Spasmolyt

Spasmolyt

trospium chloride

Manufacturer:

Mylan Healthcare

Distributor:

Antah Pharma
Full Prescribing Info
Contents
Trospium chloride.
Description
Spasmolyt also contains the following excipients: Wheat starch, microcrystalline cellulose, lactose monohydrate, povidone, croscarmellose sodium, stearic acid, anhydrous colloidal silica, talc, sucrose, carmellose sodium, calcium carbonate E170, macrogol 8000, titanium dioxide E171, hydrated yellow iron oxide E172, white beeswax and carnauba wax.
Each coated tablet corresponds to carbohydrate 0.06 g (equivalent to 0.005 bread units).
Action
Pharmacology: Pharmacodynamics: 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 acetycholine, the body's endogenous transmitter at postsynaptic, parasympathetic 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 anticholinergic 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 genitourinary tract. Furthermore, it can inhibit the secretion of bronchial mucus, saliva, sweat and the ocular accommodation. No effects on the central nervous system have so far been observed.
In 2 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-dependent heart rate accelerating effect. A long-term clinical trial with trospium chloride 20 mg twice daily found an increase of QT >60 msec in 1.5% (3/197) of included patients. The clinical relevance of these findings has not been established. Routine safety monitoring in 2 other placebo-controlled clinical trials of 3-months duration do not support such an influence of trospium chloride.
In the 1st study, an increase of QTcF ≥60 msec was seen in 4/258 (1.6%) in trospium-treated patients versus 9/256 (3.5%) in placebo-treated patients. Corresponding figures in the 2nd trial were 8/326 (2.5%) in trospium-treated patients versus 8/325 (2.5%) in placebo-treated patients.
Pharmacokinetics: After oral administration of trospium chloride, maximum plasma levels are reached at 4-6 hrs. Following a single dose of 20 mg, the maximum plasma level is about 4 ng/mL. Within the tested interval, 20-60 mg as a single dose, the plasma levels are proportional to the administered dose. The absolute bioavailability of a single oral dose of trospium chloride 20 mg (1 coated tablet) is 9.6±4.5% (mean value ± standard deviation). At steady state, the intraindividual variability is 16% and the interindividual variability is 36%. Simultaneous intake of food, especially high-fat diets, reduces the bioavailability of trospium chloride. After a high-fat meal, the mean peak plasma concentration (Cmax) and area under the concentration-time curve (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 hrs. 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), the 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).
Toxicology: Preclinical Safety Data: 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.
Indications/Uses
Symptomatic treatment of urge incontinence and/or increased urinary frequency and urgency as may occur in patients with overactive bladder (eg, idiopathic or neurologic detrusor overactivity).
Dosage/Direction for Use
1 coated tab twice daily (equivalent to trospium chloride 40 mg/day).
The need for continued treatment should be reassessed at regular intervals of 3-6 months.
Severe Renal Impairment (Creatinine Clearance Between 10 and 30 mL/min/1.73 m2): Recommended Dosage: 1 coated tab/day or every 2nd day (equivalent to trospium chloride 20 mg/day or every 2nd day).
Administration: The coated tablet should be swallowed whole with a glass of water before meals on an empty stomach.
Overdosage
After the administration of a maximum single dose of trospium chloride 360 mg to healthy volunteers, dryness of the mouth, tachycardia and micturition disorders 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 (eg, activated charcoal), local administration of pilocarpine to glaucoma patients, catheterisation in patients with urinary retention, treatment with a parasympathomimetic agent (eg, neostigmine) in the case of severe symptoms, administration of β-blockers in the case of insufficient response, pronounced tachycardia and/or circulatory instability (eg, initially propranolol IV 1 mg along with ECG and blood pressure monitoring).
Contraindications
Hypersensitivity to trospium chloride or to any of the excipients of Spasmolyt.
Patients with urinary retention, severe gastrointestinal condition (including toxic megacolon), myasthenia gravis, narrow-angle glaucoma and tachyarrhythmia.
Use in children: Since no data are available, the use in children <12 years is contraindicated.
Special Precautions
Patients with obstructive conditions of the gastrointestinal tract eg, pyloric stenosis; obstruction of the urinary flow with the risk of formation of urinary retention; autonomic neuropathy; hiatus hernia associated with reflux oesophagitis; and in whom fast heart rates are undesirable eg, those with hyperthyroidism, coronary artery disease and congestive heart failure.
Hepatic Impairment: As there are no data in patients with severe hepatic impairment, treatment of these patients with trospium chloride is not recommended. Caution should be exercised in patients with mild to moderate hepatic impairment.
Renal Impairment: Trospium chloride is mainly eliminated by renal excretion. Marked elevations in the plasma levels have been observed in patients with severe renal impairment. Therefore, caution should be exercised in patients with mild to moderate renal impairment (see Dosage & Administration).
Before commencing therapy, organic causes of urinary frequency, urgency, and urge incontinence eg, heart diseases, kidney diseases, polydipsia or infections, or tumours of urinary organs should be excluded.
Spasmolyt contains lactose monohydrate, sucrose and wheat starch. Patients with rare hereditary problems of galactose intolerance, the Lapp-lactase deficiency or glucose-galactose malabsorption, and fructose intolerance or sucrase-isomaltase insufficiency should therefore not take Spasmolyt.
Patients with wheat allergy (different from coeliac disease) should not take Spasmolyt. Apart from that, trospium chloride is suitable for people with coeliac disease.
Effects on the Ability to Drive or Operate Machinery: Principally, disorders of accommodation can lower the ability to actively participate in road traffic and to use machines.
However, examinations of parameters characterising 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.
Use in pregnancy & lactation: Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see Pharmacology: Toxicology under Actions).
In rats, placental transfer and passage into the maternal milk of trospium chloride occurs.
Use In Pregnancy & Lactation
Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see Pharmacology: Toxicology under Actions).
In rats, placental transfer and passage into the maternal milk of trospium chloride occurs.
Adverse Reactions
Anticholinergic effects eg, dry mouth, dyspepsia and constipation may occur during treatment with trospium chloride.
The following adverse events are defined according to body system and frequency as: Very Common (≥10%): Gastrointestinal System: Dry mouth.
Common (≥1%): Gastrointestinal System: Dyspepsia, constipation, abdominal pain, nausea.
Uncommon (<1%): Gastrointestinal System: Flatulence.
Rare (<0.1%): Urinary System: Micturition disorders (eg, formation of residual urine).
Cardiovascular System: Tachycardia.
Vision Disorders: Disorders of accommodation (applies in particular to patients who are hypermetropic and whose vision has not been adequately corrected).
Gastrointestinal System: Diarrhoea.
Respiratory System: Dyspnoea.
Skin: Rash.
Body as a Whole: Asthenia, chest pain.
Very Rare (<0.01%): Urinary System: Urinary retention.
Cardiovascular System: Tachyarrhythmia.
Musculoskeletal System: Myalgia, arthralgia.
Skin: Angio-oedema.
Liver and Biliary System: Mild to moderate increase in serum transaminase levels.
Body as a Whole: Anaphylaxis.
Central Nervous System: Headache, dizziness, hallucination*, agitation*, confusion*.
*These adverse effects occurred mostly in elderly patients and can be facilitated by neurological disease and/or concomitant intake of other anticholinergic drugs.
Drug Interactions
Pharmacodynamic Interactions: The following potential pharmacodynamic interactions may occur: Potentiation of the effect of drugs with anticholinergic action (eg, amantadine, tricyclic antidepressants), enhancement of the tachycardic action of β-sympathomimetics; decrease in efficacy of prokinetic agents (eg, metoclopramide).
Since trospium chloride may influence gastrointestinal 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, cholestyramine 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 P-450 enzymes involved in drug metabolism (P-450, 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 substances eliminated by active tubular secretion cannot be excluded.
Incompatibilities: Not applicable.
Storage
Store below 30°C in a dry place.
Shelf-Life: 5 years.
MIMS Class
Drugs for Bladder & Prostate Disorders
ATC Classification
G04BD09 - trospium ; Belongs to the class of urinary antispasmodics.
Presentation/Packing
Tab 20 mg (coated, brownish-yellow, glossy, biconvex) x 100's.
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