Presentation: Tolthen XL 4 mg prolonged-release capsules, hard. Indications: Symptomatic treatment of urge incontinence and/or increased urinary frequency and urgency as may occur in patients with overactive bladder syndrome. Dosage and 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. In case of troublesome undesirable effects the dose may be reduced from 4 mg to 2 mg once daily. The effect of treatment should be re-evaluated after 2-3 months Paediatric population: The efficacy of tolterodine SR has not been demonstrated in children. Therefore, Tolthen XL is not recommended for children.
Method of administration: The prolonged-release capsules, hard can be taken with or without food and must be swallowed whole
Contraindications: Tolterodine is contraindicated in patients with:
– Hypersensitivity to the active substance or to any of the excipients listed in section 6.1
– Urinary retention
– Uncontrolled narrow angle glaucoma
– Myasthenia gravis
– Severe ulcerative colitis
– Toxic megacolon.
Warnings and Precautions: 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)
– Autonomic neuropathy
– Hiatus hernia
– 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 including:
– Congenital or documented acquired QT prolongation
– Electrolyte disturbances such as hypokalaemia, hypomagnesaemia and hypocalcaemia
– Bradycardia
– Relevant pre-existing cardiac diseases (i.e. cardiomyopathy, myocardial ischaemia, arrhythmia, congestive heart failure)
– Concomitant administration of medicinal products known to prolong QT-interval including Class IA (e.g. quinidine, procainamide) and Class III (e.g. amiodarone, sotalol) anti-arrhythmics.
This especially holds true when taking potent CYP3A4 inhibitors (see section 5.1).
Concomitant treatment with potent CYP3A4 inhibitors should be avoided (see section 4.5, Interactions).
As with all treatments for symptoms of urgency and urge incontinence, organic reasons for urge and frequency should be considered before treatment.
This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
This medicinal product contains 0.00404 mmol (or 0.092988 mg) sodium per dose. To be taken into consideration by patients on a controlled sodium diet.
Interactions: 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 due to increased serum concentrations of tolterodine in poor CYP2D6 metabolisers with (subsequent) risk of overdose (see section 4.4).
Concomitant medication with other medicinal products that possess antimuscarinic properties may result in more pronounced therapeutic effect and undesirable effects. Conversely, the therapeutic effect of tolterodine may be reduced by concomitant administration of muscarinic cholinergic receptor agonists.
The effect of prokinetics like metoclopramide and cisapride may be decreased by tolterodine.
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.
Drug interaction studies have shown no interactions with warfarin or 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 active substances metabolised by these isoenzymes is not expected when dosed in 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 The potential risk for humans is unknown. Consequently, tolterodine is not recommended during pregnancy.
Breast-feeding:
No data concerning the excretion of tolterodine into human milk are available. Tolterodine should be avoided during lactation.
Fertility:
No data from fertility studies are available.
Effects on ability to drive and use machines:
Since this medicinal product may cause accommodation disturbances and influence reaction time, the ability to drive and use machines may be negatively affected.
Undesirable effects:
Due to the pharmacological effect of tolterodine it may cause mild to moderate antimuscarinic effects, like dryness of the mouth, dyspepsia and dry eyes.
Adverse reactions are listed in thye full SmPC, by system organ class and by frequency. Frequencies are defined as: very common ( 1/10) common ( 1/100 to < 1/10), uncommon ( 1/1,000 to < 1/100), rare ( 1/10,000 to <1/1,000); very rare (< 1/10,000) and not known (cannot be estimated from available data). Pack size and Price: Tolthen XL 2 mg prolonged-release capsules, hard x 28 = £6.99; Tolthen XL 4 mg prolonged-release capsules, hard x 28 = £6.99. Legal Category: POM. MA Number: PL 48259/0050. MA Holder: Northumbria Pharma Ltd, NetPark Incubator, Thomas Wright Way, Sedgefield, County Durham, TS21 3FD, UK. Date of Revision: August 2019