Vesicar tablets p / o 5mg, No. 30

Symptomatic treatment of urinary incontinence, urinary frequency and urgency in patients with overactive bladder syndrome.

Adults, including the elderly
Take 5 mg once a day by mouth, whole with a liquid, regardless of meal time. If necessary, the dose can be increased to 10 mg once a day.

Children The
safety and effectiveness of Vesicar in children has not been studied. Therefore, Vesicar should not be used in children.

Patients with renal impairment
No dose adjustment is required in patients with mild or moderate renal impairment (creatinine clearance> 30 ml / min). Patients with severe renal impairment (creatinine clearance <30 ml / min) should be prescribed solifenacin with caution and should not be given more than 5 mg per day.

Patients with hepatic impairment
No dose adjustment is required in patients with mild hepatic impairment. Patients with moderate hepatic impairment (Child-Pugh stage B) should be prescribed solifenacin with caution and should not be given more than 5 mg per day.

Patients receiving strong inhibitors of the isoenzyme CYP3A4 The
maximum dose of Vesicar should be limited to 5 mg when taken in conjunction with ketoconazole or a therapeutic dose of another inhibitor of the isoenzyme CYP3A4 (ritonavir, nelfinavir, itraconazole).

Each 5 mg tablet contains:

tablet core composition: solifenacin succinate 5.0 mg, lactose monohydrate 107.5 mg, corn starch 30.0 mg, hypromellose 3 mPa s - 6.0 mg, magnesium stearate - 1.5 mg, purified water * - 54.0 mg;
the composition of the film coating of the tablet: opadry yellow 03F12967 - 4.0 mg (hypromellose 6 mPa-s - 61.83%, talc - 18.54%, macrogol 8000 - 11.6%, titanium dioxide - 7.88%, iron oxide yellow - 0.15%), purified water * - 36.0 mg.

* - water is removed during the production process.

• delay in urination.

• severe gastrointestinal diseases (including toxic megacolon).

• myasthenia gravis.

• angle-closure glaucoma.

• hypersensitivity to the active substance or any of the excipients.

• carrying out hemodialysis.

• severe liver failure.

• severe renal impairment or hepatic impairment of moderate severity while being treated with strong inhibitors of the CYP3A4 isoenzyme, such as ketoconazole (see section 'Interaction with other medicinal products').

• lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

• children under 18 years of age.

Carefully

Before starting treatment with Vesicar, you should establish whether there are other causes of urinary disorders (heart failure or kidney disease). If a urinary tract infection is identified, appropriate antibiotic treatment should be initiated. Vesicar should be used with caution in patients:

• with clinically significant obstruction of the bladder outlet, leading to the risk of urinary retention.

• with gastrointestinal diseases with obstruction.

• with the risk of decreased gastrointestinal motility.

• with severe renal (creatinine clearance <30 ml per minute) and moderate hepatic impairment (stage B according to Child-Pugh classification); doses for these patients should not exceed 5 mg.

• concomitantly taking a strong inhibitor of the isoenzyme CYP3A4, for example, ketoconazole. with a hiatal hernia, gastroesophageal reflux, and in patients concurrently taking medications (such as bisphosphonates) that can cause or worsen esophagitis.

• with autonomic neuropathy.

Trade name:

Vesicar

International Non-proprietary Name (INN):

Solifenacin

Dosage form:

film-coated tablets

Composition

Each 5 mg tablet contains:

tablet core composition: solifenacin succinate 5.0 mg, lactose monohydrate 107.5 mg, corn starch 30.0 mg, hypromellose 3 mPa s - 6.0 mg, magnesium stearate - 1.5 mg, purified water * - 54.0 mg;
the composition of the film coating of the tablet: opadry yellow 03F12967 - 4.0 mg (hypromellose 6 mPa-s - 61.83%, talc - 18.54%, macrogol 8000 - 11.6%, titanium dioxide - 7.88%, iron oxide yellow - 0.15%), purified water * - 36.0 mg.

Each 10 mg tablet contains: the
composition of the tablet core: solifenacin succinate 10.0 mg, lactose monohydrate 102.5 mg, corn starch 30.0 mg, hypromellose 3 mPas - 6.0 mg, magnesium stearate - 1.5 mg, purified water * - 54.0 mg;
the composition of the film coating of the tablet: pink opadry 03F14895 - 4.0 mg (hypromellose 6 mPa s - 62.0%, talc - 18.59%, macrogol 8000 - 11.63%, titanium dioxide - 7.75%, iron oxide red - 0.03%), purified water * - 36.0 mg.

* - water is removed during the production process.

Description

Vesicar 5 mg Round, biconvex, light yellow film-coated tablets marked '150' and the company logo on one side.

Vesicar 10 mg Round, biconvex film-coated tablets, light pink in color, marked '151' and the company logo on one side.

Pharmacotherapeutic group:

Drugs for the treatment of frequent urination and urinary incontinence, antispasmodic.

ATX code: G04BD08

Pharmacological properties

Mechanism of action

Solifenacin is a specific competitive antagonist of muscarinic receptors. The bladder is innervated by parasympathetic cholinergic nerves. Acetylcholine acts on muscarinic receptors (mainly M3) and causes detrusor contraction. Pharmacological studies carried out in vitro and in vivo have shown that solifenacin is a specific competitive inhibitor of muscarinic receptors of the M3 subtype. Solifenacin has also been found to have low or no affinity for various other receptors and ion channels.

Pharmacodynamics

The efficacy of Vesicar in doses of 5 mg and 10 mg, studied in several double-blind, randomized, controlled clinical trials in men and women with overactive bladder syndrome, was observed during the first week of treatment and stabilized over the next 12 weeks of treatment. A long-term, open-label clinical trial has shown that efficacy lasts for at least 12 months. After 12 weeks of use, approximately 50% of the pretreatment urinary incontinence patients have ceased to experience urinary incontinence, and 35% of the patients have achieved a urinary incontinence rate of less than 8 per day. Treatment of overactive bladder (OAB) symptoms resulted in significant improvements in quality of life. The maximum effect of Vesikar can be detected after 4 weeks.

Pharmacokinetics

General characteristics

Absorption: The maximum plasma concentration (Cmax) is reached after 3-8 hours. The time to reach the maximum concentration (tmax) does not depend on the dose. Cmax and area under the curve (AUC) of the concentration versus time increase in proportion to the dose increase from 5 to 40 mg. Absolute bioavailability is 90%. Food intake does not affect the Cmax and AUC of solifenacin.

Distribution: The volume of distribution of solifenacin after intravenous administration is approximately 600 liters. Solifenacin is largely (about 98%) associated with plasma proteins, mainly with ? 1-acid glycoprotein.

Metabolism: Solifenacin is extensively metabolized by the liver, mainly by the isoenzyme CYP3A4. However, there are alternative metabolic pathways through which solifenacin can be metabolized. The systemic clearance of solifenacin is about 9.5 l / h, and the final half-life is 45-68 hours. After oral administration of the drug in plasma, in addition to solifenacin, the following metabolites were identified: one pharmacologically active (4R-hydroxysolifenacin) and three inactive (N-glucuronide, N-oxide and 4R-hydroxy-N-oxide of solifenacin).

Excretion: After a single injection of 10 mg of 14C-labeled solifenacin, after 26 days, about 70% of the radioactivity was found in urine and 23% in feces. In urine, about 11% of radioactivity was found in the form of an unchanged active substance, about 18% in the form of an N-oxide metabolite, 9% in the form of a 4R-hydroxy-N-oxide metabolite, and 8% in the form of a 4R-hydroxy metabolite (active metabolite). The pharmacokinetics of solifenacin are linear over the therapeutic dose range.

Features of pharmacokinetics in certain categories of patients

Age:
There is no need to adjust the dose depending on the age of the patients. Studies have shown that the exposure of solifenacin (5 and 10 mg), expressed as AUC, was similar in healthy elderly individuals (65 to 80 years old) and in healthy young individuals (<55 years old).
The mean rate of absorption, expressed as tmax, was slightly lower, and the terminal half-life was about 20% longer in the elderly. These minor differences are not clinically significant.
The pharmacokinetics of solifenacin have not been determined in children and adolescents.

Gender: The pharmacokinetics of solifenacin are independent of the sex of the patient.

Race: Race does not affect the pharmacokinetics of solifenacin.

Renal failure: AUC and Cmax of solifenacin in patients with mild to moderate renal failure do not differ significantly from those in healthy volunteers. In patients with severe renal failure (creatinine clearance <30 ml / min), the exposure of solifenacin is significantly higher - the increase in Cmax is about 30%, AUC is more than 100% and t1 / 2 is more than 60%. There was a statistically significant relationship between creatinine clearance and solifenacin clearance. Pharmacokinetics in patients undergoing hemodialysis has not been studied.

Hepatic impairment: In patients with moderate hepatic impairment (stage B according to Child-Pugh classification), the Cmax value does not change, AUC increases by 60%, t1 / 2 doubles. Pharmacokinetics in patients with severe hepatic impairment has not been determined.

Indications for use

Symptomatic treatment of urinary incontinence, urinary frequency and urgency in patients with overactive bladder syndrome.

Contraindications

• delay in urination.

• severe gastrointestinal diseases (including toxic megacolon).

• myasthenia gravis.

• angle-closure glaucoma.

• hypersensitivity to the active substance or any of the excipients.

• carrying out hemodialysis.

• severe liver failure.

• severe renal impairment or hepatic impairment of moderate severity while being treated with strong inhibitors of the CYP3A4 isoenzyme, such as ketoconazole (see section 'Interaction with other medicinal products').

• lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

• children under 18 years of age.

Carefully

Before starting treatment with Vesicar, you should establish whether there are other causes of urinary disorders (heart failure or kidney disease). If a urinary tract infection is identified, appropriate antibiotic treatment should be initiated. Vesicar should be used with caution in patients:

• with clinically significant obstruction of the bladder outlet, leading to the risk of urinary retention.

• with gastrointestinal diseases with obstruction.

• with the risk of decreased gastrointestinal motility.

• with severe renal (creatinine clearance <30 ml per minute) and moderate hepatic impairment (stage B according to Child-Pugh classification); doses for these patients should not exceed 5 mg.

• concomitantly taking a strong inhibitor of the isoenzyme CYP3A4, for example, ketoconazole. with a hiatal hernia, gastroesophageal reflux, and in patients concurrently taking medications (such as bisphosphonates) that can cause or worsen esophagitis.

• with autonomic neuropathy.

Application during pregnancy and during breastfeeding

There are no clinical data on women who become pregnant while taking solifenacin. Animal studies have shown no direct adverse effects on fertility, embryo / fetal development, or childbirth. Caution should be exercised when prescribing this drug to pregnant women only if the potential benefit to the mother outweighs the potential risk to the fetus.

There is no evidence of excretion of solifenacin in breast milk. In mice, solifenacin and / or its metabolites were excreted in breast milk and caused a dose-dependent developmental disorder in neonatal mice. The use of Vesikar is not recommended during breastfeeding.

Method of administration and dosage

Adults, including the elderly
Take 5 mg once a day by mouth, whole with a liquid, regardless of meal time. If necessary, the dose can be increased to 10 mg once a day.

Children The
safety and effectiveness of Vesicar in children has not been studied. Therefore, Vesicar should not be used in children.

Patients with renal impairment
No dose adjustment is required in patients with mild or moderate renal impairment (creatinine clearance> 30 ml / min). Patients with severe renal impairment (creatinine clearance <30 ml / min) should be prescribed solifenacin with caution and should not be given more than 5 mg per day.

Patients with hepatic impairment
No dose adjustment is required in patients with mild hepatic impairment. Patients with moderate hepatic impairment (Child-Pugh stage B) should be prescribed solifenacin with caution and should not be given more than 5 mg per day.

Patients receiving strong inhibitors of the isoenzyme CYP3A4 The
maximum dose of Vesicar should be limited to 5 mg when taken in conjunction with ketoconazole or a therapeutic dose of another inhibitor of the isoenzyme CYP3A4 (ritonavir, nelfinavir, itraconazole).

Side effect

Vesicar can cause side effects associated with the anticholinergic effect of solifenacin, often of mild to moderate severity. The frequency of these unwanted effects depends on the dose. The most commonly reported side effect of Vesicar is dry mouth. It was observed in 11% of patients who received a dose of 5 mg per day, in 22% of patients who received a dose of 10 mg per day, and 4% who received a placebo. The severity of dry mouth was usually mild and only in rare cases led to interruption of treatment. Overall, adherence to treatment (compliance) was very high. About 90% of patients receiving Vesicar completed the 12-week course of treatment.

Overdose

Solifenacin overdose can potentially lead to severe anticholinergic effects. The highest dose of solifenacin that was randomly given to one patient was 280 mg over 5 hours. This dose led to a change in the patient's mental state, but did not require hospitalization. In cases of overdose, activated charcoal should be prescribed, gastric lavage is effective for an hour, but vomiting should not be induced. As with overdose of other anticholinergics, symptoms should be treated as follows:

• with severe anticholinergic effects of central action (hallucinations, severe excitability) - physostigmine or carbachol.

• with convulsions or severe excitability - benzodiazepines.

• with respiratory failure - artificial respiration.

• with tachycardia - beta-blockers.

• with acute urinary retention - catheterization.

• with mydriasis - instill pilocarpine in the eyes and / or place the patient in a dark room.

As in the case of overdose of other anticholinergic drugs, special attention should be paid to patients with an established risk of prolongation of the QT interval (i.e., with hypokalemia, bradycardia and concomitant use of drugs that cause prolongation of the QT interval) and patients with previously diagnosed heart disease (myocardial ischemia , arrhythmias, congestive heart failure).

Interaction with other medicinal products

‘армакологическое взаимодействие
—опутствующее лечение лекарственными средствами с антихолинергическими свойствами может привести к более выраженным терапевтическим и нежелательным эффектам. ѕосле прекращени¤ приема солифенацина следует сделать примерно недельный перерыв, прежде чем начинать лечение другим антихолинергическим препаратом. “ерапевтический эффект может быть снижен при одновременном приеме агонистов холинергических рецепторов. —олифенацин может снизить эффект лекарственных препаратов, стимулирующих моторику желудочно-кишечного тракта, например - метоклопрамида и цизаприда.

‘армакокинетическое взаимодействие
»сследовани¤ invitro показали, что в терапевтических концентраци¤х солифенацин не ингиби-рует изоферменты CYP1A1/2, 2—9, 2—19, 2D6 или «ј4, выделенные из микросом печени челођвека. ѕоэтому маловеро¤тно, что солифенацин изменит клиренс лекарств, метаболизируемых этими CYP-ферментами.

¬оздействие других лекарственных средств на фармакокинетику солифенацина
—олифенацин метаболизируетс¤ изофермент CYP3A4. ќдновременное введение кетоконазола (200 мг в день), сильного ингибитора изофермента CYP3A4, вызывало двукратное увеличение AUC зависимости концентрации от времени солифенацина, а в дозе 400 мг/день - трехкратное увеличение. ѕоэтому максимальна¤ доза ¬езикара не должна превышать 5 мг, если больной одновременно принимает кетоконазол или терапевтические дозы других сильных ингибиторов изофермента CYP3A4 (таких, как ритонавир, нелфинавир, итраконазол). ќдновременное лечение солифенацином и сильным ингибитором изофермента CYP3A4 противопоказано пациентам с т¤желой почечной недостаточностью или с умеренной печеночной недостаточностью. Ќе изучались ¤влени¤ индукции ферментов на фармакокинетику солифенацина и его метаболитов, а так же вли¤ние высокоафинных субстратов изофермента CYP3A4 на действие солифенацина.

ѕоскольку солифенацин метаболизируетс¤ изоферментом CYP3A4, возможны фармако-кинетические взаимодействи¤ с другими субстратами изофермента CYP3A4 с более высоким сродством (верапамил, дилтиазем) и с индукторами изофермента CYP3A4 (рифампицин, фени-тоин, карбамазепин).

¬ли¤ние солифенацина на фармакокинетику других лекарственных средств
ѕероральные контрацептивы: Ќе вы¤влено фармакокинетического взаимодействи¤ солифенацина и комбинированных пероральных контрацептивов (этинилэстрадиол / левоноргестрел).
¬арфарин: ѕрием ¬езикара не вызывал изменений фармакокинетики R-варфарина или S-варфарина или их вли¤ни¤ на протромбиновое врем¤.
?игоксин: ѕрием ¬езикара не оказывал вли¤ни¤ на фармакокинетику дигоксина.

ќсобые указани¤

” пациентов с такими факторами риска, как существующее удлинение интервала QT и гипокалиеми¤, наблюдалась удлинение интервала QTи желудочкова¤ тахикарди¤ по типу Ђпируэтї. Ёффективность и безопасность не изучалась у пациентов с нейрогенной дисфункцией мочевого пузыр¤. Ѕыло доложено о нескольких случа¤х ангионевротического отека с обструкцией дыхательных путей у пациентов, принимающих солифенацин. ѕоэтому, при возникновении ангионевротического отека, должен быть прекращен прием солифенацина и прин¤ты соответствующие меры.

Ѕыло доложено о нескольких случа¤х анафилактических реакций у пациентов, принимающих солифенацин. ѕоэтому, при возникновении анафилактической реакции, должен быть прекращен прием солифенацина и прин¤ты соответствующие меры.

¬ли¤ние на способность управл¤ть транспортными средствами, механизмами

Solifenacin, like other anticholinergic drugs, can cause blurred vision, as well as (rarely) drowsiness and fatigue, which can adversely affect the ability to drive and operate machinery.

Release form

Film-coated tablets 5 mg, 10 mg.

10 tablets in a blister made of PVC film and aluminum foil.

1 or 3 blisters, together with instructions for use, are placed in a cardboard box.

Storage conditions

Store at a temperature not exceeding 25 ? C, out of the reach of children.

Shelf life

3 years.

The drug should not be used after the expiration date indicated on the package.

Vacation conditions

On prescription.