Symptomatic treatment of urge incontinence and/or increased urinary frequency and urgency as may
occur in patients with overactive bladder (e.g. idiopathic or neurologic detrusor overactivity).

Posology:
One coated tablet twice daily (equivalent to 40 mg of trospium chloride per day).
Patients with renal impairment
In patients with severe renal impairment (creatinine clearance between 10 and 30 mL/min/1.73 m2)
the recommended dosage is: One Spasmolyt 20 mg coated tablet per day or one Spasmolyt 20 mg
coated tablet every second day (equivalent to 20 mg of trospium chloride per day or every second
day).

Paediatric population
The safety and efficacy of Spasmolyt in children and adolescents under 12 years of age have not been
established.
Method of administration
The coated tablet should be swallowed whole with a glass of water before the meals on empty
stomach.
The need for continued treatment should be reassessed at regular intervals of 3-6 months.

Trospium chloride is contraindicated in patients with urinary retention, severe gastro-intestinal condition (including toxic megacolon), myasthenia gravis, narrow-angle glaucoma, and tachyarrhythmia. Spasmolyt is also contraindicated in patients who have demonstrated hypersensitivity to the active substance, wheat starch or to any of the excipients.

Trospium chloride should be used with caution by patients:
- with obstructive conditions of the gastrointestinal tract such as pyloric stenosis
- with obstruction of the urinary flow with the risk of formation of urinary retention with
autonomic neuropathy
- with hiatus hernia associated with reflux oesophagitis
- in whom fast heart rates are undesirable e.g. those with hyperthyroidism, coronary artery disease
and congestive heart failure.
As there are no data in patients with severe hepatic impairment, treatment of these patients with
trospium chloride is not recommended. In patients with mild to moderate liver impairment caution
should be exercised.
Trospium chloride is mainly eliminated by renal excretion. Marked elevations in the plasma levels
have been observed in patients with severe renal impairment. Therefore in this population but also in
patients with mild to moderate renal impairment caution should be exercised (see section 4.2).
Before commencing therapy organic causes of urinary frequency, urgency, and urge incontinence,
such as heart diseases, diseases of the kidneys, polydipsia, or infections, or tumours of urinary organs
should be excluded.
Spasmolyt 20 mg contains lactose-monohydrate, sucrose and wheat starch.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or
glucose-galactose malabsorption should not take this medicine.
Patients with rare hereditary problems of fructose intolerance or sucrase-isomaltase insufficiency
should not take Spasmolyt 20 mg.
Wheat starch may contain small amounts of gluten, which however are deemed to be tolerable for
people with coeliac disease.

Pharmacodynamic interactions:
The following potential pharmacodynamic interactions may occur:
- potentiation of the effect of drugs with anticholinergic action (such as amantadine, tricyclic
antidepressants),
- enhancement of the tachycardic action of ß-sympathomimetics, and
- decrease in efficacy of pro-kinetic agents (e.g. metoclopramide).
Since trospium chloride may influence gastro-intestinal motility and secretion, the possibility cannot
be excluded that the absorption of other concurrently administered drugs may be altered.

 

Pharmacokinetic interactions:
An inhibition of the absorption of trospium chloride with drugs like guar, colestyramine and
colestipol cannot be excluded. Therefore the simultaneous administration of these drugs with
trospium chloride is not recommended.
Metabolic interactions of trospium chloride have been investigated in vitro on cytochrome P450
enzymes involved in drug metabolism (P450 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, 3A4). No influence on
their metabolic activities was observed. Since trospium chloride is metabolised only to a low extent
and since ester hydrolysis is the only relevant metabolic pathway, no metabolic interactions are
expected.
Though trospium chloride was shown not to affect pharmacokinetics of digoxin, an interaction with
other active substances eliminated by active tubular secretion cannot be excluded.

Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy,
embryonal/foetal development, parturition or postnatal development (see section 5.3). In rats,
placental transfer and passage into the maternal milk of trospium chloride occurs.
For Spasmolyt 20 mg no clinical data on exposed pregnancies are available.
Caution should be exercised when prescribing to pregnant or breastfeeding women.

Disturbance of visual accommodation is the main reason for the impaired the ability to drive and to
use machines.
However, investigations into other parameters for measuring the ability to participate in road traffic
(visual orientation, general ability to react, reaction under stress, concentration and motor
coordination) have not revealed any effects of trospium chloride.

Undesirable effects observed with trospium chloride such as dry mouth, dyspepsia and constipation
mainly reflect the typical anticholinergic properties of the active substance.
In Phase-III clinical studies, dry mouth was very common and occurred in approximately 18% of
patients treated with trospium chloride and in approximately 6% treated with placebo (total of
1931 patients of which 911 received placebo).
The following table lists possibly related drug reactions reported for patients treated with
Spasmolyt 20 mg:

 

Wheat starch may cause hypersensitivity reactions.

 

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the 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 the national reporting system listed in:
To report side effect(s):
Saudi Arabia:
- The National Pharmacovigilance and Drug Safety Centre (NPC)
Fax: +966-11-205-7662,
Call NPC at +966-11-2038222, Ext 2317-2356-2340
Reporting hotline: 19999
E-mail: npc.drug@sfda.gov.sa
Website: www.sfda.gov.sa/npc
- Other GCC States:
Please contact the relevant competent authority.

After the administration of a maximum single dose of 360 mg trospium chloride to healthy volunteers,
dryness of the mouth, tachycardia and disorders of micturition were observed to an increased extent.
No manifestations of severe overdosage or intoxication in humans have been reported to date.
Increased anticholinergic symptoms are to be expected as signs of intoxication.
In the case of intoxication the following measures should be taken:
- gastric lavage and reduction of absorption (e.g. activated charcoal)
- local administration of pilocarpine to glaucoma patients
- catheterisation in patients with urinary retention
- treatment with a parasympathomimetic agent (e.g. neostigmine) in the case of severe symptoms
- administration of beta blockers in the case of insufficient response, pronounced tachycardia
and/or circulatory instability (e.g. initially 1 mg propranolol intravenously along with monitoring
of ECG and blood pressure).

Pharmacotherapeutic group: Urinary Antispasmodic, ATC code G04BD 09
Trospium chloride is a quaternary derivative of nortropane and therefore belongs to the class of
parasympatholytic or anticholinergic drugs, as it competes concentration-dependently with
acetylcholine, the body's endogenous transmitter at postsynaptic, parasympathic binding sites.
Trospium chloride binds with high affinity to muscarinic receptors of the so called M1-, M2- and M3-
subtypes and demonstrates negligible affinity to nicotinic receptors.
Consequently, the anticholinercic effect of trospium chloride exerts a relaxing action on smooth
muscle tissue and organ functions mediated by muscarinic receptors.
Both in preclinical as well as in clinical experiments, trospium chloride diminishes the contractile
tone of smooth muscle in the gastrointestinal and genito-urinary tract.
Furthermore, it can inhibit the secretion of bronchial mucus, saliva, sweat and the occular
accommodation. No effects on the central nervous system have so far been observed.
In two specific safety studies in healthy volunteers Trospium chloride has been proven not to affect
cardiac repolarisation, but has been shown to have a consistent and dose dependant heart rate
accelerating effect.
A long term clinical trial with Trospium chloride 20 mg bid found an increase of QT> 60 ms in 1.5%
(3/197) of included patients. The clinical relevance of these findings has not been established.

Routine safety monitoring in two other placebo-controlled clinical trials of three months duration does
not support such an influence of trospium chloride: In the first study an increase of QTcF >= 60 msec
was seen in 4/258 (1.6%) in trospium-treated patients vs. 9/256 (3.5%) in placebo-treated patients.
Corresponding figures in the second trial were 8/326 (2.5%) in trospium-treated patients vs. 8/325
(2.5%) in placebo-treated patients.

After oral administration of trospium chloride maximum plasma levels are reached at 4-6 hours.
Following a single dose of 20 mg the maximum plasma level is about 4 ng/mL. Within the tested
interval, 20 to 60 mg as a single dose, the plasma levels are proportional to the administered dose. The
absolute bioavailability of a single oral dose of 20 mg of trospium chloride (1 coated tablet
Spasmolyt 20 mg) is 9.6 ± 4.5% (mean value ± standard deviation). At steady state the intraindividual
variability is 16%, the interindividual variability is 36%.
Simultaneous intake of food, especially high fat diets, reduces the bioavailability of trospium chloride.
After a high-fat meal mean Cmax and AUC are reduced to 15-20% of the values in the fasted state.
Trospium chloride exhibits diurnal variability in exposure with a decrease of both Cmax and AUC for
evening relative to morning doses.
Most of the systemically available trospium chloride is excreted unchanged by the kidneys, though a
small portion (10% of the renal excretion) appears in the urine as the spiroalcohol, a metabolite
formed by ester hydrolysis. The terminal elimination half-life is in the range of 10-20 hours. No
accumulation occurs. The plasma protein binding is 50-80%.
Pharmacokinetic data in elderly patients suggests no major differences. There are also no gender
differences.
In a study in patients with severe renal impairment (creatinine clearance 8-32 mL/min) mean AUC
was 4-fold higher, Cmax was 2-fold higher and the mean half-life was prolonged 2-fold compared with
healthy subjects.
Pharmacokinetic results of a study with mildly and moderately hepatically impaired patients do not
suggest a need for dose adjustment in patients with hepatic impairment, and are consistent with the
limited role of hepatic metabolism in the elimination of trospium chloride.
The Blood Brain Barrier permeability of trospium chloride is virtually absent due to its chemical
properties (low lipophilicity as a quaternary amine).

Preclinical data reveal no special hazard to humans based on conventional studies of safety
pharmacology, repeated dose toxicity, genotoxicity, carcinogenicity, and toxicity to reproduction.
Placental transfer and passage of trospium chloride into the maternal milk occurs in rats.

Tablet core: Wheat starch
Microcrystalline cellulose
Lactose monohydrate
Povidone (K 29-32)
Croscarmellose sodium
Stearic acid
Silica colloidal anhydrous
Talc

 

Tablet coat: Sucrose
Carmellose sodium
Talc
Silica colloidal anhydrous
Calcium carbonate (E 170)
Macrogol 8000
Titanium dioxide (E 171)
Iron oxide hydrate yellow (E 172)
Beeswax white
Carnauba wax
Note for diabetics:
Each Spasmolyt 20 mg coated tablet corresponds to 0.06 g carbohydrate (equivalent to 0.005 bread
units).

Not applicable.

3 years

Store below 30°C

PVC foiled aluminium blister
Original packs with 30, 50, 84 und 100 coated tablets.
Clinic packs with 500 (10 x 50) coated tablets.

No special requirements.
Any unused product or waste material should be disposed of in accordance with local requirements.