Detrusitol 2mg & 4mg Prolonged Release Capsule

DETRUSITOL SR capsules are indicated for the treatment of overactive bladder with symptoms of urinary urgency, frequency and/or urge incontinence.

DETRUSITOL SR 2 mg and 4 mg capsules can be taken with or without food and must be swallowed whole.

Adults: The recommended dose is 4 mg once daily. The total daily dose may be reduced to 2 mg, based on individual tolerability.

Use in impaired renal or hepatic function: The recommended dose is 2 mg once daily. For patients receiving ketoconazole or other potent cytochrome P4503A4 inhibitors, the recommended daily dose is 2 mg. After 6 months of treatment, the need for further treatment should be reconsidered.

DETRUSITOL SR is contraindicated in patients with:

• Known hypersensitivity to tolterodine or excipients.
• Urinary retention.
• Gastric retention.
• Uncontrolled narrow angle glaucoma.
• Myasthenia gravis.
• Severe ulcerative colitis.
• Toxic megacolon.

Safety and efficacy in children have not yet been established.

DETRUSITOL SR should be used with caution in the following patients:

• At risk of urinary retention.
• Controlled narrow angle glaucoma.
• At risk of decreased gastrointestinal motility obstructive disorders e.g. pyloric stenosis.
• With impaired renal function.
• With impaired hepatic function.
• With myasthenia gravis.
• Autonomic neuropathy.
• Hiatus hernia.

Organic causes for urgency, frequency and/or urge incontinence should be excluded before considering treatment with DETRUSITOL SR.

Concomitant medication with other medicines that possess anticholinergic properties may result in more pronounced therapeutic effect and side effects. Conversely, the therapeutic effect of DETRUSITOL SR capsules may be reduced by concomitant administration of cholinergic receptor agonists. The effects of prokinetics like metoclopramide and cisapride may be decreased by DETRUSITOL SR capsules. Pharmacokinetic interaction is possible with other drugs metabolised by or inhibiting cytochrome P450 2D6 e.g. fluoxetine. Concomitant treatment with fluoxetine results in a 25 % increase in the combined exposure of unbound DETRUSITOL SR capsules and the equipotent metabolite. No dosage adjustment is usually required. A clinical study with marker drugs for the major P450 isoenzymes has not shown any evidence that the activity of CYP2D6, 2C19, 2C9, 3A4 or 1A2 will be inhibited by DETRUSITOL SR. Patients on concomitant medication with potent cytochrome P4503A4 inhibitors e.g. macrolide antibiotics (erythromycin and clarithromycin) or azole antifungal agents (e.g. ketoconazole, itraconazole and miconazole) should be treated with caution. Ketoconazole, a potent inhibitor of cytochrome P4503A4, significantly increased plasma concentrations of tolterodine when co-administered to poor metabolisers (i.e. patients devoid of cytochrome P4502D6 metabolic pathway) (see DOSAGE AND DIRECTIONS FOR USE). Prolongation of the QTc interval has occurred and should be considered in patients who are taking Class IA (e.g. quinidine, procainamide) or Class III (e.g. amiodarone, sotalol) antiarrhythmic medications. No interaction with warfarin or combined oral contraceptives (ethinyl oestradiol/ levonorgestrel) occurs. Co-administration with diuretic agents (indapamide, hydrochlorothiazide, triamterene or furosemide) does not cause any adverse ECG effects.

The safety of this medicine has not been established in pregnant and breastfeeding women. Women of childbearing potential should be advised to ensure adequate contraceptive cover.

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

DETRUSITOL SR may cause mild to moderate antimuscarinic effects, like dryness of the mouth, dyspepsia and reduced lacrimation. The side effects reported in clinical trials were categorised utilising the incidence rate as follows: Very common: u2265 1/10 (u2265 10 %); Common: u2265 1/100 and < 1/10 (u2265 1 % and < 10 %); Uncommon: u2265 1/1 000 and < 1/100 (u2265 0,1 % and < 1 %); Rare: u2265 1/10 000 and < 1/1 000 (u2265 0,01 % and < 0,1 %).

System Organ Class Frequency Adverse events Infections and infestations Common Bronchitis, sinusitis Immune system disorders Uncommon Allergic reactions Psychiatric disorders Uncommon Confusion Nervous system disorders Common Dizziness, headache, somnolence Eye disorders Common Abnormal vision (including abnormal accommodation), dry eyes (reduced lacrimation) Ear and labyrinth disorders Common Vertigo Vascular disorders Uncommon Flushed skin Gastrointestinal disorders Very common Dry mouth Common Abdominal pain, constipation, dyspepsia, flatulence Uncommon Gastroesophageal reflux Skin and subcutaneous tissue disorders Common Dry skin Renal and urinary disorders Common Dysuria Uncommon Urinary retention General disorders and administration site conditions Common Chest pain, fatigue Investigations Common Increased weight

The following side effects were reported during post-marketing surveillance: Immune system disorders: Anaphylactoid reactions. Psychiatric disorders: Disorientation, hallucinations. Nervous system disorders: Memory impairment. Cardiac disorders: Tachycardia, palpitations. Gastrointestinal disorders: Diarrhoea. Skin and subcutaneous tissue disorders: Angioedema. General disorders and administration site conditions: Peripheral oedema. Cases of aggravation of symptoms of dementia (e.g. confusion, disorientation, delusion) have been reported after DETRUSITOL SR therapy was initiated in patients taking cholinesterase inhibitors for the treatment of dementia.

The most severe adverse events observed were accommodation disturbances and micturition difficulties. Overdosage with DETRUSITOL SR capsules can potentially result in severe central antimuscarinic effects and should be treated accordingly. In the event of an overdose, treat with gastric lavage and give activated charcoal. Standard supportive measures for managing QT prolongation should be adopted. Treat the symptoms/signs as follows:

• Severe central anticholinergic effects (e.g. severe excitation, hallucinations) u2013 treat with physostigmine.
• Convulsions or pronounced excitation u2013 treat with benzodiazepines.
• Respiratory insufficiency u2013 treat with artificial ventilation.
• Tachycardia u2013 treat with beta-blockers.
• Urinary retention u2013 treat with catheterization.
• Mydriasis u2013 treat with pilocarpine eye drops and/or place patient in dark room.