VESIKEAR table. 5 mg. 30 table
VESIKEAR table. 5 mg. 30 table
Qualitative and quantitative composition
Vesicare 5 mg tablet
1 tablet contains the active ingredient solifenacin succinate 5 mg, corresponding to 3.8 mg solifenacin
Vesicare 5 mg film-coated tablets
Round, light-yellow tablet, marked with company logo and "150" on the same side.
Symptomatic treatment of urge incontinence and / or increased frequency of urination may occur in patients with symptoms of overactive bladder.
Posology and method of administration
Adults, including the elderly
The recommended dose is 5 mg solifenacin succinate once daily. If necessary, it can be increased to 10 mg solifenacin succinate once daily.
Children and adolescents
Safety and effectiveness in pediatric patients have not been established because Vesicare should not be used in children.
Patients with renal insufficiency
In patients with mild to moderate renal insufficiency (creatinine clearance> 30 ml / min) no dose adjustment is required.
In patients with severe renal insufficiency (creatinine clearance <30 ml / min) should be treated with caution and the daily dose should not exceed 5 mg (see section 5.2).
Patients with hepatic impairment
In patients with mild hepatic impairment do not require dose adjustments. In patients with moderate hepatic impairment (Child-Pugh score 7 to 9) therapy should be treated with caution and the daily dose should not exceed 5 mg.
Patients concomitantly treated with potent cytochrome P450 ZA4
The maximum dose should be Vesicare 5 mg, when patients received therapeutic doses of ketoconazole or other potent inhibitors of CYP3A4, such as ritonavir, nelfinavir, itraconazole (see section 4.5).
Route of administration
Vesicare is taken orally and tablets should be swallowed whole with liquid, either with or without food.
Solifenacin is contraindicated in patients with urinary retention, severe gastrointestinal complaints (including toxic megacolon), myasthenia gravis or narrow-angle glaucoma and in patients at risk for the following conditions:
Patients who are hypersensitive to the active substance or to any of the excipients
Patients undergoing hemodialysis (see section 5.2)
Patients with severe hepatic impairment (see section 5.2)
Patients with severe renal or moderate hepatic impairment and in patients who are currently treated with a potent inhibitor of CYP3A4, eg. ketoconazole (see section 4.5).
Special warnings and precautions
Before starting treatment with Vesicare should determine whether frequent urination due to other factors (heart failure or kidney disease). If you have a urinary tract infection should initiate appropriate antimicrobial therapy.
Vesicare should be used with caution in patients with:
Clinically significant obstruction of the bladder outflow at risk for urinary retention
Gastrointestinal obstructive disorders
Risk of decreased gastrointestinal motility
Severe renal insufficiency (creatinine clearance 30 ml / min; see 4.2 and 5.2) and the dose should not exceed 5 mg
Moderate hepatic impairment (Child-Pugh score 7 to 9, see sections 4.2 and 5.2) and the dose should not exceed 5 mg
Concomitant use of potent CYP3A4 inhibitor, eg. ketoconazole (see section 4.2 and 4.5)
Hernia / gastroesophageal reflux and / or who are concurrently taking drugs (such as bisphosphonates) that can cause or exacerbate esophagitis
Safety and effectiveness in patients with neurogenic cause for detrusor overactivity has not been established. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or malabsorption of glucose-galactose should not take this product.
The maximum effect of Vesicare can be detected as early as 4 weeks.
Drug interactions and other interactions
Concomitant administration of other drugs with anticholinergic properties may enhance the therapeutic effects and undesirable effects to go around one week after stopping treatment with Vesicare before commencing other anticholinergic agent. The therapeutic effect of solifenacin may be reduced by concomitant administration of cholinergic receptor agonists.
Solifenacin can reduce the effect of medicines that stimulate the motility of the gastrointestinal tract, eg. metoclopramide and cisapride.
Studies "in vitro" show that at therapeutic concentrations, solifenacin does not inhibit CYP1A1 / 2,2 C9, 2C19, 2D6, or ZA4 derived from human liver microsomes. Therefore it is not expected to alter the clearance of drugs metabolized by these CYP enzymes.
Effect of other drugs on the pharmacokinetics of solifenacin
Solifenacin is metabolised by SURZA4.
Co-administration of ketoconazole (200 mg daily), a potent inhibitor of SURZ A4 induces fold increase in AUC of solifenacin, while ketoconazole at a dose of 400 mg caused a threefold increase in AUC of solifenacin. Therefore, the maximum dose of Vesicare should be limited to 5 mg, when used concomitantly with ketoconazole or therapeutic doses of other potent SURZA4 inhibitors (eg, ritonavir, nelfinavir, itraconazole) (see section 4.2).
Concomitant treatment with solifenacin and potent inhibitor of SURZA4 is contraindicated in patients with severe renal impairment or moderate hepatic insufficiency.
The effects of enzyme induction on the pharmacokinetics of solifenacin and its metabolites have not been studied as well as the effect of SURZA4 in contact with solifenacin. Since metabolism of solifenacin SURZA4 are possible pharmacokinetic interactions with other substrates SURZA4 with high affinity (eg, verapamil, diltiazem) and SURZA4 inducers (eg rifampicin, phenytoin, carbamazepine).
Effect of solifenacin on the pharmacokinetics of other medicinal products.
Intake of Vesicare showed no pharmacokinetic interaction of solifenacin on combined oral contraceptives (ethinyl estradiol / levonorgestrel).
The use of Vesicare did not alter the pharmacokinetics of R-warfarin and S-warfarin, and their effect on prothrombin time.
Intake of Vesicare no effect on the pharmacokinetics of digoxin.
Pregnancy and lactation
No clinical data on women who became pregnant while taking solifenacin. Animal studies do not indicate direct harmful effects on fertility, embryonic and fetal development and parturition (see section 5.3). The potential risk for humans is unknown, so it should be prescribed with caution in pregnant women.
There are no data on the excretion of solifenacin in human milk. In mice, solifenacin and / or its metabolites are excreted in the breast milk and cause dose-dependent growth inhibition in neonatal mice (see section 5.3). For this reason, the use of Vesicare should be avoided during lactation.
Effects on ability to drive and use machines
Since solifenacin, like other anticholinergics may cause blurred vision and less sleepiness and fatigue (see section 4.8 Undesirable effects), effects on ability to drive and use machines may be negative.
Due to the pharmacological effect of solifenacin Vesicare can cause mild to moderate side effects. The incidence of anticholinergic side effects is dose related. The most commonly reported dry mouth. It occurred in 11% of patients with a daily dose of 5 mg, 22% of those with 10 mg and 4% of placebo-treated patients.
The severity of dry mouth is light and only rarely led to discontinuation of treatment. General medicine is very high (99%) and approximately 90% of patients have received full period of 12 weeks of treatment in a clinical trial.
The highest dose of solifenacin succinate, a reception given to volunteers was 100 mg. At this dose, the most common adverse reactions were headache (mild), dry mouth (moderate), dizziness (moderate), somnolence (mild) and blurred vision (moderate). No reports of acute overdose of solifenacin succinate. In case of overdose of solifenacin succinate to give activated charcoal can perform gastric lavage, but should not induce vomiting.
As with other anticholinergic agents, the symptoms can be treated as follows:
In severe central anticholinergic effects, such as hallucinations or pronounced excitation applied physostigmine or carbachol.
If convulsions or pronounced excitation benzodiazepine
Respiratory failure - artificial respiration
Tachycardia - beta-blockers
For retention - catheterization
If mydriasis - pilocarpine eye drops and / or placing the patient in a dark room
As with other antimuscarinic agents in case of overdose should pay special attention to patients at risk of prolonged QT-interval (eg, hypokalemia, bradycardia and concomitant medicinal products) are known to prolong the QT- interval and in patients with heart disease (myocardial ischemia, arrhythmia, congestive heart failure).
Pharmacotherapeutic group: urinary antispasmodics agents ATC code: G04B D08
Mechanism of action:
Solifenacin is a competitive specific antagonist of cholinergic receptors.
The bladder is innervated by cholinergic parasympathetic nerves. Acetylcholine causes contraction of the detrusor smooth muscle through muscarinic receptor subtype predominantly by Mz. Pharmacological studies "in vitro" and "in vivo" have shown that solifenacin is a competitive inhibitor of the muscarinic M3 receptor. Moreover, it is a specific antagonist of muscarinic receptors, with little or no affinity for other receptors and ion channels that have been studied.
Vesicare treatment at doses of 5 mg and 10 mg daily has been studied in several double-blind randomized clinical trial in men and women with overactive bladder. As shown in the table below, both doses Vesicare 5 mg and 10 mg produced statistically significant improvements in primary and secondary points compared with placebo. The results obtained after one week of treatment and stabilized for a period of 12 weeks.
Long open-label study suggests that the effectiveness is maintained for at least 12 months. After 12 weeks of treatment, approximately 50% of patients suffering from incontinence before treatment should have had cases of incontinence and the other 35% of the patients achieved urinary frequency less than 8 times a day. Treatment of symptoms of overactive bladder has a good quality of life with an overall feeling of good health by reducing incontinence episodes, physical and social constraints, unpleasant emotions, symptom severity, strict restrictions and sleep disorder / vitality.