Tolterodine

Concomitant medication with other medicinal products that possess antimuscarinic properties may result in more pronounced therapeutic effect and side effects of tolterodine. Conversely, the therapeutic effect of tolterodine may be reduced by concomitant administration of muscarinic cholinergic receptor agonists.

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 drugs known to prolong QT-interval including Class IA (e.g. quinidine, procainamide) and Class III (e.g. amiodarone, sotalol) anti-arrhythmics

In patients with impaired liver function or severely impaired renal function (GFR≤30 ml/min) the recommended dose is 1 mg twice daily.

Tolterodine shall be used with caution in patients with:

• Renal impairement
• Hepatic disease
• Autonomic neuropathy

Concomitant systemic medication with potent CYP3A4 inhibitors such as macrolide antibiotics (e.g. erythromycin and claritromycin), 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 overdosage.

The effect of prokinetics like metoclopramide and cisapride may be decreased by tolterodine.

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
• Hiatus hernia
• Risk for decreased gastrointestinal motility

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.

No data concerning the excretion of tolterodine into human milk are available. Tolterodine should be avoided during lactation.

Since this drug may cause accommodation disturbances and influence reaction time, the ability to drive and use machines may be negatively affected.

Summary of safety profile

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 tolterodine in clinical trials and from postmarketing experience. The most commonly reported adverse reaction was dry mouth, which occurred in 35% of patients treated with tolterodine film-coated tablets and in 10% of placebo treated patients. Headaches were also reported very commonly and occurred in 10.1% of patients treated with tolterodine film-coated tablets and in 7.4% of placebo treated patients.

Tabulated list of adverse reactions

The adverse drug reactions listed in the table below are presented by System Organ Class (SOC) and frequency categories, defined using the following convention: 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), or not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Adverse drug reactions:

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.

Paediatric population

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).