Vesicare, 30 pcs., 10 mg, film-coated tablets

pharmachologic effect

Solifenacin is a specific inhibitor of membrane proteins responsible for signal transmission at neuromuscular synapses, acetylcholine muscarinic receptors (m-cholinergic receptors). The medication has an antispasmodic and anticholinergic effect (reduces the tone of the smooth muscle tissue of the urinary tract). Solifenacin is characterized by an almost complete lack of affinity for ion channels and other receptors.

When using Vesicare, a cumulative effect is observed - the maximum effect is recorded after a month of use and persists in case of long-term use (at least 1 year).

Pharmacodynamics and pharmacokinetics

When taken orally, the time to reach Cmax (maximum concentration) of solifenacin in blood plasma is 3-8 hours. Solifenacin reacts with plasma proteins and is approximately 98% bound to them. These indicators do not depend on food intake and time of intake. There is also no dependence on the gender and age of the patient. In patients with renal failure, an increase in the maximum concentration of the active substance in the blood by 30% may be observed.

The medication is metabolized in the hepatic system. It is excreted in urine and feces, and there is also an alternative pathway of metabolism (4R-hydroxysolifenacin, N-oxide and other metabolites have been identified in plasma). The half-life of the drug is 45-68 hours.

Vesicare 10 mg 30 pcs. film-coated tablets

pharmachologic effect

Antispasmodic.

Composition and release form Vesicare 10 mg 30 pcs. film-coated tablets

Tablets - 1 tablet:

• composition of the tablet core: 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;
• 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.

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

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

Description of the dosage form

Round, biconvex, light yellow film-coated tablets, marked “150” and the company logo on one side.

Directions for use and doses

Adults, including the elderly

5 mg once a day orally, with liquid, regardless of meal time. If necessary, the dose can be increased to 10 mg once a day.

Children

The safety and effectiveness of Vesicare® in children have not been studied. Therefore, Vesicare® should not be used in children.

Patients with kidney failure

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

Patients with liver failure

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

Patients receiving strong CYP3A4 inhibitors

The maximum dose of Vesicare should be limited to 5 mg when co-administered with ketoconazole or a therapeutic dose of another CYP3A4 inhibitor (ritonavir, nelfinavir, itraconazole).

Pharmacodynamics

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 conducted 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 effectiveness of Vesicare® at 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 within the first week of treatment and stabilized over the subsequent 12 weeks of treatment. A long-term, open-label clinical study showed that effectiveness was maintained for at least 12 months. After 12 weeks of use, approximately 50% of patients who suffered from urinary incontinence before treatment ceased to experience urinary incontinence, and 35% of patients achieved a reduction in frequency of urination of less than 8 per day. Treatment of overactive bladder (OAB) symptoms resulted in significant improvements in quality of life scores. The maximum effect of Vesicare® can be detected after 4 weeks.

Pharmacokinetics

General characteristics

Absorption: Maximum plasma concentration (Cmax) is reached after 3-8 hours. The time to reach maximum concentration (tmax) does not depend on the dose. Cmax and area under the curve (AUC) of concentration versus time increase in proportion to increasing doses from 5 to 40 mg. Absolute bioavailability - 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 L. Solifenacin is largely (about 98%) bound to plasma proteins, predominantly to α1-acid glycoprotein.

Metabolism: Solifenacin is extensively metabolized by the liver, predominantly by the CYP3A4 isoenzyme. However, there are alternative metabolic pathways through which solifenacin can be metabolized. The systemic clearance of solifenacin is approximately 9.5 L/hour, and the terminal 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).

Elimination: After a single dose of 10 mg 14C-labeled solifenacin, approximately 70% of the radioactivity was detected in urine and 23% in feces after 26 days. In urine, approximately 11% of the radioactivity was found as unchanged active substance, about 18% as the N-oxide metabolite, 9% as the 4R-hydroxy-N-oxide metabolite, and 8% as the 4R-hydroxy metabolite (the active metabolite).

The pharmacokinetics of solifenacin is 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 solifenacin (5 and 10 mg) exposure, expressed as AUC, was similar in healthy older individuals (65 to 80 years of age) and healthy younger individuals (

The pharmacokinetics of solifenacin have not been determined in children and adolescents.

Gender: The pharmacokinetics of solifenacin does not depend on the gender of the patient.

Race: Race does not affect the pharmacokinetics of solifenacin.

Renal impairment: The AUC and Cmax of solifenacin in patients with mild to moderate renal impairment are not significantly different from the corresponding values ​​in healthy volunteers. In patients with severe renal failure (creatinine clearance ≤ 30 ml/min), the exposure to 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 have not been studied.

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

Indications for use Vesicare 10 mg 30 pcs. film-coated tablets

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

Contraindications

• Urinary retention;
• severe gastrointestinal diseases (including toxic megacolon);
• myasthenia gravis;
• angle-closure glaucoma;
• hypersensitivity to the active substance or any of the excipients;
• hemodialysis;
• severe liver failure;
• severe renal failure or moderate liver failure during concomitant treatment with strong inhibitors of the CYP3A4 isoenzyme, such as ketoconazole;
• lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
• children under 18 years of age.

Carefully:

Before starting treatment with Vesicar®, it should be determined whether there are other causes of urinary problems (heart failure or kidney disease). If a urinary tract infection is detected, appropriate antibacterial treatment should be started.

Vesicare® should be administered with caution to patients:

• with clinically significant obstruction of the bladder outlet, leading to the risk of developing urinary retention;
• with gastrointestinal diseases with obstruction;
• with a risk of reduced gastrointestinal motility;
• with severe renal disease (creatinine clearance
• while taking a strong inhibitor of the CYP3A4 isoenzyme, for example, ketoconazole;
• with hiatal hernia, gastroesophageal reflux and patients concomitantly taking medications (for example, bisphosphonates) that can cause or worsen esophagitis;
• with autonomic neuropathy.

Application Vesicare 10 mg 30 pcs. film-coated tablets during pregnancy and breastfeeding

There are no clinical data on women who became pregnant while taking solifenacin. Animal studies have shown no direct adverse effects on fertility, embryonic/fetal development or childbirth. Caution should be used 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 data on the excretion of solifenacin into breast milk. In mice, solifenacin and/or its metabolites were excreted into breast milk and caused dose-dependent developmental impairment in neonatal mice. The use of Vesicare® is not recommended during breastfeeding.

special instructions

QT prolongation and torsade de pointes (TdP) have been observed in patients with risk factors such as existing QT prolongation and hypokalemia.

Efficacy and safety have not been studied in patients with neurogenic bladder dysfunction.

Several cases of angioedema with airway obstruction have been reported in patients taking solifenacin. Therefore, if angioedema occurs, solifenacin should be discontinued and appropriate measures taken.

Several cases of anaphylactic reactions have been reported in patients taking solifenacin. Therefore, if an anaphylactic reaction occurs, solifenacin should be discontinued and appropriate measures taken.

Impact on the ability to drive vehicles and operate machinery

Solifenacin, like other anticholinergic drugs, may cause blurred vision and (rarely) drowsiness and fatigue, which may impair the ability to drive and operate machines.

Overdose

Overdose of solifenacin can potentially lead to severe anticholinergic effects. The highest dose of solifenacin that was accidentally given to one patient was 280 mg over 5 hours. This dose resulted in a change in the patient's mental status 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 anticholinergic drugs, symptoms should be treated as follows:

• for severe anticholinergic effects of central action (hallucinations, severe excitability) - physostigmine or carbachol;
• for convulsions or severe excitability - benzodiazepines;
• in case of respiratory failure - artificial respiration;
• for tachycardia - beta blockers;
• for acute urinary retention - catheterization;
• for mydriasis, instill pilocarpine into the eyes and/or place the patient in a dark room.

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

Side effects Vesicare 10 mg 30 pcs. film-coated tablets

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

The table below lists the remaining side effects reported in clinical trials of Vesicare®:

*observed in the post-marketing period

Reporting Adverse Events

Reporting of suspected adverse events after a drug is authorized on the market is very important as the company continuously monitors the risk/benefit ratio.

Drug interactions

Pharmacological interaction

Concomitant treatment with drugs with anticholinergic properties may lead to more pronounced therapeutic and undesirable effects. After stopping solifenacin, take approximately a week off before starting treatment with another anticholinergic drug.

The therapeutic effect may be reduced by concomitant use of cholinergic receptor agonists.

Solifenacin may reduce the effect of drugs that stimulate gastrointestinal motility, such as metoclopramide and cisapride.

Pharmacokinetic interaction

In vitro studies have shown that, at therapeutic concentrations, solifenacin does not inhibit CYP1A 1/2, 2C9, 2C19, 2D6 or 3A4 isoenzymes isolated from human liver microsomes. Therefore, solifenacin is unlikely to alter the clearance of drugs metabolized by these CYP enzymes.

Effect of other drugs on the pharmacokinetics of solifenacin

Solifenacin is metabolized by the CYP3A4 isoenzyme. Co-administration of ketoconazole (200 mg/day), a strong inhibitor of the CYP3A4 isoenzyme, caused a two-fold increase in the AUC concentration-time dependence of solifenacin, and at a dose of 400 mg/day - a three-fold increase. Therefore, the maximum dose of Vesicare should not exceed 5 mg if the patient is simultaneously taking ketoconazole or therapeutic doses of other strong CYP3A4 inhibitors (such as ritonavir, nelfinavir, itraconazole). Concomitant treatment with solifenacin and a strong CYP3A4 inhibitor is contraindicated in patients with severe renal impairment or moderate hepatic impairment.

The phenomena of enzyme induction on the pharmacokinetics of solifenacin and its metabolites, as well as the influence of high-affinity substrates of the CYP3A4 isoenzyme on the action of solifenacin, have not been studied. Since solifenacin is metabolized by the CYP3A4 isoenzyme, pharmacokinetic interactions with other CYP3A4 isoenzyme substrates with higher affinity (verapamil, diltiazem) and with inducers of the CYP3A4 isoenzyme (rifampicin, phenytoin, carbamazepine) are possible.

Effect of solifenacin on the pharmacokinetics of other drugs

Oral contraceptives:

There was no pharmacokinetic interaction between solifenacin and combined oral contraceptives (ethinyl estradiol/levonorgestrel).

Warfarin:

Taking Vesicare® did not cause changes in the pharmacokinetics of R-warfarin or S-warfarin or their effect on prothrombin time.

Digoxin:

Taking Vesicare® had no effect on the pharmacokinetics of digoxin.

Contraindications

• severe gastrointestinal diseases ;
• liver failure in severe and terminal forms;
• renal failure (including when taking CYP3A4 inhibitors);
• hemodialysis;
• myasthenia gravis;
• urinary retention;
• angle-closure form of glaucoma ;
• hypersensitivity or intolerance to the components of the drug;
• childhood and adolescence;
• galactosemia and lactose deficiency.

There is no data on the effect of this drug on the body under 18 years of age. There are no contraindications for the elderly. Use with caution during pregnancy and lactation .

Vesicare drug interactions

Concomitant use of other drugs with anticholinergic properties may have a more pronounced therapeutic effect, as well as more pronounced side effects. After stopping taking Vesicare, an interval of about 1 week should be maintained before prescribing other drugs with anticholinergic effects. The therapeutic effect of solifenacin may be reduced by concomitant use of cholinergic receptor agonists. Solifenacin may reduce the effectiveness of gastrointestinal motility stimulants (metoclopramide, cisapride). When taking ketoconazole or other active inhibitors of the CYP3A4 enzyme (for example, ritonavir, nelfinavir, itraconazole), the dose of Vesicare should be reduced to 5 mg. Concomitant administration of solifenacin and an active CYP3A4 enzyme inhibitor is contraindicated in patients with severe renal or moderate hepatic impairment. Since solifenacin is metabolized by the CYP3A4 enzyme, pharmacokinetic interactions with other substrates of this enzyme (eg verapamil, diltiazem) and inducers of the CYP3A4 enzyme (eg rifampicin, phenytoin, carbamazepine) are possible. There was no pharmacokinetic interaction of solifenacin with combined oral contraceptives (ethinyl estradiol/levonorgestrel). Vesicare does not affect the pharmacokinetics of warfarin and digoxin.

Side effects

Often noted:

• constipation;
• vomiting and nausea;
• epigastric pain;
• disturbances of accommodation;
• dry throat and mouth;
• urinary retention;
• dry eyes;
• drowsiness;
• dryness of the nasal cavity and skin;
• swelling of the lower extremities;
• feeling tired.

Rarely recorded:

• intestinal obstruction;
• dizziness , moderate lethargy and headache ;
• acute ischuria (urinary retention);
• vomit;
• hallucinations;
• drowsiness;
• allergic responses ( itching , rash , hives ).

Side effects of Vesicare

When using Vesicare, side effects associated with the anticholinergic effect of solifenacin are possible, which, as a rule, are mild or moderate and dose-dependent. The most common side effect is dry mouth, which is usually mild and only in isolated cases requires discontinuation of the drug. The frequency of side effects is classified: very often (≤1/10, ≥1/100); uncommon (≤1/100, ≥1/1000); rare or isolated cases (≤1/1000, ≥1/10,000). From the gastrointestinal tract: often - nausea, dyspepsia, constipation, abdominal pain; infrequently - dryness of the pharyngeal mucosa, gastroesophageal reflux; rarely, in isolated cases - obstruction of the large intestine, coprostasis. From the side of the central nervous system: infrequently - drowsiness, taste disturbance. From the senses: often - blurred vision (impaired accommodation), infrequently - dry eyes. Infections and infestations: uncommon - urinary tract infections. General disorders: infrequently - increased fatigue, swelling of the lower extremities. From the respiratory system: not often - dryness of the nasal mucosa. From the skin: infrequently - dry skin. From the urinary system: infrequently - difficulty urinating, in isolated cases - urinary retention.

Instructions for Vesicare (Method and dosage)

The drug is administered orally with plenty of liquid, 1 tablet with a solifenacin concentration of 5 mg once a day. According to indications, the dose can reach 10 mg. The medication can be taken regardless of the time of day or meal.

Instructions for use of Vesicare indicate the possible effect of the active substance on the quality of visual perception and the functioning of the central nervous system. You should not take the drug when working with complex mechanisms or driving vehicles.

special instructions

Before prescribing the drug, the presence of other possible causes of urinary disorders ( urinary tract infections , kidney and ureter diseases, heart failure ) should be established. If a genitourinary tract infection is detected, antimicrobial treatment before starting this medication. You should take the drug with care when working with vehicles and when engaging in hazardous activities.

Special instructions for the use of Vesicare

Before starting treatment with the drug, it is necessary to establish the likelihood of other causes of frequent urination (kidney disease, heart failure, etc.). If a urinary tract infection is detected, appropriate antibiotic therapy should be started. The drug should be prescribed with caution to patients with clinically significant obstruction of the bladder outlet, obstructive gastrointestinal diseases, gastrointestinal motility disorders, severe renal (creatinine clearance ≤30 ml/min) and moderately severe liver failure (7-9 points on the Child-Pugh scale; dose for these patients should not exceed 5 mg), autonomic neuropathy, hiatal hernia and gastroesophageal reflux and/or concomitant use of drugs that can cause or worsen esophagitis (e.g. bisphosphonates), while using an active CYP3A4 inhibitor (e.g. ketoconazole) . The drug should not be prescribed to patients with congenital galactose sensitivity disorder, lactase deficiency or glucose-galactose malabsorption. The effect of using the drug is noted already in the 1st week of treatment, but the maximum effect is achieved after 4 weeks of therapy. There are no data on the use of the drug in children. Since the drug, like other anticholinergic drugs, can cause disturbances in accommodation and a decrease in the speed of psychomotor reactions, the question of the possibility of performing potentially hazardous activities should be decided only after assessing the patient’s individual response to the drug. There are no clinical data on the use of solifenacin during pregnancy, however, experimental studies have not revealed any direct adverse effects on fertility, fetal development or the course of labor. In this regard, caution should be exercised when using the drug in pregnant women. There is no data on the excretion of solifenacin in breast milk, therefore the use of Vesicare during breastfeeding is not recommended.

Analogues of Vesicare

Level 4 ATC code matches:
Oxybutynin

Detrusitol

Urochol

Urocholum

Cystenal

Driptan

Urotol

Spazmex

Structural analogues have not been developed. Medicines with a similar mechanism of action:

• Driptan
• Spazmex
• Uro-Vaxom
• Urotol

The price of analogues varies from 300 to 500 rubles.

Reviews about Vesicare (patients' opinions)

Reviews about Vesicare on medical forums indicate that the drug has not been able to establish itself as the most highly effective remedy in the fight against the problem of urinary incontinence. Most patient stories do not report any relief after taking the drug. In addition, many users report frequent side effects.

However, there is evidence of cases where the best result among analogues was observed precisely after taking Vesicare; when other medications did not help. It is important to remember that the treatment of overactive bladder syndrome is complex and largely depends on the individuality of each individual organism.

Vesicare drug overdose, symptoms and treatment

The maximum dose of the drug used was 100 mg once. Side effects such as mild headache, moderate dry mouth, dizziness, drowsiness, and blurred vision were noted. In case of overdose, it is necessary to rinse the stomach and prescribe activated charcoal. As with an overdose of other anticholinergic drugs, the following measures are taken: for pronounced central effects (hallucinations, agitation) - physostigmine or carbachol; for seizures - benzodiazepines; in case of respiratory failure - mechanical ventilation; for urinary retention - catheterization of the bladder; for mydriasis - instilling pilocarpine into the eyes or placing the patient in a darkened room; for tachycardia - β-adrenergic receptor blockers. Particular attention should be paid to patients at risk of prolongation of the QT on the ECG (with hypokalemia, bradycardia, simultaneous use of drugs that can cause prolongation of the QT ) and patients with heart disease (coronary artery disease, arrhythmia, chronic heart failure).

Vesicare price, where to buy

The cost of the drug in Russian pharmacies varies from 1200 to 1550 rubles for 30 tablets. The price of Vesicare depends on the region of sale and pharmacy chain.

• Online pharmacies in RussiaRussia
• Online pharmacies in UkraineUkraine
• Online pharmacies in KazakhstanKazakhstan

Pharmacy Dialogue

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  RUB 1,037 order
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  RUR 729 order

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Pharmacy24

• Vesicare 5 mg No. 30 tablets Astellas Pharma Europe B.V., Netherlands
  346 UAH.order

PaniPharmacy

• Vesicare tablets Vesicare tablets. p/o 5 mg No. 30 Netherlands, Astellas Pharma Europe

  369 UAH. order

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