A. MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH
RELEASE
Name and address of the manufacturer responsible for batch release
Recordati Industria Chimica e Farmaceutica S.p.A.
Via M. Civitali 1
I-20148 Milan
Italy
B. CONDITIONS OF THE MARKETING AUTHORISATION
•
Medicinal product subject to medical prescription.
•
CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND
EFFECTIVE USE OF THE MEDICINAL PRODUCT
The MAH shall ensure that all eye surgeons in the EU Countries in which silodosin will be marketed
are provided with the following information:
•
the Direct Healthcare Professional Communication (DHPC) on the association of Silodosin with
Intraoperative Floppy Iris Syndrome and the two literature references mentioned in the text of
the communication (at launch);
•
a flow-chart describing the management of patients for which cataract surgery is scheduled (at
launch and after launch);
•
an educational program on the prevention and management of IFIS (at launch and after launch);
covering the following topics:
1. clinicallyrelevant
literature references
on the prevention and management of IFIS;
2.
pre-operative assessment
: eye surgeons and ophthalmic teams should establish whether
patients scheduled for cataract surgery are being or have been treated with silodosin in
order to ensure that appropriate measures are in place to manage IFIS during surgery.
3.
recommendation to surgeons and ophthalmic teams
: discontinuing treatment with α1-
adrenoceptor antagonists 2 weeks prior to cataract surgery has been recommended, but the
benefit and duration of stopping therapy prior to cataract surgery has not yet been
established.
•
OTHER CONDITIONS
Pharmacovigilance system
The MAH must ensure that the system of pharmacovigilance, as described in version 2 presented in
Module 1.8.1. of the Marketing Authorisation Application, is in place and functioning before and
whilst the product is on the market.
Risk Management Plan
The MAH commits to performing the studies and additional pharmacovigilance activities detailed in
the Pharmacovigilance Plan, as agreed in version 4 of the Risk Management Plan (RMP) presented in
Module 1.8.2. of the Marketing Authorisation Application and any subsequent updates of the RMP
agreed by the CHMP.
19
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, the
updated RMP should be submitted at the same time as the next Periodic Safety Update Report
(PSUR).
In addition, an updated RMP should be submitted
•
When new information is received that may impact on the current Safety Specification,
Pharmacovigilance Plan or risk minimisation activities
•
Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being
reached
•
At the request of the EMEA
The data lock point (DLP) and the PSUR cycle will be based on the International Birth Date (IBD) of
silodosin.
20
ANNEX III
LABELLING AND PACKAGE LEAFLET
21
A. LABELLING
22
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
CARTON
1.
Silodyx 4 mg hard capsules
silodosin
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each hard capsule contains 4 mg silodosin.
3.
LIST OF EXCIPIENTS
4.
5 hard capsules
10 hard capsules
20 hard capsules
30 hard capsules
50 hard capsules
90 hard capsules
100 hard capsules
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Read the package leaflet before use.
Oral use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Do not store above 30°C.
23
Store in the original package in order to protect from light and moisture.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Recordati Ireland Ltd.
Raheens East
Ringaskiddy Co. Cork
Ireland
12.
EU/1/09/607/001
EU/1/09/607/002
EU/1/09/607/003
EU/1/09/607/004
EU/1/09/607/005
EU/1/09/607/006
EU/1/09/607/007
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Silodyx 4 mg
24
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS
PVC/PVDC/aluminium foil blisters
1.
Silodyx 4 mg hard capsules
silodosin
2.
Recordati Ireland Ltd.
3.
EXPIRY DATE
EXP
4.
BATCH NUMBER
Lot
5.
OTHER
25
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
CARTON
1.
Silodyx 8 mg hard capsules
silodosin
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each hard capsule contains 8 mg silodosin.
3.
LIST OF EXCIPIENTS
4.
5 hard capsules
10 hard capsules
20 hard capsules
30 hard capsules
50 hard capsules
90 hard capsules
100 hard capsules
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Read the package leaflet before use.
Oral use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Do not store above 30°C.
26
Store in the original package in order to protect from light and moisture.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Recordati Ireland Ltd.
Raheens East
Ringaskiddy Co. Cork
Ireland
EU/1/09/607/008
EU/1/09/607/009
EU/1/09/607/010
EU/1/09/607/011
EU/1/09/607/012
EU/1/09/607/013
EU/1/09/607/014
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Silodyx 8 mg
27
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS
PVC/PVDC/aluminium foil blisters
1.
Silodyx 8 mg hard capsules
silodosin
2.
Recordati Ireland Ltd.
3.
EXPIRY DATE
EXP
4.
BATCH NUMBER
Lot
5.
OTHER
28
B. PACKAGE LEAFLET
29
PACKAGE LEAFLET: INFORMATION FOR THE USER
Silodyx 8 mg hard capsules
Silodyx 4 mg hard capsules
Silodosin
Read all of this leaflet carefully before you start using this medicine.
-
Keep this leaflet. You may need to read it again.
-
This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even
if their symptoms are the same as yours.
-
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,
please tell your doctor or pharmacist.
In this leaflet
:
1.
What Silodyx is and what it is used for
3.
How to take Silodyx
4.
Possible side effects
5.
How to store Silodyx
6.
Further information
1.
WHAT SILODYX IS AND WHAT IT IS USED FOR
What Silodyx is
Silodyx belongs to a group of medicines called alpha
1A
-adrenoreceptor blockers.
Silodyx is selective for the receptors located in the prostate, bladder and urethra. By blocking these
receptors, it causes smooth muscle in these tissues to relax. This makes it easier for you to pass water
and relieves your symptoms.
What Silodyx is used for
Silodyx is used in male patients to treat the urinary symptoms associated with benign enlargement of
the prostate (prostatic hyperplasia), such as:
•
difficulty in starting to pass water,
•
a feeling of not completely emptying the bladder,
•
a more frequent need to pass water, even at night.
2.
BEFORE YOU TAKE SILODYX
Do NOT take Silodyx
•
You must not take Silodyx
if you are allergic (hypersensitive) to silodosin or any of the other
ingredients of this medicine.
Take special care with Silodyx
•
If you are undergoing eye surgery because of cloudiness of the lens (
cataract surgery
), it is
important that you
immediately inform your eye specialist
that you are using or have previously
used Silodyx. This is because some patients treated with this kind of medicine experienced a
loss of muscle tone in the iris (the coloured circular part of the eye) during such a surgery. The
30
-
If you have any further questions, ask your doctor or pharmacist.
2.
Before you take Silodyx
specialist can take appropriate precautions with respect to medicine and surgical techniques to
be used. Ask your doctor whether or not you should postpone or temporarily stop taking
Silodyx when undergoing cataract surgery.
•
If you have ever fainted or felt dizzy when suddenly standing up, please inform your doctor
before taking Silodyx.
Dizziness
when standing up and occasionally
fainting
may occur when taking Silodyx,
particularly when starting treatment or if you are taking other medicines that lower blood
pressure. If this occurs, make sure you
sit or lie down
straight away until the symptoms have
disappeared and
inform your doctor as soon as possible
(see also section “Driving and using
machines”).
•
If you have
severe liver problems,
you should not take Silodyx, as it was not tested in this
condition.
•
If you have
problems with your kidneys
, please ask your doctor for advice.
If you have moderate kidney problems, your doctor will start Silodyx with caution and possibly
with a lower dose (see section 3 “Dose”).
If you have severe kidney problems, you should not take Silodyx.
•
Since a benign enlargement of the prostate and prostate cancer may present the same symptoms,
your doctor will check you for prostate cancer before starting treatment with Silodyx. Silodyx
does not treat prostate cancer.
•
The treatment with Silodyx may lead to an abnormal ejaculation (decrease in the amount of
semen released during sex) that may temporarily affect male fertility. This effect disappears
after discontinuation of Silodyx. Please inform your doctor if you are planning to have children.
•
Silodyx is not recommended for use in patients aged below 18 years since there is no relevant
indication for this age group.
Using other medicines
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines,
including medicines obtained without a prescription.
Tell your doctor
in particular, if you take:
•
medicines which lower blood pressure
(in particular, medicines called alpha
1
-blockers, such
as prazosin or doxazosin) as there may be the potential risk that the effect of these medicines is
increased whilst taking Silodyx.
•
antifungal medicines
(such as ketoconazole or itraconazole),
medicines used for HIV-AIDS
(such as ritonavir) or
medicines used after transplants to prevent organ rejection
(such as
cyclosporin) because these medicines can increase the blood concentration of Silodyx.
•
medicines used for treating problems in getting or keeping an erection
(such as sildenafil or
tadalafil), since the concomitant use with Silodyx might lead to a slight decrease in blood
pressure.
•
medicines for epilepsy or rifampicin
(a medicine to treat tubercolosis), since the effect of
Silodyx may be reduced.
Taking Silodyx with food and drink
Take Silodyx always with food (see section 3 “When and how to take Silodyx”).
Driving and using machines
Do not drive or operate machines if you feel faint, dizzy, drowsy or have blurred vision.
31
3.
HOW TO TAKE SILODYX
Always use Silodyx exactly as your doctor has told you. You should check with your doctor or
pharmacist if you are not sure.
Dose
The
usual dose
is one capsule of Silodyx 8 mg per day by oral administration.
Patients with kidney problems
If you have moderate kidney problems, your doctor may prescribe a different dose. For this purpose
Silodyx 4 mg hard capsules are available.
When and how to take Silodyx
Take the capsule always with food, preferably at the same time every day. Do not break or chew the
capsule, but swallow it whole, preferably with a glass of water.
If you use more Silodyx than you should
If you have taken more than one capsule, inform your doctor as soon as possible. If you become dizzy
or feel weak, tell your doctor straight away.
If you forget to use Silodyx
You may take your capsule later the same day if you have forgotten to take it earlier. If it is almost
time for the next dose, skip the dose you missed. Do not take a double dose to make up for a forgotten
capsule.
If you stop using Silodyx
If you stop treatment, your symptoms may re-appear.
If you have any further questions on the use of this product, ask your doctor or pharmacist.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, Silodyx can cause side effects, although not everybody gets them.
The most common side effect is a decrease in the amount of semen released during sex. This effect
disappears after discontinuation of Silodyx. Please inform your doctor if you are planning to have
children.
Dizziness
, including dizziness when standing up, and occasionally
fainting
, may occur.
If you do feel weak or dizzy, make sure you
sit or lie down
straight away until the symptoms have
disappeared. If dizziness when standing up or fainting occurs,
please inform your doctor as soon as
possible
.
Silodyx may cause complications during a
cataract surgery
(eye surgery because of cloudiness of the
lens, see section “Take special care with Silodyx”).
It is important that you
immediately inform your eye specialist
if you are using or have previously
used Silodyx.
32
The frequency of possible side effects listed below is defined using the following convention:
Very common
affects more than 1 user in 10
Common
affects 1 to 10 users in 100
Uncommon
affects 1 to 10 users in 1,000
Not known
frequency cannot be estimated from the available data
Very common side effects
•
Abnormal ejaculation (less or no noticeable semen is released during sex, see section ‘Take
special care with Silodyx’)
Common side effects
•
Dizziness, including dizziness when standing up (see also above, in this section)
•
Runny or blocked nose
•
Diarrhoea
Uncommon side effects
•
Decreased sexual drive
•
Nausea
•
Dry mouth
•
Difficulties in getting or keeping an erection
Not known
•
Floppy pupil during cataract surgery (see also above, in this section)
•
Fainting
If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please
tell your doctor or pharmacist.
If you feel that your sexual life is affected, please tell your doctor.
5.
HOW TO STORE SILODYX
Keep out of the reach and sight of children.
Do not use Silodyx after the expiry date which is stated on the carton and blister after EXP. The expiry
date refers to the last day of that month.
Do not store above 30°C.
Store in the original package in order to protect from light and moisture.
Do not use any Silodyx pack that is damaged or shows signs of tampering.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These measures will help to protect the environment.
6.
FURTHER INFORMATION
What Silodyx contains
Silodyx 8 mg
•
The active substance is silodosin. Each capsule contains 8 mg of silodosin.
33
•
The other ingredients are pregelatinised maize starch, mannitol (E421), magnesium stearate,
sodium laurilsulfate, gelatin, titanium dioxide (E171).
Silodyx 4 mg
•
The active substance is silodosin. Each capsule contains 4 mg of silodosin.
•
The other ingredients are pregelatinised maize starch, mannitol (E421), magnesium stearate,
sodium laurilsulfate, gelatin, titanium dioxide (E171), yellow iron oxide (E172).
What Silodyx looks like and contents of the pack
Silodyx 8 mg are white, opaque, hard gelatin capsules.
Silodyx 4 mg are yellow, opaque, hard gelatin capsules.
Silodyx is available in packs containing 5, 10, 20, 30, 50, 90, 100 capsules. Not all pack sizes may be
marketed.
Marketing Authorisation Holder
Recordati Ireland Ltd.
Raheens East
Ringaskiddy Co. Cork
Ireland
Manufacturer
Recordati Industria Chimica e Farmaceutica S.p.A.
Via Matteo Civitali 1
I-20148 Milan
Italy
For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder:
België/Belgique/Belgien
ZAMBON nv-sa
Tel: + 32 2 777 02 00
Luxembourg/Luxemburg
ZAMBON nv-sa
Tel: + 32 2 777 02 00
България
Recordati Ireland Ltd.
Tel: + 353 21 4379400
Magyarország
Recordati Ireland Ltd.
Tel: + 353 21 4379400
Česká republika
Recordati Ireland Ltd.
Tel: + 353 21 4379400
Malta
Recordati Ireland Ltd.
Tel: + 353 21 4379400
Danmark
Recordati Ireland Ltd.
Tel: + 353 21 4379400
Nederland
Zambon Nederland B.V.
Tel: + 31 33 4504370
Deutschland
Recordati Ireland Ltd.
Tel: + 353 21 4379400
Norge
Recordati Ireland Ltd.
Tel: + 353 21 4379400
34
Eesti
Recordati Ireland Ltd.
Tel: + 353 21 4379400
Österreich
Recordati Ireland Ltd.
Tel: + 353 21 4379400
Ελλάδα
ΒΙΑΝΕΞ Α.Ε.
Tel: + 30 210 8009111
Polska
Recordati Ireland Ltd.
Tel: + 353 21 4379400
España
Almirall, S.A.
Tel: +34 93 291 30 00
Portugal
Nycomed Portugal - Produtos Farmacêuticos, Lda.
Tel: + 351 214 460 200
France
ZAMBON France
Tel: + 33 (0)1 58 04 41 41
România
Recordati Ireland Ltd.
Tel: + 353 21 4379400
Ireland
Recordati Ireland Ltd.
Tel: + 353 21 4379400
Slovenija
Recordati Ireland Ltd.
Tel: + 353 21 4379400
Ísland
Recordati Ireland Ltd.
Tel: + 353 21 4379400
Slovenská republika
Recordati Ireland Ltd.
Tel: + 353 21 4379400
Italia
Nycomed S.p.A.
Tel: + 39 02 641601
Suomi/Finland
Recordati Ireland Ltd.
Tel: + 353 21 4379400
Κύπρος
Recordati Ireland Ltd.
Tel: + 353 21 4379400
Sverige
Recordati Ireland Ltd.
Tel: + 353 21 4379400
Latvija
Recordati Ireland Ltd.
Tel: + 353 21 4379400
United Kingdom
Recordati Ireland Ltd.
Tel: + 353 21 4379400
Lietuva
Recordati Ireland Ltd.
Tel: + 353 21 4379400
This leaflet was last approved in
{MM/YYYY}.
Detailed information on this medicine is available on the European Medicines Agency (EMEA) web
site: http://www.emea.europa.eu/.
35
Source: European Medicines Agency
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