United Kingdom - English - eMC (Electronic Medicines Compendium)
XL 4mg Capsules
The name of your medicine is Detrusitol XL 4mg Capsules but will be
referred to as Detrusitol XL throughout this leaflet.
Read all of this leaflet carefully before you start using 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 get serious, or if you notice any side effects not
listed in this leaflet, please tell your doctor or pharmacist.
In this leaflet:
1. What Detrusitol XL is and what it is used for
2. Before you take Detrusitol XL
3. How to take Detrusitol XL
4. Possible side effects
5. How to store Detrusitol XL
6. Further information
1. WHAT DETRUSITOL XL IS AND WHAT IT IS USED FOR
The active substance in Detrusitol XL is tolterodine. Tolterodine belongs to
a class of medicinal products called antimuscarinics.
Detrusitol XL is used for the treatment of the symptoms of overactive
bladder syndrome. If you have overactive bladder syndrome, you may find
you are unable to control urination,
you need to rush to the toilet with no advance warning and/or go to the
2. BEFORE YOU TAKE DETRUSITOL XL
Do not take Detrusitol XL if you:
are allergic (hypersensitive) to tolterodine or any of the other ingredients
in Detrusitol XL
are unable to pass urine from the bladder (urinary retention)
have an uncontrolled narrow-angle glaucoma (high pressure in the eyes
with loss of eyesight that is not being adequately treated)
suffer from myasthenia gravis (excessive weakness of the muscles)
suffer from severe ulcerative colitis (ulceration and inflammation of the
suffer from a toxic megacolon (acute dilatation of the colon).
Take special care with DETRUSITOL XL
If you have difficulties in passing urine and/or a poor stream of urine
If you have a gastro-intestinal disease that affects the passage and/or
digestion of food
If you suffer from kidney problems (renal insufficiency)
If you have a liver condition
If you suffer from neuronal disorders that affect your blood pressure,
bowel or sexual function (any neuropathy of the autonomic nervous
If you have a hiatal hernia (herniation of an abdominal organ)
If you ever experience decreased bowel movements or suffer from
severe constipation (decreased gastro-intestinal motility)
If you have a heart condition such as:
an abnormal heart tracing (ECG);
a slow heart rate (bradycardia);
relevant pre-existing cardiac diseases such as:
cardiomyopathy (weak heart muscle)
myocardial ischaemia (reduced blood flow to the heart)
arrhythmia (irregular heartbeat)
and heart failure
If you have abnormally low levels of potassium (hypokalaemia), calcium
(hypocalcaemia) or magnesium (hypomagnesaemia) in your blood.
Talk to your doctor or pharmacist before starting your treatment with
Detrusitol XL if you think any of these might apply to you.
Taking other medicines
Tolterodine, the active substance of Detrusitol XL, may interact with other
It is not recommended to use tolterodine in combination with:
some antibiotics (containing e.g. erythromycin, clarithromycin)
medicinal products used for the treatment of fungal infections (containing
e.g. ketoconazole, itraconazole)
medicinal products used for the treatment of HIV.
Detrusitol XL should be used with caution when taken in combination with:
medicines that affect the passage of food (containing e.g.
metoclopramide and cisapride)
medicines for the treatment of irregular heartbeat (containing e.g.
amiodarone, sotalol, quinidine, procainamide)
other medicines with a similar mode of action to Detrusitol XL
(antimuscarinic properties) or medicines with an opposite mode of action
to Detrusitol XL (cholinergic properties). Ask your doctor if you are
Please tell your doctor if you are taking or have recently taken any other
medicines, including medicines obtained without a prescription.
Taking Detrusitol XL with food and drink
Detrusitol XL can be taken before, after or during a meal.
Pregnancy and breast-feeding
You should not use Detrusitol XL when you are pregnant. Tell your doctor
immediately if you are pregnant, think you are pregnant or are planning to
It is not known if tolterodine, the active substance of Detrusitol XL, is
excreted in the mother’s breast milk. Breast-feeding is not recommended
during administration of Detrusitol XL.
Ask your doctor or pharmacist for advice before taking any medicine.
Driving and using machines
Detrusitol XL may make you feel dizzy, tired or affect your sight; your ability
to drive or operate machinery may be affected.
Important information about some of the ingredients of Detrusitol XL
This medicine contains sucrose (a type of sugar). If you have been told by
your doctor that you have an intolerance to some sugars, contac
doctor before taking this medicine. Patients with rare hereditary problems of
fructose intolerance, glucose-galactose malabsorption or sucrose
isomaltase insufficiency should not take this medicine.
3. HOW TO TAKE DETRUSITOL XL
Always take Detrusitol XL exactly as your doctor has told you. You should
check with your doctor or pharmacist if you are not sure.
The usual dose is one 4 mg prolonged-release capsule daily, except for
patients who have a kidney or a liver condition or troublesome side effects,
in which case your doctor may reduce your dose to 2 mg Detrusitol daily.
Detrusitol XL is not recommended for children.
The prolonged-release capsules are for oral use and should be swallowed
whole. Do not chew the capsules.
Duration of treatment
Your doctor will tell you how long your treatment with Detrusitol XL 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 prolonged-
release capsules prescribed by your doctor. If you have not noticed any
effect by then, talk to your doctor.
The benefit of the treatment should be re-evaluated after 2 or 3 months.
Always consult your doctor if you are thinking of stopping the
If you have taken more Detrusitol XL than you should
If you or somebody else takes too many prolonged-release capsules,
contact your doctor or pharmacist immediately.
If you forget to take Detrusitol XL
If you forget to take a dose at the usual time, take it as soon as you
remember unless it is almost time for your next dose. In that case, omit the
forgotten dose and follow the normal dose schedule.
Do not take a double dose to make up for a forgotten one.
If you have any further questions on the use of this product, ask your doctor
4. POSSIBLE SIDE EFFECTS
Like all medicines, Detrusitol XL can cause side effects, although not
everybody gets them.
You should see your doctor immediately or go to the casualty department if
you experience symptoms of angioedema, such as;
swollen face, tongue or pharynx
difficulty to swallow
hives and difficulty in breathing
You should also seek medical attention if you experience a hypersensitivity
reaction (for example itching, rash, hives, difficulty breathing). This occurs
uncommonly (occurs in less than 1 in 100 patients).
Tell your doctor immediately or got to the casualty department if you notice
any of the following:
chest pain, difficulty breathing or getting tired easily (even at rest),
difficulty breathing at night, swelling of the legs.
These may be symptoms of heart failure. This occurs uncommonly (occurs
in less than 1 in 100 patients).
The following side effects have been observed during treatment with
Detrusitol XL with the following frequencies.
Very common side effects (occurs in more than 1 in 10 patients) are:
Common side effects (occurs in less than 1 in 10 patients) are:
Dizziness, sleepiness, headache
Dry eyes, blurred vision
Difficulty with digestion (dyspepsia), constipation, abdominal pain,
excessive amounts of air or gases in the stomach or the intestine
Painful or difficult urination
Extra fluid in the body causing swelling (e.g. in the ankles)
Uncommon side effects (occurs in less than 1 in 100 patients) are:
Sensation of pins and needles in the fingers and toes
Palpitations, heart failure, irregular heartbeat
Inability to empty the bladder
Additional reactions reported include severe allergic reactions, confusion,
hallucinations, increased heart rate, flushed skin, heart burn, vomiting,
angioedema dry skin, and disorientation. There have also been reports of
worsening symptoms of dementia in patients being treated for dementia.
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This
includes any possible side effects not listed in this leaflet. You can also
report side effects directly via the Yellow Card Scheme at:
www.mhra.gov.uk/yellowcard. By reporting side effects, you can help
provide more information on the safety of this medicine.
5. HOW TO STORE DETRUSITOL XL
Keep Detrusitol XL out of the sight and reach of children.
Do not store above 30°C. Store in the original pack.
Do not use Detrusitol XL after the expiry/use before date printed on the
If your doctor tells you to stop taking this medicine, return any unused
capsules to your doctor for safe disposal. Only keep the capsules if your
doctor tells you to.
If your capsules become discoloured or show any other signs of
deterioration, consult your doctor or pharmacist who will tell you what to do.
6. FURTHER INFORMATION
What Detrusitol XL contains
Detrusitol XL 4mg prolonged release capsules contain 4mg of tolterodine L-
tartrate, equivalent to 2.74mg of tolterodine.
The other ingredients are sucrose, maize starch, ethylcellulose, medium
chain triglycerides, oleic acid, hypromellose, gelatin, shellac glaze, indigo
carmine (E132), simeticone and macrogol, titanium dioxide (E171).
What Detrusitol XL looks like and contents of the pack
Detrusitol XL are blue colour capsules, printed ‘Freedom figure’ on the cap
and ‘4’ on the body with white ink.
Detrusitol XL are available in the following pack sizes:
Blister packs containing 28 prolonged release capsules or 84 prolonged
Manufacturer and Product Licence Holder
Manufactured by Pfizer Italia S.r.l., Ascoli, Italy and is procured from within
the EU by Product Licence holder Star Pharmaceuticals Ltd.,
5 Sandridge Close, Harrow, Middlesex, HA1 1XD. Repackaged by
Leaflet revision and issue date (Ref) 15.04.15
is a trademark of Pfizer Ltd.
SUMMARY OF PRODUCT CHARACTERISTICS
NAME OF THE MEDICINAL PRODUCT
Detrusitol XL 4 mg, prolonged-release capsules, hard
QUALITATIVE AND QUANTITATIVE COMPOSITION
corresponding to 2.74 mg tolterodine.
Each 4 mg prolonged-release capsule contains a maximum of 123.07 mg of
For a full list of excipients see section 6.1
Prolonged-release capsule, hard
The 4 mg prolonged-release capsule is blue with white printing (symbol and
frequency and urgency as may occur in patients with overactive bladder
Posology and method of administration
Adults (including the elderly):
The recommended dose is 4 mg once daily except in patients with impaired
liver function or severely impaired renal function (GFR
30 ml/min) for
whom the recommended dose is 2 mg once daily (see sections 4.4 and 5.2). In
case of troublesome side-effects the dose may be reduced from 4 mg to 2 mg
The prolonged-release capsules can be taken with or without food and must be
The effect of treatment should be re-evaluated after 2-3 months (see section
Efficacy of Detrusitol XL has not been demonstrated in children (See section
5.1). Therefore, Detrusitol XL is not recommended for children.
Tolterodine is contraindicated in patients with
Uncontrolled narrow angle glaucoma
Known hypersensitivity to tolterodine or excipients
Severe ulcerative colitis
Special warnings and precautions for use
Tolterodine shall be used with caution in patients with
Significant bladder outlet obstruction at risk of urinary retention
Gastrointestinal obstructive disorders, e.g. pyloric stenosis
Renal impairment (see sections 4.2 and 5.2)
Hepatic disease (see sections 4.2 and 5.2)
Risk of decreased gastrointestinal motility
Multiple oral total daily doses of immediate release 4 mg (therapeutic) and 8 mg
(supratherapeutic) tolterodine have been shown to prolong the QTc interval (see section
5.1). The clinical relevance of these findings is unclear and will depend on individual
patient risk factors and susceptibilities present.
Tolterodine should be used with caution in patients with risk factors for QT prolongation
Congenital or documented acquired QT prolongation
Electrolyte disturbances such as hypokalaemia, hypomagnesaemia and
Relevant pre-existing cardiac diseases (i.e. cardiomyopathy, myocardial
ischaemia, arrhythmia, congestive heart failure)
Concomitant administration of drugs known to prolong QT-interval including
Class IA (e. g. quinidine, procainamide) and Class III (e. g. amiodarone, sotalol)
This especially holds true when taking potent CYP3A4 inhibitors (see section 5.1).
Concomitant treatment with potent CYP3A4 inhibitors should be avoided (see section
As with all treatments for symptoms of urgency and urge incontinence, organic reasons
for urge and frequency should be considered before treatment.
The combination of tolterodine with strong inhibitors of CYP3A4 is not recommended
(see Section 4.5. Interactions).
Patients with rare hereditary problems of fructose intolerance, glucose-galactose
malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
Interaction with other medicinal products and other forms of interaction
Concomitant systemic medication with potent CYP3A4 inhibitors such as
macrolide antibiotics (erythromycin and clarithromycin), antifungal agents
(e.g. ketoconazole and itraconazole) and antiproteases is not recommended
metabolisers with (subsequent) risk of overdosage (see section 4.4).
properties may result in more pronounced therapeutic effect and side-effects.
concomitant administration of muscarinic cholinergic receptor agonists.
The effect of prokinetics like metoclopramide and cisapride may be decreased
Concomitant treatment with fluoxetine (a potent CYP2D6 inhibitor) does not
result in a clinically significant interaction since tolterodine and its CYP2D6-
dependent metabolite, 5-hydroxymethyl tolterodine are equipotent.
combined oral contraceptives (ethinyl estradiol/levonorgestrel).
A clinical study has indicated that tolterodine is not a metabolic inhibitor of
CYP2D6, 2C19, 2C9, 3A4 or 1A2. Therefore an increase of plasma levels of
combination with tolterodine.
Fertility, pregnancy and lactation
There are no adequate data from the use of tolterodine in pregnant women.
Studies in animals have shown reproductive toxicity (see section 5.3). The
potential risk for humans is unknown.
Consequently, Detrusitol XL is not recommended during pregnancy.
No data concerning the excretion of tolterodine into human milk are available.
Tolterodine should be avoided during lactation.
Effects on ability to drive and use machines
Since this drug may cause accommodation disturbances and influence reaction
time, the ability to drive and use machines may be negatively affected.
Due to the pharmacological effect of tolterodine it may cause mild to moderate
antimuscarinic effects, like dryness of the mouth, dyspepsia and dry eyes.
The table below reflects the data obtained with Detrusitol XL in clinical trials
and from post marketing experience. The most commonly reported adverse
reaction was dry mouth, which occurred in 23.4 % of patients treated with
Detrusitol XL and in 7.7 % of placebo-treated patients.
estimated from the
Cases of aggravation of symptoms of dementia (e.g. confusion, disorientation,
delusion) have been reported after tolterodine therapy was initiated in patients
taking cholinesterase inhibitors for the treatment of dementia.
In two paediatric phase III randomised, placebo-controlled, double-blind
studies conducted over 12 weeks where a total of 710 paediatric patients were
recruited, the proportion of patients with urinary tract infections, diarrhoea and
abnormal behaviour was higher in patients treated with tolterodine than
placebo (urinary tract infection: tolterodine 6.8 %, placebo 3.6 %; diarrhoea:
tolterodine 3.3 %, placebo 0.9 %; abnormal behaviour: tolterodine 1.6 %,
placebo 0.4 %). (See section 5.1)
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal
product is important. It allows continued monitoring of the benefit/risk balance
of the medicinal product. Healthcare professionals are asked to report any
suspected adverse reactions via Yellow Card Scheme Website:
The highest dose given to human volunteers of tolterodine tartrate is 12.8 mg
as a single dose of the immediate release formulation. The most severe adverse
activated charcoal. Treat symptoms as follows:
excitation): treat with physostigmine
Convulsions or pronounced excitation: treat with benzodiazepines
Respiratory insufficiency: treat with artificial respiration
Tachycardia: treat with beta-blockers
Urinary retention: treat with catheterisation
Mydriasis: treat with pilocarpine eye drops and/or place patient in dark
An increase in QT interval was observed at a total daily dose of 8 mg
immediate release tolterodine (twice the recommended daily dose of the
immediate release formulation and equivalent to three times the peak exposure
of the prolonged release capsule formulation) administered over four days. In
the event of tolterodine overdose, standard supportive measures for managing
QT prolongation should be adopted.
Pharmacotherapeutic group: Urinary antispasmodics
ATC code: G04B D07
Tolterodine is a competitive, specific muscarinic receptor antagonist with a
selectivity for the urinary bladder over salivary glands in vivo. One of the
pharmacological profile similar to that of the parent compound. In extensive
metabolisers this metabolite contributes significantly to the therapeutic effect
Effect of the treatment can be expected within 4 weeks.
In the Phase III program, the primary endpoint was reduction of incontinence
episodes per week and the secondary endpoints were reduction of micturitions
per 24 hours and increase of mean volume voided per micturition. These
parameters are presented in the following table.
Effect of treatment with Detrusitol XL 4 mg once daily after 12 weeks,
compared with placebo. Absolute change and percentage change relative to
baseline. Treatment difference Detrusitol vs. placebo: Least Squares estimated
mean change and 95% confidence interval.
XL 4 mg
per 24 hours
*) 97.5% confidence interval according to Bonferroni
After 12 weeks of treatment 23.8% (121/507) in the Detrusitol XL group and
15.7% (80/508) in the placebo group reported that they subjectively had no or
minimal bladder problems.
The effect of tolterodine was evaluated in patients, examined with urodynamic
assessment at baseline and, depending on the urodynamic result, they were
allocated to a urodynamic positive (motor urgency) or a urodynamic negative
(sensory urgency) group. Within each group, the patients were randomised to
receive either tolterodine or placebo. The study could not provide convincing
evidence that tolterodine had effects over placebo in patients with sensory
The clinical effects of tolterodine on QT interval were studied in ECGs
obtained from over 600 treated patients, including the elderly and patients with
pre-existing cardiovascular disease. The changes in QT intervals did not
significantly differ between placebo and treatment groups.
The effect of tolterodine on QT-prolongation was investigated further in 48
administered 2 mg BID and 4 mg BID tolterodine as the immediate release
concentration (1 hour) showed mean QTc interval increases of 5.0 and 11.8
msec for tolterodine doses of 2 mg BID and 4 mg BID respectively and 19.3
msec for moxifloxacin (400mg) which was used as an active internal control.
increases in poor metabolisers (devoid of CYP2D6) treated with tolterodine
receiving 4mg BID. At both doses of tolterodine, no subject, irrespective of
their metabolic profile, exceeded 500 msec for absolute QTcF or 60 msec for
change from baseline that are considered thresholds of particular concern. The
4mg BID dose corresponds to a peak exposure (C
) of three times that
obtained with the highest therapeutic dose of Detrusitol XL capsules.
studies were conducted using tolterodine extended release capsules. A total of
710 paediatric patients (486 on tolterodine and 224 on placebo) aged 5-10
years with urinary frequency and urge urinary incontinence were studied. No
significant difference between the two groups was observed in either study
episodes/week. (See section 4.8)
Pharmacokinetic characteristics specific for this formulation: Tolterodine prolonged-
release capsules give a slower absorption of tolterodine than the immediate-release
tablets do. As a result, the maximum serum concentrations are observed 4 (2-6) hours
after administration of the capsules. The apparent half-life for tolterodine given as the
capsule is about 6 hours in extensive and about 10 hours in poor metabolisers (devoid
of CYP2D6). Steady state concentrations are reached within 4 days after
administration of the capsules.
There is no effect of food on the bioavailability of the capsules.
Absorption: After oral administration tolterodine is subject to CYP2D6 catalysed
first-pass metabolism in the liver, resulting in the formation of the 5-hydroxymethyl
derivative, a major pharmacologically equipotent metabolite.
The absolute bioavailability of tolterodine is 17 % in extensive metabolisers, the
majority of the patients, and 65% in poor metabolisers (devoid of CYP2D6).
Distribution: Tolterodine and the 5-hydroxymethyl metabolite bind primarily to
orosomucoid. The unbound fractions are 3.7% and 36%, respectively. The volume of
distribution of tolterodine is 113 l.
Elimination: Tolterodine is extensively metabolised by the liver following oral
dosing. The primary metabolic route is mediated by the polymorphic enzyme
CYP2D6 and leads to the formation of the 5-hydroxymethyl metabolite. Further
metabolism leads to formation of the 5-carboxylic acid and N-dealkylated 5-
carboxylic acid metabolites, which account for 51 % and 29 % of the metabolites
recovered in the urine, respectively. A subset (about 7%) of the population is devoid
of CYP2D6 activity. The identified pathway of metabolism for these individuals
(poor metabolisers) is dealkylation via CYP3A4 to N-dealkylated tolterodine, which
does not contribute to the clinical effect. The remainder of the population is referred
to as extensive metabolisers. The systemic clearance of tolterodine in extensive
metabolisers is about 30 L/h. In poor metabolisers the reduced clearance leads to
significantly higher serum concentrations of tolterodine (about 7-fold) and negligible
concentrations of the 5-hydroxymethyl metabolite are observed.
The 5-hydroxymethyl metabolite is pharmacologically active and equipotent with
tolterodine. Because of the differences in the protein-binding characteristics of
tolterodine and the 5-hydroxymethyl metabolite, the exposure (AUC) of unbound
tolterodine in poor metabolisers is similar to the combined exposure of unbound
tolterodine and the 5-hydroxymethyl metabolite in patients with CYP2D6 activity
given the same dosage regimen. The safety, tolerability and clinical response are
similar irrespective of phenotype.
The excretion of radioactivity after administration of
-tolterodine is about 77% in
urine and 17% in faeces. Less than 1% of the dose is recovered as unchanged drug,
and about 4% as the 5-hydroxymethyl metabolite. The carboxylated metabolite and
the corresponding dealkylated metabolite account for about 51% and 29% of the
urinary recovery, respectively.
The pharmacokinetics is linear in the therapeutic dosage range.
Specific patient groups:
Impaired liver function: About 2-fold higher exposure of unbound tolterodine and the
5-hydroxymethyl metabolite is found in subjects with liver cirrhosis (see section 4.2
Impaired renal function: The mean exposure of unbound tolterodine and its 5-
hydroxymethyl metabolite is doubled in patients with severe renal impairment (inulin
30 ml/min). The plasma levels of other metabolites were markedly
(up to 12-fold) increased in these patients. The clinical relevance of the increased
exposure of these metabolites is unknown. There is no data in mild to moderate renal
impairment (see section 4.2 and 4.4).
The exposure of the active moiety per mg dose is similar in adults and adolescents.
The mean exposure of the active moiety per mg dose is approximately two-fold
higher in children between 5-10 years than in adults (See sections 4.2 and 5.1).
Preclinical safety data
In toxicity, genotoxicity, carcinogenicity and safety pharmacology studies no
clinically relevant effects have been observed except those related to the
pharmacological effect of the drug.
Reproduction studies have been performed in mice and rabbits.
In mice, there was no effect of tolterodine on fertility or reproductive function.
Tolterodine produced embryo death and malformations at plasma exposures
or AUC) 20 or 7 times higher than those seen in treated humans.
In rabbits, no malformative effect was seen, but the studies were conducted at
20 or 3 times higher plasma exposure (C
or AUC) than those expected in
Tolterodine, as well as its active human metabolites prolong action potential
therapeutic levels) and block the K+-current in cloned human ether-a-go-go-
related gene (hERG) channels (0.5 – 26.1 times therapeutic levels). In dogs