Solifenacin is a competitive muscarinic receptor antagonist. It has the highest affinity for M3, M1, and M2 muscarinic receptors. 80% of the muscarinic receptors in the bladder are M2, while 20% are M3. Solifenacin's antagonism of the M3 receptor prevents contraction of the detrusor muscle, while antagonism of the M2 receptor may prevent contraction of smooth muscle in the bladder.

Symptomatic treatment of urge incontinence and/or increased urinary frequency and urgency as may occur in patients with overactive bladder syndrome.

The recommended dose for adults and the elderly: Solifenacin Succinate 5 mg once daily. If needed, the dose may be increased to Solifenacin Succinate 10 mg once daily.

Use in children: Safety and effectiveness in children have not yet been established. Therefore, Solifenacin Succinate should not be used in children.

Solifenacin is contraindicated in patients with hypersensitivity to solifenacin or to any of the excipients. It is also contraindicated in myasthenia gravis, urinary retention, uncontrolled narrow angle glaucoma, severe gastro-intestinal condition (including toxic megacolon), patients undergoing haemodialysis, patients with severe hepatic impairment, patients with severe renal impairment or moderate hepatic impairment and on treatment with a strong CYP3A4 inhibitor, e.g. ketoconazole.

Due to the pharmacological effect of Solifenacin, it may cause anticholinergic undesirable effects of (in general) mild or moderate severity. The frequency of anticholinergic undesirable effects is dose related. The most commonly reported adverse reactionwith Solifenacin is dry mouth. It occurred in 11% of patients treated with 5 mg once daily, in 22% of patients treated with 10 mg once daily and in 4% of placebo-treated patients. The severity of dry mouth was generally mild and only occasionally led to discontinuation of treatment. In general,medicinal product compliance was very high (approximately 99%) and approximately 90% of the patients treated with Solifenacin completed the full study period of 12 weeks treatment.

• Gastrointestinal disorders: very common- dry mouth, common-constipation, nausea, dyspepsia, abdominal pain, uncommon- gastroesophageal reflux diseases, dry throat, rare- colonic obstruction, faecal impaction, very rare- vomiting.
• Infections and infestations: uncommonurinary tract infection, cystitis.
• nervous system disorders: uncommon- somnolence, dysgeusia, very rare-dizziness, headache.
• psychiatric disorders: very rare- hallucinations.
• eye disorders: common- blurred vision, uncommon- dry eyes.
• General disorders and administration site conditions: uncommon- fatigue, peripheral oedema.
• Respiratory, thoracic and mediastinal disorders: uncommon nasal dryness.
• skin and subcutaneous tissue disorders: uncommon- dry skin, very rare- pruritus, rash, urticaria.
• renal and urinary disorders: uncommon- difficulty in micturition, rare- urinary retention.

Overdose Effects

Over dosage with Solifenacin Succinate can potentially result in severe anticholinergic effects. The highest dose of Solifenacin Succinate accidentally given to a single patient was 280 mg in a 5 hour period, resulting in mental status changes not requiring hospitalization. In the event of overdose with Solifenacin Succinate, the patient should be treated with activated charcoal. Gastric lavage is useful if performed within 1 hour, but vomiting should not be induced. As for other anticholinergics, symptoms can be treated as follows:

• Severe central anticholinergic effects such as hallucinations or pronounced excitation: treat with physostigmine or carbachol.
• Convulsions or pronounced excitation: treat with benzodiazepines.
• Respiratory insufficiency: treat with artificial respiration.
• Tachycardia: treat with beta-blockers.
• Urinary retention: treat with catheterisation.
• Mydriasis: treat with pilocarpine eye drops and/or place patient in a dark room.

As with other antimuscarinics, in case of overdosing, specific attention should be paid to patients with known risk for QT-prolongation (i.e. hypokalaemia, bradycardia and concurrent administration of medicinal products known to prolong QT interval) and relevant pre-existing cardiac diseases (i.e. myocardial ischaemia, arrhythmia, congestive heart failure).

Other causes of frequent urination (heart failure or renal disease) should be assessed before treatment with Solifenacin Succinate. If urinary tract infection is present, an appropriate antibacterial therapy should be started. Solifenacin Succinate should be used with caution in patients with: clinically significant bladder outflow obstruction at risk of urinary retention, gastrointestinal obstructive disorders, risk of decreased gastrointestinal motility, severe renal impairment (creatinine clearance 30 ml/min), moderate hepatic impairment (Child-Pugh score of 7 to 9) and doses should not exceed 5 mg for these patients. Caution should be taken in concomitant use of a potent CYP3A4 inhibitor e.g. Ketoconazole, hiatus hernia/ gastroesophageal reflux and/or who are concurrently taking medicinal products (such as Bisphosphonates) that can cause or exacerbate oesophagitis, autonomic neuropathy. Safety and efficacy have not yet been established in patients with a neurogenic cause for detrusor overactivity. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. The maximum effect of Solifenacin Succinate can be determined after 4 weeks at the earliest.

Use in Special Populations

Patients with renal impairment: No dose adjustment is necessary for patients with mild to moderate renal impairment (creatinine clearance >30 ml/min). Patients with severe renal impairment (creatinine clearance <30 ml/min) should be treated with caution and receive no more than 5 mg once daily.

Patients with hepatic impairment: No dose adjustment is necessary for patients with mild hepatic impairment. Patients with moderate hepatic impairment (Child-Pugh score of 7 to 9) should be treated with caution and receive no more than 5 mg once daily.

Potent inhibitors of cytochrome P450 3A4: The maximum dose of Solifenacin Succinate should be limited to 5 mg when treated simultaneously with Ketoconazole or therapeutic doses of other potent CYP3A4 inhibitors e.g. Ritonavir, Nelfinavir, Itraconazole. Solifenacin Succinate tablet should be taken orally and should be swallowed whole with liquids. It can be taken with or without food.

Pregnancy & Lactation

No clinical data are available from women who became pregnant while taking Solifenacin. Animal studies do not indicate direct harmful effects on fertility, embryonal / foetal development or parturition. The potential risk for humans is unknown. Caution should be exercised when prescribing to pregnant women. No data on the excretion of Solifenacin in human milk are available. In mice, Solifenacin and/or its metabolites was excreted in milk, and caused a dose dependent failure to thrive in neonatal mice. The use of Solifenacin should therefore be avoided during breast-feeding.