Symptomatic treatment of urge incontinence and/or increased urinary frequency and urgency as?may occur in patients with overactive bladder syndrome.
Anticholinergics (antimuscarinics)/ Anti-spasmodics
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.
Adults, including the elderly: The recommended dose is Solifenacin Succinate 5 mg once daily. If needed, the dose may be increased to Solifenacin Succinate 10 mg once daily. Children and adolescents: Safety and effectiveness in children have not yet been established. Therefore, Solifenacin Succinate should not be used in children.
Concomitant medication with other medicinal products with anticholinergic properties may result in more pronounced therapeutic effects and undesirable effects. An interval of approximately one week should be allowed after stopping treatment with Solifenacin Succinate before commencing other anticholinergic therapy. The therapeutic effect of Solifenacin may be reduced by concomitant administration of cholinergic receptor agonists. Solifenacin can reduce the effect of medicinal products that stimulate the motility of the gastrointestinal tract, such as Metoclopramide and Cisapride. In vitro studies have demonstrated that at therapeutic concentrations, Solifenacin does not inhibit CYP1A1/2, 2C9, 2C19, 2D6, or 3A4 derived from human liver microsomes. Therefore, Solifenacin is unlikely to alter the clearance of drugs metabolized by these CYP enzymes. Solifenacin is metabolized by CYP3A4. Simultaneous administration of Ketoconazole (200 mg/day), a potent CYP3A4 inhibitor, resulted in a two-fold increase of the AUC of Solifenacin, while Ketoconazole at a dose of 400 mg/day resulted in a three-fold increase of the AUC of Solifenacin. Therefore, the maximum dose of Solifenacin Succinate should be restricted to 5 mg when used simultaneously with Ketoconazole or therapeutic doses of other potent CYP3A4 inhibitors (e.g. Ritonavir, Nelfinavir, Itraconazole).
Simultaneous treatment of Solifenacin and a potent CYP3A4 inhibitor is contra-indicated in patients with severe renal impairment or moderate hepatic impairment. The effects of enzyme induction on the pharmacokinetics of Solifenacin and its metabolites have not been studied as well as the effect of higher affinity CYP3A4 substrates on Solifenacin exposure. Since Solifenacin is metabolised by CYP3A4, pharmacokinetic interactions are possible with other CYP3A4 substrates with higher affinity (e.g. Verapamil, Diltiazem) and CYP3A4 inducers (e.g. Rifampicin, Phenytoin, Carbamazepine).
Effect of Solifenacin on the pharmacokinetics of other medicinal products:
Oral Contraceptives: Intake of Solifenacin showed no pharmacokinetic interaction on combined oral contraceptives (Ethinylestradiol/Levonorgestrel).
Warfarin: Intake of Solifenacin did not alter the pharmacokinetics of R-warfarin or S-warfarin or their effect on prothrombin time.
Digoxin: Intake of Solifenacin showed no effect on the pharmacokinetics of digoxin.
Effects on ability to drive and use machines: Since Solifenacin, like other anticholinergics may cause blurred vision and, uncommonly, somnolence and fatigue, the ability to drive and use machines may be negatively affected.
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. Other causes of frequent urination (heart failure or renal disease) should be assessed before treatment with Solifenacin. 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, concomitant use of a strong CYP3A4 inhibitor, e.g. ketoconazole
The most common side effects are blurred vision, dry mouth, constipation & heat prostration. Other side effects include dizziness, fatigue, edema, palpitation and skin reactions. Disorientation, hallucination and convulsion may occur.
Use in pregnancy: There are no adequate data from the use of solifenacin succinate in pregnant women. Caution should be exercised while prescribing solifenacin to pregnant women. Use in lactating mother: No data concerning the excretion of solifenacin into breast milk are available. The use of Solifenacin is avoided in lactating mother.
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).
Store in a cool and dry place, protected from light.
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