Solifenacin Succinate is indicated for the symptomatic treatment of urge incontinence, increased urinary frequency, and urgency associated with overactive bladder syndrome.

Solifenacin is a competitive muscarinic receptor antagonist. It shows highest affinity for M3, M1, and M2 muscarinic receptors. Approximately 80% of muscarinic receptors in the bladder are M2 type, while about 20% are M3 type. By blocking M3 receptors, Solifenacin reduces detrusor muscle contraction. In addition, antagonism of M2 receptors may also reduce smooth muscle activity in the bladder, contributing to its therapeutic effect.

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.

Concomitant use with other anticholinergic drugs may enhance both therapeutic and adverse effects. An interval of about one week should be allowed after stopping Solifenacin Succinate before starting other anticholinergic therapy. Cholinergic receptor agonists may reduce the therapeutic effect of Solifenacin. It may also reduce the effect of drugs that stimulate gastrointestinal motility, such as Metoclopramide and Cisapride.In vitro studies show Solifenacin does not inhibit CYP1A1/2, CYP2C9, CYP2C19, CYP2D6, or CYP3A4 at therapeutic concentrations, so clinically significant interactions via these enzymes are unlikely.

Solifenacin is metabolized mainly by CYP3A4. Ketoconazole (a strong CYP3A4 inhibitor) increases Solifenacin exposure approximately 2-fold at 200 mg/day and 3-fold at 400 mg/day. Therefore, the maximum dose should be limited to 5 mg when used with strong CYP3A4 inhibitors such as ketoconazole, ritonavir, nelfinavir, or itraconazole.

Concomitant use with strong CYP3A4 inhibitors is contraindicated in patients with severe renal impairment or moderate hepatic impairment. Potential interactions may also occur with CYP3A4 substrates or inducers such as verapamil, diltiazem, rifampicin, phenytoin, and carbamazepine.

Effect on other medicines:

• Oral contraceptives: no significant pharmacokinetic interaction
• Warfarin: no effect on pharmacokinetics or prothrombin time
• Digoxin: no significant interaction observed
• Effect on ability to drive and use machines: Solifenacin may cause blurred vision, somnolence, and fatigue; therefore, it may impair the ability to drive or operate machinery.

Solifenacin is contraindicated in patients with hypersensitivity to solifenacin or any excipients. It is also contraindicated in: Myasthenia gravis, Urinary retention, Uncontrolled narrow-angle glaucoma, Severe gastrointestinal conditions (including toxic megacolon), Patients undergoing haemodialysis, Severe hepatic impairment.  Severe renal impairment or moderate hepatic impairment when using strong CYP3A4 inhibitors (e.g., ketoconazole)

Due to its pharmacological action, Solifenacin may cause anticholinergic side effects, which are usually mild to moderate in severity. The frequency of these effects is dose-dependent. The most commonly reported adverse reaction is dry mouth. It occurs in about 11% of patients taking 5 mg once daily, 22% of patients taking 10 mg once daily, and 4% of placebo-treated patients. Dry mouth is generally mild and only rarely leads to discontinuation. Overall treatment compliance is very high (about 99%), and nearly 90% of patients complete the full 12-week treatment period.

• Gastrointestinal disorders: very common – dry mouth; common – constipation, nausea, dyspepsia, abdominal pain; uncommon – gastro-oesophageal reflux disease, dry throat; rare – colonic obstruction, faecal impaction; very rare – vomiting.
• Infections and infestations: uncommon – urinary 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.

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. However, the potential risk to humans is unknown; therefore, caution is advised when prescribing to pregnant women. No human data are available regarding excretion in breast milk. In animal studies, Solifenacin and/or its metabolites were excreted in milk and caused a dose-dependent failure to thrive in neonatal animals. Therefore, use of Solifenacin should be avoided during breastfeeding.

Other causes of frequent urination (such as heart failure or renal disease) should be evaluated before initiating Solifenacin Succinate. If urinary tract infection is present, appropriate antibacterial therapy should be started first. Solifenacin should be used with caution in patients with: Clinically significant bladder outlet obstruction (risk of urinary retention), Gastrointestinal obstructive disorders, Reduced gastrointestinal motility risk, Severe renal impairment (creatinine clearance <30 ml/min), Moderate hepatic impairment (Child-Pugh score 7–9). In these patients, the dose should not exceed 5 mg once daily. Caution is required when used with strong CYP3A4 inhibitors (e.g., ketoconazole), in patients with hiatus hernia or gastroesophageal reflux, or those taking drugs that may cause or worsen esophagitis (e.g., bisphosphonates). Use with caution in autonomic neuropathy. Safety and efficacy have not been established in patients with neurogenic detrusor overactivity. Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine. Maximum therapeutic effect may take at least 4 weeks.

Renal impairment: No dose adjustment is required in mild to moderate renal impairment (creatinine clearance >30 ml/min). In severe renal impairment (<30 ml/min), use with caution; maximum dose is 5 mg once daily.

Hepatic impairment: No adjustment is required in mild hepatic impairment. In moderate hepatic impairment (Child-Pugh 7–9), use with caution; maximum dose is 5 mg once daily.

CYP3A4 inhibitors: When used with potent CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, nelfinavir, itraconazole), the maximum dose should not exceed 5 mg once daily. Tablets should be taken orally, swallowed whole with liquids, and may be taken with or without food.

Overdose of Solifenacin may result in severe anticholinergic effects. The highest reported accidental dose was 280 mg over 5 hours, causing mental status changes without hospitalization.

Management includes activated charcoal. Gastric lavage may be useful if performed within 1 hour; vomiting should not be induced.

Symptomatic treatment:

• Severe central effects (hallucinations, agitation): physostigmine or carbachol
• Seizures or severe agitation: benzodiazepines
• Respiratory depression: assisted ventilation
• Tachycardia: beta-blockers
• Urinary retention: catheterization
• Mydriasis: pilocarpine eye drops or dark environment

Caution is required in patients at risk of QT prolongation (e.g., hypokalemia, bradycardia, QT-prolonging drugs) and those with pre-existing cardiac conditions (myocardial ischemia, arrhythmia, congestive heart failure).

Anticholinergics (antimuscarinics) / Antispasmodics / Drugs for BPH, urinary retention, and urinary incontinence

Store in a cool, dry place, protected from light.