ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS
1.
Emselex 7.5 mg prolonged-release tablets
2.
Each tablet contains 7.5 mg of darifenacin (as hydrobromide)
For a full list of excipients, see section 6.1.
3.
Prolonged-release tablet
White round, convex tablet, debossed with “DF” on one side and “7.5” on the reverse.
4.
Symptomatic treatment of urge incontinence and/or increased urinary frequency and urgency as may
occur in adult patients with overactive bladder syndrome.
Adults
The recommended starting dose is 7.5 mg daily. After 2 weeks of starting therapy, patients should be
reassessed. For those patients requiring greater symptom relief, the dose may be increased to 15 mg
daily, based on individual response.
Emselex is for oral use. The tablets should be taken once daily with liquid. They can be taken with or
without food, and must be swallowed whole and not chewed, divided or crushed.
Elderly patients (≥ 65 years)
The recommended starting dose for the elderly is 7.5 mg daily. After 2 weeks of starting therapy,
patients should be reassessed for efficacy and safety.
For those patients who have an acceptable
tolerability profile but require greater symptom relief, the dose may be increased to 15 mg daily, based
on individual response (see section 5.2).
Children
Emselex is not recommended for use in children below 18 years of age due to a lack of data on safety
and efficacy.
Use in renal impairment
No dose adjustment is required in patients with impaired renal function. However, caution should be
exercised when treating this population (see section 5.2).
Use in hepatic impairment
No dose adjustment is required in patients with mild hepatic impairment (Child Pugh A). However,
there is a risk of increased exposure in this population (see section 5.2).
Patients with moderate hepatic impairment (Child Pugh B) should only be treated if the benefit
outweighs the risk, and the dose should be restricted to 7.5 mg daily (see section 5.2). Emselex is
contraindicated in patients with severe hepatic impairment (Child Pugh C) (see section 4.3).
2
Patients receiving concomitant treatment with substances that are potent inhibitors of CYP2D6 or
moderate inhibitors of CYP3A4
In patients receiving substances that are potent CYP2D6 inhibitors, such as paroxetine, terbinafine,
quinidine and cimetidine, treatment should start with the 7.5 mg dose. The dose may be titrated to
15 mg daily to obtain an improved clinical response provided the dose is well tolerated. However,
caution should be exercised.
In patients receiving substances that are moderate CYP3A4 inhibitors, such as fluconazole, grapefruit
juice and erythromycin, the recommended starting dose is 7.5 mg daily. The dose may be titrated to
15 mg daily to obtain an improved clinical response provided the dose is well tolerated. However,
caution should be exercised.
Emselex
is contraindicated in patients with:
-
Hypersensitivity to the active substance or to any of the excipients.
-
Gastric retention.
-
Uncontrolled narrow-angle glaucoma.
-
Myasthenia gravis.
-
Severe hepatic impairment (Child Pugh C).
-
Severe ulcerative colitis.
-
Toxic megacolon.
-
Concomitant treatment with potent CYP3A4 inhibitors (see section 4.5).
Emselex should be administered with caution to patients with autonomic neuropathy, hiatus hernia,
clinically significant bladder outflow obstruction, risk for urinary retention, severe constipation or
gastrointestinal obstructive disorders, such as pyloric stenosis.
Emselex should be used with caution in patients being treated for narrow-angle glaucoma (see
section 4.3).
Other causes of frequent urination (heart failure or renal disease) should be assessed before treatment
with Emselex. If urinary tract infection is present, an appropriate antibacterial therapy should be
started.
Emselex should be used with caution in patients with risk of decreased gastrointestinal motility,
gastro-oesophagal reflux and/or who are concurrently taking medicinal products (such as oral
bisphosphonates) that can cause or exacerbate oesophagitis.
Safety and efficacy have not yet been established in patients with a neurogenic cause for detrusor
overactivity.
Caution should be used when prescribing antimuscarinics to patients with pre-existing cardiac
diseases.
Effects of other medicinal products on darifenacin
Darifenacin metabolism is primarily mediated by the cytochrome P450 enzymes CYP2D6 and
CYP3A4. Therefore, inhibitors of these enzymes may increase darifenacin exposure.
3
-
Urinary retention.
CYP2D6 inhibitors
In patients receiving substances that are potent CYP2D6 inhibitors (e.g. paroxetine, terbinafine,
cimetidine and quinidine) the recommended starting dose should be 7.5 mg daily. The dose may be
titrated to 15 mg daily to obtain an improved clinical response provided the dose is well tolerated.
Concomitant treatment with potent CYP2D6 inhibitors results in an increase in exposure (e.g. of 33%
with 20 mg paroxetine at the 30 mg dose of darifenacin).
CYP3A4 inhibitors
Darifenacin should not be used together with potent CYP3A4 inhibitors (see section 4.3) such as
protease inhibitors (e.g. ritonavir), ketoconazole and itraconazole. Potent P-glycoprotein inhibitors
such as ciclosporin and verapamil should also be avoided. Co-administration of darifenacin 7.5 mg
with the potent CYP3A4 inhibitor ketoconazole 400 mg resulted in a 5-fold increase in steady-state
darifenacin AUC. In subjects who are poor metabolisers, darifenacin exposure increased
approximately 10-fold. Due to a greater contribution of CYP3A4 after higher darifenacin doses, the
magnitude of the effect is expected to be even more pronounced when combining ketoconazole with
darifenacin 15 mg.
When co-administered with moderate CYP3A4 inhibitors such as erythromycin, clarithromycin,
telithromycin, fluconazole and grapefruit juice, the recommended starting dose of darifenacin should
be 7.5 mg daily. The dose may be titrated to 15 mg daily to obtain an improved clinical response
provided the dose is well tolerated. Darifenacin AUC
24
and C
max
from 30 mg once daily dosing in
subjects who are extensive metabolisers were 95% and 128% higher when erythromycin (moderate
CYP3A4 inhibitor) was co-administered with darifenacin than when darifenacin was taken alone.
Enzyme inducers
Substances that are inducers of CYP3A4, such as rifampicin, carbamazepine, barbiturates and St
John’s wort (
Hypericum perforatum
) are likely to decrease the plasma concentrations of darifenacin.
Effects of darifenacin on other medicinal products
CYP2D6 substrates
Darifenacin is a moderate inhibitor of the enzyme CYP2D6. Caution should be exercised when
darifenacin is used concomitantly with medicinal products that are predominantly metabolised by
CYP2D6 and which have a narrow therapeutic window, such as flecainide, thioridazine, or tricyclic
antidepressants such as imipramine. The effects of darifenacin on the metabolism of CYP2D6
substrates are mainly clinically relevant for CYP2D6 substrates which are individually dose titrated.
CYP3A4 substrates
Darifenacin treatment resulted in a modest increase in the exposure of the CYP3A4 substrate
midazolam. However the data available do not indicate that darifenacin changes either midazolam
clearance or bioavailability. It can therefore be concluded that darifenacin administration does not alter
the pharmacokinetics of CYP3A4 substrates
in vivo
. The interaction with midazolam lacks clinical
relevance, and therefore no dose adjustment is needed for CYP3A4 substrates.
Warfarin
Standard therapeutic prothrombin time monitoring for warfarin should be continued. The effect of
warfarin on prothrombin time was not altered when co-administered with darifenacin.
Digoxin
Therapeutic drug monitoring for digoxin should be performed when initiating and ending darifenacin
treatment as well as changing the darifenacin dose. Darifenacin 30 mg once daily (two times greater
than the recommended daily dose) co-administered with digoxin at steady state resulted in a small
increase in digoxin exposure (AUC: 16% and C
max
: 20%). The increase in digoxin exposure could be
caused by competition between darifenacin and digoxin for P-glycoprotein. Other transporter-related
interactions cannot be excluded.
4
Antimuscarinic agents
As with any other antimuscarinic agents, concomitant use of medicinal products that possess
antimuscarinic properties, such as oxybutynin, tolterodine and flavoxate, may result in more
pronounced therapeutic and side effects. The potentiation of anticholinergic effects with anti-
parkinson agents and tricyclic antidepressants may also occur if antimuscarinic agents are used
concurrently with such medicinal products. However, no studies involving the interaction with anti-
parkinson agents and tricyclic antidepressants have been performed.
Fertility
There are no human fertility data for darifenacin. Darifenacin had no effect on male or female fertility
in rats or any effect in the reproductive organs of either sex in rats and dogs (for details, see section
5.3). Women of child bearing potential should be made aware of the lack of fertility data, and Emselex
should only be given after consideration of individual risks and benefits.
Pregnancy
There are limited amount of data from the use of darifenacin in pregnant women. Studies in animals
have shown toxicity to parturition (for details, see section 5.3). Emselex is not recommended during
pregnancy.
Lactation
Darifenacin is excreted in the milk of rats. It is not known whether darifenacin is excreted in human
milk. A risk to the nursing child cannot be excluded. A decision whether to avoid breast-feeding or to
abstain from Emselex therapy during lactation should be based on a benefit and risk comparison.
No studies of the effects of Emselex on the ability to drive and use machines have been performed. As
with other antimuscarinic agents, Emselex may produce effects such as dizziness, blurred vision,
insomnia and somnolence. Patients experiencing these side effects should not drive or use machines.
For Emselex, these side effects have been reported to be uncommon.
Consistent with the pharmacological profile, the most commonly reported adverse reactions were dry
mouth (20.2% and 35% for the 7.5 mg and 15 mg dose, respectively, 18.7% after flexible dose
titration, and 8% - 9% for placebo) and constipation (14.8% and 21% for the 7.5 mg and 15 mg dose,
respectively, 20.9% after flexible dose titration, and 5.4% - 7.9% for placebo). Anticholinergic effects,
in general, are dose-dependent.
However, the patient discontinuation rates due to these adverse reactions were low (dry mouth: 0% -
0.9% and constipation: 0.6% - 2.2% for darifenacin, depending on the dose; and 0% and 0.3% for
placebo, for dry mouth and constipation, respectively).
5
Table 1: Adverse reactions with Emselex 7.5 mg and 15 mg prolonged-release tablets
Frequency estimate: very common (1/10), common (1/100 to <1/10), uncommon (1/1,000 to
<1/100), not known (cannot be estimated from the available data)
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Infections and infestations
Uncommon
Urinary tract infection
Psychiatric disorders
Uncommon
Insomnia, thinking abnormal
Nervous system disorders
Common
Headache
Uncommon
Dizziness, dysgeusia, somnolence
Eye disorders
Common Dry eye
Uncommon Visual disturbance, including vision blurred
Vascular disorders
Uncommon Hypertension
Respiratory, thoracic and mediastinal disorders
Uncommon
Dyspnoea, cough, rhinitis
Gastrointestinal disorders
Very common
Common
Abdominal pain, nausea, dyspepsia
Uncommon
Flatulence, diarrhoea, mouth ulceration
Skin and subcutaneous tissue disorders
Uncommon
Not known
Rash, dry skin, pruritus, hyperhidrosis
Renal and urinary disorders
Uncommon
Urinary retention, urinary tract disorder, bladder pain
Reproductive system and breast disorders
Uncommon Erectile dysfunction, vaginitis
General disorders and administration site conditions
Uncommon
Oedema peripheral, asthenia, face oedema, oedema
Investigations
Uncommon Aspartate aminotransferase increased, alanine
aminotransferase increased
Injury, poisoning, and procedural complications
Uncommon
Injury
In the pivotal clinical trials with doses of Emselex 7.5 mg and 15 mg, adverse reactions were reported
as presented in the table above. Most of the adverse reactions were of mild or moderate intensity and
did not result in discontinuation in the majority of the patients.
Treatment with Emselex may possibly mask symptoms associated with gallbladder disease. However,
there was no association between the occurrence of adverse events related to the biliary system in
darifenacin-treated patients and increasing age.
The incidence of adverse reactions with the doses of Emselex 7.5 mg and 15 mg decreased during the
treatment period up to 6 months. A similar trend is also seen for the discontinuation rates.
Post-marketing experience
The following events have been reported in association with darifenacin use in worldwide post-
marketing experience: generalised hypersensitivity reactions including angioedema, depressed
mood/mood alterations, hallucination. Because these spontaneously reported events are from the
6
Constipation, dry mouth
Angioedema
worldwide post-marketing experience, the frequency of events cannot be estimated from the available
data.
Emselex has been administered in clinical trials at doses up to 75 mg (five times maximum therapeutic
dose). The most common adverse reactions seen were dry mouth, constipation, headache, dyspepsia
and nasal dryness. However, overdose with darifenacin can potentially lead to severe anticholinergic
effects and should be treated accordingly. Therapy should be aimed at reversing the anticholinergic
symptoms under careful medical supervision. The use of agents such as physostigmine can assist in
reversing such symptoms.
5.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Urinary antispasmodic, ATC code: G04BD10.
Darifenacin is a selective muscarinic M3 receptor antagonist (M
3
SRA)
in vitro
. The M3 receptor is
the major subtype that controls urinary bladder muscle contraction. It is not known whether this
selectivity for the M3 receptor translates into any clinical advantage when treating symptoms of
overactive bladder syndrome.
Cystometric studies performed with darifenacin in patients with involuntary bladder contractions
showed increased bladder capacity, increased volume threshold for unstable contractions and
diminished frequency of unstable detrusor contractions.
Treatment with Emselex administered at dosages of 7.5 mg and 15 mg daily has been investigated in
four double-blind, Phase III, randomised, controlled clinical studies in male and female patients with
symptoms of overactive bladder. As seen in Table 2 below, a pooled analysis of 3 of the studies for the
treatment with both Emselex 7.5 mg and 15 mg provided a statistically significant improvement in the
primary endpoint, reduction in incontinence episodes, versus placebo.
Table 2: Pooled analysis of data from three Phase III clinical studies assessing fixed doses of 7.5 mg
and 15 mg Emselex
Dose
N
Incontinence episodes per week
95% CI
P value
2
Baseline
(median)
Week 12
(median)
Change from
baseline
(median)
Differences
from placebo
1
(median)
Emselex 7.5 mg
once daily
335
16.0
4.9
-8.8 (-68%)
-2.0
(-3.6, -0.7)
0.004
Placebo
271
16.6
7.9
-7.0 (-54%)
--
--
--
Emselex 15 mg
once daily
330
16.9
4.1
-10.6 (-77%)
-3.2
(-4.5, -2.0) <0.001
Placebo
384
16.6
6.4
-7.5 (-58%)
--
--
--
1
Hodges Lehmann estimate: median difference from placebo in change from baseline
2
Stratified Wilcoxon test for difference from placebo.
Emselex 7.5 mg and 15 mg doses significantly reduced both the severity and number of urinary
urgency episodes and the number of micturitions, while significantly increasing the mean volume
voided from baseline.
7
Emselex 7.5 mg and 15 mg were associated with statistically significant improvements over placebo in
some aspects of quality of life as measured by the Kings Health Questionnaire including incontinence
impact, role limitations, social limitations and severity measures.
For both doses of 7.5 mg and 15 mg, the percentage median reduction from baseline in the number of
incontinence episodes per week was similar between males and females. The observed differences
from placebo for males in terms of percentage and absolute reductions in incontinence episodes was
lower than for females.
The effect of treatment with 15 mg and 75 mg of darifenacin on QT/QTc interval was evaluated in a
study in 179 healthy adults (44% male: 56% females) aged 18 to 65 for 6 days (to steady state).
Therapeutic and supra-therapeutic doses of darifenacin resulted in no increase in QT/QTc interval
prolongation from baseline compared to placebo at maximum darifenacin exposure.
5.2 Pharmacokinetic properties
Darifenacin is metabolised by CYP3A4 and CYP2D6. Due to genetic differences, about 7% of the
Caucasians lack the CYP2D6 enzyme and are said to be poor metabolisers. A few percent of the
population have increased CYP2D6 enzyme levels (ultrafast metabolisers). The information below
applies to subjects who have normal CYP2D6 activity (extensive metabolisers) unless otherwise
stated.
Absorption
Due to extensive first-pass metabolism darifenacin has a bioavailability of approximately 15% and
19% after 7.5 mg and 15 mg daily doses at steady state. Maximum plasma levels are reached
approximately 7 hours after administration of the prolonged-release tablets and steady-state plasma
levels are achieved by the sixth day of administration. At steady state, peak-to-trough fluctuations in
darifenacin concentrations are small (PTF: 0.87 for 7.5 mg and 0.76 for 15 mg), thereby maintaining
therapeutic plasma levels over the dosing interval. Food had no effect on darifenacin pharmacokinetics
during multiple-dose administration of prolonged-release tablets.
Distribution
Darifenacin is a lipophilic base and is 98% bound to plasma proteins (primarily to alpha-1-acid-
glycoprotein). The steady-state volume of distribution (V
ss
) is estimated to be 163 litres.
Metabolism
Darifenacin is extensively metabolised by the liver following oral administration.
Darifenacin undergoes significant metabolism by cytochrome CYP3A4 and CYP2D6 in the liver and
by CYP3A4 in the gut wall. The three main metabolic routes are as follows:
monohydroxylation in the dihydrobenzofuran ring;
dihydrobenzofuran ring opening and
N-dealkylation of the pyrrolidine nitrogen.
The initial products of the hydroxylation and N-dealkylation pathways are major circulating
metabolites but none contribute significantly to the overall clinical effect of darifenacin.
The pharmacokinetics of darifenacin at steady state are dose-dependent, due to saturation of the
CYP2D6 enzyme.
Doubling the darifenacin dose from 7.5 mg to 15 mg result in a 150% increase in steady-state
exposure. This dose-dependency is probably caused by saturation of the CYP2D6 catalysed
metabolism possibly together with some saturation of CYP3A4-mediated gut wall metabolism.
8
Excretion
Following administration of an oral dose of
14
C-darifenacin solution to healthy volunteers,
approximately 60% of the radioactivity was recovered in the urine and 40% in the faeces. Only a small
percentage of the excreted dose was unchanged darifenacin (3%). Estimated darifenacin clearance is
40 litres/hour. The elimination half-life of darifenacin following chronic dosing is approximately
13-19 hours.
Special patient population
Gender
A population pharmacokinetic analysis of patient data indicated that darifenacin exposure was 23%
lower in males than females (see section 5.1).
Elderly patients
A population pharmacokinetic analysis of patient data indicated a trend for clearance to decrease with
age (19% per decade based on Phase III population pharmacokinetic analysis of patients aged 60–
89 years), see section 4.2.
Paediatric patients
The pharmacokinetics of darifenacin have not been established in the paediatric population.
CYP2D6 poor metabolisers
The metabolism of darifenacin in CYP2D6 poor metabolisers is principally mediated by CYP3A4. In
one pharmacokinetic study the steady-state exposure in poor metabolisers was 164% and 99% higher
during treatment with 7.5 mg and 15 mg once daily, respectively. However, a population
pharmacokinetic analyses of Phase III data indicated that on average steady-state exposure is 66%
higher in poor metabolisers than in extensive metabolisers. There was considerable overlap between
the ranges of exposures seen in these two populations (see section 4.2).
Renal insufficiency
A small study of subjects (n=24) with varying degrees of renal impairment (creatinine clearance
between 10 ml/min and 136 ml/min) given darifenacin 15 mg once daily to steady state demonstrated
no relationship between renal function and darifenacin clearance (see section 4.2).
Hepatic insufficiency
Darifenacin pharmacokinetics were investigated in subjects with mild (Child Pugh A) or moderate
(Child Pugh B) impairment of hepatic function given darifenacin 15 mg once daily to steady state.
Mild hepatic impairment had no effect on the pharmacokinetics of darifenacin. However, protein
binding of darifenacin was affected by moderate hepatic impairment. Unbound darifenacin exposure
was estimated to be 4.7-fold higher in subjects with moderate hepatic impairment than subjects with
normal hepatic function (see section 4.2).
5.3 Preclinical safety data
Preclinical data reveal no special hazard for humans based on conventional studies of safety
pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential. There were no effects
on fertility in male and female rats treated at oral doses up to 50 mg/kg/day (78 times the AUC
0-24h
of
free plasma concentration at maximum recommended human dose [MRHD]). There were no effects on
reproductive organs in either sex in dogs treated for 1 year at oral doses up to 6 mg/kg/day (82 times
the AUC
0-24h
of free plasma concentration at MRHD). Darifenacin was not teratogenic in rats and
rabbits at doses up to 50 and 30 mg/kg/day, respectively. At the dose of 50 mg/kg/day in rats (59 times
the AUC
0-24h
of free plasma concentration at MRHD), delay in the ossification of the sacral and caudal
vertebrae was observed. At the dose of 30 mg/kg/day in rabbits (28 times the AUC
0-24h
of free plasma
concentration at MRHD), maternal toxicity and foetotoxicity (increased post implantation loss and
decreased number of viable foetuses per litter) were observed. In peri and post-natal studies in rats,
dystocia, increased foetal deaths
in utero
and toxicity to post-natal development (pup body weight and
development land marks) were observed at systemic exposure levels up to 11 times the AUC
0-24h
of
free plasma concentration at MRHD.
9
6.
6.1 List of excipients
Tablet core:
Calcium hydrogen phosphate, anhydrous
Hypromellose
Magnesium stearate
Film coat:
Polyethylene glycol
Hypromellose
Titanium dioxide (E171)
Talc
6.2 Incompatibilities
Not applicable
6.3 Shelf life
3 years
6.4 Special precautions for storage
Keep the blister packs in the outer carton in order to protect from light.
6.5 Nature and contents of container
Clear PVC/CTFE/aluminium or PVC/PVDC/aluminium blisters in cartons containing 7, 14, 28, 49, 56
or 98 tablets as unit pack or in multipacks containing 140 (10x14) tablets.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
7.
Novartis Europharm Limited
Wimblehurst Road
Horsham
West Sussex, RH12 5AB
United Kingdom
8.
EU/1/04/294/001-006
EU/1/04/294/013
EU/1/04/294/015-020
EU/1/04/294/027
10
9.
Date of first authorisation: 22.10.2004
Date of latest renewal: 22.10.2009
11
1.
Emselex 15 mg prolonged-release tablets
2.
Each tablet contains 15 mg of darifenacin (as hydrobromide)
For a full list of excipients, see section 6.1.
3.
Prolonged-release tablet
Light peach round, convex tablet debossed with “DF” on one side and “15” on the reverse.
4.
Symptomatic treatment of urge incontinence and/or increased urinary frequency and urgency as may
occur in adult patients with overactive bladder syndrome.
Adults
The recommended starting dose is 7.5 mg daily. After 2 weeks of starting therapy, patients should be
reassessed. For those patients requiring greater symptom relief, the dose may be increased to 15 mg
daily, based on individual response.
Emselex is for oral use. The tablets should be taken once daily with liquid. They can be taken with or
without food, and must be swallowed whole and not chewed, divided or crushed.
Elderly patients (≥ 65 years)
The recommended starting dose for the elderly is 7.5 mg daily. After 2 weeks of starting therapy,
patients should be reassessed for efficacy and safety.
For those patients who have an acceptable
tolerability profile but require greater symptom relief, the dose may be increased to 15 mg daily, based
on individual response (see section 5.2).
Children
Emselex is not recommended for use in children below 18 years of age due to a lack of data on safety
and efficacy.
Use in renal impairment
No dose adjustment is required in patients with impaired renal function. However, caution should be
exercised when treating this population (see section 5.2).
Use in hepatic impairment
No dose adjustment is required in patients with mild hepatic impairment (Child Pugh A). However,
there is a risk of increased exposure in this population (see section 5.2).
Patients with moderate hepatic impairment (Child Pugh B) should only be treated if the benefit
outweighs the risk, and the dose should be restricted to 7.5 mg daily (see section 5.2). Emselex is
contraindicated in patients with severe hepatic impairment (Child Pugh C) (see section 4.3).
12
Patients receiving concomitant treatment with substances that are potent inhibitors of CYP2D6 or
moderate inhibitors of CYP3A4
In patients receiving substances that are potent CYP2D6 inhibitors, such as paroxetine, terbinafine,
quinidine and cimetidine, treatment should start with the 7.5 mg dose. The dose may be titrated to
15 mg daily to obtain an improved clinical response provided the dose is well tolerated. However,
caution should be exercised.
In patients receiving substances that are moderate CYP3A4 inhibitors, such as fluconazole, grapefruit
juice and erythromycin, the recommended starting dose is 7.5 mg daily. The dose may be titrated to
15 mg daily to obtain an improved clinical response provided the dose is well tolerated. However,
caution should be exercised.
Emselex
is contraindicated in patients with:
-
Hypersensitivity to the active substance or to any of the excipients.
-
Gastric retention.
-
Uncontrolled narrow-angle glaucoma.
-
Myasthenia gravis.
-
Severe hepatic impairment (Child Pugh C).
-
Severe ulcerative colitis.
-
Toxic megacolon.
-
Concomitant treatment with potent CYP3A4 inhibitors (see section 4.5).
Emselex should be administered with caution to patients with autonomic neuropathy, hiatus hernia,
clinically significant bladder outflow obstruction, risk for urinary retention, severe constipation or
gastrointestinal obstructive disorders, such as pyloric stenosis.
Emselex should be used with caution in patients being treated for narrow-angle glaucoma (see
section 4.3).
Other causes of frequent urination (heart failure or renal disease) should be assessed before treatment
with Emselex. If urinary tract infection is present, an appropriate antibacterial therapy should be
started.
Emselex should be used with caution in patients with risk of decreased gastrointestinal motility,
gastro-oesophagal reflux and/or who are concurrently taking medicinal products (such as oral
bisphosphonates) that can cause or exacerbate oesophagitis.
Safety and efficacy have not yet been established in patients with a neurogenic cause for detrusor
overactivity.
Caution should be used when prescribing antimuscarinics to patients with pre-existing cardiac
diseases.
Effects of other medicinal products on darifenacin
Darifenacin metabolism is primarily mediated by the cytochrome P450 enzymes CYP2D6 and
CYP3A4. Therefore, inhibitors of these enzymes may increase darifenacin exposure.
13
-
Urinary retention.
CYP2D6 inhibitors
In patients receiving substances that are potent CYP2D6 inhibitors (e.g. paroxetine, terbinafine,
cimetidine and quinidine) the recommended starting dose should be 7.5 mg daily. The dose may be
titrated to 15 mg daily to obtain an improved clinical response provided the dose is well tolerated.
Concomitant treatment with potent CYP2D6 inhibitors results in an increase in exposure (e.g. of 33%
with 20 mg paroxetine at the 30 mg dose of darifenacin).
CYP3A4 inhibitors
Darifenacin should not be used together with potent CYP3A4 inhibitors (see section 4.3) such as
protease inhibitors (e.g. ritonavir), ketoconazole and itraconazole. Potent P-glycoprotein inhibitors
such as ciclosporin and verapamil should also be avoided. Co-administration of darifenacin 7.5 mg
with the potent CYP3A4 inhibitor ketoconazole 400 mg resulted in a 5-fold increase in steady-state
darifenacin AUC. In subjects who are poor metabolisers, darifenacin exposure increased
approximately 10-fold. Due to a greater contribution of CYP3A4 after higher darifenacin doses, the
magnitude of the effect is expected to be even more pronounced when combining ketoconazole with
darifenacin 15 mg.
When co-administered with moderate CYP3A4 inhibitors such as erythromycin, clarithromycin,
telithromycin, fluconazole and grapefruit juice, the recommended starting dose of darifenacin should
be 7.5 mg daily. The dose may be titrated to 15 mg daily to obtain an improved clinical response
provided the dose is well tolerated. Darifenacin AUC
24
and C
max
from 30 mg once-daily dosing in
subjects who are extensive metabolisers were 95% and 128% higher when erythromycin (moderate
CYP3A4 inhibitor) was co-administered with darifenacin than when darifenacin was taken alone.
Enzyme inducers
Substances that are inducers of CYP3A4, such as rifampicin, carbamazepine, barbiturates and St
John´s wort (
Hypericum perforatum
) are likely to decrease the plasma concentrations of darifenacin.
Effects of darifenacin on other medicinal products
CYP2D6 substrates
Darifenacin is a moderate inhibitor of the enzyme CYP2D6. Caution should be exercised when
darifenacin is used concomitantly with medicinal products that are predominantly metabolised by
CYP2D6 and which have a narrow therapeutic window, such as flecainide, thioridazine, or tricyclic
antidepressants such as imipramine. The effects of darifenacin on the metabolism of CYP2D6
substrates are mainly clinically relevant for CYP2D6 substrates which are individually dose titrated.
CYP3A4 substrates
Darifenacin treatment resulted in a modest increase in the exposure of the CYP3A4 substrate
midazolam. However the data available do not indicate that darifenacin changes either midazolam
clearance or bioavailability. It can therefore be concluded that darifenacin administration does not alter
the pharmacokinetics of CYP3A4 substrates
in vivo
. The interaction with midazolam lacks clinical
relevance, and therefore no dose adjustment is needed for CYP3A4 substrates.
Warfarin
Standard therapeutic prothrombin time monitoring for warfarin should be continued. The effect of
warfarin on prothrombin time was not altered when co-administered with darifenacin.
Digoxin
Therapeutic drug monitoring for digoxin should be performed when initiating and ending darifenacin
treatment as well as changing the darifenacin dose. Darifenacin 30 mg once daily (two times greater
than the recommended daily dose) co-administered with digoxin at steady state resulted in a small
increase in digoxin exposure (AUC: 16% and C
max
: 20%). The increase in digoxin exposure could be
caused by competition between darifenacin and digoxin for P-glycoprotein. Other transporter-related
interactions cannot be excluded.
14
Antimuscarinic agents
As with any other antimuscarinic agents, concomitant use of medicinal products that possess
antimuscarinic properties, such as oxybutynin, tolterodine and flavoxate, may result in more
pronounced therapeutic and side effects. The potentiation of anticholinergic effects with anti-
parkinson agents and tricyclic antidepressants may also occur if antimuscarinic agents are used
concurrently with such medicinal products. However, no studies involving the interaction with anti-
parkinson agents and tricyclic antidepressants have been performed.
Fertility
There are no human fertility data for darifenacin. Darifenacin had no effect on male or female fertility
in rats or any effect in the reproductive organs of either sex in rats and dogs (for details, see section
5.3). Women of child bearing potential should be made aware of the lack of fertility data, and Emselex
should only be given after consideration of individual risks and benefits.
Pregnancy
There are limited amount of data from the use of darifenacin in pregnant women. Studies in animals
have shown toxicity to parturition (for details, see section 5.3). Emselex is not recommended during
pregnancy.
Lactation
Darifenacin is excreted in the milk of rats. It is not known whether darifenacin is excreted in human
milk. A risk to the nursing child cannot be excluded. A decision whether to avoid breast-feeding or to
abstain from Emselex therapy during lactation should be based on a benefit and risk comparison.
No studies of the effects of Emselex on the ability to drive and use machines have been performed. As
with other antimuscarinic agents, Emselex may produce effects such as dizziness, blurred vision,
insomnia and somnolence. Patients experiencing these side effects should not drive or use machines.
For Emselex, these side effects have been reported to be uncommon.
Consistent with the pharmacological profile, the most commonly reported adverse reactions were dry
mouth (20.2% and 35% for the 7.5 mg and 15 mg dose, respectively, 18.7% after flexible dose
titration, and 8% - 9% for placebo) and constipation (14.8% and 21% for the 7.5 mg and 15 mg dose,
respectively, 20.9% after flexible dose titration, and 5.4% - 7.9% for placebo). Anticholinergic effects,
in general, are dose-dependent.
However, the patient discontinuation rates due to these adverse reactions were low (dry mouth: 0% -
0.9% and constipation: 0.6% - 2.2% for darifenacin, depending on the dose; and 0% and 0.3% for
placebo, for dry mouth and constipation, respectively).
15
Table 1: Adverse reactions with Emselex 7.5 mg and 15 mg prolonged-release tablets
Frequency estimate: very common (1/10), common (1/100 to <1/10), uncommon (1/1,000 to
<1/100), not known (cannot be estimated from the available data)
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Infections and infestations
Uncommon
Urinary tract infection
Psychiatric disorders
Uncommon
Insomnia, thinking abnormal
Nervous system disorders
Common
Headache
Uncommon
Dizziness, dysgeusia, somnolence
Eye disorders
Common Dry eye
Uncommon Visual disturbance, including vision blurred
Vascular disorders
Uncommon Hypertension
Respiratory, thoracic and mediastinal disorders
Uncommon
Dyspnoea, cough, rhinitis
Gastrointestinal disorders
Very common
Common
Abdominal pain, nausea, dyspepsia
Uncommon
Flatulence, diarrhoea, mouth ulceration
Skin and subcutaneous tissue disorders
Uncommon
Not known
Rash, dry skin, pruritus, hyperhidrosis
Renal and urinary disorders
Uncommon
Urinary retention, urinary tract disorder, bladder pain
Reproductive system and breast disorders
Uncommon Erectile dysfunction, vaginitis
General disorders and administration site conditions
Uncommon
Oedema peripheral, asthenia, face oedema, oedema
Investigations
Uncommon Aspartate aminotransferase increased, alanine
aminotransferase increased
Injury, poisoning, and procedural complications
Uncommon
Injury
In the pivotal clinical trials with doses of Emselex 7.5 mg and 15 mg, adverse reactions were reported
as presented in the table above. Most of the adverse reactions were of mild or moderate intensity and
did not result in discontinuation in the majority of the patients.
Treatment with Emselex may possibly mask symptoms associated with gallbladder disease. However,
there was no association between the occurrence of adverse events related to the biliary system in
darifenacin-treated patients and increasing age.
The incidence of adverse reactions with the doses of Emselex 7.5 mg and 15 mg decreased during the
treatment period up to 6 months. A similar trend is also seen for the discontinuation rates.
Post-marketing experience
The following events have been reported in association with darifenacin use in worldwide post-
marketing experience: generalised hypersensitivity reactions including angioedema, depressed
mood/mood alterations,
hallucination
. Because these spontaneously reported events are from the
16
Constipation, dry mouth
Angioedema
worldwide post-marketing experience, the frequency of events cannot be estimated from the available
data.
Emselex has been administered in clinical trials at doses up to 75 mg (five times maximum therapeutic
dose). The most common adverse reactions seen were dry mouth, constipation, headache, dyspepsia
and nasal dryness. However, overdose with darifenacin can potentially lead to severe anticholinergic
effects and should be treated accordingly. Therapy should be aimed at reversing the anticholinergic
symptoms under careful medical supervision. The use of agents such as physostigmine can assist in
reversing such symptoms.
5.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Urinary antispasmodic, ATC code: G04BD10.
Darifenacin is a selective muscarinic M3 receptor antagonist (M
3
SRA)
in vitro
. The M3 receptor is
the major subtype that controls urinary bladder muscle contraction. It is not known whether this
selectivity for the M3 receptor translates into any clinical advantage when treating symptoms of
overactive bladder syndrome.
Cystometric studies performed with darifenacin in patients with involuntary bladder contractions
showed increased bladder capacity, increased volume threshold for unstable contractions and
diminished frequency of unstable detrusor contractions.
Treatment with Emselex administered at dosages of 7.5 mg and 15 mg daily has been investigated in
four double-blind, Phase III, randomised, controlled clinical studies in male and female patients with
symptoms of overactive bladder. As seen in Table 2 below, a pooled analysis of 3 of the studies for the
treatment with both Emselex 7.5 mg and 15 mg provided a statistically significant improvement in the
primary endpoint, reduction in incontinence episodes, versus placebo.
Table 2: Pooled analysis of data from three Phase III clinical studies assessing fixed doses of 7.5 mg
and 15 mg Emselex
Dose
N
Incontinence episodes per week
95% CI
P value
2
Baseline
(median)
Week 12
(median)
Change from
baseline
(median)
Differences
from placebo
1
(median)
Emselex 7.5 mg
once daily
335
16.0
4.9
-8.8 (-68%)
-2.0
(-3.6, -0.7)
0.004
Placebo
271
16.6
7.9
-7.0 (-54%)
--
--
--
Emselex 15 mg
once daily
330
16.9
4.1
-10.6 (-77%)
-3.2
(-4.5, -2.0) <0.001
Placebo
384
16.6
6.4
-7.5 (-58%)
--
--
--
1
Hodges Lehmann estimate: median difference from placebo in change from baseline
2
Stratified Wilcoxon test for difference from placebo.
Emselex 7.5 mg and 15 mg doses significantly reduced both the severity and number of urinary
urgency episodes and the number of micturitions, while significantly increasing the mean volume
voided from baseline.
17
Emselex 7.5 mg and 15 mg were associated with statistically significant improvements over placebo in
some aspects of quality of life as measured by the Kings Health Questionnaire including incontinence
impact, role limitations, social limitations and severity measures.
For both doses of 7.5 mg and 15 mg, the percentage median reduction from baseline in the number of
incontinence episodes per week was similar between males and females. The observed differences
from placebo for males in terms of percentage and absolute reductions in incontinence episodes was
lower than for females.
The effect of treatment with 15 mg and 75 mg of darifenacin on QT/QTc interval was evaluated in a
study in 179 healthy adults (44% male: 56% females) aged 18 to 65 for 6 days (to steady state).
Therapeutic and supra-therapeutic doses of darifenacin resulted in no increase in QT/QTc interval
prolongation from baseline compared to placebo at maximum darifenacin exposure.
5.2 Pharmacokinetic properties
Darifenacin is metabolised by CYP3A4 and CYP2D6. Due to genetic differences, about 7% of the
Caucasians lack the CYP2D6 enzyme and are said to be poor metabolisers. A few percent of the
population have increased CYP2D6 enzyme levels (ultrafast metabolisers). The information below
applies to subjects who have normal CYP2D6 activity (extensive metabolisers) unless otherwise
stated.
Absorption
Due to extensive first-pass metabolism darifenacin has a bioavailability of approximately 15% and
19% after 7.5 mg and 15 mg daily doses at steady state. Maximum plasma levels are reached
approximately 7 hours after administration of the prolonged-release tablets and steady-state plasma
levels are achieved by the sixth day of administration. At steady state, peak-to-trough fluctuations in
darifenacin concentrations are small (PTF: 0.87 for 7.5 mg and 0.76 for 15 mg), thereby maintaining
therapeutic plasma levels over the dosing interval. Food had no effect on darifenacin pharmacokinetics
during multiple-dose administration of prolonged-release tablets.
Distribution
Darifenacin is a lipophilic base and is 98% bound to plasma proteins (primarily to alpha-1-acid-
glycoprotein). The steady-state volume of distribution (V
ss
) is estimated to be 163 litres.
Metabolism
Darifenacin is extensively metabolised by the liver following oral administration.
Darifenacin undergoes significant metabolism by cytochrome CYP3A4 and CYP2D6 in the liver and
by CYP3A4 in the gut wall. The three main metabolic routes are as follows:
monohydroxylation in the dihydrobenzofuran ring;
dihydrobenzofuran ring opening and
N-dealkylation of the pyrrolidine nitrogen.
The initial products of the hydroxylation and N-dealkylation pathways are major circulating
metabolites but none contribute significantly to the overall clinical effect of darifenacin.
The pharmacokinetics of darifenacin at steady state are dose-dependent, due to saturation of the
CYP2D6 enzyme.
Doubling the darifenacin dose from 7.5 mg to 15 mg result in a 150% increase in steady-state
exposure. This dose-dependency is probably caused by saturation of the CYP2D6 catalysed
metabolism possibly together with some saturation of CYP3A4-mediated gut wall metabolism.
18
Excretion
Following administration of an oral dose of
14
C-darifenacin solution to healthy volunteers,
approximately 60% of the radioactivity was recovered in the urine and 40% in the faeces. Only a small
percentage of the excreted dose was unchanged darifenacin (3%). Estimated darifenacin clearance is
40 litres/hour. The elimination half-life of darifenacin following chronic dosing is approximately
13-19 hours.
Special patient population
Gender
A population pharmacokinetic analysis of patient data indicated that darifenacin exposure was 23%
lower in males than females (see section 5.1).
Elderly patients
A population pharmacokinetic analysis of patient data indicated a trend for clearance to decrease with
age (19% per decade based on Phase III population pharmacokinetic analysis of patients aged 60–
89 years), see section 4.2.
Paediatric patients
The pharmacokinetics of darifenacin have not been established in the paediatric population.
CYP2D6 poor metabolisers
The metabolism of darifenacin in CYP2D6 poor metabolisers is principally mediated by CYP3A4. In
one pharmacokinetic study the steady-state exposure in poor metabolisers was 164% and 99% higher
during treatment with 7.5 mg and 15 mg once daily, respectively. However, a population
pharmacokinetic analyses of Phase III data indicated that on average steady-state exposure is 66%
higher in poor metabolisers than in extensive metabolisers. There was considerable overlap between
the ranges of exposures seen in these two populations (see section 4.2).
Renal insufficiency
A small study of subjects (n=24) with varying degrees of renal impairment (creatinine clearance
between 10 ml/min and 136 ml/min) given darifenacin 15 mg once daily to steady state demonstrated
no relationship between renal function and darifenacin clearance (see section 4.2).
Hepatic insufficiency
Darifenacin pharmacokinetics were investigated in subjects with mild (Child Pugh A) or moderate
(Child Pugh B) impairment of hepatic function given darifenacin 15 mg once daily to steady state.
Mild hepatic impairment had no effect on the pharmacokinetics of darifenacin. However, protein
binding of darifenacin was affected by moderate hepatic impairment. Unbound darifenacin exposure
was estimated to be 4.7-fold higher in subjects with moderate hepatic impairment than subjects with
normal hepatic function (see section 4.2).
5.3 Preclinical safety data
Preclinical data reveal no special hazard for humans based on conventional studies of safety
pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential. There were no effects
on fertility in male and female rats treated at oral doses up to 50 mg/kg/day (78 times the AUC
0-24h
of
free plasma concentration at maximum recommended human dose [MRHD]). There were no effects on
reproductive organs in either sex in dogs treated for 1 year at oral doses up to 6 mg/kg/day (82 times
the AUC
0-24h
of free plasma concentration at MRHD). Darifenacin was not teratogenic in rats and
rabbits at doses up to 50 and 30 mg/kg/day, respectively. At the dose of 50 mg/kg/day in rats (59 times
the AUC
0-24h
of free plasma concentration at MRHD), delay in the ossification of the sacral and caudal
vertebrae was observed. At the dose of 30 mg/kg/day in rabbits (28 times the AUC
0-24h
of free plasma
concentration at MRHD), maternal toxicity and foetotoxicity (increased post implantation loss and
decreased number of viable foetuses per litter) were observed. In peri and post-natal studies in rats,
dystocia, increased foetal deaths
in utero
and toxicity to post-natal development (pup body weight and
development land marks) were observed at systemic exposure levels up to 11 times the AUC
0-24h
of
free plasma concentration at MRHD.
19
6.
6.1 List of excipients
Tablet core:
Calcium hydrogen phosphate, anhydrous
Hypromellose
Magnesium stearate
Film coat:
Polyethylene glycol
Hypromellose
Talc
Titanium dioxide (E171)
Yellow iron oxide (E172)
Red iron oxide (E172)
6.2 Incompatibilities
Not applicable
6.3 Shelf life
3 years
6.4 Special precautions for storage
Keep the blister packs in the outer carton in order to protect from light.
6.5 Nature and contents of container
Clear PVC/CTFE/aluminium or PVC/PVDC/aluminium blisters in cartons containing 7, 14, 28, 49, 56
or 98 tablets as unit pack or in multipacks containing 140 (10x14) tablets.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
7.
Novartis Europharm Limited
Wimblehurst Road
Horsham
West Sussex, RH12 5AB
United Kingdom
8.
EU/1/04/294/007-012
EU/1/04/294/014
EU/1/04/294/021-026
EU/1/04/294/028
20
9.
Date of first authorisation: 22.10.2004
Date of latest renewal: 22.10.2009
21
ANNEX II
A. MANUFACTURING AUTHORISATION HOLDER
RESPONSIBLE FOR BATCH RELEASE
B. CONDITIONS OF THE MARKETING AUTHORISATION
22
A. MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH
RELEASE
Name and address of the manufacturer responsible for batch release
Novartis Pharma GmbH
Roonstraße 25
D-90429 Nuremberg
Germany
B. CONDITIONS OF THE MARKETING AUTHORISATION
Medicinal product subject to medical prescription
CONDITIONS OR RESTRICTIONS REGARDING THE SAFE AND EFFECTIVE USE
OF THE MEDICINAL PRODUCT
Not applicable.
OTHER CONDITIONS
PSURs
The MAH will continue to submit yearly PSURs, unless otherwise specified by the CHMP.
23
ANNEX III
LABELLING AND PACKAGE LEAFLET
24
A. LABELLING
25
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
CARTON OF UNIT PACK
1.
Emselex 7.5 mg prolonged-release tablets
Darifenacin
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each tablet contains 7.5 mg darifenacin (as hydrobromide).
3.
LIST OF EXCIPIENTS
4.
7 tablets
14 tablets
28 tablets
49 tablets
56 tablets
98 tablets
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Oral use.
Read the package leaflet before 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
Keep the blister packs in the outer carton in order to protect from light.
26
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Novartis Europharm Limited
Wimblehurst Road
Horsham
West Sussex, RH12 5AB
United Kingdom
EU/1/04/294/001
7 tablets (PVC/CTFE/alu blisters)
EU/1/04/294/002
14 tablets (PVC/CTFE/alu blisters)
EU/1/04/294/004
49 tablets (PVC/CTFE/alu blisters)
EU/1/04/294/005
56 tablets (PVC/CTFE/alu blisters)
EU/1/04/294/006
98 tablets (PVC/CTFE/alu blisters)
EU/1/04/294/015
7 tablets (PVC/PVDC/alu blisters)
EU/1/04/294/016
14 tablets (PVC/PVDC/alu blisters)
EU/1/04/294/017
28 tablets (PVC/PVDC/alu blisters)
EU/1/04/294/018
49 tablets (PVC/PVDC/alu blisters)
EU/1/04/294/019
56 tablets (PVC/PVDC/alu blisters)
EU/1/04/294/020
98 tablets (PVC/PVDC/alu blisters)
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Emselex 7.5 mg
27
EU/1/04/294/003
28 tablets (PVC/CTFE/alu blisters)
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON OF MULTIPACKS (INCLUDING BLUE BOX)
1.
Emselex 7.5 mg prolonged-release tablets
Darifenacin
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each tablet contains 7.5 mg darifenacin (as hydrobromide).
3.
LIST OF EXCIPIENTS
4.
140 tablets
Multipack comprising 10 packs, each containing 14 tablets.
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Oral use.
Read the package leaflet before 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
Keep the blister packs in the outer carton in order to protect from light.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
28
Novartis Europharm Limited
Wimblehurst Road
Horsham
West Sussex, RH12 5AB
United Kingdom
EU/1/04/294/013
(PVC/CTFE/alu blisters)
EU/1/04/294/027
(PVC/PVDC/alu blisters)
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Emselex 7.5 mg
29
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
INTERMEDIATE CARTON OF MULTIPACKS (WITHOUT BLUE BOX)
1.
Emselex 7.5 mg prolonged-release tablets
Darifenacin
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each tablet contains 7.5 mg darifenacin (as hydrobromide).
3.
LIST OF EXCIPIENTS
4.
14 tablets
Component of a multipack comprising 10 packs, each containing 14 tablets.
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Oral use.
Read the package leaflet before 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
Keep the blister packs in the outer carton in order to protect from light.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
30
Novartis Europharm Limited
Wimblehurst Road
Horsham
West Sussex, RH12 5AB
United Kingdom
EU/1/04/294/013
(PVC/CTFE/alu blisters)
EU/1/04/294/027
(PVC/PVDC/alu blisters)
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Emselex 7.5 mg
31
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS
1.
Emselex 7.5 mg prolonged-release tablets
Darifenacin
2.
Novartis Europharm Limited
3.
EXPIRY DATE
EXP
4.
BATCH NUMBER
Lot
5.
OTHER
32
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
CARTON OF UNIT PACK
1.
Emselex 15 mg prolonged-release tablets
Darifenacin
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each tablet contains 15 mg darifenacin (as hydrobromide).
3.
LIST OF EXCIPIENTS
4.
7 tablets
14 tablets
28 tablets
49 tablets
56 tablets
98 tablets
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Oral use.
Read the package leaflet before 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
Keep the blister packs in the outer carton in order to protect from light.
33
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Novartis Europharm Limited
Wimblehurst Road
Horsham
West Sussex, RH12 5AB
United Kingdom
EU/1/04/294/007
7 tablets (PVC/CTFE/alu blisters)
EU/1/04/294/008
14 tablets (PVC/CTFE/alu blisters)
EU/1/04/294/010
49 tablets (PVC/CTFE/alu blisters)
EU/1/04/294/011
56 tablets (PVC/CTFE/alu blisters)
EU/1/04/294/012
98 tablets (PVC/CTFE/alu blisters)
EU/1/04/294/021
7 tablets (PVC/PVDC/alu blisters)
EU/1/04/294/022
14 tablets (PVC/PVDC/alu blisters)
EU/1/04/294/023
28 tablets (PVC/PVDC/alu blisters)
EU/1/04/294/024
49 tablets (PVC/PVDC/alu blisters)
EU/1/04/294/025
56 tablets (PVC/PVDC/alu blisters)
EU/1/04/294/026
98 tablets (PVC/PVDC/alu blisters)
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Emselex 15 mg
34
EU/1/04/294/009
28 tablets (PVC/CTFE/alu blisters)
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON OF MULTIPACKS (INCLUDING BLUE BOX)
1.
Emselex 15 mg prolonged-release tablets
Darifenacin
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each tablet contains 15 mg darifenacin (as hydrobromide).
3.
LIST OF EXCIPIENTS
4.
140 tablets
Multipack comprising 10 packs, each containing 14 tablets.
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Oral use.
Read the package leaflet before 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
Keep the blister packs in the outer carton in order to protect from light.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
35
Novartis Europharm Limited
Wimblehurst Road
Horsham
West Sussex, RH12 5AB
United Kingdom
EU/1/04/294/014
(PVC/CTFE/alu blisters)
EU/1/04/294/028
(PVC/PVDC/alu blisters)
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Emselex 15 mg
36
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
INTERMEDIATE CARTON OF MULTIPACKS (WITHOUT BLUE BOX)
1.
Emselex 15 mg prolonged-release tablets
Darifenacin
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each tablet contains 15 mg darifenacin (as hydrobromide).
3.
LIST OF EXCIPIENTS
4.
14 tablets
Component of a multipack comprising 10 packs, each containing 14 tablets.
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Oral use.
Read the package leaflet before 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
Keep the blister packs in the outer carton in order to protect from light.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
37
Novartis Europharm Limited
Wimblehurst Road
Horsham
West Sussex, RH12 5AB
United Kingdom
EU/1/04/294/014
(PVC/CTFE/alu blisters)
EU/1/04/294/028
(PVC/PVDC/alu blisters)
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Emselex 15 mg
38
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS
1.
Emselex 15 mg prolonged-release tablets
Darifenacin
2.
Novartis Europharm Limited
3.
EXPIRY DATE
EXP
4.
BATCH NUMBER
Lot
5.
OTHER
39
B. PACKAGE LEAFLET
40
PACKAGE LEAFLET: INFORMATION FOR THE USER
Emselex 7.5 mg prolonged-release tablets
Darifenacin
Read all of this leaflet carefully before you start taking this medicine.
-
Keep this leaflet. You may need to read it again.
-
If you have any further questions, ask your doctor or pharmacist.
-
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 Emselex is and what it is used for
3.
How to take Emselex
4.
Possible side effects
5.
How to store Emselex
6.
Further information
1.
WHAT EMSELEX IS AND WHAT IT IS USED FOR
How Emselex works
Emselex reduces the activity of an overactive bladder. This enables you to wait longer before you go
to the toilet and it increases the amount of urine that your bladder can hold.
What Emselex can be used for
Emselex belongs to a class of medicines which relax the muscles of the bladder. It is used in adults for
the treatment of the symptoms of overactive bladder conditions - such as a sudden urge to rush to the
toilet, needing to go to the toilet frequently and/or not getting to the toilet in time and wetting yourself
(urge incontinence).
2.
BEFORE YOU TAKE EMSELEX
Do not take Emselex:
if you are allergic (hypersensitive) to darifenacin or any of the other ingredients of Emselex.
if you suffer from urinary retention (inability to empty your bladder).
if you have gastric retention (problems emptying the contents of the stomach).
if you suffer from uncontrolled narrow-angle glaucoma (high pressure in the eyes with loss of
eyesight that is not being adequately treated).
if you have myasthenia gravis (a disease marked by abnormal tiredness and weakness of
selected muscles).
if you have severe ulcerative colitis or toxic megacolon (acute dilation of the colon due to
complication of infection or inflammation).
if you have severe liver problems.
There are some medicines such as ciclosporin (a medicine used in transplantation to prevent
organ rejection or for other conditions, e.g. rheumathoid arthritis or atopic dermatitis),
verapamil (a medicine used to lower blood pressure, to correct hearth rhythm or to treat angina
pectoris), antifungal medicines (e.g. ketoconazole and itraconazole) and some antiviral
medicines (e.g. ritonavir) that must not be taken with Emselex.
41
2.
Before you take Emselex
Take special care with Emselex:
if you have autonomic neuropathy (damage to the nerves that communicate between the brain
and internal organs, muscles, skin, and blood vessels to regulate vital functions, including the
heart rate, blood pressure and bowel function) – your doctor will have told you if you have this.
if you have heartburn and belching.
if you have difficulties in passing urine and a weak stream of urine.
if you have severe constipation (less than or equal to 2 bowel movements per week).
if you have a digestive motility disorder.
if you have an obstructive gastrointestinal disorder (any obstruction of the passage of intestinal
or gastric contents, such as narrowing of the pylorus, the lower part of the stomach) – your
doctor will have told you if you have this.
if you are taking medicinal products that can cause or worsen inflammation of the oesophagus
such as oral bisphosphonates (a class of medicinal products that prevent the loss of bone mass
and are used to treat osteoporosis).
if you are receiving treatment for narrow-angle glaucoma.
if you have liver problems.
if you have kidney problems.
if you have heart diseases.
If any of these apply to you, tell your doctor before you take Emselex.
Use in children (age below 18 years)
Emselex is not recommended for use in children.
Taking other medicines with Emselex
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines,
including medicines obtained without a prescription. This is particularly important if you are taking
any of the following as your doctor may need to adjust your dose of Emselex and/or the other product:
certain antibiotics (e.g. erythromycin, clarithromycin and rifampicin), antifungal medicines (e.g.
ketoconazole and itraconazole), antipsychotic medicines (e.g. thioridazine), certain antidepressants
(e.g. imipramine), antiviral medicines (e.g. nelfinavir and ritonavir), certain anticonvulsants
(carbamazepine, barbiturates), certain medicines used to treat heart problems (e.g. flecainide,
verapamil and digoxin) and other antimuscarinic medicines (e.g. tolterodine, oxybutynin and
flavoxate). Please also inform your doctor if you are taking products containing St John’s wort.
Taking Emselex with food and drink
Eating food has no effect on Emselex. Grapefruit juice may interact with Emselex. However, the
adjustment of Emselex doses is not necessary.
Pregnancy and breast-feeding
If you are pregnant or think you may be pregnant,
tell your doctor
. Emselex is not recommended
during pregnancy.
If you are breast-feeding,
ask your doctor for advice
. Emselex should be taken with caution while
breast-feeding.
Driving and using machines
Emselex may cause effects such as dizziness, blurred vision, trouble sleeping or drowsiness. If you
have any of these symptoms whilst taking Emselex, consult your doctor for advice on changing the
dose or considering an alternative treatment. You should not drive or use machines if you are affected
by these symptoms. For Emselex, these side effects have been reported to be uncommon (see
section 4).
42
3.
HOW TO TAKE EMSELEX
Always take Emselex exactly as your doctor has told you. You should check with your doctor or
pharmacist if you are not sure. If you have the impression that the effect of Emselex is too strong or
too weak, talk to your doctor or pharmacist.
How much Emselex to take
The recommended starting dose, including for patients aged over 65 years, is 7.5 mg daily. Depending
on your response to Emselex, your doctor may increase your dose to 15 mg daily, two weeks after
starting therapy.
These doses are suitable for people with mild liver problems or people with kidney problems.
Take Emselex tablets once a day with water, at about the same time each day.
The tablet may be taken with or without food. Swallow the tablet whole. Do not chew, split or crush it.
How long to take Emselex
Your doctor will tell you how long your treatment with Emselex will last. Do not stop treatment early
because you do not see an immediate effect. Your bladder will need some time to adapt. Finish the
course of treatment prescribed by your doctor. If you have not noticed any effect by then, discuss it
with your doctor.
If you take more Emselex than you should
If you have taken more tablets than you have been told to take, or if someone else accidentally takes
your tablets, go to your doctor or hospital for advice immediately. When seeking medical advice,
make sure that you take this leaflet and your remaining tablets with you to show them to the doctor.
People who have taken an overdose may have dry mouth, constipation, headache, indigestion and
hospital.
If you forget to take Emselex
If you forget to take Emselex at the usual time, take it as soon as you remember, unless it is the time
for your next dose. Do not take a double dose to make up for a forgotten dose.
If you stop taking Emselex
It has been shown that taking all doses at the appropriate times can greatly increase the effectiveness
of your medicine. Therefore, it is important to keep taking Emselex correctly, as described above. Do
not stop taking Emselex until your doctor tells you to. You should not experience any effects when
you stop treatment.
If you have any further questions on the use of this product, ask your doctor or pharmacist.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, Emselex can cause side effects, although not everybody gets them. The side effects
caused by Emselex are usually mild and temporary.
These side effects may occur with certain frequencies, which are defined as follows:
very common: affects more than 1 patient in 10
common: affects 1 to 10 patients in 100
uncommon: affects 1 to 10 patients in 1,000
rare: affects 1 to 10 patients in 10,000
very rare: affects less than 1 patient in 10,000
not known: frequency cannot be estimated from the available data.
43
Some side effects could be serious
Serious allergic reactions including swelling, mainly of the face and throat.
Other side effects
Very common side effects
Dry mouth, constipation.
Common side effects
Headache, abdominal pain, indigestion, feeling sick, dry eyes.
Uncommon side effects
Fatigue, accidental injury, facial swelling, high blood pressure, diarrhoea, flatulence, inflammation of
the mucous membrane of the mouth, increased liver enzymes, swelling, dizziness, sleeplessness,
drowsiness, abnormal thinking, runny nose (rhinitis), cough, shortness of breath, dry skin, itching,
rash, sweating, visual disturbance including blurred vision, taste disturbance, urinary tract disorder or
infection, impotence, discharge and itching in the vagina, bladder pain, inability to empty your
bladder.
Not known side effects
Depressed mood/mood alterations, hallucination.
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.
5.
HOW TO STORE EMSELEX
Keep out of the reach and sight of children.
Do not use after the expiry date which is stated on the carton.
Keep the blister packs in the outer carton in order to protect from light.
Do not use if the pack is damaged or shows signs of tampering.
6.
FURTHER INFORMATION
What Emselex contains
-
The active substance is darifenacin. Each tablet contains 7.5 mg darifenacin (as hydrobromide).
-
The other ingredients are calcium hydrogen phosphate (anhydrous), hypromellose, magnesium
stearate, polyethylene glycol, titanium dioxide (E171) and talc.
What Emselex looks like and contents of the pack
Emselex 7.5 mg prolonged-release tablets are round, convex white tablets and are debossed with “DF”
on one side and “7.5” on the other.
The tablets are available in blister packs containing 7, 14, 28, 49, 56 or 98 tablets or in multipacks
containing 140 (10x14) tablets. Not all pack sizes may be available in your country.
Marketing Authorisation Holder
Novartis Europharm Limited
Wimblehurst Road
Horsham
West Sussex, RH12 5AB
United Kingdom
44
Manufacturer
Novartis Pharma GmbH
Roonstraße 25
D-90429 Nuremberg
Germany
If you have any questions about this medicine, please contact the local representative of the Marketing
Authorisation Holder.
België/Belgique/Belgien
Novartis Pharma N.V.
Tél/Tel: +32 2 246 16 11
Luxembourg/Luxemburg
Novartis Pharma GmbH
Tél/Tel: +49 911 273 0
България
Novartis Pharma Services Inc.
Тел.: +359 2 489 98 28
Magyarország
Bayer Hungária Kft.
Tel.: +36 1 487 41 00
Česká republika
Novartis s.r.o.
Tel: +420 225 775 111
Malta
Novartis Pharma Services Inc.
Tel: +356 2298 3217
Danmark
Novartis Healthcare A/S
Tlf: +45 39 16 84 00
Nederland
Zambon Nederland B.V.
Tel: +31 33 45 04 371
Deutschland
Bayer Vital GmbH
Tel: +49-(0) 214-3051348
Norge
Novartis Norge AS
Tlf: +47 23 05 20 00
Eesti
Novartis Pharma Services Inc.
Tel: +372 66 30 810
Österreich
Novartis Pharma GmbH
Tel: +43 1 86 6570
Ελλά
Novartis (Hellas) A.E.B.E.
Τηλ: +30 210 281 17 12
Polska
Novartis Poland Sp. z o.o.
Tel.: +48 22 550 8888
España
Novartis Farmacéutica, S.A.
Tel: +34 93 306 42 00
Portugal
Novartis Farma - Produtos Farmacêuticos, S.A.
Tel: +351 21 000 8600
France
Novartis Pharma S.A.S.
Tél: +33 1 55 47 66 00
România
Novartis Pharma Services Inc.
Tel: +40 21 31299 01
Ireland
Novartis Ireland Limited
Tel: +353 1 260 12 55
Slovenija
Novartis Pharma Services Inc.
Tel: +386 1 300 75 50
Ísland
Vistor hf.
Sími: +354 535 7000
Slovenská republika
Novartis Slovakia s.r.o.
Tel: +421 2 5542 5439
45
Italia
Novartis Farma S.p.A.
Tel: +39 02 96 54 1
Suomi/Finland
Novartis Finland Oy
Puh/Tel: +358 (0)10 6133 200
Κύπρς
Δημητριάης κι Ππέλληνς Λτ
Τηλ: +357 22 690 690
Sverige
Novartis Sverige AB
Tel: +46 8 732 32 00
Latvija
Novartis Pharma Services Inc.
Tel: +371 67 887 070
United Kingdom
Novartis Pharmaceuticals UK Ltd.
Tel: +44 1276 698370
Lietuva
Novartis Pharma Services Inc.
Tel: +370 5 269 16 50
This leaflet was last approved in
46
PACKAGE LEAFLET: INFORMATION FOR THE USER
Emselex 15 mg prolonged-release tablets
Darifenacin
Read all of this leaflet carefully before you start taking this medicine.
-
Keep this leaflet. You may need to read it again.
-
If you have any further questions, ask your doctor or pharmacist.
-
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 Emselex is and what it is used for
3.
How to take Emselex
4.
Possible side effects
5.
How to store Emselex
6.
Further information
1.
WHAT EMSELEX IS AND WHAT IT IS USED FOR
How Emselex works
Emselex reduces the activity of an overactive bladder. This enables you to wait longer before you go
to the toilet and it increases the amount of urine that your bladder can hold.
What Emselex can be used for
Emselex belongs to a class of medicines which relax the muscles of the bladder. It is used in adults for
the treatment of the symptoms of overactive bladder conditions - such as a sudden urge to rush to the
toilet, needing to go to the toilet frequently and/or not getting to the toilet in time and wetting yourself
(urge incontinence).
2.
BEFORE YOU TAKE EMSELEX
Do not take Emselex:
if you are allergic (hypersensitive) to darifenacin or any of the other ingredients of Emselex.
if you suffer from urinary retention (inability to empty your bladder).
if you have gastric retention (problems emptying the contents of the stomach).
if you suffer from uncontrolled narrow-angle glaucoma (high pressure in the eyes with loss of
eyesight that is not being adequately treated).
if you have myasthenia gravis (a disease marked by abnormal tiredness and weakness of
selected muscles).
if you have severe ulcerative colitis or toxic megacolon (acute dilation of the colon due to
complication of infection or inflammation).
if you have severe liver problems.
There are some medicines such as ciclosporin (a medicine used in transplantation to prevent
organ rejection or for other conditions, e.g. rheumathoid arthritis or atopic dermatitis),
verapamil (a medicine used to lower blood pressure, to correct hearth rhythm or to treat angina
pectoris), antifungal medicines (e.g. ketoconazole and itraconazole) and some antiviral
medicines (e.g. ritonavir) that must not be taken with Emselex.
47
2.
Before you take Emselex
Take special care with Emselex:
if you have autonomic neuropathy (damage to the nerves that communicate between the brain
and internal organs, muscles, skin, and blood vessels to regulate vital functions, including the
heart rate, blood pressure and bowel function) – your doctor will have told you if you have this.
if you have heartburn and belching.
if you have difficulties in passing urine and a weak stream of urine.
if you have severe constipation (less than or equal to 2 bowel movements per week).
if you have a digestive motility disorder.
if you have an obstructive gastrointestinal disorder (any obstruction of the passage of intestinal
or gastric contents, such as narrowing of the pylorus, the lower part of the stomach) – your
doctor will have told you if you have this.
if you are taking medicinal products that can cause or worsen inflammation of the oesophagus
such as oral bisphosphonates (a class of medicinal products that prevent the loss of bone mass
and are used to treat osteoporosis).
if you are receiving treatment for narrow-angle glaucoma.
if you have liver problems.
if you have kidney problems.
if you have heart diseases.
If any of these apply to you, tell your doctor before you take Emselex.
Use in children (age below 18 years)
Emselex is not recommended for use in children.
Taking other medicines with Emselex
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines,
including medicines obtained without a prescription. This is particularly important if you are taking
any of the following as your doctor may need to adjust your dose of Emselex and/or the other product:
certain antibiotics (e.g. erythromycin, clarithromycin and rifampicin), antifungal medicines (e.g.
ketoconazole and itraconazole), antipsychotic medicines (e.g. thioridazine), certain antidepressants
(e.g. imipramine), antiviral medicines (e.g. nelfinavir and ritonavir), certain anticonvulsants
(carbamazepine, barbiturates), certain medicines used to treat heart problems (e.g. flecainide,
verapamil and digoxin) and other antimuscarinic medicines (e.g. tolterodine, oxybutynin and
flavoxate). Please also inform your doctor if you are taking products containing St John’s wort.
Taking Emselex with food and drink
Eating food has no effect on Emselex. Grapefruit juice may interact with Emselex. However, the
adjustment of Emselex doses is not necessary.
Pregnancy and breast-feeding
If you are pregnant or think you may be pregnant,
tell your doctor
. Emselex is not recommended
during pregnancy.
If you are breast-feeding,
ask your doctor for advice
. Emselex should be taken with caution while
breast-feeding.
Driving and using machines
Emselex may cause effects such as dizziness, blurred vision, trouble sleeping or drowsiness. If you
have any of these symptoms whilst taking Emselex, consult your doctor for advice on changing the
dose or considering an alternative treatment. You should not drive or use machines if you are affected
by these symptoms. For Emselex, these side effects have been reported to be uncommon (see
section 4).
48
3.
HOW TO TAKE EMSELEX
Always take Emselex exactly as your doctor has told you. You should check with your doctor or
pharmacist if you are not sure. If you have the impression that the effect of Emselex is too strong or
too weak, talk to your doctor or pharmacist.
How much Emselex to take
The recommended starting dose, including for patients aged over 65 years, is 7.5 mg daily. Depending
on your response to Emselex, your doctor may increase your dose to 15 mg daily, two weeks after
starting therapy.
These doses are suitable for people with mild liver problems or people with kidney problems.
Take Emselex tablets once a day with water, at about the same time each day.
The tablet may be taken with or without food. Swallow the tablet whole. Do not chew, split or crush it.
How long to take Emselex
Your doctor will tell you how long your treatment with Emselex will last. Do not stop treatment early
because you do not see an immediate effect. Your bladder will need some time to adapt. Finish the
course of treatment prescribed by your doctor. If you have not noticed any effect by then, discuss it
with your doctor.
If you take more Emselex than you should
If you have taken more tablets than you have been told to take, or if someone else accidentally takes
your tablets, go to your doctor or hospital for advice immediately. When seeking medical advice,
make sure that you take this leaflet and your remaining tablets with you to show them to the doctor.
People who have taken an overdose may have dry mouth, constipation, headache, indigestion and
hospital.
If you forget to take Emselex
If you forget to take Emselex at the usual time, take it as soon as you remember, unless it is the time
for your next dose. Do not take a double dose to make up for a forgotten dose.
If you stop taking Emselex
It has been shown that taking all doses at the appropriate times can greatly increase the effectiveness
of your medicine. Therefore, it is important to keep taking Emselex correctly, as described above. Do
not stop taking Emselex until your doctor tells you to. You should not experience any effects when
you stop treatment.
If you have any further questions on the use of this product, ask your doctor or pharmacist.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, Emselex can cause side effects, although not everybody gets them. The side effects
caused by Emselex are usually mild and temporary.
These side effects may occur with certain frequencies, which are defined as follows:
very common: affects more than 1 patient in 10
common: affects 1 to 10 patients in 100
uncommon: affects 1 to 10 patients in 1,000
rare: affects 1 to 10 patients in 10,000
very rare: affects less than 1 patient in 10,000
not known: frequency cannot be estimated from the available data.
49
Some side effects could be serious
Serious allergic reactions including swelling, mainly of the face and throat.
Other side effects
Very common side effects
Dry mouth, constipation.
Common side effects
Headache, abdominal pain, indigestion, feeling sick, dry eyes.
Uncommon side effects
Fatigue, accidental injury, facial swelling, high blood pressure, diarrhoea, flatulence, inflammation of
the mucous membrane of the mouth, increased liver enzymes, swelling, dizziness, sleeplessness,
drowsiness, abnormal thinking, runny nose (rhinitis), cough, shortness of breath, dry skin, itching,
rash, sweating, visual disturbance including blurred vision, taste disturbance, urinary tract disorder or
infection, impotence, discharge and itching in the vagina, bladder pain, inability to empty your
bladder.
Not known side effects
Depressed mood/mood alterations, hallucination.
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.
5.
HOW TO STORE EMSELEX
Keep out of the reach and sight of children.
Do not use after the expiry date which is stated on the carton.
Keep the blister packs in the outer carton in order to protect from light.
Do not use if the pack is damaged or shows signs of tampering.
6.
FURTHER INFORMATION
What Emselex contains
-
The active substance is darifenacin. Each tablet contains 15 mg darifenacin (as hydrobromide).
-
The other ingredients are calcium hydrogen phosphate (anhydrous), hypromellose, magnesium
stearate, polyethylene glycol, talc, titanium dioxide (E171), red iron oxide (E172) and yellow
iron oxide (E172).
What Emselex looks like and contents of the pack
Emselex 15 mg prolonged-release tablets are round, convex light peach tablets and are debossed with
“DF” on one side and “15” on the other.
The tablets are available in blister packs containing 7, 14, 28, 49, 56 or 98 tablets or in multipacks
containing 140 (10x14) tablets. Not all pack sizes may be available in your country.
Marketing Authorisation Holder
Novartis Europharm Limited
Wimblehurst Road
Horsham
West Sussex, RH12 5AB
United Kingdom
50
Manufacturer
Novartis Pharma GmbH
Roonstraße 25
D-90429 Nuremberg
Germany
If you have any questions about this medicine, please contact the local representative of the Marketing
Authorisation Holder.
België/Belgique/Belgien
Novartis Pharma N.V.
Tél/Tel: +32 2 246 16 11
Luxembourg/Luxemburg
Novartis Pharma GmbH
Tél/Tel: +49 911 273 0
България
Novartis Pharma Services Inc.
Тел.: +359 2 489 98 28
Magyarország
Bayer Hungária Kft.
Tel.: +36 1 487 41 00
Česká republika
Novartis s.r.o.
Tel: +420 225 775 111
Malta
Novartis Pharma Services Inc.
Tel: +356 2298 3217
Danmark
Novartis Healthcare A/S
Tlf: +45 39 16 84 00
Nederland
Zambon Nederland B.V.
Tel: +31 33 45 04 371
Deutschland
Bayer Vital GmbH
Tel: +49-(0) 214-3051348
Norge
Novartis Norge AS
Tlf: +47 23 05 20 00
Eesti
Novartis Pharma Services Inc.
Tel: +372 66 30 810
Österreich
Novartis Pharma GmbH
Tel: +43 1 86 6570
Ελλά
Novartis (Hellas) A.E.B.E.
Τηλ: +30 210 281 17 12
Polska
Novartis Poland Sp. z o.o.
Tel.: +48 22 550 8888
España
Novartis Farmacéutica, S.A.
Tel: +34 93 306 42 00
Portugal
Novartis Farma - Produtos Farmacêuticos, S.A.
Tel: +351 21 000 8600
France
Novartis Pharma S.A.S.
Tél: +33 1 55 47 66 00
România
Novartis Pharma Services Inc.
Tel: +40 21 31299 01
Ireland
Novartis Ireland Limited
Tel: +353 1 260 12 55
Slovenija
Novartis Pharma Services Inc.
Tel: +386 1 300 75 50
Ísland
Vistor hf.
Sími: +354 535 7000
Slovenská republika
Novartis Slovakia s.r.o.
Tel: +421 2 5542 5439
51
Italia
Novartis Farma S.p.A.
Tel: +39 02 96 54 1
Suomi/Finland
Novartis Finland Oy
Puh/Tel: +358 (0)10 6133 200
Κύπρς
Δημητριάης κι Ππέλληνς Λτ
Τηλ: +357 22 690 690
Sverige
Novartis Sverige AB
Tel: +46 8 732 32 00
Latvija
Novartis Pharma Services Inc.
Tel: +371 67 887 070
United Kingdom
Novartis Pharmaceuticals UK Ltd.
Tel: +44 1276 698370
Lietuva
Novartis Pharma Services Inc.
Tel: +370 5 269 16 50
This leaflet was last approved in
52
Source: European Medicines Agency
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